DC L LM SNG

BI 1. KHI NIM V THUC 1.1. Khi nim v thuc : Thuc l nhng sn phm c ngun gc t ng vt, thc vt, khong vt, ha dc hay sinh hm : + Phng bnh, cha bnh. + Phc hi, iu chnh chc nng c th. + Lm gim triu chng bnh. + Chn on bnh. + Phc hi hoc nng cao sc khe. + Lm mt cm gic mt b phn c th hay ton thn. + Lm nh hng n qu trnh sinh sn. + Lm thay i hnh dng c th 1.2. Tn thuc : 1.2.1. Tn ha hc : nu hot cht ca thuc l cht ha hc. 1.2.2. M s : c s dng trong qu trnh thuc cn ang c th nghim tin lm sng v lm sng. V d dch chit t l Bch qu ( Ginkgo biloba L. ) trong qu trnh th nghim mang m s EGb 761. 1.2.3. Tn chung ( nonproprietary name ), cn c gi l tn gc ( generic name ; nom generique ). Tng ng vi mi thuc nht nh, mi nc c mt tn chung c chp thun s dng trong nc . V d Php, tn chung cc thuc c ghi trong Dc in quc gia. Cn M, tn chung ca thuc do mt hi ng xem xt la chn. 1.2.4. Tn chung quc t ( INN = international nonproprietary name hay DCI = Denomination commune internationale ). Nm 1953, WHO ngh nn chn cho mi dc cht mt tn chung c quc t tha nhn da trn cc nguyn tc : ngn gn, d c, d vit, kh nhm ln, tin s dng, phn nh nhm tc dng dc l{ cng nh i din cu trc ha hc. 1.2.5. Tn bit dc hay tn c ch ( trade mark name; brand name; nom de marque; sp cialit pharmaceutique; tn thng mi ). Sau tn bit dc c th c du hiu chng t tn thuc c ng k{ ti Vn phng sng ch ( M ) hoc

cu chng ti Ta n ( Php ). WHO khuyn co cc nc khng nn dng tn chung quc t lm tn bi?t dc. * V d cc tn thuc : paracetamol. + Tn chung quc t ( INN, DCI ) : paracetamol. + Tn chung M : acetaminophen. Tn chung Php : paracetamol. + Tn ha hc : N-acetyl paminophenol; P.acetamidophenol; 4-hydroxyacetanilid. + Tn bit dc : algotropin, cetamol, datril, efferalgan, panadol, paradon 1.3. Hn dng : + Hn dng thuc l khong thi gian c n nh cho mt loi thuc m trong thi gian ny thuc c bo qun trong iu kin quy nh phi m bo t cht lng theo tiu chun ng k{. + Hn dng thuc thng c ghi bng s hoc bng ch trn nhn thuc nhm ch r sau thi hn ny, thuc khng cn gi tr s dng. + Mt s k hiu v hn dng : HD ( Vit Nam ), expiry date, EXP. date, EXP., EXD., E.D.; Exp., use by, best before ( Anh ) + Cc k hiu tng t : validity, shelf-life ( tui th ca thuc ).1.4. Tiu chun cht lng thuc: 1.4.1. Tiu chun GMP ( good pharmaceutical manufacturing practice ) : do WHO quy nh. K hiu : GMP 1.4.2. Tiu chun cc Dc in quc t hoc quc gia c uy tn : + Dc in M ( USP = The United states pharmacopoeia ). c USP 24 ( USP XXIV 2000 ) + Dc in Anh ( BP = British pharmacopoeia ). + Dc in Chu u ( EP = European pharmacopoeia ). + Dc in Hn Quc ( KP = Korean pharmacopoeia ) 1.4.3. Tiu chun FDA ( Food and drug administration - C quan qun l thc phm v thuc ): - KFDA = Korea food and drug administration. - US-FDA = The United states food and drug administration.

1.4.4. Cc cp tiu chun Vit Nam v thuc : a- Tiu chun Dc in Vit Nam ( DVN ): l tiu chun cp nh nc v thuc. C DVN III ( 2002 ).b- Tiu chun c s : + L tiu chun do c s sn xut thuc bin son, p dng i vi cc sn phm do c s sn xut ra. Vit tt : TCCS. + C 2 loi tiu chun c s : - TCCS ca nhng sn phm lu hnh th trng : phi ng k{ vi c quan c thm quyn. Cc mc tiu chun cht lng khng c thp hn cc mc quy nh trong tiu chun DVN. - TCCS ca cc thuc pha ch trong n v (khng lu hnh trn th trng): do th trng n v xt duyt v ban hnh 1.4.5. Tiu chun ca cc nh sn xut nc ngoi + l tiu chun do nh sn xut t t ra cho cc sn phm ca mnh. Tiu chun ny thng tng ng vi tiu chun ca cc Dc in quc gia hoc quc t c uy tn cao ( BP, USP, EP, KP ). + K hiu : home standard, in-house, munufacturers ( standard, specification ) BI 2. CHUYN HA THUC 1. Hu qu ca chuyn ha thuc 2. Ni chuyn ha v cc enzym chnh xc tc + Nim mc rut : protease, lipase, decarboxylase. + Huyt thanh : esterase. + Phi : oxydase. + Vi khun rut : reductase, decarboxylase. + H TKT : MAO, decarboxylase. + Gan : l ni chuyn ha chnh, cha hu ht cc enzym tham gia chuyn ha thuc. 3. Cc pha chuyn ha Thng thng cc thuc c chuyn ha qua 2 pha. 3.1. Pha I: bao gm cc phn ng: oxy ho, oxy kh v phn ng thu phn. 3.1.1. Phn ng oxy ho: L phn ng ph bin nht, cxc tc bi cc enzym oxy ho (mixed function oxydase enzym - mfO) c nhiu trong microsom g?an - h enzym cytochrom P450

(Cyt P450). Phn ng c thc hin theo nhiu bc: a.C cht (thuc, RH) phn ng vi dng oxy ho ca Cyt - P450(Fe3+) to thnh phc hp RH - P450 (Fe3+). b.Phc hp RH - P450 (Fe3+) nhn 1 electron t NADPH, b kh thnh RH - P450 (Fe2+). c.Sau , phc hp RH - P450 (Fe2+) phn ng vi 1 phn t oxy v 1 electron th 2 t NADPH to thnh phc hp oxy hot ho. d.Cui cng, 1 nguyn t oxy c gii phng to H2O. Cn nguyn t oxy th 2 s oxy ho c cht (thuc): RH ROH, v Cyt - P450 c ti to. Phn ng cho s oxy ha thuc c tm tt nh sau :R-H + 2e- + 2H+ + O2 ROH + H2O* Nhng phn ng oxy ho khc: M AO nm ti np th gan, thn, h thn kinh trung ng, xc tc cho ging ho catecholamin v serotonin h thn kinh, lm mt tc dng ca nhiu thuc c cha amin. 3.1.2. Phn ng kh: kh cc dn xut nitro, cc aldehyd, bi enzym nitro reductase, dehydrogenase. RNO2 RNO RNHOH RNH2 (Nitrobenzen, Cloramphenicol, Clorazepam) 3.1.3. Phn ng thu phn: Cc ester (procain, aspirin, succinylcholin, clofibrat) : R1COOR2 RCOOH + R2OH Cc amid (procainamid, lidocain, indomethacin) : RCONHR1 R- COOH + R1NH2 Mt s thuc v mt s cht l este hoc amid c thy phn nh esterase hoc amidase gan, rut, huyt tng, no Sau khi thy phn, cc cht ny l ra cc nhm chc OH hoc NH2 v d dng lin hp vi acid glucuronic hoc acid acetic hay acid sulfuric. Amidase hot tnh yu hn esterase nn Procainamid kh chuyn ha hn Procain. Do vy, Procainamid tc dng k o di hn Procain. Acetylcholin l cht trung gian ha hc ca h thn kinh cng b thu phn thnh acid acetic v cholin di s xc tc ca cholinesterase. *a s cc thuc c chuyn ho pha I; Cc thuc sau khi c chuyn ho s: Gim tc dng hoc mt c tnh. Hoc s to ra mt s nhm chc trong cu trc phn t: - OH, - COOH, - NH2, - SHtham gia vo phn ng lin hp pha II *Tuy nhin

: + Mt s cht phi qua chuyn ha mi c tc dng : - Levo dopa chuyn ha thnh Dopamin - Aldomet chuyn ha thnh a- metyl noradrenalin + Mt s t cht qua chuyn ha c tc dng bng hoc mnh hn cht m VD: Phenacetin Paracetamol - Diazepam Oxazepam - Digitoxin Digoxin - Prednisolon Prednison (C th s dng cht con sn xut thuc). + Mt s t qua chuyn ha lm tng c tnh : - Parathion Paraoxon (dit cn trng) - Carbon tetraclorid CCl- Carbon tetraclorid CCl (Cl - gy hoi t gan) 3.2. Pha II : Sau khi ging ho pha I, cht chuyn ho va to thnh lin hp vi mt phn t ni sinh: acid acetic, acid glucuronic, acid sulfuric, acid amin (glycin). . . cui cng cho cht lin hp t tan trong lipid, d b ion ho, khng hp thu, khng cn hot tnh, d tan trong nc v b thi tr - l qu trnh kh c: iu kin: cc phn ng ny i hinng lng v c cht ni sinh Cc phn ng lin hp chnh: 3.2.1. Vi acid glucuronic : C nhiu cht lin hp vi acid glucuronic : cc acid mch thng hoc acid c nhn thm (acid salicylic, acid nicotinic) cho dn xut N-glucuronid. Nhng ch xc t t c S khi glucuro - hp s to dn xut S - glucuronid. Phn ng c th tm tt nh sau : Dng glucuronid ca thuc va c to thnh s c tnh acid, ion ho c PH sinh l, rt tan trong nc, cho nn s thi nhanh qua nc tiu hoc qua mt. Nh vy phn ng glucuro lin hp r rng l mt qu trnh gii c ca thuc. 3.2.2. Lin hp vi acid sulfuric Cc cht c nhm chc ru hoc phenol, v d Cloramphenicol, Estrol, Butanol s lin hp vi acid sulfuric trong cytosol ca t bo di s xc tc ca enzym sulfotransferase. PAPS + R-OH R-SO4 + PAP H C6H5OH + H2SO4 SO4

3.2.3. Vi acid acetic Nhng thuc c cha amin bc nht (nh histamin), cc sulfamid, cc hydrazin (nh isoniazid), u c th acetyl ho; sulfanilamid sau khi aceto hp s cho nhng tinh th sc cnh kh tan, gy tn thng b my tit niu. Trong c th cc phn ng chuyn ha thuc pha I, II xy ra ch yu gan, ngoi ra cn xy ra mt s c quan nh thn, nim mc rut, phi, da t bo, phn ng chuyn ha xy ra li ni bo, cytosol, ty lp th, nhn v mng bo tng. 4. c ch enzym v cm ng enzym chuyn ha thuc, hu qu 4.1. c ch enzym microsom Vi thuc no mt tc dng sau khi b oxy ha microsom gan, sau khi enzym chuyn ha b c ch, thuc s tng tc dng, tng c tnh. Mt vi v d ngi : 4.2. Cm ng enzym microsom : Hin tng lm tng tng hp cc protein - enzym gi l cm ng enzym. (Induction); cht gy c hin tng cm ng enzym l cht gy cm ng. (Inductor). n nay tm thy trn trn 200 cht gy c cm ng enzym oxy ha thuc microsom gan, gip thuc chuyn ha nhanh hn bnh thng, mt tc dng nhanh (hoc mt c tnh nhanh). Sau y l danh mc mt vi cht gy cm ng enzym m ta thng gp : Glutethimid, Barbiturat, Diphenylhydantoin, Meprobamat, Diazepam, Chlorpromazin, Promazin, Iproniazid, Imipramin, Nikethamid, Phenylbutazon, Tolbutamid, Carbutamid, Diphenhydramin, Rifampycin Nhn xt :khi kt hp thuc cng mt lc - Nu cht chuyn ho t tc dng hn cht m, th qua cm ng enzym, thuc s gim nhanh tc dng v gim c tnh nh vi Meprobamat, Barbiturat, Tolbutamid v.v.. - Nu phi qua chuyn ho th thuc mi c tc dng hoc tng tc dng, th cm ng enzym, ngc li, i k o theo tng mnh tc dng dc l{ (v c tnh) ca thuc , v d Parathion CCl4, Primaquin, Imipramin v.v.. - Nu thuc khng chuyn ho qua miorosom gan, th bt c loi cht gy cm ng no cng chng lm thay i dc ng hc v tc dng ca thuc , v d vi Acetazolamid, Aspirin, Barbital, khng sinh loi Aminoglycosid, Lithium v.v. - C thuc dng lin tc dn n gy cm ng enzym chuyn ho ca chnh thuc : Rifampycin, Carbamazepin, mt s Barbiturat, Meprobamat, Diphenylhydantoin, Phenylbutazon, Corticoid

5. ngha thc tin ca chuyn ho thuc qua gan 5.1. Qua chuyn ho nh hng n tc dng ca thuc : 5.1.1. Qua chuyn ho mt tc dng : + a s cc thuc qua chuyn ho to thnh cht t tan trong lipid, d lin hp, d ion ho pH sinh l, mt tc dng v d thi tr ra ngoi. V d : Clopromazin, cc Barbiturat, Phenytoin v.v.. + Nhiu cht chuyn ho qu nhanh, nn mt tc dng nhanh. Do vy, ko di tc dng ca thuc c th thay i cu trc bng cch thay i cc nhm chc d b chuyn ho hoc bao vy cc nhm chc bng cch to ra cc lin kt khc. V d : - Thay nhm methyl ca Tolbutamid bng Cl ta c Clopropamid c t/2 ko di 12 - 24 h, trong khi Tolbutamid c t/2 = 4 - 7 h. - Procain b esterase thu phn mt tc dng nhanh. Khi thay i cu trc to thnh Procainamid b chuyn ho chm hn nn tc dng k o di hn. 5.1.2. Qua chuyn ho mi c tc dng : + Mt s tin thuc (prodrugs bn thn cha c tc dng dc l{. Sau khi vo c th, cc thuc ny b chuyn ho to ra cht chuyn ho c tc dng dc l. V d : Cyclophosphamid Aldophosphamid + Vi nhng thuc thng qua chuyn ho mi c tc dng, khi phi hp vi cc cht gy cm ng enzym s lm tng tc dng ca thuc. Ngc li dng km vi cc cht c ch s lm gim tc dng. 5.1.3. Qua chuyn ho vn gi nguyn tc dng : Mt s cht sau khi chuyn ho sinh ra cht chuyn ho c tc dng nh cht m, thm ch c cht t tc dng ph hn cht m. VD: Phenacetin Paracetamol 5.2. Qua chuyn ho tng c tnh * Carbontetraclorid sau khi chuyn ho qua gan to thnh gc t do CCl3. Chnh gc t do triclomethyl gy c vi gan. Khi kt hp cc cht gy cm ng enzym oxy ho cng lm tng c tnh ca CCl4 . * Parathion l cht dit cn trng, bn thn n khng c ch cholinesterase ca cn trng, vt ch, nhng trong c th cn trng v ngi parathion b chuyn ho qua MFO to ra cht paraoxon c tc dng c ch cholinesterase ca cn trng v ngi, gy c cho ngi v cn trng. * Primaquin l thuc chng st r t khi vo c th b chuyn ho thnh demethylprimaquin, 5 - OH - primaquin v 5 - OH - demethylprimaquin.

Chnh 3 cht chuyn ho ny gy met-Hb hoc thiu mu tan mu. Isoniasid (Rimifon) nh phn ng lin hp vi acid acetic to ra cc acetylisoniasid. Acetylisoniasid b thy phn tip tc to ra acetylhydrazin v cht chuyn ha ny b chuyn ha qua MFO to ra cht chuyn ha c vi t bo gan. Trong iu tr lao, phi hp INH vi Rifampycin (mt cht gy cm ng enzym microsom gam) s lm tng tn thng gan. PHN PHI THUC Gn thuc vo protein huyt tngSau khi thuc hp thu, thuc qua mu chuyn n ni c tc dng, ti mu, thuc c chia lm 2 dng : - Dng kt hp vi protein huyt tng - Dng t do * Kh nng gn vo protein huyt tng tuz theo tng loi thuc : Gn mnh 75 - 98% : Sulfamid chm, Quinin, Rifampicin, Digoxin, Lincomycin, indomethaxin, Dicumarol. . . Gn yu : 1 - 8% : Sulfaguanidin, Barbital Mt s t cht khng gn c vo protein huyt tng, l nhng phn t nh, tan nhiu trong nc : Ure, ouabain, Glucocorticoid ngha : - Mt khi dng kt hp th thuc cha thm qua mng, cha c hot tnh ch dng t do mi c tc dng v c tnh ( phc hp thuc - protein ). Protein huyt tng l kho d tr thuc phc hp ( thuc- protein ) ko di s c mt ca thuc mu, khng ging ho, khng khuych tn qua mng sinh vt, khng thi. Phc hp l ngun cung cp thng xuyn dng t do, ko di tc d?ng ca thuc. - Do c gn vo protein huyt tng tnh ho tan ca thuc trong nc cng tng theo ( Dicoumarol t tan trong nc s tr nn d tan trong huyt tng ). - Nu hai thuc cng c i lc vi nhng ni ging nhau protein huyt tng, chng s i khng cnh tranh, phn t do ca thuc tng, tc dng v c tnh tng theo, do cn lu { phi hp thuc trong iu tr : ngi b bnh dng Tolbutamid v Phenlbutazon ( y Tolbutamid b y, bnh nhn d b chong do gim ng huyt t ngt). - Tr em : kh nng gn thuc km, d nhy cm vi thuc. * Trong qu trnh iu tr bnh nhng liu u tin ca thuc gn mnh vo protein huyt tng bao gi cng phi cao ( liu tn cng ) bo ho

v tr gn, lm cho nhng liu tip tc ( liu duy tr ) c th t hiu lc. * Nu thuc cng gn mnh vo protein huyt tng v vo t chc khc ( tc dng chn lc ) th iu trn khng cn ng. V d : Digital gn vo protein, nhng cn gn mnh vo t chc tim ( Gp 5 ln protein huyt tng ) tc dng r tim. BI 3. I CNG V DC NG HC 1. CC CCH VN CHUYN THUC QUA MNG SINH HC 1.1. c tnh l ha ca thuc - Thuc l cc phn t thng c trng lng phn t P M 600. Chng u l cc acid hoc cc base yu. - Kch thc phn t ca thuc c th thay i t rt nh (P M = 7 nh ion lithi) cho ti rt ln (nh alteplase- tPA- l protein c P M = 59.050). Tuy nhin, a s c P M t 100- 1000. gn kht vo 1 loi receptor, phn t thuc cn t c mt kch c duy nht vi kch thc ca receptor c hiu thuc khng gn c vo cc receptor khc (mang tnh chn lc). Kinh nghim cho thy P M nh nht phi t khong 100 v khng qu 1000, v ln qu th khng qua c cc mng sinh hc ti ni tc dng. Mt s thuc l acid yu: l phn t trung tnh c th phn ly thun nghch thnh mt anion (in tch (-)) v mt proton (H +). C8H7O2COOH C8H7O2COO + H+ Apirin trung tnh Aspirin anion Proton Mt s thuc l base yu : l mt phn t trung tnh c th to thnh mt cation (in tch (+)) bng cch kt hp vi 1 proton: C12H11ClN3NH3 C12H11ClN3NH2 + H + Pyrimethamin cation Pyrimethamin Proton trung tnh - Cc phn t thuc c sn xut di cc dng bo ch khc nhau : Tan c trong nc (dch tiu ha, dch khe), do d c hp thu. Tan c trong m thm qua c mng t bo gy ra c tc dng dc l v mng t bo cha nhiu phospholipid . V vy c hp thu vo t bo thun li nht, thuc cn c mt t l tan trong nc/ tan trong m thch hp. - Cc phn t thuc cn c c trng bi hng s phn ly pKa pKa c suy ra t phng trnh Hend erson-HasselbACh:

K l hng s phn ly ca 1 acid; pKa = - logKa pKa dng cho c acid v base. pKa +pKb=14 Mt acid hu c c pKa thp l 1 acid mnh v ngc li. Mt base c pKa thp l 1 base yu, v ngc li. Ni mt cch khc, khi mt thuc c hng s pKa bng vi pH ca mi trng th 50% thuc c dng ion ha (khng khuch tn c? qua mng) v 50% dng khng ion ha (c th khuch tn c). V khi , nng phn t/ nng ion= 1 v log 1 = 0. Ni chung, mt thuc phn tn tt, d c hp thu khi C trng lng phn t thp t b ion ha: ph thuc vo hng s phn ly (pKa) ca thuc v pH ca mi trng. D tan trong dch tiu ha (tan trong nc) ho tan trong lipid cao d qua mng ca t bo 1.2. Vn chuyn thuc bng cch lc Nhng thuc c trng lng phn t thp (1 00- 200), tan c trong nc nhng khng tan c trong m s chui qua cc ng dn (d= 4 - 40 ) ca mng sinh hc do s chnh lch p lc thu tnh. ng dn ca mao mch c vn c ng knh l 30 , ca mao mch no l 7 - 9, v th nhiu thuc khng vo c thn kinh trung ng. 1.3. Vn chuyn bng khuch tn th ng (theo bc thang nng ). Nhng phn t thuc tan c trong nc/ m s chuyn qua mng t ni c nng cao sang ni c nng thp. iu kin ca s khuch tn th ng l thuc t b ion ho v c nng cao b mt mng . Cht ion ha s d tan trong nc, cn cht khng ion ha s tan c trong m v d hp thu qua mng. S khuch tn ca acid v base yu ph thuc vo hng s phn ly pKa ca thuc v pH ca mi trng. Th d: khi ung 1 thuc l acid yu, c pKa = 4, gian 1 d dy c pH= 1 v gian 2 l huyt tng c pH = 7 (H.1)

p dng phng trnh Henderson - Hasselbach, ta c: gian 1 (d dy): [ R- COOH ] log = 4 - 1 = 3; Log ca 3 = 1000

[ R - COO- ] gian 2 (mu): [ R- COOH ] log = 4 - 7 = - 3; Log ca - 3 = 1/1000 [ R - COO- ] V ch phn khng ion ha v c nng cao mi khuch tn c qua mng cho nn acid ny s chuyn t gian 1 (d dy) sang gian 2 (mu) v c hp thu. Tr s pKa ca mt s thuc l acid yu v base yu c g hi bng1. Nn nh rng base c pKa cao l base mnh v acid c pKa cao l acid yu. cid yu pKa Base yu pKa Salicylic acid Acetylsalicylic acid Sulfadiazin Barbital Boric acid Reserpin 6.6 Codein 7.9 Quinin 8.4 Procain 8.8 Atropin 9. Bng 1.1: Tr s pKa ca mt s thuc l acid v base yu ( nhit 250C) Nh vy, salicylic acid (aspirin) uc hp thu nhiu d dy v phn trn ca ng tiu ha. Quabng ny cho thy khi b ng c thuc, mun ngn cn hp thu hoc thuc b hp thu ra ngoi, ta c th thay i pH ca mi t rng. Th d phenobarbital (Luminal, Gardenal) l mt acid yu c pKa = 7,2; nc tiu bnh thng c pH cng bng 7,2 nn phenobarbital b ion ha 50%. Khi nng pH ca nc tiu ln 8, ion ha ca thuc s l 86%, do thuc khng thm c vo t b o. iu ny c dng trong iu tr nhim c phenobarbital: truyn dung dch NaHCO 3 1,4% base ha nc tiu, thuc s b tng thi tr. i vi mt cht kh (th d thuc m bay hi), s khuch tn t khng kh ph nang vo mu ph thuc vo p lc ring phn ca cht kh gy m c trong khng kh th vo v ha tan ca kh m trong mu. 1.4. Vn chuyn tch cc Vn chuyn tch cc l s ti thuc t bn ny sang bn kia mng sinh hc nh mt cht vn ch?uyn (carrier) c hiu c sn trong mng sinh hc. * c im ca s vn chuyn ny l: - C tnh bo ha: do s lng carrier c hn

- C tnh c hiu: mi carrier ch to phc vi vi cht c cu trc c hiu vi n. - C tnh cnh tranh: cc thuc c cu trc gn ging nhau c th gn cnh tranh vi 1 carrier, cht no c i lc mnh hn s gn c nhiu hn. - C th b c ch: mt s thuc (nh actinomycin D) lm carrier gim kh nng gn thuc vn chuyn. * Hnh thc vn chuyn: c hai cch - Vn chuyn thun li (Vn chuyn tch cc th pht) : khi km theo carrier li c c s chnh lch bc thang nng , v vy s vn chuyn ny khng cn nng lng. Th d vn chuyn glucose, pyramidon theo bc thang nng ca Na +Vn chuyn tch cc thc th (Vn chuyn tch cc nguyn pht): l vn chuyn i ngc bc thang nng , t ni c nng thp sang ni c nng cao hn. V vy i hi phi c nng lng c cung cp do ATP thu phn, thng c gi l cc bm, th d s vn chuyn ca Na+, K+, Ca++,I-, acid amin.

Hnh 1.3. Cc cch vn chuyn thuc qua mng sinh hc 2. CC QU TRNH DC NG HC 2.1. S hp thu Hp thu l s vn chuyn thuc t ni dng thuc (ung, tim) vo mu ri i khp c th, ti ni tc dng. Nh vy s hp thu s ph thuc vo: - ha tan ca t huc. Thuc dng di dng dung dch nc d hp thu hn dng du, dch treo hoc dng cng - pH ti ch hp thu v c nh hng n ion ha v tan ca thuc. - Nng ca thuc. Nng cng cao cng hp thu nhanh. - Tun hon ti vng hp thu: cn g nhiu mch, cng hp thu nhanh. - Din tch vng hp thu. Phi, nim mc rut c din tch ln, hp thu nhanh. T nhng yu t cho thy ng a thuc vo c th s c nh hng ln n s hp thu. Ngoi tr ng tim tnh mch, trong qu trnh hp thu vo vng tun hon, mt phn thuc s b ph hu do cc enzym ca ng tiu ha, ca t bo rut v c bit l gan, ni c i lc vi nhiu thuc. Phn thuc b ph hu trc khi vo vng tun hon c gi l first pass metabolism (chuyn ha do hp thu hay

chuyn ha qua gan ln th nht v thng l ung thuc). Phn vo c tun hon mi pht huy tc dng dc l{, c gi l sinh kh dng (bioavailability) ca thuc (xin xem phn sau) Sau y s im qua cc ng dng thuc thng thng v cc c im ca chng. 2.1.1. Qua ng tiu ha u im l d dng v l ng hp thu t nhin. Nhc im l b cc enzym tiu ha ph hu hoc thuc to phc vi thc n lm chm hp thu. i khi thuc kch thch nim mc tiu ha, gy vim lot 2.1.1.1. Qua nim mc ming: thuc ngm di li Do thuc vo thng vng tun hon nn khng b dch v ph hu, khng b chuyn ha qua gan ln th nht 2.1.1.2. Thuc ung Thuc s qua d dy v qua rut vi cc c im sau: * d dy: - C pH = 1- 3 nn ch hp thu cc acid yu, t b ion ha, nh aspirin, phenylbutazon, barbiturat?. - Ni chung t hp thu v nim mc t mch mu, li cha nhiu cholesterol, thi gian thuc d dy khng lu. - Khi i hp thu nhanh hn, nhng d b kch thch * rut non: L ni hp thu ch yu v c din tch hp thu rt rng (> 40 m 2), li c ti mu nhiu, pH tng dn ti base (pH t 6 n 8). - Thuc t b ion ha nhng nu t hoc khng tan trong lipid (sulfaguanidin, streptomycin) th t c hp thu. - Thuc mang amin bc 4 s b ion ha mnh kh hp thu, th d cc loi cura. - Cc anion sulfat SO 4 khng c hp thu: MgSO 4, Na2SO4 ch c tc dng ty.2.1.1.3. Thuc t trc trngKhi khng dng ng ung c (do nn, do hn m, hoc tr em) th c d ng thuc t vo hu mn. Khng b enzym tiu ha ph hu, khong 50% thuc hp thu qua trc trng s qua gan, chu chuyn ha ban u. Nhc im l hp thu khng hon ton v c th gy kch ng nim mc hu

mn. 2.1.2. Thuc tim - Tim di da: do c n hiu si thn kinh cm gic nn au, t mch mu nn thuc hp thu chm - Tim bp: khc phc c hai nhc im trn ca tim di da - mt s thuc c th gy hoi t c nh ouabain, calci clorid th khng c tim bp. - Tim tnh mch: thuc hp thu n hanh, hon ton, c th iu chnh liu c nhanh. Dng tim cc dung dch nc hoc cc cht kch ng khng tim bp c v lng mch t nhy cm v mu pha long thuc nhanh nu tim chm.Thuc tan trong du, thuc lm kt ta cc thnh phn ca mu h ay thuc lm tan hng cu u khng c tim mch mu. 2.1.3. Thuc dng ngoi - Thm qua nim mc: thuc c th bi, nh git vo nim mc mi, hng, m o, bng quang iu tr ti ch. i khi, do thuc thm nhanh, li trc tip vo mu, khng b c c enzym ph hu trong qu trnh hp thu nn vn c tc dng ton thn: ADH dng bt xng mi; thuc t (lidocain, cocain) bi ti ch, c th hp thu, gy c ton thn. - Qua da: t thuc c th thm qua c da lnh. Cc thuc dng ngoi (thuc m, thu c xoa bp, cao dn) c tc dng nng ti ch st khun, chng nm, gim au. Tuy nhin, khi da b tn thng, vim nhim, bng thuc c th c hp thu. Mt s cht c d tan trong m c th thm qua da gy c ton thn (thuc tr su ln hu c, cht c cng nghip anilin) Gi m ni bi thuc (bng p), xoa bp, dng thuc gin mch ti ch, dng phng php ion -di (iontophoresis) u lm tng ngm thuc qua da. Hin c dng thuc cao dn mi, lm gii phng thuc chm v u qua da, duy tr c lng thuc n nh trong mu: cao dn scopolamin, estrogen, nitrit Da tr s sinh v tr nh, c lp sng mng manh, tnh thm mnh, d b kch ng cho nn cn thn trng khi s dng, hn ch din tch bi thuc. - Thuc nh mt: ch yu l tc dng t i ch. Khi thuc chy qua ng mi l xung nim mc mi, thuc c th c hp thu trc tip vo mu, gy

tc dng khng mong mun. 2.1.4. Cc ng khc - Qua phi: cc cht kh v cc thuc bay hi c th c hp thu qua cc t bo biu m ph nang, nim mc ng h hp. V din tch rng (80 - 100 m2?) nn hp thu nhanh. y l ng hp thu v thi tr chnh ca thuc m hi. S hp thu ph thuc vo nng thuc m trong khng kh th vo, s thng kh h hp, ha tan ca thuc m trong mu ( hay h s phn ly mu: kh ) Mt s thuc c th dng di dng phun sng iu tr ti ch (hen ph qun). - Tim tu sng: thng tim vo khoang di nhn hoc ngoi mng cng gy t vng thp (chi di, khung chu) bng dung dch c t trng cao (hyperbaric solution) hn dch no tu. 2.1.5. Thng s dc ng hc ca s hp thu: sinh kh dng (F) 2.1.5.1. nh ngha: Sinh kh dng F (bioavailability) l t l phn trm lng thuc vo c vng tun hon dng cn hot tnh v vn tc hp thu t huc (biu hin qua C max v Tmax) so vi liu dng . Sinh kh dng phn nh s hp thu thuc. 2.1.5.2. ngha

BI 4. KHI NIM TNG TC THUC 1. Mt s khi nim c bn Tng tc thuc l hin tng xy ra khi hai thuc tr ln c s dng ng thi. S phi hp lm thay i tc dng hoc c tnh ca mt trong nhng th thuc . Khi phi hp thuc nhm li dng tng tc thuc theo hng c li tng hiu qu iu tr, gim tc dng ph hoc gii c thuc. Th nhng, trong thc t iu tr c nhng tnh hung hon ton bt ng: cng mt thuc mc liu iu tr m khi phi hp vi thuc ny li gim hoc mt tc dng, ngc li, dng vi thuc kia th li xy ra ng c.

T l tng tc thuc tng theo cp s nhn vi s loi thuc phi hp, c ngha l nguy c ri ro, tht bi cng tng theo. Do vic cho thuc v phi hp thuc trong iu tr l 1 vn phc tp, lun t ra cho ngi thy thuc phi cn nhc v lun phi quan tm n hin tng tng tc thuc c th xy ra. Nhn nh v tng tc thuc hng dn cho bnh nhn khi s dng thuc v c nhng li khuyn vi bc s khi gp nhng n thuc phi hp khng ng. Cc tnh hung c th xy ra khi phi hp thuc c tm tt nh sau: 2. S phi hp thuc dn ti tng tc dng - tng tc c tnh hip ng S phi hp thuc lm tng hiu qu tc dng l mc tiu trong iu tr. l s tng tc mang tnh hip ng thuc, n xy ra ti cc receptor khc nhau, nhng c cng ch tc dng l: lm tng hiu qu iu tr. Cc kh nng c th xy ra vi loi tng tc ny l: 2.1.Hip ng cng (Additive) * Khi phi hp hai hay nhiu thuc vi nhau m tc dng thu c bng tng tc dng ca cc cht thnh phn, ta c hp ng cng. Th d: Nh c s phi hp ny m Olcandomycin ni rng c ph tc dng, cn Tetraxyclin th gim c liu, do gim c c tnh. * Nhng tng tc c th xy ra ti cc receptor khc nhau nhng c cng ch tc dng rt ph bin trong iu tr. V d: Phi hp thuc li tiu - an thn vi cc thuc chng tng huyt p iu tr bnh huyt p cao. Phi hp khng sinh vi cc thuc gim tit HCL iu tr vin lo t ng tiu ho. Phi hp? khng sinh c c ch tc dng khc nhau trong iu tr lao * Cc phi hp ny thng c p dng ph bin trong iu tr, tuy nhin cng hay gp nhng tng tc bt li do bc s v tnh phi hp cc thuc c tn bit dc khc nhau, nhng thc t li l cng mt hot cht . V d: Phi hp cc khng sinh nhm Aminoglycozid: Gentamycin + Streptomycin > lm tng suy thn v ic khng hi phc. 2.2. Hip ng tng cng (Potencial) * Khi tc dng phi hp vt tng tc dng ca cc cht thnh phn, ta c hip ng tng cng. Loi hip ng ny thng xy ra khi cc cht thnh phn tc dng ln nhng khu khc nhau trn cng mt chui phn ng:

V d: P.A.BA FH2 FH4 (-) (-) Sulffamid Trimethoprim Pyrimetamin Acid Folic l Coenzym gip vi khun to nn cc base purin, thymin v cc acid amin cn tng hp ADN, ARN vi khun pht trin. Sunfamid do cnh tranh vi P.A.B lm gim lng FH2, cn cc dn cht Pirimidin (trimethoprim, pirimethamin) li c ch enzym DHFR xc tc cho qu trnh chuyn FH2 thnh FH4, lm gim lng FH4. Kt qu cui cng l thiu acid Folic, v vy c ch s pht trin vi khun. Hai loi thuc dng chung s c tc dng hip ng vt mc (ch khng phi mt php cng thng thng), mnh hn hn khi dng n c tng loi, l nguyn tc to nn cng thc thuc khng khun hoc thuc chng st rt c hiu lc cao. * Khi phi hp li hai thuc tc dng km khun nh trong ch phm : Co trimoxazol (Bactrim) gm: Sulfamethoxazol + Trimethoprim) , ta li thu c tc dng dit khun. Ch phm ny c tc dng rt tt vi nhng vi khun khng cc khng sinh khc. Ch phm Fansidar: (Sulfadoxin + Pyrimethamin). Hip ng vt mc cn c to nn khi cht chnh - cht ch vn, c tng tim lc nh cht phi hp c th khng tc dng ln mt c quan ch vi cht chnh. V d: Clofibrat dng chung vi thuc khng Vitamin K lm tng tc dng chng ng mu, mc d Clofibrat khng c tc dng chng ng. Thuc co mch adrenalin s lm tng tc dng gy t tng vng ca novocain khi dng phi hp . Khi iu tr cao huyt p thng phi hp thuc li tiu vi thuc gin mch, thuc li tiu lm gim lu lng tun hon v thuc gin mch c tc dng h huyt p tt hn. Tt c nhng tng tc hip ng k trn, u thuc loi tng tc v mt dc lc, ngha l hip ng v mt tc dng. 3. S phi hp thuc dn ti gim tc dng - tng tc c tnh i khng.

* Khi phi hp thuc ngi ta c gng trnh nhng phi hp lm gim tc dng ca nhau. Tuy nhin, nhiu lc tng tc ny li c s dng nh mt v kh li hi gii c thuc hoc lm gim nhng tc dng ph ca cht ch vn. C nhng kh nng i khng sau i khng Ho hc Dc l Vt l Dc ng hc Dc lc hc Hp thu Phn b Chuyn ho Thi tr Cnh tranh Khng cnh 3.1. i khng ho hc * Tng tc ho hc c th gp vi tt c cc loi phn ng ho hc m ta bit. Khi trn chung cc thuc ngoi c th nu xy ra hin tng ta, c khi chuyn thnh dng kh bay ln, hoc dung dch i ?mu ta c th d dng nhn bit v trnh c. V d: Cc mui ca kim hu c v acid hu c, khi trn chung s xy ra phn ng trao i, dn n gim tan: Streptomycin sulfat trn vi natri benzyl penicilin, dimedrol clohydrat vi barbital natri (ta dimedrrol v barbital). iu ng ch { l c nhng phn ng ta khng nhn thy c nhng n li to ra cc sn phm khng c hot tnh hoc c vi c th. V d: - Khng nn trn vitamin B12 vi bt kz mt vitamin no trong syrine v coban s ph hu cc vitamin. Khi trn B12 vi B1, sn phm to thnh s gy d ng do tc ng ca B12 n B1. - Glucose l mt cht c tnh kh, v vy vic pha mt thuc nh morphin, noradrenalin, glycozid tr tim vo dung dch ny truyn nh git hoc tht trc trng l khng nn. Nhng tng tc xy ra ngoi c th gi l tng k (incompatility), cn tnh n c kh nng phn ng khi thuc vo c th. Cc alcaloit b ta bi thuc cha tanin, tetraxyclin to chelate vi cc ion kim loi ho tr II.III lc thuc s khng c hp thu. Hin tng gi l tng tc thuc (interaction). - Nhng tng tc i lp rt cn trnh v lm gim tc dng ca thuc V d: Khng ung vitamin B1 cng mt lc vi cc penicilin hoc streptomycin v vitamin B1 ph hu cc khng sinh ny. Nu ng thi dng vitamin B1 vi vitamin B6 th pyridoxin s ngn cn qu

trnh photphorin ho ca vitamin B1, tc l cn tr vitamin B1 chuyn thnh dng c hot tnh sinh hc. Khng ung acid nicotinic (vitamin PP) vi vitamin B6 v vitamin PP s ph hu vitamin B6 (vitamin PP l cofactor ca enzym NADP). - Nn nh rng vitamin B6 l ng yu t hot ho ca enzym vn chuyn nhm NH2 v kh carboxyl ca cc acid amin; Do khi iu tr bnh Parkinson khng nn phi hp Levodopa vi vitamin B6 liu cao. 3.2. i khng vt l Cc thuc bc : albumin (lng trng trng), tinh bt s gim tc dng ca mt s thuc kch ng (corticoid). Than hot l cht hp ph tt nhiu thuc khi ng c. 3.3. i khng dc l: bao gm i khng dc lc hc v i khng dc ng hc. 3.3.i khng dc lc hc L i khng do i lp v tc dng v c ch tc dng. C 2 loi i khng: 3.3.1. i khng cnh tranh: 2 thuc tc dng ln cng mt receptor (Rp), thuc no c i lc mnh hn vi Rp s pht huy c tc dng. Ni mt cch khc: cht ch vn (agonist) v cht i khng (antagonist) cnh tranh vi nhau cng mt ni ca receptor, thuc no c i lc mnh hn vi receptor s pht huy tc dng. V d: Nalorxon - morphin Atropin - Pilocarpin (Rp M) Histamin - phenergan (Rp H1) Histamin - cimetidin (Rp H2) Acetylcholin - piperazin (Rp N ca c giun) Isoproterenol - propranolon (Rp b) 3.3.2. i khng khng cnh tranh Cht i khng c th tc ng ln Rp v tr khc vi cht ch vn; cht i khng lm cho Rp bin dng, qua Rp s gim i lc vi cht ch vn v nu c tng liu cht ch vn cng khng t c hiu lc ti a. V d: mt s cht khng histamin Rp H1 : terfenadin ,astemizol Cc thuc lm mt tc dng ca nhau do tc dng i lp nhau: + Strychnin hn?g phn tu sng, lm tng cng kin c, cn thuc t hoc

cura i khng khng cnh tranh vi tc dng ny ca strychnin. + Acetylcholin - cura + Atropin lm mt tc dng co c vng ca Morphin do thng c phi hp vi Morphin gim au do co tht ng mt, ng niu + Ephedrin c tc dng cng ph giao cm s b cn tr nu dng cng Pilocacpin - cht cng giao cm. + Cc khng sinh nhm Beta - lactam s b gim tc dng nu dng cng vi Tetraxtyclin v tc dng gim tng hp protein trong t bo vi khun ca Tetraxyclin s lm chm s phn bo v do lm Penicilin kh ph v v vi khun hn. 3.4. i khng dc ng hc * Loi tng tc ny xy ra trong sut qu trnh tun hon ca thuc trong c th, k t khi bt u thm nhp n lc o thi. 3.4.1. Tng tc lc hp thu (Absorption = A) * Do thay i ion ho ca thuc S vn chuyn thuc qua mng sinh hc ch yu theo c ch khuch tn th ng v do ph thuc vo h s phn b m / nc ca thuc. Ch nhng cht khng ion ho mi phn tn tt trong m v d qua mng theo c ch ny. Theo phng trnh trn ta nhn thy: Cc cht c bn cht acid yu s hp thu tt trong mi trng acid: Phenylbutazon, cc Barbiturat, Aspirin hp thu tt d dy. Cc cht c bn cht base yu s hp thu tt trong mi trng kim: Quinin, Ephedrin, Atropin, Morphin hp thu tt rut. Vic thay i mi trng ca mt thuc c th do cc thuc dng km gy nn, cng c th do thc n v cc cht lng dng ung thuc to ra. + Khi iu tr bng Levodopa, nn trnh dng nhng ch phm m thu phn v Levodopa s b gim hp thu, cc cht m khi vo c th s phn hu thnh acid amin v cnh tranh carrier vi levodopa khi hp thu. + Thuc chng toan d dy lm tng pH ng tiu ho, ngn cn hp thu thuc l acid yu ( aspirin, barbiturat, sulfamid, cumarin) . + Hydroxyd AL cn tr hp thu INH, Doxycyclin. + Khi ung Tetraxyclin nn trnh dng nhng ch phm cha kim loi nng nh Fe, Al, Mg v Tetraxyclin r to chelate vi kim loi nng do khng hp thu c. + Cholestyramin - mt cht lm ta mui mt, dng ngn cn qu trnh

hp thu cc cht bo, gy h mc choles terol/ mu, cng c th to phc vi mt s thuc v cn tr hp thu. + Cholestyramin lm gim hp thu cc vitamin tan trontg du (A.D.E.K) acid folic, vitamin B12. Nu dng cholestyramin ko di, cn b cung cc vitamin trn. + INH iu tr lao, nn b xung vitamin B6 (20 mg - 25 mg/ ngy) v INH to phc vi B6 c th gy ri lon chc phn thn kinh do thiu B6 (Pyridoxin). 3.4.2. Tng tc trong qu trnh phn b: (Ditribution = D) * Khi tun hon trong mu, thuc thng dng lin kt vi Protein ca huyt tng. Dng ny khng c tc dng dc l{ v cng khng b chuyn ho. Tuy nhin lun tn ti mt cn bng ng gia dng thuc lin kt v thuc t do. Dng t do l dng c tc dng dc l. Nu s dng hai thuc c cng mt im gn trn phn t protein, thuc no c i lc mnh s y thuc kia ra khi v tr v chim ly protein. V d: Tolbutamid + Phenylbutazon ( y tolbutamid b y), d b chong do gim ng huyt t ng n ki t. y l loi tng tc bt li gp nhiu trong k n bi v thng xy ra bt ng trong sut qu trnh tun hon ca thuc trong c th. 3.4.3. Tng tc giai on chuyn ho: (Metabolism = M) Gan l c quan chuyn ho thuc quan trng nht ca c th. S suy gim chc nng gan k o theo nhng thay i cc thng s dc ng hc ca thuc: * Nhng thuc c tc dng tng cm ng enzym s lm tng tc chuyn ho ca cc thuc dng phi hp hoc ngay c chnh n khi dng lp li, do lm gim tc dng. Cc thuc thng gp l: Phenobarbital, Rifampicin, Doxycyclin, Spironolacton * Nhng thuc c tc dng c ch enzym microsom gan: Cloramphenicol, Cimetidin. Quercetin, Levodopa, INH lm cho nhiu thuc khc ko di tc dng v tng c tnh. V d: Cimetidin lm chm chuyn ho qua gan ca Diazepam, DPH, Theophilin, Carbamazepin, Lidocain, Metromidazol Cc thuc cn lu { khi phi hp vi cc cht trong bng trn l cc hormon (thyroid, corticoid, estrogen), theophylin, thuc chng ng kinh, thuc chng ng mu dng ung, thuc h ng huyt, thuc tim mch chuyn ho qua gan 3.4.4.Tng tc thuc giai on thi tr: (Elimination = E) Cc cht kim s lm tng tc o thi cc thuc c tnh acid nh Barbiturat, Aspirin do vy lm gim tc dng ca cc cht ny. Ngc li cc cht c tnh acid nh vitamin c, dch p hoa qu s tng o thi cc alcaloid.

Vic gim tc dng do nhng tng tc dc ng hc gy ra thng rt kh trnh v n bt ng; hu qu rt phc tp. Trc y nhiu trng hp xy ra khi phi hp thuc khng gii thch c . Ti sao cng mt thuc liu iu tr nhng lc th khng hiu lc, lc th c nguy c ng c. Ngy nay nh s pht trin ca dc ng hc, nhiu vn c sng t. Chnh v vy trong bn hng dn s dng thuc by gi thng c thm mc dc ng hc (pharmacokinetics) v tng tc thuc (interactions). iu gip cho ngi s dng nh hng tt hn, trnh c nhng tai bin v nng cao hiu qu iu tr. Cc thuc b nh hng nhiu l thuc bi xut ch yu qua thn dng cn hot tnh. Thuc phi hp c th lm qu trnh bi xut ca thuc dng km theo c ch: Thay i pH ca nc tiu: * Cc antacid nh NaHCO3, Maalox, Kavet gy kim ho nc tiu, do lm tng thi tr cc thuc c bn cht acid yu nh barbiturat, salicylat; Ngc li, vi cc thuc l alcaloid (th d: quinidin, theophylin) th tc bi xut li c nguy c b gim, dn n tng tc dng. * Vitamin C liu cao (>2 g) gy acid ho nc tiu, lm tng thi tr cc thuc c bn cht alcaloid dn n gim tc dng, nhng li ko di thi gian tn ti ca cc salicylat gy tng nguy c chy mu. nh hng n c ch trao i cht ng thn: V d: Probenecid s cnh tranh carrier bi xut ca nhiu loi thuc (cc penicilin, cephalosporin) v lm chm qu trnh bi xut ca cc thuc ny. Corticoid cn tr tc dng ca cc thuc li tiu do i lp v c ch bi xut mui nc. { ngha ca tng tc thuc: Li dng - Ci thin tc dng dc l - Ci thin dc ng? hc ca thuc - Gii c Trnh - Phi hp lm tng c tnh v tc dng ph - Phi hp lm gim tc dng dc l v hiu qu iu tr.

BI 5. CC LOI TNG TC THUC 1.TNG TC THUC - THUC Nhiu thuc khi cho dng cng mt lc s c tc dng qua li ln nhau, c gi l tng tcthuc. Trong lm sng, thy thuc mun phi hp thuc lm tng t c dng iu tr, gim cctc dng khng mong mun. Song trong thc t, nhiu k hi khng t c nh th. V vy, khi k n c t 2 thuc tr ln, thy thuc rt cn hiu r s tng tc gia chng. 1.1. Tng tc dc lc hc L tng tc ti cc receptor, mang tnh c hiu 1.1.1. Tng tc trn cng receptor: tng tc cnh tranh Thng lm gim hoc mt tc dng ca cht ng vn (a gonist), do cht i kh ng (antagonist) c i lc vi receptor hn nn ngn cn cht ng vn gn vo receptor: atropin khng acetylcholin v pilocarpin ti receptor M; nalorphin khng morphin ti receptor ca morphin; cimetidin khng histamin ti receptor H2. Thuc cng nhm c cng c ch tc dng, khi dng chung tc dng khng tng b ng tng liu ca mt thuc m c tnh li tng hn: CVKS, aminosid vi dy VIII. 1.1.2. Tng tc trn cc receptor khc nhau: tng tc chc phn. - C cng ch tc dng: do lm tng hiu qu iu tr. Th d: trong iu tr bnh cao huyt p, phi hp thuc gin mch, an thn v li tiu; trong iu tr lao, phi hp nhiu khng sinh (DOTS) tiu dit vi khun cc v tr v cc gi ai on pht trin khc nhau. C ch tc dng i lp, gy ra c chc phn i lp, dng iu tr nhim c: strychnin liu cao, kch thch ty sng gy co cng c, cura do c ch dn truyn tm vn ng, lm mm c; histamin tc ng trn receptor H 1 gy gin mch, tt huyt p, trong khi noradrenalin tc ng ln receptor 1 gy co mch, tng huyt p. 1.2. Tng tc dc ng hc L cc tng tc nh hng ln nhau thng qua cc qu trnh hp thu, phn phi, chuyn ha v thi tr v th n khng mang tnh c hiu.

1.2.1. Thay i s hp thu c a thuc - Do thay i ion ha ca thuc: Nh ta bit, ch nhng phn khng ion ha ca thuc mi d dng qua c m ng sinh hc v d phn tn hn trong lipid. phn ly ca thuc ph thuc vo hng s pKa ca thuc v pH ca mi trng. Cc thuc c bn cht acid yu (nh aspirin) s hp thu tt trong mi trng acid (d dy), nu ta trung ha acid ca dch v th s hp thu aspirin d dy s gim i. Vi cc thuc dng theo ng ung: khi dng vi thuc lm thay i nhu ng r ut s lm thay i thi gian lu gi thuc trong rut, thay i s hp thu ca thuc qua ru t. Mt khc cc thuc d tan trong lipid, khi dng cng vi parafin (hoc thc n c m) s lm tng hp thu. Vi cc thuc dng theo ng tim bp, di da: procain l thuc t , khi trn v i adrenalin l thuc co mch th procain s chm b hp thu vo mu do thi gian gy t s c ko di. Insulin trn v?i protamin v km (protemin - zinc- insulinPZI) s lm ko di thi gian hp thu insulin vo mu, ko di tc dng h ng huyt ca insulin. - Do to phc, thuc s kh c hp thu: Tetracyclin to phc vi Ca ++ hoc cc cation kim loi khc rut, b gim hp thu. Cholestyramin lm ta mui mt, ngn cn hp thu lipid, dng lm thuc h cholesterol mu. - Do cn tr c hc: Sucralfat, smecta, maaloc (Al 3+) to mng bao nim mc ng tiu ha, lm kh hp thu cc thuc khc. trnh s to phc hoc cn tr hp thu, 2 thuc nn ung cch nhau t nht 2 gi. 1.2.2. Thay i s phn b thuc

 l tng tc trong qu trnh g n thuc vo protein huyt tng. Nhiu thuc, nht l thuc loi acid yu, gn thun nghch vi protein (albumin, globulin) s c s tranh chp , ph thuc vo i lc v nng ca thuc trong huyt tng. Ch c thuc dng t do mi c tc dng dc l. V vy, tng tc ny c bit c ngha vi thuc c t l gn vo protei n huyt tng cao (trn 90%) v c phm vi iu tr hp nh: . Thuc chng ng mu loi khng vitamin K: dicumarol, warfarin . Sulfamid h ng huyt: tolbutamid, clopropamil . Thuc chng ung th, c bit l methotrexat Tt c u b cc thuc chng vim phi steroid d dng y khi protein huyt tng, c th gy nhim c. 1.2.3. Thay i chuyn ha Nhiu thuc b chuyn ha gan do cc enzym chuyn ha thuc ca microsom g a n (xin xem phn dc ng hc). Nhng enzym ny li c th c tng hot tnh (gy cm ng) hoc b c ch bi cc thuc khc. Do s lm gim t/2, gim hiu lc (nu l thuc gy c m ng enzym) hoc lm tng t/2, tng hiu lc (nu l thuc c ch enzy m) ca thucdng cng. - Cc thuc gy cm ng (inductor) enzym gan: phenobarbital, phenytoin, carbamazepin, griseofulvin, rifampicin - Cc thuc c ch (inhibitor) enzym gan: allopurinol, cloramphenicol, cimetidin, MAOI, erythromycin, isoniazid, dicuma rol. Cc thuc hay phi hp vi cc loi trn thng gp l cc hormon (thyroid, cortic oid, estrogen), thuc chng ng kinh, thuc h ng huyt, thuc tim mch. Ph n ang dng thuc trnh thai ung, nu b lao dng thm rifampicin, hoc b ng kinh dng phenytoin, c th s b v k hoch do estrogen trong thuc trnh thai

b gim hiu qu v b chuyn ha nhanh, hm lng tr nn thp. 1.2.4. Thay i thi tr thuc Thi tr (elimination) thuc gm 2 qu trnh l chuyn ha thuc gan ( ni phn trn ) v bi xut (excretion) thuc qua thn. Nu thuc bi xut qua thn dng cn hot tnh th s tng/ gim bi xut s c nh hng n tc dng ca thuc. - Thay i pH ca nc tiu: khi mt thuc lm thay i pH ca nc tiu, s lm thay i ion ha ca thuc dng km, lm thay i bi xut ca thuc. Th d barbital c pK a = 7,5; pH = 7,5 th 50% thuc b ion ha; pH = 6,5 th ch c 9% b ion ha pH = 9,5 th 91% barbital b ion ha. V vy, khi ng c cc thuc barbiturat, truyn dch NaHCO3 base ha nc tiu s tng bi xut barbiturat. Cc thuc l acid yu (vitamin C, amoni clorid) dng liu? cao, lm acid ha nc tiu s lm tng thi tr thuc loi alcaloid (quinin, morphin). - Bi xut tranh chp ti ng thn: do 2 cht cng c c ch bi xut chung ti ng thn nn tranh chp nhau, cht ny lm gim bi xut cht khc. Dng probenecid s lm chm thi tr penicilin, thiazid lm gim thi tr acid uric nn c th gy bnh gut. 1.3. Kt qu v ngha ca tng tc thuc 1.3.1. Tc dng hip ng Thuc A c tc dng l a, thuc B c tc dng l b. Khi kt hp thuc A vi thuc B c tc dng c. Nu c = a + b, ta c hip ng cng (additive effect) c > a + b, ta c hip ng tng mc (synergysm) Hip ng cng thng khng c dng lm s ng v nu cn th tng liu thu c ch khng phi hp thuc. Hip ng tng mc thng dng trong iu tr lm tng tc dng iu tr v l m gim tc dng ph, tc dng c hi. Hai thuc c hip ng tng mc c th qua tng t c dc ng hc (tng hp thu, gim thi tr) hoc tng tc dc

lc hc (trc tip hoc gin tip qua receptor) 1.3.2. Tc dng i khng Nh trong nh ngha trn, nhng khi tc dng c ca thuc A + B li nh hn tc d ng cng ca tng thuc (c < a + b) ta gi l tc dng i khng. i khng c th ch mt phn (partial antagonism) khi c < a + b, nhng cng c th i khng hon ton khi a lm mt h on ton tc dng ca b. Trong lm sng, thng dng tc dng i khng gii c. i khng c th xy ra ngoi c th, gi l t ng k (incompatibility), mt loi tng tc thun ty l ha: + Acid gp base: to mui khng tan. Khng tim khng sinh loi acid (nhm lactam) vo ng dn dch truyn c tnh base. + Thuc oxy ha (vitamin C, B 1, penicilin) khng trn vi thuc oxy kh (vitamin B2) + Thuc c bn cht l protein (insulin, heparin) khi gp mui kim loi s d kt ta. + Than hot, tanin hp ph hoc lm kt ta nhiu alcaloid (quinin, atropin) v cc mui kim loi (Zn, Pb, Hg) - i khng xy ra trong c th: Khi thuc A lm gim nng ca thuc B trong mu (qua dc ng hc) hoc l m gim tc dng ca nhau (qua dc lc hc), ta gi l i khng (antagonism) V dc lc hc, c ch ca tc dng i khng c th l: + Tranh chp trc tip ti receptor: ph thuc vo i lc v nng ca thuc ti receptor. Th d: acetylcholin v atropin ti receptor M cholinergic; histamin v cimetidin trn receptor H 2 d dy. + i khng chc phn: hai cht ng vn (agonist) tc dng trn 2 receptor khc nhau nhng chc phn li i khng trn cng mt c quan. Strychnin kch thch tu sng, gy co git; cura c ch dn truyn tm vn ng, gy mm c, chng c co git. Histamin

kc h thch receptor H1 lm co c trn kh qun, gy hen; albuterol (Ventolin), kch thch rec eptor 2 adrenergic lm gin c trn kh qun, dng iu tr cn hen. 1.3.3. o ngc tc dng Adrenalin va c tc dng kch tch receptor adrenergic (co mch, tng huyt p), va c tc dng kch thch receptor adrenergic (gin mch, h huyt p). Khi dng mt mnh, do tc dng mnh hn nn adrenelin gy t uyng huyt p. Khi dng phentolamin (Regitin) l thuc c ch chn lc receptor ri mi tim adrenalin th do ch kch thch c receptor nn adrenelin gy h huyt p, tc dng b o ngc. ngha ca tng tc thuc Trong lm sng, thy thuc dng thuc phi hp vi mc ch: - Lm tng tc dng ca thuc chnh (hip ng tng mc) - Lm gim tc dng khng mong mun ca thuc iu tr - Gii c (thuc i khng, thuc lm tng thi tr, gim hp thu, trung ha) - Lm gim s quen thuc v khng thuc Tuy nhin, nu khng hiu r tc dng phi hp, thy thuc c th lm gim tc d ng iu trhoc tng tc dng c ca thuc. Trong cc sch hng dn dng thu c, thng c mc tngtc ca tng thuc. 2. TNG TC THUC - THC N- UNG 2.1. Tng tc thuc - thc n: Thng hay gp l thc n lm thay i dc ng hc ca thuc. 2.1.1. Thc n lm thay i hp thu thuc: - S hp thu ph thuc vo thi gian rng ca d dy. D dy khng phi l ni c ch c nng hp thu ca b my tiu ha. Tuy nhin, do pH rt acid (khi i, pH 1; khi no pH 3) cho nn cn lu : + Ung thuc lc i, thuc ch gi li trong d dy khong 10 - 30 pht. + Ung thuc vo lc no, thuc b gi li trong d dy khong 1 - 4 gi, do : . Nhng thuc t tan s c thi gian tan, khi xung rut s c hp thu nhanh hn (penicilin V). Tuy nhin, nhng thuc d to phc vi nhng thnh phn ca thc n s

b gi m hp thu (tetracyclin to phc vi Ca ++ v mt s cation ho tr 2 khc). . Cc thuc km bn trong mi trng acid (ampicilin, erythromycin) nu b gi l u d dy s b ph hu nhiu. . Vin bao tan trong rut s b v (cn ung trc ba n 0,5 - 1h hoc sau ba n 1 - 2 gi) . Nhng thuc d kch ng ng tiu ha, n n ung vo lc no. S hp thu cn ph thuc vo dng bo ch: aspirin vin nn ung sau khi n s g im hp thu 50%, trong khi vin si bt li c hp thu hon ton. 2.1.2. Thc n lm thay i chuyn ha v thi tr thuc Thc n c th nh hng n enzym c huyn ha thuc ca gan, nh hng n pH ca nc tiu, v qua nh hng n chuyn ha v bi xut thuc. Tuy nhin, nh hng khng ln. Ngc li, thuc c th nh hng n chuyn ha mt s cht trong thc n. Thuc c ch enzym mono- amin- oxydase (MAOI) nh iproniazid - l enzym kh amin - oxy ha ca nhiu amin ni, ngoi sinh c th gy cn tng huyt p kch pht khi n cc thc n c nhiu tyramin (nh khng c chuyn ha kp, lm gii phng nhiu noradrenalin ca h giao c m trong thi gian ngn. 2.2. Tng tc thc n ung 2.2.1. Nc Nc l ung (dung mi) thch hp nht cho mi loi thuc v khng xy ra t ng k khi ha tan thuc. - Nc l phng tin dn thuc (dng vin) vo d dy rut, lm tng tan r v ha tan hot cht, gip hp thu d dng. V vy cn ung nc (100 200 mL cho mi ln ung thuc) trnh ng vin thuc ti thc qun, c th gy kch ng, lot. - c bit cn ch : + Un?g nhiu nc trong qu trnh dng thuc (1,5 2 l/ ngy) lm tng tc dng ca thu c (cc loi thuc ty), lm tng thi tr v lm tan cc dn xut chuyn ha ca thuc (sulfamid, cyclophosphamid). + Ung t nc hn bnh thng duy tr nng thuc cao trong rut khi

ung thuc ty sn, ty giun (niclosamid, mebendazol). + Trnh dng nc qu, nc khong base hoc cc loi nc ngt ng hp c g as v cc loi nc ny c th lm hng thuc hoc gy hp thu qu nhanh. 2.2.2. Sa Sa cha calci caseinat. Nhiu thuc to phc vi calci ca sa s khng c hp thu (tetracyclin, lincomyc in, mui Fe) Nhng thuc d tan trong lipid s tan trong lipid ca sa chm c hp thu. Protein ca sa cng gn thuc, lm cn tr hp thu. Sa c pH kh cao nn lm gim s kch ng d dy ca cc thuc acid. 2.2.3. C ph, ch Hot cht cafein tr ong c ph, nc ch lm tng tc dng ca thuc h st gim au aspirin, paracetamol; nhng li lm tng tc dng ph nh nhc u, tng nhp tim, tng huyt p nhng bnh nhn ang dng thuc loi MAOI. - Tanin trong ch gy ta cc thuc c Fe hoc al caloid - Cafein cng gy ta aminazin, haloperidol, lm gim hp thu; nhng li lm tng ha tan ergotamin, lm d hp thu. 2.2.4. Ru ethylic Ru c rt nhiu nh hng n thn kinh trung ng, h tim mch, s hp thu ca ng tiu ha. Ngi nghin ru cn b gim protein huyt tng, suy gim chc nng gan, nhng li gy cm ng enzym chuyn ha thuc ca gan (xin xem bo ru), v th ru c t ng tc vi rt nhiu thuc v cc tng tc ny u l bt li. Do khi dng thuc th khn g ung ru. Vi ngi nghin ru cn phi dng thuc, thy thuc cn kim tra chc nng g an, tnh trng tm thn chn thuc v dng liu lng thch hp, trong thi gian dng thu c cng phi ngng ung ru. 3. THI IM UNG THUC Sau khi nhn r c tng tc g ia thuc- thc n- ung, vic chn thi im ung thuc hp l t c nng cao trong mu, t c hiu qu mong mun cao v gi m c tc dng ph l rt cn thit.

Nn nh rng: ung thuc vo lc i, thuc ch b gi li d dy 10 30 pht, vi pH 1; ung lc no (sau n), thuc b gi li 1 - 4 gi vi pH 3,5. Nh vy, tuz theo tnh cht ca thuc, mc ch ca iu tr, c mt s gi chn thi im ung thuc nh sau: 3.1.Thuc nn ung vo lc i (trc ba n 1/2 - 1 gi) - Thuc bc d dy cha lo t trc khi thc n c mt, nh sucralfat. Cc thuc khng nn gi li lu trong d dy nh: cc thuc km bn vng trong mi trng acid (ampicilin, erythromycin), cc loi vin bao tan trong rut hoc cc thuc gii phng ch m. 3.2. Thuc nn ung vo lc no (trong hoc ngay sau ba n) Thuc kch thch bi tit dch v (ru khai v), cc enzym tiu ha (pancreatin) ch ng i tho ng loi c ch gluconidase nn ung trc ba n 10 - 15 pht. - Thuc kch thch d dy, d gy vim lot ng tiu ha: cc thuc chng vim phi steroid, mu?i kali, quinin Nhng thuc c thc n lm tng hp thu, hoc do thc n lm chm di chuy n thuc nn ko di thi gian hp thu: cc vitamin, cc vin nang amoxicilin, cephalexin, cc vin nn digoxin, sulfamid. - Nhng thuc c hp thu qu nhanh lc i, d gy tc dng ph: levodopa, thuc khng histamin H1. 3.3. Thuc t b nh hng bi thc n, ung lc no cng c: prednisolon, theophylin, augmentin, digoxin. 3.4. Thuc nn ung v o bui sng, ban ngy - Cc thuc kch thch thn kinh trung ng, cc thuc li niu trnh nh hng n gic ng. - Cc corticoid: thng ung 1 liu vo 8 gi sng duy tr c nng n nh trong mu. 3.5. Thuc nn ung vo bui ti, trc khi i ng. - Cc thuc an thn, thuc ng

Cc thuc khng acid, chng lot d dy. Dch v acid thng tit nhiu vo ban m, cho nn ngoi vic dng thuc theo ba n, cc thuc khng acid dng cha lot d dy n n c ung mt liu vo trc khi i ng . Cn nh rng khng nn nm ngay sau khi ung thuc, m cn ngi 15 - 20 pht v ung nc (100- 200 mL nc) thuc xung c d dy. Dc l thi khc (chronopharmacology) cho thy c nhiu thuc c hiu lc hoc c tnh thay i theo nhp ng y m. Tuy nhin, trong iu tr, vic cho thuc cn tuz th uc vo thi gian xut hin triu chng. BI 6. IU TR NG C THUC CP TNH 1. I CNG 1.1. Nguyn nhn ng c thuc cp tnh : + Do nhm ln : ca thy thuc hoc ca bnh nhn + Do nhm ln : - Loi thuc, - Liu lng - ng dng - Thi gian dng + Do c : - Ca bnh nhn : t t - Ca ngi khc : uc 1.2. Triu chng ng c thuc cp tnh : Khng c hiu : + Ri lon thn kinh : ng li b, hn m hoc kch ng, co git + Ri lon tim mch : ri lon nhp tim, gim hoc tng huyt p + Ri lon h hp : kh th, tng tit m ri, ri lon h hp chu kz + Ri lon tiu ha : au bng d di, nn ma, xut huyt tiu ha + Ri lon thn - tit niu : b i, thiu niu, v niu ( suy thn cp ). 1.3. Nguyn tc iu tr : + Nhanh chng loi tr cht c ra khi c th. + Trung ha cht c c hp thu vo c th. + iu tr triu chng v hi sc cho bnh nhn.

2. CC BIN PHP IU TR : 2.1. Loi tr cht c ra khi c th : 2.1.1. Qua ng tiu ha : a- Gy nn : + Siro ipeca 15 - 20 ml, pha long trong 250 ml nccho bnh nhn ung. Nu sau 15 ph bnh nhn khng nn c th dng nhc li. + Trng hp khng c thuc, bnh nhn cn tnh, c th ngoy hng, cho ung mn tht, hoc ung 250 ml dung dch natri clorid ( NaCl ) u trng. + CC : bnh nhn hn m, ng c cc acid, base mnh. b- Ra d dy :bng dung dch thuc tm ( KMnO4 ) 0,1 %, tanin ( acid tanic ) 5% hoc nc m cho ti khi nc ra tr thnh trong. + Vi cc thuc hp thu nhanh nh aspirin, cloroquin, meprobamat, thuc ng barbiturat, colchicin th ra d dy v gy nn ch c tc dng trong vng 6 h u, khi cht c cn d dy. + i v?i nhim c cc loi thuc ng BZD, cc thuc c chu kz gan-rut?, nhim c hn hp hoc nhim c cc cht khng r th nn ra d dy trong vng 24 h ( nu khng c chng ch nh ) + BZD : benzodiazepin, + Cc thuc c chu kz gan-rut : morphin, strychnin, cloramphenicol, chlorpromazin,tetracyclin, quinin, sulfamid chm, cc hormon sinh dc, digitoxin, imipramin + CC : bnh nhn hn m ( v d a nhm ng cao su vo kh qun hoc cht nn quay ngc ng vo phi, gy t vong ), ng c cc cht n mn ( nh acid, base mnh v ng cao su c th lm rch thc qun ). c- Dng cc cht hp ph : Sau khi ra d dy, cho ung than hot 30 - 40 g/ln, cch 4 h/ln ( u im ? ). + C nhiu u im : - Hon ton khng c, - R tin, - S dng n gin, thun tin - Ngn cn c chu kz gan - rut ca cc thuc thi theo ng mt. + Cht thay th ? Cht thay th :kaolin hoc bt than ci, bt go, bt ng rang chy tn nh. 2.1.2. Qua ng h hp : + Ch nh :ng c cc thuc thi qua ng h hp nh cc thuc m th kh ( ether, halothan), ru, kh t, xng, carbon monoxyd ( CO ), ace-

ton + Cc thuc hay dng : - Pentetrazol ( BD : cardiazol, corazol, tetracor.. ), ng 1 - 5 - 10 ml dd 10 %. Tim SIV, IM 0,5 -1,0 g tuz BN. L 10 - 30 ml dd 10 % : ung 20 git/ln x 2 - 3 ln/24 h. Vin nn 0,10 : ung 1 - 2 vin/ln x 2 - 3 ln/24 h. - Lobelin : ng 3 - 10 mg/1 ml. Tim IM, SC 10 mg hoc tim IV chm 3 mg + H hp nhn to. 2.1.3. Qua ng tit niu : a- Thuc li niu thm thu : + Mannitol ( BD : mannidex, osmitrol, osmosal ). L 100 - 250 - 500 - 1.000 ml dd 10 - 20 %. Truyn IV 1 - 2 g/kg, tc 10 - 20 ml/1 ph ( tuz bnh nhn ). + Glucose u trng 10 - 20 - 30 % + Ringer lactat ( 1 l dd cha 3,1 g natri lactat; 6 g NaCl; 0,4 g KCl; 0,4 g CaCl2 ). t dng. * Chng ch nh chung: suy thn nng, suy tim nng, ph phi cp, tng huyt p, try tim mch nng * Ch : ch nn dng cc thuc li niu thm thu khi chc chn chc nng thn cn tt. Khi dng cc thuc ny s lm tng thi tr cc khng sinh nn cn phi tng liu khng sinh. b- Kim ha nc tiu :p dng khi iu tr ng c cp cc thuc c bn cht l acid yu ( thuc ng barbiturat, NSAID ( aspirin, diclofenac, indomethacin, phenylbutazon )). Thng dng 2 loi sau : + Natri hydrocarbonat ( NaHCO3 ). L 500 ml dd ng trng 1,4 %. Truyn nh git IV 2 - 3 l/24 h. - Nhc im : a thm Na+ vo c th, do d gy tai bin ph no khi chc nng thn khng tt ( 1 g NaHCO3 c 0,273 g Na ). + Trometamol ( THAM, trihydroxymetylaminmetan ). - Bit dc : alcaphor, talatrol, thamac tat, tham E - L 250 ml dd tim truyn 9,15 g km 1,5 g acid acetic kt tinh v pH 8,6. Ngi ln truyn IV 1 g/3 kg/24 h ( 250 - 500 ml ). c- Acid ha nc tiu : p dng khi iu tr ng c cc thuc c bn cht base hu c : quinin, cloroquin, dn xut quinolein, imipramin, mecamy-

lamin, quinacrin, nicotin, procain, phenothiazin Hay dng : + Amoni clorid ( TK : amchlor, acid-amon ). Dng bt, ung 3,0 - 6,0 g/24 h ( c th 10,0 - 12,0 g/24 h ), chia lm 2 - 3 ln. + Acid phosphoric : ung 15 - 100 git/24 h ( pha vi nc ). Vic acid ha kh thc hin hn vic kim ha nc tiu, ng thi c th chu ?ng tnh trng nhim toan k m hn tnh trng nhim kim nn cng d gy nguy him cho c th. 2.2. Trung ho cht c : Trong lm sng thng hay dng cc cht tng k ha hc ngn cn hp thu cc cht c, lm mt hot tnh hoc i khng vi tc dng ca cht c. 2.2.1. Cc cht tng k ha hc ti d dy : ngn cn hp thu cht c vo c th, sau khi ra d dy c th cho bnh nhn ung cc thuc : + Tanin 1 - 2 %, 100 - 200 ml ( tanin 5 % ra d dy ) + C th thay bng nc ch xanh, l i, sim, b gic Tanin c tc dng lm kt ta nhiu alcaloid nh strychnin, quinin, quinidin, apomorphin, morphin, cocain, cc kim loi nng ( mui km, coban, ng, ch, thy ngn ). + Sa, lng trng trng ( 6 qu trng/1 l nc ) : ngn cn hp thu cc mui thy ngn, phenol. + Than hot ( BD : carbolenum, ostacol, medicoal ). C dng bt, vin nn 0,25 0,50 g , nh dch 2 %. Ung 30 - 40 g bt/ln, ngy 3 - 4 ln, cch nhau 4 h. C th thay bng bt go, bt ng rang chy, kaolin. Than hot c tc dng hp ph mnh trong cc trng hp nhim c cc alcaloid ( morphin, strychnin ), cc mui kim loi nng ( sublime - HgCl2 ), cc cht mang in tch (+) v (-) cho nn c th p dng c trong hu ht cc trng hp nhim c qua ng tiu ha. 2.2.2. Cc cht tng k ha hc dng ng ton thn : To Met-Hb : khi iu tr ng c acid cyanhydric - HCN ( Sn ). + Natri nitrit 3 % ( l 0,3 g/10 ml ) Tim IV 1 l trong 3, sau 5 tim IV 50 ml dd natri thiosulfat 50 % ( cn c ng natri thiosulfat 0,5 g/5 ml, 2 g/10 ml ). + Dimercaprol ( BAL = British anti Lewisit ). ( BD : antoxol, dicaptol, dithioglycerin ), ng 100 mg/1 ml v 200 mg/2 ml. - iu tr ng c cc kim loi nng ( arsen, vng, thu ngn ).

Lewisit = yperit : cht c gy ngt Tim IM 2 - 3 mg/kg/ln : - Ngy N1, 2 : cch 4 h tim 1 ln, - Ngy N3 : cch 6 h tim 1 ln. - Cc ngy sau : 2 ln/24h. + EDTA ( ethylen diamino tetraacetic acid ) hoc cc mui Na v Ca ca acid ny ( EDTA calci dinatri v EDTA dinatri ( Na2EDTA ) iu tr ng c cc ion ha tr 2 nh Pb2+, Fe2+, Cr2+, Cu2+ v digitalis ( thi tr Ca2+ ). - EDTA dinatri ng 0,5 g/10 ml. Pha vo dung dch glucose hoc NaCl ng trng, truyn IV rt chm 1 - 2 ng/24h ( trong 2h ) ( trnh cn tetani ). t iu tr 5 ngy, ngh 7 ngy mi c iu tr t tip theo. - EDTA calci dinatri ng 0,5 g/10 ml. Cch dng : ng IV : pha 1 ng trong 250 - 500 ml dd glucose 5 %, truyn IV chm trong 2 h, chia lm 2 ln/ngy. Liu trung bnh : 15 - 25 mg/kg/24 h, ti a 50 mg/kg/24 h. t iu tr 5 ngy, ngh 2 ngy gia 2 t iu tr. ng tim IM : dd 20 %. Liu lng : 12,5 mg/kg/ln, cch 4 - 6 h tim 1 ln, ti a 50 mg/kg/24 h. Ha thm dd procain 1 % tim IM. 2.2.3. S dng cc thuc i khng dc l c hiu : + V d : naloxon ( BD : nalon, narcan ), ng 0,4 mg/1 ml; tim IV, tim IM iu tr ng c morphin v cc thuc gim au gy nghin. Tuy phng php ny iu tr c hiu qu nhanh v tt, nhng do c rt t thuc c tc dng i khng c l{ c hiu, cho nn phn ln phi iu tr theo triu chng. 2.3. iu tr triu chng v iu tr hi sc cho bnh nhn : 2.3.1. S dng cc thuc i khng sinh l : + Dng cc thuc kch thch TKTW iu tr ng c cc thuc c ch TKTW v ngc li. - Thuc kch thch TKTW: bemegrid, cafein, amphetamin, long no, pentetrazol - Thuc c ch TKTW : thuc ng barbiturat, thuc an thn, thuc m.. + Dng thuc gin c cura iu tr ng c cc thuc gy co git ( pentetrazol, strychnin ). * Nhc im : phi dng thuc i khng vi liu cao, thng l liu c cho

nn c hi cho bnh nhn. 2.3.2. Hi sc tng hp : a- Hi sc tim mch : dng cc thuc tr tim gi n nh huyt p, chng try tim mch. + VD : dng nordrenalin ng 1 mg/1 ml. Pha 1-4 ng trong 500 - 1000 ml dd glucose 5 %, truyn SIV ( tc 2 - 4 mg/1 ph ). + DOCA ( desoxycorticosteron acetat ), ng 5 - 10 mg, vin t di li 5 mg. Tim IM 1 2 ng/24 h. Nu nh cho ngm di li 1 - 2 vin/24 h. b- Hi sc h hp : dng cc thuc kch thch h hp : + Pentetrazol ( BD : cardiazol, corazol ) ng 0,10 g/1 ml. Tim IM, SC, IV ti 6 - 8 ng/24 h. + Cafein ng 0,07 - 0,25 - 0,40 g/1 ml. Tim SC 0,07 - 1,5 g/24 h. + H hp nhn to, th oxy. c- Thm phn phc mc hoc chy thn nhn to: + Ch nh : - Cc trng hp nhim c nng ( ng c cc kim loi nng, sulfamid, barbiturat liu cao ) - Khi thn suy, cc phng php iu tr thng thng khng mang li kt qu. - Khi c chng ch nh dng cc thuc li niu thm thu. d- Thay mu :ch nh : + Ng c phospho trng : phi lm sm trc 8 h k t khi ng c mi c kh nng cu c nn nhn. + Ng c cc thuc vi liu cht : cc thuc chng st rt, cht c t bo ( cc thuc chng ung th ), isoniazid, dn xut salicylat ( nht l tr em ) + Cc cht lm tan mu : saponin, sulfon + Cc cht gy Met-Hb : anilin, thuc gim au h st dn xut anilin ( phenacetin, paracetamol ), nitrit, cloroquin Giai on u c th iu tr bng xanh methylen ng 0,10 g/ 5 ml. Pha 10 ml vo 500 ml dd glucose 5%, truyn IV. Hoc tim IV vitamin C 4,0 - 6,0g/24h. Nu khng c kt qu th phi thay mu. * Ch : bin php thay mu cn phi lm sm v khi lng mu thay

th phi ln ( 7 l ) th mi c kt qu. Nu ngy hm sau mu cn cha nhiu Met-Hb th c th phi truyn li. 2.3.3. Cng tc chm sc ngi bnh : a- Ch dinh dng :cho n cc thc n nh ( cho, sp, ph ), d tiu, ca-lo. Nu bnh nhn khng n c phi t sonde d dy hoc truyn hu mn khi c tn thng thc qun ( ng c acid, base mnh ) Cn b sung thm nhiu vitamin, nht l vitamin nhm B, C. B sung thm insulin khi truyn nhiu glucose. b- Chng bi nhim ( ph qun, phi, ng tit niu ) : khng sinh. c- Cng tc h l : gi v sinh thn th sch s, chng lo t, ht m ri BI 7. I CNG V DC LC HC Dc lc hc nghin cu tc dng ca thuc ln c th sng, gii thch c ch ca cc tc dng sinh ha v sinh l ca thuc. Phn tch cng y c cc tc dng, cng cung cp c nhng c s cho vic dng thuc hp l trong iu tr. y l nhim v c? bn nh t v cng l kh khn ln nht ca dc lc hc. 1. C CH TC DNG CA THUC 1.1. Receptor Tc dng ca phn ln cc thuc l kt qu ca s tng tc gia thuc vi recep tor (th th cm). Receptor l mt thnh phn i phn t (macromolcular) tn ti vi mt l ng gii hn trong mt s t bo ch, c th nhn bit mt cch c hiu ch mt phn t th ng tin t nhin (hormon, cht dn truyn thn kinh), hoc mt tc nhn ngoi lai (cht ha hc, t huc) gy ra mt tc dng sinh hc c hiu, l kt qu ca tc dng tng h . Thnh phn i phn t ca receptor thng l protein v ch c protein mi c cu trc phc tp

nhn bit c hiu ca mt phn t c cu trc 3 chiu. Receptor c 2 chc phn: 1) Nhn bit cc phn t thng tin (hay cn gi l ligand) bng s gn c hiu cc phn t ny vo receptor theo cc lin kt ha hc: Lin kt ion: cc cht ha hc mang in tch (nh nhm amoni bc 4 cu acetylc holin c in tch dng), s gn vo vng mang in tch tri du ca receptor theo lin kt ny, vi lc lin kt khong 5- 10 kcal/ mol. Lin kt hydro: do s phn b khng ng u electron trong phn t nn c mi lin kt gia nguyn t hydro vi cc nguyn t c in tch m cao nh oxy, nit v fluor. Lc lin kt khong 2- 5 kcal/ mol - Lin kt Van- der Waals: l lc lin kt ca mi tng h gia cc electron vi cc nhn ca cc phn t st bn. Lc lin kt ph thuc vo khong cch gia cc phn t, lc ny tng i yu, khong 0,5 kcal/ mol. Cc thuc c vng benzen, c mt electron phn b ng u thng c mi lin kt ny. Cc lc lin kt trn u l thun nghch. Lin kt cng ha tr: l lc lin kt gia cc nguyn t bng nhng cp in t c hung. V l lc lin kt ln 50- 150 kcal/ mol nn l lin kt khng thun nghch nhit c th, khng c cht xc tc. Loi lin kt ny t gp. Th d lin kt gia cht alkyl ha vi t bo ung t h, cc thuc c ch enzym mono - amin oxydase (MAOI), thuc tr su ln hu c vi cholinesterase. Mt phn t thuc c th gn vo receptor theo nhiu kiu lin kt. Th d: acetylcholin gn vo receptor M- cholinergic:

Hnh 2.1. Phc hp acetylcholin - receptor M Acetylcholin gn vo receptor M theo ng ni sau: - Hai O ca chc ester to lin kt hydro vi receptor

- Nhm CH2- CH2 gn vi receptor bng lin kt phn t (lc Van - der- Waals) - Hai gc CH3 ca amin bc 4 gn vo cc khoang ca v tr anion cng bng lc Van- der- Waals 2) Chuyn tc dng tng h gia ligand v receptor thnh mt tn hiu gy ra c p ng t bo. Cc receptor nm nhn t bo c hot ha bi cc ligand gn trn cc v tr c hiu ca ADN nm trong cc vng iu ha gen, gy ra s sao chp cc gen c hiu (r eceptor ca hormon steroid, vitamin D 3). Cc receptor nm mng t bo v xa nhn nn khng tham gia trc tip vo cc chng trnh biu hin ca gen. Khi cc ligand tc ng ln rece ptor s lm sn 2+xut ra cc phn t trung gi?an - ngi truyn tin th 2 (AMPv, GMPv, IP 3, Ca, diacetyl glycerol)- Nhng cht ny s gy ra mt lot phn ng trong t bo, dn ti mt thay i chuyn ha trong t bo, cng vi hoc khng c s thay i v biu hin gen (receptor ca adrenalin, ca benzodiazepin). Nh vy, khi thuc gn vo receptor ca t bo th gy ra c tc dng sinh l. Nhng c khi thuc gn vo t bo m khng gy ra tc dng g, ni gn thuc c gi l ni tip nhn (acceptor) hoc receptor cm, (silent receptor) nh thuc m gn vo t bo m, digitalis gn vo gan, phi, thn Thuc gn vo receptor ph thuc vo i lc (affinity) ca thuc vi receptor. Hai thuc c cng receptor, thuc no c i lc cao hn s y c thuc khc ra. Cn tc dng c a thuc l do hiu lc (efficacy) ca thuc trn receptor . i lc v hiu lc khng phi lc no cng i cng nhau: acetylcholin l cht dn truyn thn kinh ca h ph giao cm, khi gn vo r eceptor M, gy hiu lc lm tng tit nc bt, co ng t, chm nhp tim; atropin c i lc tr n receptor M mnh hn acetylcholin rt nhiu nn y c acetylcholin ra kh i receptor M, n hng bn thn n li khng c hiu lc g. lm sng, tc dng ca atropin quan st c chnh l tc dng ca s thiu vng acetylcholin trn receptor M: kh ming (gim tit nc bt), gin ng t, nhp tim nhanh 1.2. Cc c ch tc dng c a thuc 1.2.1. Tc dng ca thuc thng qua receptor

Thuc tc dng trc tip trn cc receptor ca cc cht ni sinh (hormon, cht d n truyn thn kinh): nhiu thuc tc dng trn cc receptor sinh l v thng mang tnh c hiu. Nu tc dng ca thuc ln rec eptor ging vi cht ni sinh, gi l cht ng vn hay cht ch vn (agonists), nh pilocarpin trn receptor M cholinergic. Nu thuc gn vo receptor, khng gy tc dng ging cht ni sinh, tri li, ngn cn cht ni sinh gn vo receptor, gy tc dn g c ch cht ng vn, c gi l cht i khng (antagonists), nh d tubocurarin tranh chp vi acetylcholin ti receptor N ca c vn. - Mt s thuc thng qua vic gii phng cc cht ni sinh trong c th gy tc dng: amphetamin gii phng adren alin trn thn kinh trung ng, nitrit lm gii phng NO gy gin mch Xt trn nhiu mt, protein l mt nhm quan trng ca receptor thuc. Do , ngoi receptor t bo, cc receptor ca thuc cn l: Cc enzym chuyn ha hoc iu ha cc qu trn h sinh ha c th b thuc c c h hoc hot ha: . Thuc c ch enzym: captopril c ch enzym chuyn angiotensin I khng hot tnh thnh angiotensin II c hot tnh dng cha cao huyt p; cc thuc chng vim phi steroid c ch cyclooxygenase, lm gim t ng hp prostaglandin nn c tc dng h st, chng vim; thuc tr tim digitalis c ch Na +- K+ ATPase . Thuc hot ha enzym: cc yu t vi lng nh Mg 2+, Cu2+, Zn2+ hot ha nhiu enzym protein kinase, phosphokinase tc dng ln nhiu qu trnh chuy n ha ca t bo. - Cc ion: thuc gn vo cc knh ion, lm thay i s vn chuyn ion qua mng t bo. Novocain cn tr Na + nhp vo t bo thn kinh, ngn cn kh cc nn c tc dng gy t; benzodiazepi?n lm tng nhp Cl - vo t bo, gy an thn. 1.2.2. Tc dng ca thuc khng qua receptor Mt s thuc c tc dng khng phi do kt hp vi receptor. - Thuc c tc dng do tnh cht l ha, khng c hiu: Cc mui cha cc ion kh hp thu qua mng sinh hc nh MgSO 4, khi ung s gi nc thnh rut vo lng rut v gi nc trong lng rut nn c tc dng ty; khi

tim vo tnh mch s ko nc t gian bo vo mu nn c dng cha ph no. Isosorbid, mannitol dng liu tng i cao, lm tng p lc thm thu trong huy t tng. Khi lc qua cu thn, kh ng b ti hp thu ng thn, lm tng p lc thm thu tron g ng thn, c tc dng li niu. Nhng cht to chelat hay cn gi l cht cng cua do c cc nhm c cc nh OH, -SH, NH2, d to phc vi cc ion ha tr 2, y chng ra khi c th. Cc c ht cng c ua nh EDTA (ethyl diamin tetra acetic acid), BAL (British anti lewisit dimercaprol), d- penicilamin thng c dng cha ng c kim loi nng nh Cu 2+, Pb2+, Hg2+ hoc thi tr Ca 2+ trong ng c digital. Than hot hp ph c cc hi, cc c t nn dng cha y hi, ng c. Cc base yu lm trung ha dch v acid dng cha lot d dy (khng acid), nh hydroxyd nhm, magnesi oxyd. Thuc c cu trc tng t nh nhng cht sinh ha bnh thng, c th thm n hp vo cc thnh phn cu trc ca t bo, lm thay i chc phn ca t bo. Thuc ging purin, ging pyrimidin, nhp vo acid nucleic, dng chng ung th, chng virus. Sulfamid gn ging paraamino benzoic acid (PABA), lm vi khun dng nhm, khng pht trin c. 2. CC CCH TC DNG CA THUC Khi vo c th, thuc c th c 4 cch tc dng sau: 2.1. Tc dng ti ch v ton thn: Tc dng ti ch l tc dng ngay ti ni thuc tip xc, khi thuc cha c hp thu vo mu: thuc st khun ngoi da, thuc lm sn nim mc (tani n), thuc bc nim mc ng tiu ha (kaolin, hydroxyd nhm).

Tc dng ton thn l tc dng xy ra sau khi thuc c hp thu vo mu qu a ng h hp, ng tiu ha hay ng tim: thuc m, thuc tr tim, thuc li niu. Nh vy, tc dng ton thn khng c ngha l thuc tc dng khp c th m ch l thuc vo m u i khp c th. Tc dng ti ch hoc ton thn c th gy hiu qu trc tip hoc gin tip: tim d - tubocurarin vo tnh mch, thuc trc tip tc dng ln bn vn ng lm lit c vn v gin tip lm ngng th do c honh v c lin sn b lit ch khng phi thuc c ch trung tm h hp. Mt khc, tc dng gin tip cn c th thng qua phn x: khi ngt, ngi ammoni ac, cc ngn dy thn kinh trong nim mc ng h hp b kch thch, gy phn x kch thch trung tm h hp v vn mch hnh ty, lm ngi bnh hi tnh. 2.2. Tc dng chnh v tc dng ph - Tc dng chnh l tc dng iu tr - Ngoi tc dng iu tr, thuc c th cn gy nhiu tc dng khc, khng c ngha trong iu tr, c gi l tc dng khng mong mun, tc dng dng ngoi (adverse drug reactions ADR). Cc tc dng ngo?i c th ch gy kh chu cho ngi dng (chng mt, bu n nn, mt ng), gi l tc dng ph; nhng cng c th gy ph n ng c hi (ngay vi liu iu tr) nh xut huyt tiu ha, gim bch cu, tt huyt p th ng Th d: aspirin l thuc h st, gim au, chng vim (tc dng chnh), nhng gy chy mu tiu ha (tc dng c hi). Nifedipin, thuc chn knh calci dng iu tr tng huyt p (tc dng chnh), nhng c th gy nhc u, nhp tim nhanh (tc dng ph), ho, ph chn, tng enzym gan, tt huyt p (tc dng c hi). Trong iu tr, thng phi hp thuc lm tng tc dng chnh v gim tc dn g khng mong mun. Th d ung thuc chn giao cm cng vi nifedipin s lm gim c tc dng lm tng nhp tim, nhc u ca nifedipin. Cng c th thay i ng dng thuc nh dng thuc t hu mn trnh tc dng kh ung, gy bun nn. 2.3. Tc dng hi ph c v khng hi phc

- Tc dng hi phc: sau tc dng, thuc b thi tr, chc phn ca c quan li tr v bnh thng. Sau gy m phu thut, ngi bnh li c trng thi bnh thng, tnh to. - Tc dng khng hi phc: thuc lm mt hon ton chc ph n ca t bo, c quan. Th d: thuc chng ung th dit t bo ung th, bo v t bo lnh; thuc st khun bi ngoi da dit vi khun nhng khng nh hng n da; khng sinh cloramphenicol c tai bin gy suy ty xng. 2.4. Tc dng chn lc Tc dng chn l c l tc dng iu tr xy ra sm nht, r rt nht. Th d aspirin ung liu 1 2 g/ ngy c tc dng h st v gim au, ung liu 4 - 6 g/ ngy c c tc dng chng vim; digitalis gn vo tim, no, gan, thn nhng vi liu iu tr, ch c tc dng trn tim; albuterol (Salbutamol- Ventolin) kch thch chn lc receptor 2 adrenergic Thuc c tc dng chn lc lm cho vic iu tr tr nn d dng hn, hiu qu h n, trnh c nhiu tc dng khng mong mun. 3. NHNG YU T NH HUNG N TC DNG CA THUC: 3.1. V thuc 3.1.1. Thay i cu trc lm thay i dc lc hc ca thuc. Nh ta bit, thuc mun c tc dng, phi gn c vo receptor (i lc vi re ceptor) v sau l hot ha c receptor (c hiu lc hay tc dng dc l). Receptor ma ng tnh c hiu cho nn thuc cng phi c cu trc c hiu. Receptor c v nh kha v thuc l cha kha. Mt s thay i nh v cu trc ha hc (hnh dng phn t ca thuc) cng c th gy ra nhng thay i ln v tc dng. Nh vy vic tng hp cc thuc mi thng nhm: Lm tng tc dng iu tr v gim tc dng khng mong mun. Khi thm F vo v tr 9 v CH 3vo v tr 16 ca corticoid (hormon v thng thn), ta c betametason c tc dng chng vim gp 25 ln v khng c tc dng gi Na + nh corticoid, trnh phi n nht. - Lm thay i tc dng dc l{: thay i cu trc ca isoniazid (thuc chng

lao), ta c iproniazid, c tc dng chng trm cm, do gn vo receptor hon ton khc.

Sulfanilamid PABA (para amino benzoic acid) Khng histamin H1 c cng thc gn ?ging vi his tamin, tranh chp vi histamin ti receptor H 1. Cc ng phn quang hc hoc ng phn hnh hc ca thuc cng lm thay i cng tc dng, hoc lm thay i hon ton tc dng ca thuc. l. isoprenalin c tc dn g kch thch receptor adrenergic 500 ln mnh hn d. isoprenalin. l. quinin l thuc cha st rt, d. quinin (quinidin) l thuc cha lon nhp tim. Cng ngy ngi ta cng hiu r c siu cu trc ca receptor v sn xut cc t huc rt c hiu, gn c vo di typ ca receptor: receptor adrenergic 1, 2, 1, 2, 3, receptor cholinergic M1, M2, M3, receptor dopaminergic D 1, D2, D7. 3.1.2. Thay i cu trc thuc, lm thay i dc ng hc ca thuc Khi cu trc ca thuc thay i, lm tnh cht l ha ca thuc thay i, nh hng n s ha tan ca thuc trong nc hoc trong lipid, nh hng n s gn thuc vo prote in, ion ha ca thuc v tnh vng bn ca thuc. Mt s v d: Dopamin khng qua c hng ro mu no, nhng l. dopamin (Levo dopa), cht tin thn ca dopamin th qua c. Estradiol thin nhin khng ung c v b chuyn ha mnh gan. dn xut et hinyl estradiol (-C CH gn v tr 17) rt t b chuyn ha nn ung c. -

Tolbutamid b microsom gan oxy ha gc CH 3 v tr para, c t/2 huyt tng l 4 - 8 h. Thay gc CH3 bng Cl (Clorpropamid) s rt kh b chuyn ha, lm t/2 ca thuc ko di ti 35 h. - Cc thiobarbituric t b phn ly hn barbituric pH ca ng thn nn b thi tr chm hn. Qua y ta c th nhn th y rng, khi thuc gn vo receptor gy hiu lc, kh ng phi ton b phn t thuc m ch c nhng nhm chc phn gn vo receptor. Khi thay i cu trc ca nhm hoc vng chc phn, dc lc hc ca thuc s thay i. Cn khi thay i cu trc ngoi vng chc phn, c th thay i dc ng hc ca thuc. 3.2. Dng thuc Dng thuc l hnh thc trnh by c bit ca dc cht a dc cht vo c th. Dng thuc phi c bo ch sao cho tin bo qun, vn chuyn, s dng v pht huy ti a hiu lc cha bnh ca thuc. C th tm tt qu trnh hnh thnh v pht huy tc dng ca mt dng thuc tro ng c th nh sau:

Qua s , ta thy t 1 dc cht, cc nh bo ch c th a ra th trng nhiu loi bit dc (dng thuc) khc nhau, c sinh kh dng khc nhau do c nh hng khc nhau ti hiu qu iu tr. 3.2.1. Trng thi ca dc cht - tn nh: thuc cng mn, din tip xc cng tng, hp thu thuc cng nhanh. - Dng v nh hnh v dng tinh th: thuc rn dng v nh hnh d tan, d hp thu. 3.2.2. T dc T dc khng phi ch l cht n bao gi thuc m cn nh hng n ha tan, khuch tnca thuc. Khi thay calci sulfat (thch cao, t dc c in) bng lactose dp vin diphenylhydantoin, gy

hng lot ng c diphenylhydantoin do lng thuc c hp thu nhiu hn (c, 1968). Nguyn nhn l t dc calci sulfat ch ng vai tr mt khung mang, khng tiu v xp, lm dc cht ?c gii phng t t trong ng tiu ha. Cn la ctose li lm dc cht d tan, nn c hp thu nhanh trong thi gian ngn. 3.2.3. K thut bo ch v dng thuc K thut bo ch l mt yu t khng km phn quan trng c tc ng trc tip n sinh kh dng ca thuc, c th kim sot c s gii phng dc cht v v tr thuc gii phng ( gii phng ti ch). V vy n thng c cc nh sn xut gi b mt. Hin c rt nhiu dng thuc khc nhau c sn xut theo cc k thut khc nhau sao cho: - Hot tnh ca thuc c vng bn - Dc cht c gii phng vi tc n nh - Dc cht c gii phng ti ni cn tc ng (gii phng ti ch, targetting medication) - Thuc c sinh kh dng cao. 3.3. V ngi dng thuc 3.3.1. c im v tui (xin xem phn dc ng hc) 3.3.1.1. Tr em: Tr em khng phi l ngi ln thu nh li, ngha l khng phi ch gim liu thuc ca ngi ln th thnh liu ca tr em, m tr em cn c nhng c im ring ca s pht trin, l: S gn thuc vo protein huyt tng cn t, mt khc, mt phn protein huyt t ng cn gn bilirubin, d b thuc y ra, gy ng c bilirubin. - H enzym chuyn ha thuc cha pht trin - H thi tr thuc cha pht trin - H thn kinh cha pht trin, myelin cn t, hng ro mu no cha bo v nn thuc d thm qua v t bo thn kinh cn d nhy

cm (nh vi morphin) - T bo cha nhiu nc, khng chu c thuc gy mt nc. - Mi m v c quan ang pht trin, ht sc thn trng khi dng cc loi hormon. Mt s tc gi a ra cc cng thc tnh liu lng cho tr em:

BSA: Body Surface Area -Din tch c th (tra monogram) 1.7: BSA trung bnh ca ngi ln 3.3.1.2. Ngi cao tui Ngi cao tui cng c nhng c im ring cn lu {: - Cc h enzym u km hot ng v lo ha - Cc t bo t gi nc nn cng khng chu c thuc gy mt n c Ngi cao tui thng mc nhiu bnh (cao huyt p, x va mch, thp khp, ti u ng) nn phi dng nhiu thuc mt lc. Cn rt ch tng tc thuc khi k n (xin xem phn tng tc thuc) 3.3.2. c im v gii Nhn chung, khng c s kh c bit v tc dng v liu lng ca thuc gia nam v n. Tuy nhin, vi n gii, cn ch n 3 thi kz: 3.3.2.1. Thi k c kinh nguyt Khng cm hn thuc. Nu phi dng thuc di ngy, c tng t ngng thuc th nn sp xp vo lc c kinh. 3.3.2.2. Thi k c thai Trong 3 thng u, thuc d gy d tt bm sinh, to ra qui thai. Trong 3 thng gi a thuc c th nh hng xu n s pht trin ca bo thai, n chc phn pht trin ca cc c quan. Trong 3 thng cui, thuc c th gy xy thai, non. V vy, khi cn ch nh thuc cho ph n c thai, cn cn nhc tht k gia li ch cho ngi m v mc nguy hi cho bo thai. Ni

chung, trong 3 thng u, tuy?t i trnh dng mi loi thuc. i vi ngi m, khi c thai, lng nc gi li trong c th tng, th tch mu t ng, hm lng protein huyt tng c th gim, lng lipid c th tng lm nh hng n ng hc ca thuc. 3.3.2.3. Thi k cho con b Rt nhiu thuc khi dng cho ngi m s thi tr qua sa v nh vy c th gy c hi c ho con. Cc nghin cu v cc loi thuc ny ni chung cn cha c y , do tt nht l ch nn dng nhng loi thuc tht cn thit cho m. Tuyt i khng dng nhng thuc c cha thuc phin v dn xut ca thuc phin (thuc ho, codein, vin ra ) v thuc thi tr q ua sa v trung tm h hp ca tr rt nhy cm, c th b ngng th. Khng dng cc loi cortico id (lm suythng thn tr), cc khng gip trng tng hp v iod (gy ri lon tuy n gip), cloramphenicol v thuc phi hp sulfametoxa zol + trimethoprim (Co trimoxazol) v c th gy suy tu xng. Cn rt thn trng khi dng cc thuc c ch thn kinh trung ng (meprobamat, diazepam), thuc chng ng kinh, u gy m mng v li b cho tr. 4. NHNG TRNG THI TC DNG C BIT CA TH UC Trong qu trnh s dng thuc, ngoi tc dng iu tr, i khi cn gp nhng tc dng khng mong mun do s phn ng khc nhau ca tng c th vi thuc. 4.1. Phn ng c hi ca thuc (Adverse drug reactions - ADR) Mt phn ng c hi ca thuc l mt p hn ng c hi, khng nh c trc

v xut hin liu lng thng dng cho ngi (nh ngha ca Chng trnh gim st thuc quc t - WHO). ADR l tn gi chung cho mi triu chng bt thng xy ra khi dng thuc ng liu. C th ch l nhng tri u chng rt nh nh nhc u, bun nn cho n nhng triu chng rt nng dn n t vong nh sc, phn v, suy tu xng. Tuz theo nc v tuz theo tc gi, ADR c th xy ra khong 8 - 30% s ngi dng thuc. 4.2. Phn ng d ng D ng thuc cng l 1 AD R. Do thuc l 1 protein l (insulin, thyroxin ly t sc vt), l a peptid, polysacchari d c phn t lng cao, mang tnh khng nguyn. Tuy nhin, nhng thuc c phn t lng th p hoc chnh sn phm chuyn ha ca n cng c th gy d ng, chng c gi l bn khng nguyn hay hapten. Vo c th, hapten c kh nng gn vi mt protein ni sinh theo n g ni cng ha tr v to thnh phc hp khng nguyn. Nhng thuc c mang nhm NH 2 v tr para, nh benzocain, procain, sulfonamid, sulfonylurea l nhng thuc d gy mn cm v nhm NH 2 d b oxy ha v sn phm oxy ha s d gn vi nhm SH ca protein ni sinh thnh khng nguyn. Phn ng min dch d ng c chia thnh 4 typ da trn c s ca c ch min dch: Typ I hay phn ng ph n v (anaphylactic reactions) do s kt hp ca khng ng uyn vi khng th IgE, gn trn bch cu a base tun hon hoc cc dng bo. Phn ng lm gii phng nhiu cht ha hc trung gian nh histamin, leucotrien, prostaglandin, gy gin mch, ph v vi m. Cc c quan ch ca phn ng ny l ng tiu ha? (d ng thc n), da (my ay, v im da d ng), ng h hp (vim mi, hen) v h tim - mch (sc phn v) Cc phn ng ny thng xy ra ngay sau khi dng thuc. Cc thuc d gy phn ng typ I: thu c t procain, lidocain, khng sinh

nhm lactam, aminoglycosid, huyt thanh, globulin, vaccin, vitamin B 1 tim tnh mch. Typ II hay phn ng hu t bo (cytolytic reactions) xy ra khi c s kt hp khn g nguyn vi khng th IgG v IgM ng thi c s hot ha h b th. M ch ca phn ng ny l cc t bo ca h tun hon. Th d: thiu mu tan mu do penicilin, thiu mu tan mu t min do methyl dopa, ban xut huyt gim tiu cu do quinidin, gim bch cu ht do sulfamid, luput ban h thng do procainamid. Typ III hay phn ng Arthus, trung gian ch yu qua IgG c s tham gia ca b th . Phn ng gia khng nguyn v khng th to thnh phc hp min dch. Phc hp ny lng ng vo ni mc mch, gy tn thng vim hu hoi, c gi l bnh huyt thanh. Biu hin lm sng thng l: my ay, ban , au, vim khp, ni hch, st. Thng xy ra sau 6 - 12 ngy. Cc thuc c th gp l sulfonamid, penicilin, mt s thuc chng co git, iod, mu i Hg, huyt thanh. Hi chng Stevens - Johnson l biu hin nng ca typ ny. Typ IV hay phn ng nhy cm mun, trung gian qua t bo lympho T c m n cm v i thc bo. Khi cc t bo mn cm tip xc vi khng nguyn, s gii phng cc ly mphokin gy ra phn ng vim. Vim da tip xc l biu hin thng gp ca typ ny. Cc phn ng d ng thuc khng lin quan n liu lng thuc dng, s ln dn g v thng c d ng cho. V vy cn hi tin s d ng ca bnh nhn trc khi dng thuc. V i nhng thuc hay gy d ng (penicilin, lidocain,.. .) khi dng, phi c sn thuc v phng tin cp cu (adrenalin). Sc phn v c th xy ra do ng dng thuc khc nhau: vitamin B 1 dng tim tnh mch c th gy sc cht ngi, trong khi dng ung khng gy phn ng ny. 4.3. Tai bin thuc do ri lon di truyn

Thng l do thiu enzym bm sinh, mang tnh di truyn trong gia nh hay chng tc. tc. PD) hoc glutathion reductase d b thiu mu tan mu khi dng primaquin, quinin, pamaquin (xin xem bi Thuc chng st rt), sulfamid, nitrofuran quinin, pamaquin (xin xem bi Thuc chng st rt), sulfamid, nitrofuran PD nm trn chromosom X, v vy, tai bin thng xy ra nam. Ngi ta c lng c khong 100 200 triu ngi mang gen ny v thng gp trn ngi da en. Ngi thiu enzym methe moglobin reductase l nhng ngi d hp t (khong 1% dn s). Khi dng thuc st rt (pamaquin, primaquin), thuc khng sinh, st khun (cloramph enicol, sulfon, nitrofurantoin), thuc h st (phenazol, paracetamol) rt d b methemoglobin. Ngi thiu ac etyl transferase s chm acetyl ha mt s thuc nh hydralazin, isoniazid, phenelzin nn d b nhim c cc thuc ny. Hin tng c ng (idiosyncrasy) l nhy cm c nhn bm sinh vi thuc ch nh l s thiu ht di truyn 1 enzym no . 4.4. Quen thuc Quen thuc l s p ng vi thuc yu hn hn so vi ngi bnh thng dng c? ng liu. Liu iu tr tr thnh khng c tc dng, i hi ngy cng phi tng liu cao hn. Quen thuc c th xy ra t nhin ngay t ln u dng thuc do thuc t c hp thu, hoc b chuyn ha nhanh, hoc c th km mn cm vi thuc. Thng do nguyn nhn di truyn. Thng gp quen thuc do mc phi sau mt thi gian dng thuc, i hi phi tng dn liu. 4.4.1. Quen thuc nhanh (tAChyphylaxis) Thc nghim dng nhng liu Thc nghim dng nhng liu

6 ln, tc dng gy tng huyt p gim dn ri mt hn. Mt s thuc khc cng c hin tng quen thuc nhanh nh amphetamin, isoprenalin, adrenalin, histamin Nguyn nhn l: Thuc tc dng gin tip qua s gii phng cht ni sinh ca c th, lm cn kit cht ni sinh. Ephedrin, amphetamin lm gii phng adrenalin d tr ca h giao cm. - Kch thch gn nhau qu lm receptor mt mi - To cht chuyn ha c tc dng i khng vi ch t m: isoprenalin (cng giao cm) qua chuyn ha gan, to ra 3 - orthomethylisoprenalin c tc dng hu . 4.4.2. Quen thuc chm Sau mt thi gian dng thuc lin tc, tc dng ca thuc gim dn, i hi phi t ng liu hoc i thuc khc. C nhiu nguyn nhn: Do gy cm ng enzym chuyn ha thuc, lm nhng liu thuc sau b chuyn h a nhanh, mt tc dng nhanh. Barbiturat, diazepam, tolbutamid, ru ethylic u l nhng thuc gy cm ng enzym chuyn ha ca chnh n. - Do gim s lng receptor c m ng vi thuc mng t bo (iu ha gim down regulation): khi dng thuc cng giao cm, ph giao cm ko di Tri li, khi dng cc thu c phong to ko di s lm tng s lng receptor (iu ha tng - up regulation) nh dng thuc hu giao cm, thuc an thn c ch h dopaminergic. Khi ngng thuc d gy hin tng hi ng (rebound) - Do c th phn ng bng c ch ngc li dng cc thuc li niu thi Na + lu, c th mt nhiu Na+ s tng tit aldosteron gi li Na +, lm gim tc dng li niu. trnh hin tng quen thuc, trong lm sng thng dng thuc ngt qung h oc lun phin thay i cc nhm thuc (s trnh by trong phn thuc c th) 4.5. Nghin thuc

Nghin thuc l mt trng thi c bit lm cho ngi nghin ph thuc c v t m l v th cht vo thuc vi cc c im sau: - Thm thung mnh lit nn xoay s mi cch c thuc dng, k c hnh vi phm php - C khuynh hng tng liu Thuc lm thay i tm l v th cht theo hng xu: ni iu, li lao ng, b n thu, thiu o c gy hi cho bn thn v x hi - Khi cai thuc s b thuc vt hay ln cn i thuc : vt v, ln ln, d cm, v m hi, tiu chy Nu li dng thuc cn vt s ht ngay. Nhng thuc gy nghin u c tc dng ln thn kinh tr ung ng gy sng khoi lng lng, o nh, o gic (ph thuc) hoc trng thi hng phn mnh (thuc lc), c gi c hung l ma ty: morphin v cc cht loi thuc phin (heroin, pethidin, methadon), cocain, cn sa (cannabis, marijuana), metamphetamin, ectasy Ru v thuc l hin cn c coi l ma ty h?p php. C ch nghin cn cha c hon ton bit r, c nhiu gi thuyt gii thch: do c th khng sn xut morphin ni sinh; lm ri lon chc phn ca nron, gy phn ng b tr ca c th; to ra cht i khng vi ma ty nn i hi phi tng liu Hin nay khng c phng php cai nghin no c hiu qu, ngoi tr ch ca ng i nghin. V vy, nghin ma tu l mt t nn x hi phi c loi tr. BI 8. THUC TC DNG TRN H ADRENERGIC H adrenergic l h hu hch giao cm, gii phng cht trung gian ha hc gi chung l catecholamin v u mang nhn catechol (vng benzen c hai nhm OH v tr ortho v mt gc amin chui bn. Cc catecholamin gm c adrenalin (c sn xut ch yu tu thn g thn)

noradrenalin ( u tn cng cc si giao cm) v dopamin ( mt s vng trn th n kinh trung ng).

Hnh 6.1. Sinh tng hp catecholamin CHUYN HA CA CATECHOLAMIN Catecholamin c sinh tng hp t tyrosin di tc dng ca mt s enzym trong t bo a crm tu thng thn, cc nron hu hch giao cm v mt s nron ca thn kinh trung ng theo s trn (hnh 6.2)

Hnh 6.2. Chuyn vn ca catecholamin ti tn cng dy giao cm Tyrosin c vn chuyn vo u tn cng dy giao cm nh c ht vn chuyn ph thuc Na +(A). Tyrosin c chuyn ha thnh dopamin (DA) ri c cht vn c huyn (B) a vo cc ti d tr (cc ht). Cht vn chuyn ny cng vn chuyn c noradrenalin (NA) v v i amin khc. Trong ti d tr, DA c chuyn ha thn h NA. in th hot ng lm m kn h calci, Ca 2+ vo t bo, gii phng NA t ti d tr. Sau khi c tng hp, mt phn catecholamin s kt hp vi ATP hoc vi mt dng protein ha tan l chromogranin tr thnh dng khng c hot tnh, khng b cc e nzym p h hu, lu li trong cc kho d tr l nhng ht c bit nm bo tng (khong 60%), cn mt phn khc (khong 40%) vn dng t do trong bo tng, d di ng, nm ngoi ht. Gi a hai dng ny lun c s thng bng ng, khi dng t do gim i th li c b sung ngay t cc kho d tr. Lng noradrenalin trong bo tng iu chnh hot tnh ca tyrosin hydroxylase theo c ch iu ha ngc chiu: khi noradrenalin tng th hot tnh ca enzym gim, v ngc li. Mt khc, cc cht cng re ceptor 2 lm gim gii phng noradrenalin ra khe xinap v do tr lng ca nora-

drenalin trong bo tng s tng ln. Theo gi thit ca Burn v Rand (1959 1962) di nh hng ca xung tc thn kinh, ngn dy giao cm lc u tit ra acetylcholin, l m thay i tnh thm ca mng t bo, do Ca ++ t ngoi t bo thm nhp c vo trong t bo, ng vai tr nh mt enzym lm v lin kt ATP - catecholamin, gii phng catecholamin ra dng t do. Sau khi c gii phng, mt phn noradrenalin s tc n g ln cc receptor (sau v trc xinap), mt phn chuyn vo mu tun hon tc dng xa hn ri b ging ha, cn p hn ln (trn 80%) s c thu hi li, phn nh khc b mt hot tnh ngay? trong bo tng. Hnh 6.3. S phn ca n oradrenalin khi c gii phng 1. Tc dng trn receptor sau (1a) v trc (1b) xinap 2. Thu hi 3. Vo tun hon v b chuyn ha bi COMT 4. Chuyn ha trong bo tng bi MAO Catecholamin b mt hot tnh bi qu trnh oxy ha kh amin do hai enzym MAO (mono amin oxydase) v COMT (catechol - oxy- transferase) cui cng thnh acid 3 - methoxy- 4 hydroxy mandelic (hay vanyl mandelic acid VMA) thi tr qua nc tiu. MAO c nhiu trong ti th (mitochondria), v vy n ng vai tr ging ha catecholamin trong t bo hn l tun hon. Phong to MAO th lm tng catecholamin trong m nhng khng nh hng n tc dng ca catecholamin ngoi lai. COMT l enzym ging ha catecholamin ngoi t bo, c mng xinap v nhi u ni nhng m cao hn c l gan v thn. Phong to COMT th ko di c thi gian tc dng ca catecholamin ngoi lai. Receptor: Adrenalin v noradrenalin sau khi c gii phng ra s tc dng ln c c receptor ca h adrenergic. Ahlquist (1948) chia cc receptor thnh hai loi

 v do chng c tc dng khc nhau trn cc c quan (bng sau). Ta thy rng tc dng cng c tnh cht kch thch, lm co tht cc c trn, ch c c trn thnh rut l gin. Ngc li, tc dng cng c tnh cht c ch, lm gin c, tr c tim li lm p nhanh v p mnh. Land, Arnold v Mc Auliff (1966) cn chia cc receptor thnh hai nhm 1 (tc dng trn tim v chuyn ha m) v nhm 2 (lm gin mch, gin kh o v chuyn ha ng). 2 trc xinap kch thch lm tng gii phng NA, c vai tr iu ha ngc vi 2. Theo xut ca Langer (1974), cc receptor c chia thnh hai loi: loi 1 l receptor sau xinap, lm co mch tng huyt p, loi 2 l receptor trc xinap, c tc dng iu ha, khi kch thch s lm gim gii phng norad renalin ra khe xinap, ng thi lm gim tit r enin, gy h huyt p. Cc receptor 2 c nhiu h giao cm trung ng. Hin cng thy c receptor 2 sau xinap ca mch mu v t bo c trn (lm co), m m v cc t bo biu m xut tit (rut, thn, tuyn ni tit) Dopamin ch yu tc dng thn kinh trung ng, thn v cc tng, trn cc re ceptor c hiu i vi n gi l cc receptor dopaminergic (receptor delta - ) Bng 6.1: Cc receptor adrenergic Iso*: Isoproterenol Adr: adrenalin NA: noradrenalin Ghi ch ca bng 3: - Mi receptor u kch thch adenylcyclase thng qua protein G S v lm tng AMPv, ngoi ra cn lm knh calci cm ng vi in th ca c vn v ctim.Receptor 2, tri li, c ch adenylcyclase thng qua protein G i, ng thi hot ha knh kali,c ch knh calci. - Receptor 1 kch thch lm tng calci ni bo thng qua 2 cht trung gian Diacylglycerol(DAG) v Inositol triphosphat (IP 3). THUC CNG H ADRENERGIC L nhng thuc c tc dng ging adrenalin v noradrenalin , kch thch hu hch giao cm nn cn gi l thuc cng giao cm. Theo c ch tc dng c th chia cc thuc ny lm hai loi:

- Loi tc dng trc tip trn cc receptor adrenergic sau xinap nh adrenalin, noradrenalin, isoproterenol, phenylephrin Loi tc dng gin tip do kch thch cc receptor trc xi?nap, lm gii phng cate cholamin ni sinh nh tyramin (khng dng trong iu tr), ephedrin, amphetamin v phenyl ethyl- amin. Khi dng reserpin lm cn d tr catecholamin th tc dng ca cc thuc s gim i. Trong nhm ny, mt s thuc c tc dng kch thch thn kinh trung ng theo c ch cha h on ton bit r (nh ephedrin, amphetamin), reserpin khng nh hng n tc dng ny; ho c c ch mono - amin- oxydase (MAOI), lm vng bn catecholamin. 2.1.Thuc cng receptor alpha v beta 2.1.1.Adrenalin c, bng A L hormon ca tu thng thn, ly ng vt hoc tng hp. Cht t nhin l ng phn t tuyn c tc dng mnh nht. 2.1.1.1.Tc dng Adrenalin tc dng c trn v receptor. - Trn tim mch: Adrenalin lm tim p nhanh, mnh (tc dng ) nn lm tng huyt p ti a, tng p lc t ngt cung ng mch ch v xoang ng mch cnh, t pht sinh cc phn x gim p qua dy thn kinh Cyon v Hering lm cng trung tm dy X, v vy lm tim p chm dn v huyt p gim. Trn ng vt th nghim, nu ct dy X hoc tim atropin (hoc methyla tropin) trc ct phn x ny th adrenalin ch lm tim p nhanh mnh v hu yt p tng rt r.

Mt khc, adrenalin gy co mch mt s vng (mch da, mch tng receptor ) nhng li gy gin mch mt s vng khc (mch c vn, mch phi receptor ) do huyt p ti thiu khng thay i hoc c khi gim nh, huyt p tru ng bnh khng tng hoc ch t ng nh trong thi gian ngn. V l adrenalin khng c dng lm thuc tng huyt p. Tc dng lm gin v tng lu lng mch vnh ca adrenalin cng khng c d ng trong iu tr co tht mch vnh v tc dng ny li km theo lm tng cng nng v chuyn ha ca c tim. Di tc dng ca adrenalin, mch mu mt s vng co li s y mu ra nhng khu vc t chu nh hng hn, gy gin mch th ng nhng ni (nh mch no, mch phi) do d gy cc bin chng t mch no, hoc ph phi cp. - Trn ph qun: t tc dng trn ngi bnh thng. Trn ngi b co tht ph qun do hen th ad renalin lm gin rt mnh, km theo l co mch nim mc ph qun, lm gim ph cho nn nh h ng rt tt ti tnh trng bnh. Son g adrenalin b mt tc dng rt nhanh vi nhng ln dng sa u, v vy khng nn dng ct cn hen. - Trn chuyn ha: Adrenalin lm tng hu glycogen gan, lm tng glucose mu, lm tng acid bo t do trong mu, tng chuyn ha c bn, tng s dng oxy c a m. Cc c ch tc dng ca adrenalin hay catecholamin ni chung l lm tng tng h p adenosin 3 - 5- monophosphat (AMP - vng) t ATP do hot ha

adenylcyclase (xem s ) S tc ng ca catecholamin ln chuyn ha ng v m 2.1.1.2. p dng iu tr: - Chng chy mu bn ngoi (p ti ch dung dch adrenalin hydroclorid 1% lm co mch). - Tng thi gian gy t ca thuc t v adrenalin lm co mch ti ch nn lm chm hp thu thuc t. Khi tim b ngng ?t ngt, tim adrenalin trc tip vo tim hoc truyn mu c a drenalin vo ng mch hi tnh. - Sc ngt: dng adrenalin tng huyt p tm thi bng cch tim tnh mch theo phng php trng bm tim. Liu trung bnh: tim di da 0,1- 0,5 mL dung dch 0,1% adrenalin hydroclorid. Liu ti a: mi ln 1 mL; 24 gi : 5 mL ng 1 mL = 0,001g adrenalin hy droclorid 2.1.2. Noradrenalin (arterenol) c, bng A L cht dn truyn thn kinh ca cc si hu hch giao cm. Tc dng mn h trn cc receptor , rt yu trn , cho nn: - Rt t nh hng n nhp tim, v vy khng gy phn x cng dy ph v. Lm co mch mnh nn lm tng huyt p ti thiu v huyt p trung bnh (mnh hn adrenalin 1,5 ln) - Tc dng trn ph qun rt yu, v c trn ph qun c nhiu receptor 2. Tc dng trn dinh dng v chuyn ho u km adrenalin. Trn nhiu c quan, tc dng ca NA trn receptor km hn adrenalin mt cht. Nhng do t l cng tc dng gia v khc nhau nn tc dng c hung khc nhau r rt.

Trn thn kinh trung ng, noradrenalin c nhiu vng di i. Vai tr sinh l cha hon ton bit r. Cc cht lm gim d tr catecholamin no nh reserpin, methyldopa u gy tc dng an thn. Tri li, nhng thuc c ch MAO, lm tng catecholamin th u c tc dng kch thn. iu ha thn nhit ph thuc vo s cn bng gia NA, serotonin v acetylcholi n phn trc ca vng di i. C th cn tham gia vo c ch gim au: thuc lm gim lng catechola min ti m vo no tht c ch c tc dng gim au ca morphin. Ch nh: nng huyt p trong mt s tnh trng sc: sc nhim c, nhim khun, sc do d ng Ch truyn nh git tnh mch t 1 - 4 mg pha long trong 250 500 mL dung dch glucose ng trng. Khng c tim bp hoc di da v lm co mch ko di, d gy hoi t ti ni tim. ng 1 mL = 0,001g 2.1.3. Dopamin Dopamin l cht tin thn ca noradrenalin v l cht trung gian ha hc ca h dopaminergic. C rt t ngn dy giao cm. Trong no, tp trung cc nhn xm trung ng v b en vn. Trn h tim mch, tc dng ph thuc vo liu: - Liu thp 1- 2 g/ kg/ pht c gi l liu thn, tc dng ch yu trn receptor dopaminergic D1, lm gin mch thn, mch tng v mch vnh. Ch nh tt trong sc do suy tim hoc do gim th tch mu (cn phc hi th tch mu km theo). - Ti thn, liu thn ca dopamin lm tng nc tiu, tng thi Na +, K+, Cl, Ca++, tng sn xut prostaglandin E 2 nn lm gin mch thn gip thn chu ng c thiu oxy. - Liu trung bnh > 2 - 10 g/ kg/ pht, tc dng trn receptor 1, lm tng bin v tn s tim. Sc cn ngoi bin ni chung khng thay i. - Liu cao trn 10 g/ kg/ pht tc dng trn receptor 1, gy co mch tng huyt p. Trong lm sng, tuz thuc vo tng loi sc m chn liu. Dopamin

khng qua c hng ro mu no Ch nh: cc loi sc, km theo v niu ng 200 mg trong 5 mL. Truyn chm tnh mch 2 5 g/ kg/ pht. Tng gim s git theo hiu qu mong mun. Chng ng ch nh: cc bnh mch vnh 2.2. Thuc cng receptor 2.2.1. Metaraminol (Aramin) Tc dng u tin trn receptor 1. Lm co mch mnh v lu hn adrenalin, c th cn do kch thch gii phng noradrenalin, khng gy gin mch th pht. Lm tng lc co bp ca c tim, t lm thay i nhp tim. Khng kch thch thn kinh trung ng, khng nh hng n chuyn ha. V mt gc phenol trn vng benzen nn vng bn hn adrenalin. Dng nng huyt p trong cc trng hp h huyt p t ngt (chn thng, nhim khun, sc). Tim tnh mch 0,5- 5,0 mg trong trng hp cp cu. Truyn chm tnh mch dung dch 10 mg trong 1 mL. C th tim di da hoc tim bp. ng 1 mL= 0,01g metaraminol bitartrat. 2.2.2. Phenylephrin (neosynephrin) Tc dng u tin trn receptor 1. Tc dng co m ch tng huyt p ko di, nhng khng mnh bng NA. Khng nh hng n nhp tim, khng kch thch thn kinh trung ng, khng lm tng glucose huyt. Ch nh : nh noradrenalin Tim bp 5- 10 mg Truyn chm vo tnh mch 10 - 15 mg trong 1000 mL dung dch glucose ng trng Cn dng chng xung huyt v gin ng t trong mt s ch phm chuyn khoa. 2.2.3. Clonidin (Catapressan) Clonidin (dicloro - 2, 6 phenyl- amino- imidazolin) c tc dng cng receptor

2 trc xinap trung ng v thuc qua c h ng ro mu- no. Tc dng cng 2 sau xinap ngoi bin ch thong qua nn gy tng huyt p ngn. Sau , do tc dng cng 2 trung ng chim u th, clonidin lm gim gii phng NA t cc nron giao cm hnh no, gy gim nhp tim, gim trng lc giao cm, gim lu lng mu no, tng, thn v mch vnh, a n h huyt p. Clonidin lm cn bi tit nc bt, dch v, m hi, lm gim hot tnh ca renin h uyt tng, gim li niu. ng thi c tc dng an thn, gim au v gy mt mi. Mt s t c gi cho rng clonidin gn vo receptor imidazolin thn kinh trung ng, l loi receptor mi ang c nghin cu. Tc dng khng mong mun: ng g, kh ming Ch nh: tng huyt p th va v nng (xin xem bi Thuc cha tng huyt p) Chng ch nh: trng thi trm cm. Khng dng cng vi guanetidin hoc thuc lit hch v c th gy cn tng huyt p. Liu lng: vin 0,15 mg. Ung liu tng dn ti 6 vin mt ngy, tc dng xut hin chm. Dng cng vi thuc li niu, tc dng h huyt p s t ng. 2.3. Thuc cng receptor C 4 tc dng dc l chnh - Tc dng gin ph qun, dng cha hen: loi cng 2. - Tc dng gin mch: loi cng 2- Tc dng kch thch 1 lm tng tn s, tng lc co bp ca c tim, tng tc dn truyn trong c tim, tng ti mu cho c tim.

- Trn t cung c cha, thuc cng 2 lm gim co bp c dng chng da xy thai. 2.3.1. Isoproterenol (Isoprenalin, Isuprel, Aleudrin, Novodrin, Isopropyl noradrenalin) Tc dng u tin trn receptor (1 v 2). Lm tng nhp tim, tng sc co bp ca c tim v cung lng tim, gy gin mch, h huyt p, lm gin kh qun nhanh v mnh (gp 10 ln adrenalin?), ng thi lm gim tit dch nim mc nn ct cn hen rt tt. Dng trong cc trng hp nhp tim chm thng xuyn , nghn nh tht hon to n, lon nhp do nhi mu c tim: truyn tnh mch 0,5mg trong 250 500 ml dung dch glucose 5%. Tc dng tng ng huyt km adrenalin v cn trc tip kch thch t bo ty tit insulin. Trong hen ph qun v trn kh ph mc mn tnh, t di li vin 10 mg, 2-3 ln/ ngy. Khng ung v b chuyn ha nhanh. ng Novodrin 1 mL= 0,5 mg isoprenalin clohydrat Vin 10- 20 mg isoprenalin sulfat Phun dch 1 phn nghn 2.3.2. Dobutamin (Dobutrex) Cng thc gn ging dopamin: tc dng u tin trn 1 receptor. Tc dng phc tp do dobutamin raxemic c 2 ng phn; ng phn ( ) dobutamin c tc dng cng 1 mnh, gy tng huyt p; trong khi ng phn (+) dobutamin li c tc dng i lp hy 1. C hai ng phn u c tc dng cng , nhng ng phn (+) 10 ln mnh hn ng phn ( -). Tc dng ca dobutamin raxemic l tng hp ca c hai ng phn. Trn tim, do dobutamin lm tng co bp mnh v t lm tng nhp , v vy khng l m tng nhu cu s dng oxy ca c tim. Tc dng km isopr oterenol. t tc dng trn mch n hng lm gin mch vnh. Tc dng li niu ch yu l do tng lu

lng tim. Ch nh: suy tim cp sau m tim, nhi mu c tim V thi gian bn thi ch khong 2 pht nn ch dng bng ng truyn chm tnh mch. Ch phm: Dobutamin hydroclorid (Dobutrex) l 20 mL cha 250 mg dobutamin. Khi dng, ha long trong 50 mL dung dch dextrose 5%, truyn tnh mch vi liu 2,5 10 g/ kg/ pht. Nu nhp tim tng nhanh, gim tc truyn. 2.3.3. Thuc cng u tin (chn lc) rece ptor 2L thuc thng c dng iu tr ct cn hen. Tuy nhin, liu ca o cng vn kch thch c 1, lm tng nhp tim. V vy hng nghin cu ti vn l tm cch thay i cu trc c cc thuc tc dng ngy cng chn lc trn 1 hn v c sinh kh dng cao hn. ng thi dng thuc di dng kh dung trnh hp thu nhiu thuc vo ng ton thn, d gy tc dn g ph (tim p nhanh, run tay) Cc thuc cng 2 dng di dng kh dung, ngoi tc dng lm gin ph qun cn c th c ch gii phng leucotrien v histamin khi dng bo phi (xem thm bi Thuc iu chnh ri lon h hp) Chng ch nh: bnh mch vnh, lon nhp tim, cao huyt p nng, i tho ng, cng gip. Dng ko di lin tc, tc dng c th gim dn do s lng recept or 2 mng t bo sau xinap gim (down regulation) 2.3.3.1. Terbutalin Do c vng resorcinol trong cu trc nn khng b COMT metyl ha. Sau kh dung, tc dng k o di c 3- 6 gi.

2.3.3.2. Albuterol (Salbutamol - Ventolin) Tnh cht dc l v ch nh iu tr nh terbutalin. Dng ng ung hoc kh dung. Sau kh dung, tc dng ti a vo pht th 15 v duy tr c 3 - 4 gi. - Vin gii phng chm (Volmax): 4 - 8 mg 2 ln/ ngy - Vin gii phng chm (Volmax): 4 - 8 mg 2 ln/ ngy 4ln/ ngy cch nhau 4 ting. 2.3.2.3. Ritodrin Dng l?m gin t cung, chng non (xem bi Thuc tc dng trn t cung). H p thu nhanh qua ng ung nhng sinh kh dng ch c 30%. Thi tr qua nc tiu 90% di dng lin hp. Tim tnh mch, 50% thi tr di dng nguyn cht. 2.4. Thuc cng giao cm gin tip 2.4.1. Ephedrin (ephedrinum) c, bng B Ephedrin l alcaloid ca cy ma hong (Ephedra equisetina v Ephedra vulgaris). Hin nay tng hp c. Trong y hc, dng loi t tuyn v raxemic. L thuc va c tc dng gin tip lm gii phng catecholamin ra khi ni d tr , va c tc dng trc tip trn receptor. Trn tim mch, so vi noradrenalin, tc dng chm v yu hn 100 ln, nhng k o di hn ti 10 ln. Lm tng huyt p do co mch v kch th ch trc tip trn tim. Dng nhiu l n lin nhau, tc dng tng p s gim dn (hin tng quen thuc nhanh: tAChyphylaxis) Thng dng chng h huyt p v kch thch h hp trong khi gy t tu sng , trong nhim c ru, morphin, barbiturat. Kch thch trung tm h hp hnh no v lm gin ph qun nn dng ct c n hen, tc dng tt trn tr em.

Trn thn kinh trung ng, vi liu cao, kch thch lm mt ng, bn chn, run, tng h hp. Ephedrin d dng hp thu theo mi ng. Vng bn vi MAO. C huyn ha ga n, khong 40% thi tr nguyn cht qua nc tiu. Dng di th mui clohydrat hoc sulfat d ha tan. Ung 10- 60 mg / ngy. Liu ti a 24h l 150 mg Tim di da, bp tht hoc tnh mch 10 - 20 mg/ ngy Nh nim mc (mt, mi) dung dch 0, 5- 3% ng 1 mL= 0,01g ephedrin clohydrat Vin 0,01g ephedrin clohydrat Pseudoephedrin l ng phn lp th ca ephedrin, t gy tim nhanh, tng huyt p v kch thch thn kinh trung ng hn ephedrin. Thng c dng trong cc ch phm nh mi chng xung huyt nim mc. 2.4.2. Amphetamin L thuc tng hp phenylisopropanolamin. Tc dng dc l theo kiu ephedrin, gin tip lm gii phng noradrenalin (v c th cn c dopamin v serotonin) ra khi ni d tr. Khc ephedrin l thm vo thn kinh trung ng nhan h, tc dng kch thch mnh tm trng v s nhanh nhn do tc ng ln v no v h lin vng hot ha (v vy, c xp vo loi doping, cm dng trong thi u th thao). Cn c tc dng gy chn n, dng chng bo ph. Mt s dn xut ca amphetamin ( methamphetamin, dimethoxyamphetamin) kch thch thn trung ng rt mnh, gy lon thn, u xp vo cht ma tu. 2.4.3. Phenylpropanolamin t tc dng trung ng hn.

 ngoi bin, tc dng co mch thng c dng chng ngt mi, l thuc phi hp trong v in thuc chng cm cm (Atussin, Decolgen). Tuy nhin, gn y thy nhiu tc dng ph trn tim mch nn c xu hng khng dng na. THUC HU H ADRENERGIC L nhng thuc lm mt tc dng ca adrenalin v noradrenalin. Cc thuc ny thng c dng iu tr chng tng huyt p, bnh Raynaud, lon nhp tim, hi chng cng tuyn gi p (tim nhp nhanh, li mt, gin ng t, tng h hp; chnh l nhng du hiu cn g giao cm). Cc thu nhi c c chia thnh hai nhm: - Thuc hy giao cm (sympatholytic): l nh ng thuc phong to nron adrenergic trc xinap, lm gim gii phng catecholamin, khng c tc dng trn receptor sau xinap, khi ct cc dy hu hch giao cm th thuc mt tc dng. Do thiu cht dn truyn thn kinh ni sinh, tnh cm th ca cc recept or sau xinap vi catecholamin ngoi lai s tng ln. Thuc hu adrenalin (adrenolytic) l nhng thuc phong to ngay chnh cc recep tor adrenergic sau xinap, cho nn khi ct t cc si hu hch giao cm, tc dng ca thuc khn g thay i. Catecholamin c ni sinh ngoi lai u b mt tc dng. 1.1.Thuc hu giao cm Cc thuc c th c tc dng nhng khu sau: 1.1.1. c ch tng hp catecholamin Thuc hay c dng l methyl dopa (Aldomet) phong ta dopa decarboxylase, lm dopa khng chuyn thnh dopamin v 5 - hydroxytryptophan khng chuyn thnh 5 - hydroxytryptamin (5 HT serotonin). Do s lng catecholamin v serotonin c ngoi bin v thn

kinh trung ng u gim. Mt khc cn ngn cn kh nng gn catechola min vo cc ht lu tr. Ngoi ra, trong c th methyldopa cn c th chuyn thnh methyl noradrenalin, tc dng nh mt cht trung gian ha hc gi chim ch ca noradrenalin (xem bi Thuc cha tng huyt p) Tc dng ph: m mng, c ch tm thn, chng mt, nhc u, kh ming, ph. Khng dng khi c ri lon tun hon no v mch vnh, cc trng thi trm cm, ri lon gan, thn. Liu lng: ung vin 250 mg. C th dng ti 8 vin/ ngy. Ch phm: Dopegyt vin 0,25 g methyl dopa. Carbidopa v bemerazid, c ch dopa decarboxylase ngo i bin. c dng phi hp vi l - dopa iu tr bnh Parkinson. 1.1.2. Lm gim d tr catecholamin trong cc ht * Reserpin: Lm gii phng t t catecholamin t cc ht lu tr ra ngoi bo tng MAO ph hu, do lng catecholamin gim c trn thn kinh trung ng (gy an thn), c ngoi bin (lm h huyt p). Reserpin cn cn tr qu trnh gn catecholamin (c ni sinh ln ngoi sinh) vo cc ht lu tr. * Guanetidin (Ismelin) Chim ch noradrenalin trong cc ht lu tr v tr thnh cht trung gian ha hc gi. Khc reserpin l lc u guanetidin gy tng nh huyt p do lm gii phng nhanh nor adrenalin ra dng t do, mt khc guanetidin khng thm c vo thn kinh trung ng nn khng c tc dng an thn. Tc dng ti a xut hin sau 2 - 3 ngy v mt i 6 - 10 ngy sau khi ngng thuc. Khng dng cho ngi bnh c lot d dy, suy mch vnh, suy thn. Khng dng cng vi clonidin. Liu lng: lc u ung 10 mg/ ngy, sau tng dn ti 50 - 75mg/ ngy Ch phm: vin 10 v 20 mg 1.1.3. Ngn cn gii phng catecholamin Bretylium (Darentin) C ch cha tht r.

c ch gii phng catecholamin, nhng khng nh hng n tc dng ca adrenalin v noradrenalin ngoi lai. C th l bretylium lm cho mng cc ht l u tr gim tnh thm vi ion Ca ++ m lm cho catecholamin khng c gii phng ra. C tc dng gy t ti ch. V c nhiu tc dng ph (nh xung huyt nim mc mi, kh th, a lng, h huy t p, nhc c) cho nn cn t ?c s dng lm sng. 1.1.4. Thay th catecholamin bng cc cht trung gian ho hc gi Mt s cht khng c tc dng dc l, nhng chim ch ca catecholamin v c ng c gii phng ra di xc tc kch thch dy giao cm nh mt cht trung gian ha hc, c gi l cht trung gian ha hc gi: - methyldopa to thnh methyl noradrenalin - Thuc c ch MAO: tyramin chuyn thnh octopamin - Guanetidin 1.2. Thuc hu adrenalin Cc thuc phong ta tc dng trn receptor tng i c hiu hn thuc kch th ch, ngha l nhiu thuc kch thch c tc dng c trn hai loi receptor v , cn thuc phong to thng ch tc dng trn mt loi receptor m thi. Do thuc loi ny c chia thnh hai nhm: thuc hu v thuc hu adrenergic. 1.2.1. Thuc hu - adrenergic V phong to cc receptor nn lm gim tc dng tng huyt p ca nor adrenalin, lm o ngc tc dng tng p ca adrenalin. Khng c ch tc dng gin mch v tng nhp tim ca cc thuc cng giao cm v u l tc dng trn cc receptor . Hin tng o ngc tc dng tng p ca adrenalin c gii thch l cc mao m ch c c hai loi receptor v , adrenalin tc dng trn c hai loi receptor , nhng bnh thng, tc dng chim u th nn adrenalin lm tng huyt p. Khi dng thuc phong to , adrenalin ch cn gy c tc dng kch thch trn cc receptor nn lm gin mch, h huyt p. Nhm thuc ny c ch nh trong cc cn tng huyt p, chn on u tu th ng thn, iu tr bnh Raynaud. Hin ang nghin cu thuc hu 1A iu tr ph i lnh tnh tuyn tin lit. Nhc im chung l d gy h huy t p khi ng, nhp tim nhanh, xung

huyt n im mc mi, co ng t, bun nn, nn v tiu chy do tng nhu ng d dy rut. Cc thuc ch khc nhau v cng tiu chy v thi gian tc dng. 1.2.1.1.Nhm haloalkylamin: C phenoxybenzamin (dibenzylin) v diben amin. V ha hc, c cng thc gn ging nh m tc nit (nitrogen mustard). Khi vo c th, amin bc 3 c chuyn thnh etylen amoni, cht ny gn cht vo cc receptor theo lin kt cng ha tr (ch yu l receptor 1), gy c ch rt mnh v ko d i (ti 24 gi cho mt ln dng thuc) theo kiu c ch mt chiu. Liu lng: phenoxybenzamin, vin nang 10 mg, ung 2 - 10 vin/ ngy 1.2.1.2.Dn xut imidazolin C tolazolin (Priscol, Divascon) v phentolamin (Regitin) c ch tranh chp vi noradrenalin recepto r 1 v 2 nn tc dng yu v ngn hn phenoxybenzamin nhiu. Liu lng: Priscol ung hoc tim bp 25 - 50 mg/ ngy. Regitin ung 20 40 mg/ ngy Cn dng chn on u tu thng thn: nghim php c coi l dng tnh nu ngi bnh ngh ngi, hon ton yn tnh, tim bp hoc tim tnh mch 5 mg phentolamin, s au vi pht lm huyt p ti a v ti thiu h khong 4 5 cmHg, duy tr c 7 pht ri tr li huyt p ban u trong 10- 15 pht. 3.2.1.3. Prazosin (Minipress): cht in hnh phong to 1. Dng iu tr tng huyt p, ung 1 20 mg mt ngy. (xin xem bi Thuc cha tng huyt p) 3.2.1.4. Alcaloid nhn indol: Cc alcaloid c n a nm ca g (ergot de seigle; Secale cornutum; Claviceps purpure a), c chia thnh hai nhm: loi hu giao cm v lm co bp t cung (gm ergotamin, ergotoxin) v loi lm co bp t cung n thun (ergometrin).

Vi liu thp, ergotamin c tc dng cng giao cm nh v ngn cn thu hi noradrenalin ngn dy giao cm. Liu cao, tri li c tc dng phong to recepto r . Ngoi ra c n c tc dng trc tip lm co c trn, nn c th lm co mch tng huyt p, hoc hoi t u chi v vch mi trong trng hp nhim c mn tnh do n la mch m mc, lm co tht rut, ph qun v t cung. Ch nh: ct cn migren, ri l on thi kz mn kinh, chy mu t cung sau s rau Dn xut hydro ha ca cc ergot (nh dihydroergotamin, hydroergotoxin) c tc dng phong to tng ln trong khi tc dng co c trn gim xung. Ngoi tc dng phong to re ceptor , tc dng h huyt p c a ergotamin cn c gii thch l lm gim trng lc trung tm vn mch v kch thch trung tm ph giao cm. Do c dng lm thuc gin mch, h huyt p: ung 4- 6 mg/ ngy, hoc tim di da 0,1 - 0,5 mg/ ngy. Chng ch nh: c thai, ri lon m ch vnh - Yohimbin: l alcaloid ca Corynantheyo himbe c nhiu Chu Phi. Cu trc ha hc gn ging reserpin, tranh chp vi NA ti receptor 2. D vo thn kinh trung ng. Tc dng yu v ngn, nn t c dng trong iu tr. Trong lm sng cn dnglm thuc cng dng, v ngoi tc dng gin mch c n kch thch phn x tu. Liu lng: Yohimbin clorhydrat 5 - 15 mg/ ngy 1.2.2. Thuc hu adrenergic

Cn gi l thuc phong to ( blocking agent) c tc dng c ch tranh chp vi isoproterenol cc r eceptor. Cht u tin c tm ra l dicloisoproterenol (Po well v Slater, 1958). c dng nhiu trong lm sng. 1.2.2.1.Tc dng dc l: c 4 tc dng dc l chnh vi mc khc nhau gia cc thuc: * Kh nng hu giao cm : l tnh cht chung duy nht ca tt c cc thuc hu : - Trn tim: lm gim nhp tim (20 30%), gim lc co bp ca c tim, gim lu lng tim, gim cng nng v gim s dng oxy ca c tim, gim tc dn truyn ca t chc n t. Ch yu l do hu 1. - Trn kh qun: lm co, d gy h en. Ch yu l do hu 2, gy tc dng khng mong mun. - Trn thn: lm gim tit renin, h huyt p trn ngi c HA cao - Trn chuyn ha: c ch hu glycogen v hu lipid +Tc dng lm n nh mng: ging quinidin, lm gim tnh thm ca mng t bo v i s trao i ion nn c tc dng chng lon nhp tim. + C hot tnh ni ti kch thch receptor : mt s thuc phong to khi gn vo cc receptor li c tc dng kch thch mt phn. Hiu qu thc t t quan trng, nhng c th hn ch tc dng lm gim nhp tim, gim co bp c tim, gim co kh qun ca chnh n. + Tnh chn lc: nhiu thuc phong to i lp vi tt c cc tc dng cng giao cm ca (1: tim v 2: mch, kh qun). Nhng mt s thuc li ch phong to c mt trong hai loi receptor (1hoc 2), v th phn bit thnh cc loi phong to ch?n lc trn giao cm : - Loi tc dng chn lc trn 1 hay loi chn lc trn tim (cardioselectifs), nh practolol, acebutalol, atenolol. Thng dng metoprolol (Lopressor) v

atenolol (T enormin) Li ch ca loi thuc ny l: - Do rt km tc dng trn 2 ca kh qun nn hn ch c tai bin co tht kh qun. - Km tc dng trn 2 ca thnh mch s c li cho iu tr cao huyt p (gim co mch ngoi bin) - Do rt km tc dng trn 2 ca thnh mch vnh nn khng bc l tc dng cng - adrenergic (tc dng co mch vnh ca CA tun hon trong mu). Bnh thng, do c tc dng th tc dng ca b lu m. Khi b phong to th tc dng ca s c bc l ra. Do khng nh hng n cc receptor trong hu glycogen nn khng lm nng th m tnh trng h ng huyt. - Loi c tc dng chn lc trn 2, ng u l Butoxamin, t c { ngha trong lm sng. 1.2.2.2. Ch nh chnh Cn au tht ngc, ch yu do lm gim s dng oxy ca c tim . Trong nhi mu c tim, tim tnh mch ngay t gi u s lm gim lan rng nhi mu v ci thin c tin lng bnh. - Lon nhp tim: nhp nhanh xoang, nhp nhanh trn tht, tim cng gip, cung ng nh do nhim c digital. - Tng huyt p: do lm gim lu lng tim, gim sc cn ngoi bin, gim tit renin v gim gii phng noradrenalin (xin xem thm bi Thuc cha tng huyt p) Mt s ch nh khc; cng gip, migren, glocom gc m (do lm gim sn xut thu dch), run tay khng r nguyn nhn. 1.2.2.3. Chng ch nh: - Suy tim l chng ch nh chnh v n c ch c ch b tr ca tim. - Bloc nh- tht v thuc c tc dng lm gim dn truyn ni ti trong c tim. - Hen ph qun. Loi c tc dng chn lc trn receptor 1 dng cho ngi hen t ng uy him hn, nhng vi liu cao, trong iu tr tng huyt p th

cng b mt tnh chn lc. Khng dng cng vi insulin v cc sulfamid h ng huyt v c th gy h ng huyt t ngt. - C thai: khng chng ch nh tuyt i, nhng gp tr mi b chm nhp tim, h ng huyt, suy h hp, thai chm pht trin. 1.2.2.4. Cc tc dng khng mong mun c chia lm hai loi: * Loi tai bin l hu qu ca s phong to receptor - Tim: suy tim do lm yu co bp ca c tim, chm nhp tim, nh tht phn ly . Mch: hi chng Raynaud, tm lnh u chi, i khp khing, (thng gp vi prop ranolol, do b phong to th s cng). Cc thuc chn lc trn 1 v c hot tnh kch thch ni ti th t tai bin ny hn - Phi: cc thuc c tc dng hu 2 > 1 s gy co kh qun, kh th. Khng dng cho ngi hen. Thn kinh trung ng: mt mi, mt ng, hay ng m, o nh, trm cm, thng gp hn vi cc thuc d tan trong m v d thm vo t bo thn kinh (propranolol, metoprol ol), loi t tan trong m (atenolol, nadolol) t tai bin hn. Chuyn ho: lm h ng huyt (cn thn trng vi ngi b i tho ng), t ng triglycerid trong mu. * Loi tai bin khng lin quan n tc dng phong to - Hi chng mt - da- tai: xu?t hin ring hoc phi hp vi cc tn thng ca mt (vim gic mc, vim cng mc), da (sn nga lng bn tay, bn chn, dy da), tai (ic

v vi m tai nng). gp vi practolol, iu tr trong 1 - 2 nm Vim phc mc x cng: au cng bng phc mc c nhng mng dy do t ch c x . Sau khi ngng thuc hoc iu tr bng corticoid s khi. Gp sau khi iu tr ko di trn 30 thng. Trn thc nghim, gp ung th tuyn c, ung th v, lymphosarcom. Do c n theo di trn ngi khi dng liu cao ko di. 1.2.2.5. Tng tc thuc Cc thuc gy cm ng cc enzym chuyn ha gan nh phenytoin, rifampin, ph enobarbital, ht thuc l, s lm tng chuyn ha, gim tc dng ca thuc hu . - Cc mui nhm, cholestyramin lm gim hp thu - Cc thuc hu c tc dng hip ng vi thuc chn knh calci, cc thuc h huyt p - Indomethacin v cc thuc chng vim phi steroid lm gim tc dng h huyt p ca cc thuc hu . 1.2.2.6. Phn loi

S phn loi ny gip cho chn thuc trong iu tr. Th d bnh nhn c r i lon co tht ph qun th nn dng loi c tc dng chn lc trn tim; bnh nhn c nhp tim ch m th dng loi c cng ni ti 1.2.2.7. Mt s thuc chnh * Propranolol (Inderal, Avlocardyl) L isopropyl aminonaphtyl oxypropranolol. C tc dng phong t o nh nhau trn c 1 v 2, khng c hot tnh ni ti kch thch. Tc dng: - Trn tim:lm gim tn s, gim lc co bp, gim lu lng tim ti 30%. c ch tim l do tc dng ring ca propranolol ngn cn calci nhp vo t bo c tim, gim nng c al ci trong ti li ni bo.

- Trn mch vnh: lm gim lu lng 10 - 30% do c ch gin mch. Lm gim tiu th oxy ca c tim. - Trn huyt p: lm h huyt p r sau 48 gi dng thuc. Huyt p ti thiu gim nhiu. - Ngoi ra cn c tc dng chng lon n hp tim, gy t (do tc dng n nh mng) v an thn Ch nh: Tng huyt p, lon nhp tim, nhp nhanh xoang, cung ng nh, nhp nhanh trn tht, bnh cng gip, suy mch vnh. Ung liu hng ngy 120 - 160 mg Vin 40 v 160 mg - Dng trong cp cu lon nhp tim do nhim c digital hay do thng tim, do t ng ni kh qun. Tim tnh mch 5 - 10 mg. ng 5 mg Chng ch nh: ngoi chng ch nh chung, propranolol khng c dng cho ngi c thai hoc lot d dy ang tin trin. Thuc c d dng h p thu qua ng tiu ha do tan nhiu trong m. Gn vo protein huyt tng ti 90- 95%, m ti a trong mu t protein huyt tng ti 90- 95%, m ti a trong mu t propranolol v acid naphtoxyl acetic rt nhanh ti gan nn ch khong 25% liu ung vo c vng tun hon, t/2: 3 - 5 gi. Vin 40 mg. Ung trung bnh 2 - 4 vin / ngy, chia lm nhiu ln ng 1 mL= 1 mg. Dng cp cu, tim tnh mch rt chm, t 1 - 5 mg/ ngy * Pindolol (Visken); C tc dng cng ni ti v khng nh hng n v n chuyn ca ion Ca ++ nn lm tng lc co bp v tn s ca tim. Thng dng trong cc trng hp c lon nhp chm v

i liu ung 5 - ?30 mg/ ngy. Tan va trong m, sinh kh dng 75% v t/2 = 3-4 gi. * Oxprenolol (Trasicor): Dng iu tr cao huyt p, c n au tht ngc, lon nhp tim. Ung 160 - 240 mg/ ngy. * Atenolol Atenolol rt tan trong nc nn t thm vo thn kinh trung ng, sinh kh dng 50%, t/2 = 5 - 8 gi. Ung 50- 100 mg/ ngy. * Metoprolol (Lopressor). C tc d ng chn lc trn tim ( 1) nn gy cn hen ph qun ( 2). Ung 50- 150 mg/ ngy. Hp thu nhanh qua ng ung, sinh kh dng 40% v t/2 = 3 - 4 gi. BI 9. THUC TC DNG TRN H H CHOLINERGIC THUC KCH THCH H MUSCARINIC 1.1. Acetylcholin 1.1.1. Chuyn ha Trong c th, acetylch olin (ACh) c tng hp t cholin coenzym A vi s xc t c ca cholin - acetyltransferase. Acetylcholin l mt base mnh, to thnh cc mui rt d tan trong nc

Sau khi tng hp, acetylc holin c lu tr trong cc nang c ng knh khong 300 - 600 A0 ngn dy cholinergic di th phc hp khng c hot tnh. Di nh hng ca xung ng thn kinh v ca ion Ca ++, acetylcholin c gii phng ra dng t do, ng vai tr mt cht trung gian ha hc, tc dng ln cc receptor cholinergic mng sau xinap, ri b thu phn mt hot tnh rt nhanh di tc dng ca cholinesterase (ChE) thnh cholin (li tham

gia tng hp acetylcholin) v acid acetic. C hai loi cholinesterase: Acetylcholinesterase hay cholinesterase tht (cholinesterase c hiu), khu tr cc nron v bn vn ng c vn lm mt tc dng ca acetylch olin trn cc receptor. Butyryl cholinesterase, hay cholinesterse gi (cholinesterase khng c hiu, thy nhiu trong huyt tng, gan, t bo thn kinh m (nevroglia). Tc dng sinh l khng quan trng, cha hon ton bit r. Khi b phong to, khng gy nhng bin i chc phn quan trng. Qu trnh tng hp acetylcholin c th b c ch bi hemicholin. c t ca vi khu n botulinus c ch gii phng acetylcholin ra dng t do.

Hnh 5.1. Chuyn vn ca ACh ti tn cng dy ph giao cm Cholin c nhp vo u tn cng dy ph giao cm bng cht vn chuyn ph t huc Na + (A). Sau khi c tng hp, ACh c lu gi trong cc nang cng vi peptid (P) v AT P nh cht vn chuyn th hai (B). Di tc ng ca Ca 2+, ACh b y ra khi nang d tr vo khe xinap. 1.1.2. Tc dng sinh l Acetylcholin l cht dn truyn thn kinh c nhiu ni trong c th, cho nn tc dng rt phc tp: Vi liu thp (10 g/ kg tim tnh mch ch), ch yu l tc dng trn hu hch p h giao cm (h muscarinic): . Lm chm nhp ti m, gin mch, h huyt p . Tng nhu ng rut . Co tht ph qun, gy cn hen . Co tht ng t

. Tng tit dch, nc bt v m hi Atropin lm mt hon ton nhng tc dng ny. Vi liu cao (1mg/ kg trn ch) v trn sc vt c tim trc bng at ropin s ulfat phong to tc dng trn h M, acetylcholin gy tc dng ging nicotin: kch thch cc hch thc vt, tu thng thn (h N), lm tng nhp tim, co mch, tn?g huyt p v kch thch h hp qua phn x xoang cnh. V c amin bc 4 nn acetyl cholin khng qua c hng ro mu no vo thn kinh trung ng. Trong phng th nghim, mun nghin cu tc dng trung ng, phi tim acetylcholin trc tip vo no, nhng cng b cholinesterase c rt nhiu trong thn kinh trung ng ph hu nhanh. Acetylcholin l mt cht dn truyn thn kinh quan trng trong h thng t hn kinh trung ng, c tng hp v chuyn ha ngay ti ch, c vai tr kch thch cc yu t c m th (nh cc receptor nhn cm ha hc), tng phn x ty, lm gii phng cc hormo n c a tuyn yn, tc dng trn vng di i lm h thn nhit, p trc tip vo v no gy co git 1.1.3. Cc receptor ca h cholinergic

1.1.4. p dng lm sng V acetylcholin b ph hu rt nhanh trong c th nn t c dng trong lm sng . Ch dng lm gin mch trong bnh Ray - n (Raynaud- tm ti u chi) hoc cc biu hin hoi t. Tc dng gin mch ca ACh ch xy ra khi ni m mch cn nguyn vn. Theo Fur chgott v cs (1984), ACh v cc thuc cng h M lm gii phng

yu t gin mch ca ni m mch (endothelium- derived relaxing factor EDRF) m bn cht l nitric oxyd nn gy gin mch. Nu ni m mch b tn thng, ACh khng gy c gin mch. Tim di da hoc tim bp 0,05 - 0,1 g, mi ngy 2 - 3 ln ng 1 mL = 0,1 g acetylcholin clorid 1.2. Cc este cholin khc Nu thay th nhm acetyl bng nhm carbamat th bo v c thuc khi tc dng ca cholinesterase, do ko di c thi gian tc dng ca thuc. Cc thuc u c amin bc 4 nn kh thm c vo thn kinh trung ng. 1.2.1. Betanechol (Urecholin) - Dn xut tng hp Tc dng chn lc trn ng tiu ha v tit niu. Dng iu tr chng bng, y hi v b i sau khi m.

Chng ch nh: hen, lot d dy - t trng. Ung 5- 30 mg. Vin 5- 10- 2550 mg Tim di da: 2,5 - 5 mg, 3- 4 ln mt ngy. 1.2.2. CarbAChol Dng cha bnh tng nhn p, nh dung dch 0,5 -1% Cn dng lm chm nhp tim trong cc cn nhp nhanh kch pht, ri lon tun ho n ngoi bin n ngoi bin 2,0 mg/ ngy. Tim di da 0,5 - 1 mg/ ngy. 1.3. Muscarin C nhiu trong mt s nm c lo i Amanita muscaria, A.pantherina Tc dng in hnh trn h thng hu hch ph giao cm, v vy c gi l h m uscarinic. Mnh hn acetylcholin 5 - 6 ln v khng b cholinesterase ph hu. - Khng dng cha bnh. Nhng c th gp ng c muscarin do n phi nm c: ng t co, si bt mp, m hi lnh lng, kh th do kh o co tht, nn e, a chy, i d m, tim p chm, huyt p h iu tr: atropin liu cao. C th tim tnh mch tng liu 1 mg atropin sulfat.

1.4. Pilocarpin c, bng A L alcaloid ca l cy Pilocarpus jaborandi, P.microphylus Rutaceae, mc nhiu Nam M. tng hp c. Kch thch mnh hu hch ph giao cm, tc dng lu hn acetylc holin; lm tit nhiu nc bt, m hi v tng nhu ng rut. Khc vi muscarin l c c tc dn g kch thch hch, lm gii phng adrenalin t? tu thng thn, nn trn ng vt c ti m trc bng atropin, pilocarpin s lm tng huyt p. Trong cng thc, ch c amin bc 3 nn t hm c vo thn kinh trung ng, liu nh kch thch, liu cao c ch. Liu trung bnh 0,01 - 0,02g Thng ch dng nh mt dung dch du pilocarpin base 0,5 1% hoc dung dch nc pilocarpin nitrat hoc clohydrat 1 2% cha tng nhn p hoc i lp vi tc dng gin ng t ca atropin. THUC I KHNG H MUSCARINIC 2.1. Atropin c, bng A. Atropin v ng loi l alcaloid ca l cy Belladon (Atropa belladona), c c dc (Datura stramonium), thin tin t (Hyoscyamus niger) 2.1.1. Tc dng Atropin v ng loi l nhng cht i khng tranh chp vi acetylcholin r eceptor ca h muscarinic (i lc > 0; hiu lc ni ti = 0). Ch vi liu rt cao v tim vo ng m ch th mi thy tc dng i khng ny trn hch v bn vn ng c vn. V vy, cc tc dng thng thy l: Trn mt, lm gin ng t v mt kh n ng iu tit, do ch nhn c xa. D o lm c mi gin ra nn cc ng thng dch nhn cu b p li, lm tng nhn p. V vy, khng c dng atropin cho nhng ngi tng nhn p. - Lm ngng tit nc bt lng, gim tit m hi, dch v, dch rut

- Lm n kh o, nht l khi n b co tht v cng ph giao cm. t c tc dng trn kh o bnh thng. Km theo l lm gim tit dch v kch thch trung tm h hp, cho nn atropin thng c dng ct cn hen. - t tc dng trn nhu ng rut bnh thng, nhng lm gim khi rut tng nhu ng v co tht. Tc dng ca atropin trn tim th phc tp: liu thp do kch thch trung tm dy X hnh no nn lm tim p chm; liu cao hn, c ch cc receptor muscarinic ca tim, li l m tim p nhanh. Tim th khng chu s chi phi ca ph giao cm nn atropin khng c nh hng. Atropin t nh hng n huyt p v nhiu h mch khng c dy ph giao cm. Ch lm gin mch da, nht l mi trng nng, v thuc khng lm tit m hi c, nn mc h cng gin ra chng vi xu hng tng nhit. Liu c, tc ng ln no gy tnh trng kch thch, thao cung, o gic, st, cui cng l hn m v cht do lit hnh no. iu tr nhim c bng thuc khng cholinesterase (physostignin) tim tnh mc h cch 2 gi 1 ln v chng triu chng kch thch thn kinh trung ng bng benzodiazepin. 2.1.2. Chuyn ha D hp thu qua ng tiu ha v ng tim di da. C th hp thu qua nim mc khi dng thuc ti ch, cho nn tr c th gp tai bin ngay c khi nh mt. Khong 50% thuc b thi tr nguyn cht qua nc tiu. 2.1.3. p dng lm sng - Nh mt dung dch atropin sulfat 0,5 - 1% lm gin ng t ti a sau 25 pht, dng soi y mt hoc iu tr vim mng mt, vim gic mc. Phi vi ngy sau ng t mi tr li

bnh thng. C th dng eserin salicylat (dung dch 0,2%) hay pilocarpin hydrat hoc nitrat (du ng dch 1%) rt ngn tc dng ca atropin. - Tc dng lm gin c trn c dng ct cn hen?, cn au ti mt, cn au thn, au d dy. - Tim trc khi gy m trnh tit nhiu m di, trnh ngng tim do phn x ca dy ph v. - Ri lon dn truyn nh tc nh tht (Stockes Adams) hoc tim nhp chm do nh hng ca dy X. - iu tr ng c nm loi muscarin v ng c cc thuc phong to cholinesterase . Chng ch nh: bnh tng nhn p, b i do ph i tuyn tin lit. 2.1.4. Ch phm v liu lng Dng di dng base hoc sulfat. Tim tnh mch 0,1 - 0,2 mg; tim di da 0,25 0,50 mg (liu ti a 1 ln: 1 mg; 24gi: 2 mg); ung 1 - 2 mg (liu ti a 1 ln: 2 mg; 24 gi: 4 mg). Atropin sulfat ng 1 mL = 0,25 mg; vin 0,25 mg Atropin sulfat ng 1 mL = 1 mg (c bng A), ch dng iu tr ng c cc cht phong to cholinesterase. 2.2. Homatropin bromhydrat (homatropini hydrobromidum) c, bng A Tng hp. Lm gin ng t thi gian ngn hn atropin (trung bnh 1 gi). Dng s oi y mt, dung dch 0,5- 1%. 2.3. Scopolamin (scopolaminum; hyoscinum) c, bng A - L alcaloid ca cy Scopolia carniolica. Tc dng gn ging atropin. Thi gian tc dng ngn hn. Trn th n kinh trung ng, atropin kch thch cn scopolamin th c ch cho nn c dng cha bnh Parkinson, c c cn co git ca bnh lit rung, phi hp vi thuc khng histamin chng nn khi say tu, say sng. Ung hoc tim di da 0,25 - 0,5 mg

Liu ti a mi ln 0,5mg; 24 gi: 1,5mg Vin Aeron c scopolamin camphonat 0,1mg v hyoscyamin camphonat 0,4mg; d ng chng say sng, say tu: ung 1 vin 30 pht trc lc khi hnh. 2.4. Thuc bn tng hp mang amoni bc 4: Ipratropium Do gn thm nhm isopropyl vo ngu yn t N ca atropin, ipratropium mang amoni bc 4, khng hp thu c qua ng ung v khng vo c thn kinh trung ng. Thng dng di dng kh dung iu tr bnh phi tc nghn mn tnh v ct cn hen. Ch 1% hp t hu vo mu v khong 90% liu kh dung c nut vo ng tiu ha v thi tr theo phn. T c dng ti a sau 30- 90 pht v t/2 > 4 gi. Ch phm: Ipratropium bromid (Atrovent, Berodual) dng kh dung nh liu, 20 g/ nht bp 200 liu. Ngi ln mi ln bp 2 nht, mi ngy 3 - 4 ln. THUC KCH THCH H NICOTINIC Cc thuc ny t c dng trong iu tr, nhng li quan trng v mt dc l v c dng nghin cu cc thuc tc dng trn hch. Hin nay cc thuc kch thch hch c chia thnh hai nhm: nhm u gm nicotin v cc thuc tng t, tc dng kch thch trn cc receptor nicotinic ca hch, b hexametoni c ch; nhm sau gm muscarin, pilocarpin, oxotremorin, thuc phong to cholinesterase tc dng kch thch trn cc receptor muscarinic (h M 1) ca hch, khng b hexametoni, m b atropin c ch. Serotonin, histamin v cc a peptid kch thch hch c th l trn cc receptor c hiu ring. Trong phn ny ch ni ti cc cht thuc loi nicotin. 3.1. Nicotin (- pyridyl- metyl pyrrolidin) c, bng A C trong thuc l, thuc lo di hnh thc acid hu c (0,5

8,0%). Khi ht thuc, nicotin c gii phng ra di dng base t do. Trung bnh, ht 1 iu thuc l, hp thu khong 1 - ?3 mg nicotin. Liu cht t do. Trung bnh, ht 1 iu thuc l, hp thu khong 1 - 3 mg nicotin. Liu cht 1,0mg/ kg ch, tim tnh mch) kch thch; liu cao (10 - 30 mg/ kg trn ch) lm lit hch do gy bin cc v sau l tranh chp vi acetylcholin. Tc dng: Trn tim mch, gy tc dng ba pha: h huyt p tm thi, tng huyt p mnh r i cui cng l h huyt p ko di. - Trn h hp, kch thch lm tng bin v tn s - Gin ng t, tng tit dch, tng nhu ng rut Nguyn nhn ca nhng tc dng l do: Lc u nicotin kch thch hch ph giao cm v trung tm c ch tim hnh no nn lm tim p chm, h huyt p. Nhng ngay sau , nicotin kch thch hch giao cm, trung tm vn mch v cc c trn, lm tim p nhanh, tng huyt p, gin ng t v tng nhu ng rut. ng thi kch thch tu thng thn (coi nh hch giao cm khng l) l m tit adrenalin, qua cc recepto r nhn cm ha hc xoang cnh kch thch phn x ln trung tm h hp. - Cui cng l giai on lit sau khi b kch thch qu mc nn lm h huyt p ko di. Nicotin khng dng trong iu tr, ch dng trong cc phng th nghim hoc git su b. Nicotin gy nghin, nhng khi cai thuc th khng gy bin chng nh cai thuc phin. Ht thuc l c hi n tim, mch, nim mc ng h hp v khi thuc c oxyd carbon (gy carboxyhemoglobin trong mu ngi nghin), c c c base nit, cc acid bay

hi, cc phenol l nhng cht kch thch mnh nim mc. Ngoi ra cn c hc n (c hot cht l 3,4 - benzpyren, c th l mt trong nhng nguyn nhn gy ung th phi). 3.2. Cc thuc khc - Lobelin: L alcaloid ca l cy lobelia inflata. Tc dng km nicotin rt nhiu. Hu nh khng cn c dng trong lm sng na. - Tetramethylamoni (TMA) v dimethyl - phenyl- piperazin (DMPP) Tc dng ging nicotin, kch thch c hch giao cm v ph giao cm nn tc dng phc tp,khng c dng trong iu tr. Hay c dng trong thc nghim. DM PP cn kch thch thng thn tit nhiu adrenalin. THUC PHONG B H NICOTINIC c chia lm 2 loi: loi phong b hch thc vt, nh hng n hot ng c a c trn, v loi phong b trn bn vn ng ca c vn. 4.1. Loi phong b h nicotinic ca hch Cn gi l thuc lit hch, v lm ngn cn lung xung tc thn kinh t si tin hc h ti si hu hch. C ch chung l tranh chp vi acetylcholin ti receptor mng sau ca xinap ca hch. Nh ta bit, cc hch thn kinh thc vt cng c c hai loi receptor cholinergi c l N v M 1. Khi ni ti cc thuc lit hch l c ngha ch bao hm cc thuc c ch trn recep tor N ca hch m thi. Tuy cc c quan thng nhn s chi phi ca c hai h giao cm v ph giao cm, song bao gi cng c mt h chim u th. V vy, tc dng ca cc thuc lit hch trn c qua n thuc vo tnh u th y ca tng h (xem bng di):

Trong lm sng, cc thuc lit hch thng c dng lm h huyt p trong c c cn tng huyt p, h huyt p iu khin trong m x, v i khi iu tr ph ph?i

cp, do chng c nhng c im sau: - Cng c ch giao cm gy gin mch t l vi liu dng - Tc dng mt i nhanh sau khi ngng thuc, do d kim tra c hiu lc ca thuc Cc receptor adrenergic ngoi bin vn p ng c bnh thng nn cho php d dng iu tr khi c tai bin Nhng tai bin v tc dng ph thng gp l: - Do phong b hch giao cm, nn: . D gy h huyt p khi ng (phi ngi bnh nm 10 - 15 pht sau khi tim) iu tr tai bin bng adrenalin v ephedrin. . Ri lon tun hon mch no, mch vnh. . Gim tit niu . - Do phong b hch ph giao cm nn: . Gim tit dch, gim nhu ng rut, lm kh ming v to bn. . Gin ng t, ch nhn c xa. . B i do gim trng lc bng quang. Cc thuc c (tetra ethyl amoni TEA v hexametoni) u mang amoni bc 4, kh h p thu. Hin cn 2 thuc c s dng. 4.1.1. Trimethaphan (Arfonad) Phong b hch trong thi gian rt ngn. Truyn tnh mch dung dch 1 mg trong 1 mL, huyt p h nhanh. Khi ngng truyn, 5 pht sau huyt p tr v bnh thng Dng gy h huyt p iu khin trong phu thut hoc iu tr ph phi cp. ng 10 mL c 500 mg Arfonad, khi dng pha thnh 500 mL trong dung dch mn ng trng c 1 mg trong 1 mL. 4.1.2. Mecamylamin (Inversin) Mang N ha tr 2, cho nn d hp thu qua ng tiu ha, c th ung c. T c dng ko di 4 - 12 gi. Dng lu tc dng s gim dn Ung mi ln 2,5 mg, mi ngy 2 ln. Tng dn cho ti khi t c hiu qu iu tr, c th ung ti 30 mg mi ngy. Vin 2,5 mg v 10 mg

Liu cao c th kch thch thn kinh trung ng v phong to bn vn ng c vn. 4.2. Loi phong b h nicotinic ca c vn Cura v cc ch phm c, bng B 4.2.1. Tc dng Cura tc dng u tin trn h nicotinic ca cc c xng (c vn), lm ngn cn lu ng xung tc thn kinh ti c bn vn ng (Claude Bernard, 1856 ) nn lm gin c. Khi kch thch trc tip, c vn p ng c. Di tc dng ca cura, cc c khng b lit cng mt lc, m ln lt l cc c mi (gy sp mi), c mt, c c, c chi trn, chi di, c bng, cc c lin s n v cui cng l c honh, l m bnh nhn ngng h hp v cht. V tc dng ngn nn n u c h hp nhn to, chc phn cc c s c hi phc theo th t ngc li. Ngoi ra, cura cng c tc dng c ch trc tip ln trung tm h hp hnh no v lm gin mch h huyt p hoc co tht kh qun do gii phng his tamin Hu ht u mang amin bc 4 nn rt kh thm vo thn kinh trung ng, khng hp thu qua thnh rut. 4.2.2. Cc loi cura v c ch tc dng. Theo c ch tc dng, chia lm hai loi: 4.2.2.1. Loi tranh chp vi acetylc holin bn vn ng , lm cho bn vn ng k hng kh cc c, gi l loi cura chng kh cc (antidpolarisant), hoc loi ging cura (curar imimetic) hay pakicura (Bovet). Gii c bng cc thuc phong to cholinesterase (physostigmin, prostigmin tim tnh mch tng 0,5 mg, khng vt qu 3 mg. C th tim thm atropin 1 m g ngn? cn

tc dng cng h muscarinic ca thuc). Loi ny c tc dng hip ng vi thuc m, thuc ng loi barbiturat, thuc an thn loi benzodiazepin - d- Tubocurarin: l alcalo id ly t cc cy loi Chondodendron tementosum v Strychnos m th dn Nam M dng tm tn c. Tc dng ko di vi gi. Khng dng trong lm sng Galamin (flaxedil): tng hp. C thm tc dng ging atropin nn lm tim p ch m, khng lm gii phng histamin v k m c hn d - tubocurarin 10- 20 ln. Tc dng pht trin chm trn cc nhm c khc nhau, thi gian lm gin c bng n lit c honh kh di nn gii hn an ton rng hn. Ch phm: Remiolan ng 5 mL = 0,1g galamin triethyl iodid. Liu 0,5 mg/ kg Pancuronium (Pavulon): l steroid mang 2 amoni bc 4. Tc dng khi pht sau 4 Pancuronium (Pavulon): l steroid mang 2 amoni bc 4. Tc dng khi pht sau 4 180 pht. u im chnh l t tc dng trn tun hon v khng lm gii phng histamin. - Pipecuronium (Arduan): khi pht tc dng sau 2 - 4 pht v ko di 80 100 pht. L cha bt pha tim 4 mg + 2 mL dung mi. Tim tnh mch 0,06 0,08 mg/ kg 4.2.2.2. Loi tc ng nh acetylcholin, lm bn vn ng kh cc qu mnh, (depolarisant) gi l loi ging acetylcholin, (acetylcholinomimetic) ho c leptocura (Bovet). Cc thuc phong b cholinesterase lm tng c tnh. Khng c thuc gii c, tuy d tubocurarin c tc dng i khng. Trc khi lm lit c, gy git c trong vi giy.

-Decametoni bromid: gy git c v au c, c th gy tai bin ngng th ko di nn c xu hng dng succinylcholin thay th. Succinylcholin: l thuc duy nht ca nhm cura kh cc c dng lm sng. C cu trc ha hc nh 2 phn t ACh gn vo nhau: Succinylcholin Succinylcholin 8 pht, do b cholinesterase trong huyt tng thu phn. Succinylcholin y K+ t trong t bo ra nn c th lm tng K + mu 30- 50%, gy lon nhp tim. Ch phm: Myo- relaxin ng 0,25g succinylcholin bromid. Tim tnh mch t 1 mg/ kg. 4.2.3. Ch nh v liu lng - Lm mm c trong phu thut, trong chnh hnh, t ng ni kh qun. - Trong tai mi hng, dng soi thc qun, gp d vt - Chng co git c trong chong in, un vn, ng c strychnin. Khi dng phi t ng ni kh qun. Khng hp th qua nim mc tiu ha nn phi tim tnh mch. Liu lng tuz theo tng trng hp, c th tim 1 ln hoc truyn nh git vo tnh mch. Liu mm c u tin thng l: d- Tubocurarin 15 mg Methyl d- tubocurarin 5 mg Galamin (flaxedyl) 20- 100 mg Decametoni 4 mg Succinylcholin diiodua 30- 60 mg Ch : mt s thuc khi dng cng vi cura loi curarimimetic (d - tubocurarin) c th c tc dng hip ng, lm tng tc dng lit c ca cura, nn cn gim liu: - Cc thuc m nh ether, halothan, cyclopropan. - Cc khng sinh nh neomycin, streptomycin, polimycin B, kanamycin. - Quinin, quinidin THUC KHNG CHOLINESTERASE Cholinesterase l enzym thu phn lm mt tc dng ca acetylcholin. Mt phn t acetylcholin s gn vo hai v

tr hot ng ca enzym; v tr anion (anionic site) s gn vi cation N + ca acetylcholin, cn v 2 p tr gn este (esteratic site) gm mt nhm base v mt nhm acid proton ( -- H) to nn mt lin kt hai ha tr vi nguyn t C ca nhm carboxyl ca este:

Physostigmin 5.1.1. Physostigmin (physotigminum; eserin) c, bng A L alcaloid ca ht cy Physostigma venenosum. V c amin bc 3, nn d hp th v thm c c vo thn kinh trung ng Dng cha tng nhn p (nh mt dung dch eserin sulfat hoc salicylat 0,25 0,5%) , hoc kch thch nhu ng rut (tim di da, ng 0,1% - 1 mL, mi ngy 1 - 3 ng). Khi ng c, dng atropin liu cao. 5.1.2. Prostigmin (neostigmin, pros erin) c, bng A V mang amin bc 4 nn khc physostigmin l c i lc mnh hn vi cholinesterase, v khng thm c vo thn kinh trung ng. Tc dng nhanh, t tc dng trn mt, tim v huyt p. Ngoi tc dng phong to cholinesterase, prostigmin cn kch thch trc tip c vn, tc dng ny khng b atropin i khng. p dng: Prostigmin Ch nh tt trong bnh nhc c bm sinh (myasthenia gravis) v thiu ht acetyl cholin bn vn ng c vn. Cn c dng trong cc trng hp teo c, lit c . - Lit rut, b i sau khi m - Nh mt cha tng nhn p - Cha ng c cura loi tranh chp vi acetylcholin Liu lng, ch phm: - Tim di da mi ngy 0,5 - 2,0 mg

- Ung mi ngy 30 -90 mg v thuc kh thm qua d dy v d b ph hu ng 1 mL = 0,5 mg prostigmin methyl sulfat 5.1.3. Edrophonium clorid (Tensilon) Cht tng hp Tc dng mnh trn bn vn ng c vn, l thuc gii c cura loi tranh chp vi acetylcholin. Tc dng ngn hn prostigmin. Trong bnh nhc c, tim tnh mch 2 - 5 mg; gii c cura: 5- 20 mg ng 1 mL = 10 mg edrophonium clorid. Tensilon 5.2. Loi c ch khng hi phc hoc rt kh hi phc 5.2.1. Cc hp cht ca phospho hu c: cc cht ny kt hp vi cholinesterase ch v tr gn este. Enzym b phosphoryl ha rt vng bn, kh c thu phn hi phc tr li, i hi c th phi tng hp li cholinesterase mi. V vy lm tch lu nhiu acetylcholin ton b h cholinergic t vi ngy ti hng thng. c ch mnh c cholinesterase tht cng nh gi. Trong lm sng, nh gi tnh trng nhim c bng nh lng cholinesterase gi trong huyt tng. Cc cht c ch cholinesterase loi phospho hu c c cng thc chung l: Trong X c th l halogen, cyanid (CN), thiocyanat, alkoxy, thiol, pyrophosphat Ch c DFP (di- isopropyl- fluo Ch c DFP (di- isopropyl- fluo 0,05%). Cc dn xut khc c dng lm thuc tr su (TEPP, parathion,), ho c s dng lm hi c chin tranh (tabun, sarin, soman). 5.2.2. Du hiu nhim c cp: cc du hiu nhim c cp phn nh s trn ngp acetylcholin ton b h cholinergic. Du hiu kch thch h M: co ng t, sung huyt gic mc, chy nc mi, nc bt , dch kh qun, co kh qun, nn, au bng, tiu chy, tim p chm, h huyt p. - Du hiu kch thch h N: mt mi, git c, cng c, lit v nguy him hn c

l lit h hp. Du hiu kch thch thn kinh trung ng: l ln, mt ng tc, mt phn x , nh p th Cheyne - Stokes, co git ton thn, hn m, lit h hp, h huyt p do trung tm hnh tu b c ch. Nguyn nhn dn ti t vong l do suy h hp v tim mch do c 3 c ch kch thch h M, N v trung ng. 5.2.3. iu tr nhim c 5.2.3.1. Thuc hu h M: atropin sulfat liu rt cao. Tim tnh mch liu 1 2 mg, cch 5- 10 pht mt ln cho n khi ht triu chng kch thch h M, hoc bt u c du hi u nhim c atropin (gin ng t). Ngy u c th tim ti 200 mg. 5.2.3.2. Dng thuc ho t ha cholinesterase : mt s cht a nhn (nucleophylic agents) nh hydroxylamin (NH 2OH), acid hydroxamic (R - CONHOH) v oxim (R CH = NOH) c kh nng gii phng c enzym b phospho hu c phong ta v hot ha tr li. Ch t thng dng t thng dng PAM) tc dng ln ChE phosphoryl ha, to oximphosphonat b thi tr v gii phng cholinesterase. Pralidoxim (2- PAM): l 1g km ng nc 20 mL. Mi u, tim tnh mch 1 2g, sau truyn nh git tnh mch mi gi 0,5g. 5.2.3.3. iu tr h tr Thay qun o, ra cc vng da c tip xc vi cht c, ra d dy nu ng c d o ng ung. H hp h tr, th oxy. Chng co git bng diazepam (5 - 10 mg tim tnh mch) hoc natri thiopental (2,5% tim tnh mch). BI 10. I CNG H THN KINH THC VT H thn kinh thc vt (cn gi l h thn kinh t ng) chuyn iu khin cc hot ng ngoi mun, c vai tr iu ha chc phn ca nhiu c quan, h thng cho gii hn sng ca c th gi c s n nh trong mi trng sng lun lun thay i.

H thng thn kinh thc vt hnh thnh t nhng trung tm trong no v tu sng, xut pht nhng si thn kinh ti cc tng, mch mu v c nhn. Trc khi ti c quan thu nhn, cc si ny u dng mt xinap ti hch, v vy c si trc hch (hay tin hch) v si sau hch (hay hu hch). Khc vi nhng b phn do h thn kinh trung ng iu khin, cc c quan do h thn kinh thc vt chi phi vn c th hot ng t ng khi ct t nhng si thn kinh n chng. H thng thn kinh thc vt c chia thnh 2 h giao cm v ph giao cm khc nhau v c gii phu v chc phn sinh l. 1. PHN LOI THEO GII PHU 1.1. im xut pht - H giao cm xut pht t nhng t bo thn kinh sng bn ca tu sng t t sng ngc th nht n t sng tht lng th 3 (T1- L3). - H ph giao cm xut pht t no gia, hnh no v tu cng. no gia v hnh no, cc si ph giao cm i cng vi cc dy thn kinh trung ng: dy III vo mt; dy VII vo cc tuyn nc bt; dy IX vo c mi, cc tuyn tit nc mt, n c bt, tuyn tit nim mc mi, ming, hu; dy X vo cc tng trong mt, n c bt, tuyn tit nim mc mi, ming, hu; dy X vo cc tng trong S4) chi phi cc c quan trong h chu. 1.2. Hch - H giao cm c 3 nhm hch: . Chui hch cnh ct sng n m hai bn ct sng . Nhm hch trc ct sng, gm hch tng, hch mc treo v hch h v, u nm trong bng. . Nhm hch tn? cng gm nhng hch nm cnh trc trng v bng quang. - H ph giao cm: cc hch nm ngay cnh hoc ngay trong thnh c quan. 1.3. Si thn kinh - H giao cm: mt si tin hch thng tip ni vi khong 20 si hu hch cho nn khi kch thch giao cm, nh hng thng lan rng. - H ph giao cm: mt si tin hch thng ch tip ni vi mt si hu hch, cho nn xung tc thn kinh thng khu tr hn so vi xung tc giao cm. Tuy nhin, i vi dy X th m ri AuerbACh v m ri Meissner (c coi l hch) th mt si tin hch tip ni vi khong 8000 si hu hch. V hch nm ngay cnh c quan, cho nn cc si hu hch ph giao cm rt ngn.

. Hnh 4.1. Cu to gii phu ca h thn kinh thc vt 2. CHC PHN SINH L 2.1. Chc phn sinh l Chc phn sinh l ca hai h giao cm v ph giao cm trn cc c quan ni chung l i khng nhau (bng 4.1) Bng 4.1: p ng ca c quan vi h thn kinh thc vt

.Ghi ch: - Cc receptor ca h ph giao cm u l cc loi receptor M - Mc p ng t thp (+) n cao (+++) 2.2. Xinap v cht dn truyn thn kinh Khi ta kch thch cc dy thn kinh (trung ng v thc vt) th u mt ca cc dy s tit ra nhng cht ha hc lm trung gian cho s dn truyn gia cc dy tin hch vi hu hch, hoc gia dy thn kinh vi cc c quan thu nhn. Cht ha hc lm trung gian cho s dn truyn gi l cht dn truyn thn kinh. H thng thn kinh ca ngi c hng chc t nron. S thng tin gia cc nron cng da vo cc cht dn truyn thn kinh. Cc thuc nh hng n chc phn thn kinh thng l thng qua cc cht dn truyn thn kinh . Cht dn truyn thn kinh hch giao cm, ph giao cm v hu hch ph giao cm u l acetylcholin, cn hu hch giao cm l noradrenalin, adrenalin v dopamin (gi chung l catecholamin). Cc cht dn truyn thn kinh tc ng n mng sau xinap lm thay i tnh thm ca mng vi ion Na +, K+ hoc Cl- do gy ra hin tng bin cc (kh cc hoc u cc ha). Ion Ca++ ng vai tr quan trng trong s gii phng cht dn truyn thn kinh. 2.3. Cc cht dn truyn khc Trong nhng nm gn y, nhiu nghin cu cho thy rng phn ln cc nron trung ng v ngoi bin c cha 2 hoc nhiu cht dn truyn, c th c gii phng ra cng mt lc xinap khi dy thn kinh b kch thch. Nh vy, h thn kinh thc vt, ngoi acetylcholin (ACh) v noradrenalin (NA), cn c nhng cht dn truyn thn

kinh (neurotransmitters) khc cng c gii phng v c th c vai tr nh cht cng dn truyn (cotransmitters), cht iu bin thn kinh (neuromodulators) hoc chnh n cng l cht dn truyn (transmitters). Ngi ta tm thy trong tu thng thn, trong cc si thn kinh, trong hch thn kinh thc vt hoc trong cc cu trc do h thn kinh thc vt chi phi mt lot cc peptid sau: e nkephalin, cht P, somatostatin, hormon gii phng gonadotropin, cholecystokinin, vasoactive intestinal peptide (VIP), neuropeptid Y (NPY) Vai tr dn truyn ca ATP, VIP v NPY trong h thn kinh thc vt dng nh c coi l? nhng cht iu bin t c dng ca NA v ACh. Nh vy, bn cnh h thn kinh thc vt vi s dn truyn bng ACh v NA cn tn ti mt h thng dn truyn khc c gi l dn truyn khng adrenergic, khng cholinergic [Nonadrenergic, non cholinergic (NANC) transmission]. Burnstock (1969, 1986) thy c cc si thn kinh purinergic chi phi c trn ng tiu ha, ng sinh dc- tit niu v mt s mch mu. Adenosin, ATP l cht dn truyn, cc receptor gm receptor adenosin (A hoc P 1) v receptor ATP (P 2). Cc di typ rec eptor u hot ng thng qua protein G, cn receptor P 2x li thng qua knh ion (Fredholm v cs, 1994). Methylxantin (cafein, theophylin) l cht c ch cc receptor ny. Nitric oxyd cng l mt cht dn truyn ca h NANC c tc dng lm gin mch, gin ph qun. Nitric oxyd c ni m thnh mch, khi c gii phng s hot ha guanylyl cyclase, lm tng tng hp GMPv, gy gin c trn thnh mch. Cc cht dn truyn thn kinh c tng hp ngay ti t bo thn kinh, sau c lu tr di th phc hp trong cc ht c bit nm ngn dy thn kinh trnh b ph hu. Di tc dng ca nhng lung xung tc thn kinh, t cc ht d tr , cht dn truyn thn kinh c gii phng ra di dng t do, c hot tnh tc ng ti cc receptor. Sau chng c thu hi li vo chnh cc ngn dy thn kinh va gii phng ra, hoc b ph hu rt nhanh bi cc enzym c bit. Acetylcholin b cholinesterase thu phn, cn noradrenalin v adrenalin th b oxy ha v kh amin bi catechol - oxy- methyl- transferase (COMT) v mono - amin- oxydase (MAO). c bit: - Dy giao cm i ti tu thng thn khng qua mt hch no c. tu thng thn, dy ny tit ra acetylcholin kch thch tuyn tit ra adrenelin. V vy, thng thn c coi nh mt

hch giao cm khng l. - Cc ngn dy hu hch giao cm chi phi tuyn m hi ng l phi tit noradrenalin, nhng li tit ra acetylcholin. - Cc dy thn kinh vn ng i n cc c xng (thuc h thn kinh trung ng) cng gii phng ra acetylcholin. - Trong no, cc xung tc gia cc nron cng nh acetylcholin. Ngoi ra cn c nhng cht trung gian ha hc khc nh serotonin, catecholamin, acid gamaamino- butyic (GABA) 2.4. H thng thn kinh thc vt trong no Khng th tch ri hot ng ca h thn kinh tr ung ng vi h thn kinh thc vt. Gia 2 h lun lun c mi lin quan cht ch vi nhau m bo tnh thng nht ca c th. Nhng mi lin quan v ang c tm thy vng di i, h vin (systema limbicus), hi hi m (hyppocampus), l nhn g ni c cc trung tm iu ha thn nhit, chuyn ha nc, ng, m, iu ha huyt p, ni tit, hnh vi Trong h thn kinh trung ng cng thy cc cht dn truyn thn kinh v cc receptor nh ca h thng thn kinh thc vt ngoi bin. 3. PHN LOI THEO DC L Nhng thuc c tc dng ging nh tc dng kch thch giao cm c gi l thuc cng giao cm (sympathicomimetic), cn nhng thuc c tc dng ging nh kch thch ph giao cm c gi l thuc cng ph giao cm (para - sympathicomimetic ). Thuc no c tc dng km hm tc dng ca giao cm h?ay ph giao cm th gi l hu giao cm (sympathicolytic) hay hu ph giao cm (parasympathicolytic). Nh chng ta thy, hot ng ca thn kinh l nh nhng cht trung gian ha hc, cho nn cch phn loi v gi tn theo gii phu v sinh l khng ni ln c y v chnh xc tc dng ca thuc. V vy, mt cch hp l{ hn c, ng v phng din dc l, ta chia h thn kinh thc vt thnh 2 h: h phn ng vi acetylcholin, gi l h cholinergic (gm cc hch giao cm, ph giao cm; hu hch ph giao cm; bn vn ng c vn; mt s vng trn thn kinh trung ng) v h phn ng vi adrenalin, gi l h adrenergic (ch gm hu hch giao cm) Phn loi cc thuc tc dng trn h thng thn ki nh thc vt Cc thuc tc dng trn h thn kinh thc vt cng mang tnh c hiu, tc

dng chn lc trn cc receptor ring i vi chng. Cc receptor ca h cholinergic cn c chia lm 2 loi: - Loi nhn cc dy hu hch (v d tim, cc c trn v tu yn ngoi tit) cn b kch thch bi muscarin v b ngng hm bi atropin, nn c gi l h cm th vi muscarin (hay h M). - Loi nhn dy tin hch cn b kch thch bi nicotin, nn cn c gi l h cm th vi nicotin (hay h N), h ny phc tp, bao gm cc hch giao cm v ph giao cm, tu thng thn, xoang ng mch cnh (b ngng hm bi hexametoni), v bn vn ng c vn thuc h thn kinh trung ng (b ngng hm bi d - tubocurarin). Cng trn nhng c s tng t, cc receptor ca h ad renergic c chia lm 2 loi: alpha ( ) v beta (). Cc thuc kch thch c th tc ng theo nhng c ch: . Tng cng tng hp cht dn truyn thn kinh . Phong to enzym phn hu cht dn truyn thn kinh . Ngn cn thu hi cht dn truyn thn kin h v ngn dy thn kinh. . Kch thch trc tip cc receptor

BI 11. THUC CHA PARKINSON c im: Parkinson l mt bnh do hu qu ca nhng thng tn thoi ho mt s nhn xm nn no kim tra cc hot ng bn t ng v t ng. S thng tn ca nhng nhn ny s trc tip hay gin tip nh hng n h vn ng v gy nhng triu chng ngoi b thp nh: Mt cc ng tc cn c s tham gia ca mun. - Gii phng cc ng tc t ng hoc bt thng, gy run. - Tng trng lc c, gy t th cng nhc. Cc triu chng trn cng c th xy ra ng c mt s thuc [carbondioxyd, hp cht mangan, alkaloid ca cy ba gc (reserpin), clopromazin, haloperidol), gi l hi chng parkinson 1.Cc thuc cng h dopaminergic1.1.Levodopa (l-dopa, dihydroxyphenyl alamin, DOPA). V dopamin khng qua c hng ro mu-no nn trong iu tr phi dng cht tin thn ca n l L-dopa, c kh nng thm c vo thn kinh

trung ng, ti , L-dopa b kh carboxyl thnh dopamin * Tc dng dc l: - Tc dng chng parkinson: - Trn tuyn ni tit: Levodopa kch thch h khu no tit yu t c ch bi tit prolactin - Trn h tim mch: vi liu iu tr, levodopa lm tng nh nhp tim * Dc ng hc: Levodopa c hp thu ch yu ru t non bng qu trnh vn chuyn tch cc. Nng ti a t c trong mu sau 0,5 n 2 gi. Thi gian bn thi t 1 n 3 gi. Do nh hng ca dopadecarboxylase c mt nim mc rut v mu, mt lng ln levodopa c hp thu s chuyn thnh dopamin.* Tc dng khng mong mun: Do phn ln levodopa khng qua c hng ro mu no nn lng dopa v c noradrenalin ngoi bin tng cao, l nguyn nhn gy ra cc tai bin. C th gp trn 90% ngi dng thuc: Ri lon tiu ha: nn, chn n, gim cn ng tc bt thng xut hin ming li mt, cc chi, c, gy. ngi nhiu tui t gp hn Ri lon tm thn: trm cm, l ln, hoang tng Ri lon tim mch: thng gp tt huyt p khi ng; sau lon nhp, suy mch vnh, suy tim. * p dng lm sng: thuc v liu dng + Levodopa (Dopar, Larodopa) vin 100 250 hoc 500 mg Ch nh nghim ngt, theo di ti bnh vin ung liu tng dn, chia nhiu ln trong ngy v ung sau ba n. Liu trung bnh ti u t 3,0 3,5 g. Ch : trong khi ang dng L dopa: - Khng nn dng cc thuc c ch monoamin oxydase (IMAO) v c th gy cc cn tng huyt p - Liu cao vitamin B6 (trn 5 mg) s lm gim tc dng L dopa v c th lm tng qu trnh kh carboxyl ca L dopa ngoi bin. - Khi ung thuc, nn n t protein m bo hiu lc thuc (v c carrier chung). + Phi hp levodopa v thuc phong to dopa decarboxylase gim s kh carboxyl ca levodopa ngoi bin, lm tng lng lev-

odopa nhp vo no, ta dng phi hp levodopa vi thuc phong to dopa decarboxylase ngoi bin: - Modopar: vin nang cha 0,6g levodopa v 0,015g bensarrazid, thuc phong ta dopa decarboxylase (t l 4/1) - Sinemet: vin n n 100 v 250mg trong c levodopa v alpha methyl dopahyrazin hay carbidopa vi t l 10/1. Liu lng do c th gim xung ch cn 0,4 2,0g levodopa mi ngy. Mi tc dng ph cng gim i r rt. + Amantadin (mantadix, Symadin) nang 100 mg / ln x 2 ln /ngy. + Bromocriptin. + Pergolid (Permax) vin 0,05mg, 0,25 mg v 1 mg. + Selegilin (Eldepryl) vin 5 mg. 2. Cc thuc hu ph giao cm trung ng Mt s triu chng ca parkinson nh run, tng tit nc bt l th hin s cng h ph giao cm. V vy , t lu, cc thuc hu h ph giao cm hp thu qua ng tiu ho v thm nhp vo c h TKT c dng iu tr. Nhng t khi c levodopa, cc thuc ny ch c dng vi cc th khi u ca parkinson, hoc phi hp vi levodopa, c bit khi chng run chim u th. Nhc im: ca nhm thuc ny l tc dng khng cholinergic ngoi bin: gin ng t, kh ming, to bn. V vy khng dng c cho ngi c tng nhn p, ph i tuyn tin lit. Ch c cc phn t thuc mnh amin bc 3 l c hp thu v thm c vo TKT. 2.1.Loi thin nhin - Hyoscyamin: 0,1 - 0,5mg - Atropin sulphat: 0,3 m - 0,6mg - Scopolamin: 0,25 - 1,0mg 2.2.Loi tng hp - Trihexyphenydin (Artan, parkinan) Tc dng hu ph giao cm, chng parkinson k m atropin, nhng t c. Vin 2mg v 5mg. Ung 6 12mg / ngy, chia lm nhiu ln, - Dietazin (Diparcol) L dn xu t ca phenothiazin, c tc dng lit hch, hu ph giao cm, hu giao cm, khng histamin v chng co tht. Ngoi ra cn c thm tc dng h nhit, gim au v an thn nh. Tc dng rt tt i vi chng run ca bnh. Tc dng khng mong mun: chng mt, m mng, t tay chn, to

bn. Liu lng: ung mi ngy 0,05g; tng dn ti 0,5 -1,0g. - Cc thuc khc - Procyclindin (Kemadrin): 5,0 - 20mg / ngy. - Orphenadrin (Disipal): 150 - 400mg / ngy. - Benztropin (Cogentin): 1,0 - 6,0mg / ngy. BI 12. THUC AN THN TH YU Danh php : - Anxiolytics, - Sdatifs, - Minor tranquillisers 1. I CNG : 1.1. c im tc dng chung : + C tc dng an du, lm gim cnh gic, lm chm cc hot ng vn ng v lm du s bn chn. + C tc dng an thn gii lo: lm gim cc phn ng xc cm thi qu v gim cng thng tm thn. + Ch c tc dng gy ng khi mt ng c lin quan n s lo u, bn chn. + C th c tc dng gy m liu cao ( mt s Benzodiazepin - BZD). + Chng co git. + Gin c do tc dng trung ng ( xem bi Thuc gin c ) + t nh hng n h TKTV v khng gy hi chng ngoi b thp nh nhm thuc an thn ch yu. 1.2. Phn loi : + Dn xut BZD + Meprobamat + Cc thuc an thn khng histamin + Cc dn xut khc : buspiron, etifoxin 2. DN XUT BENZODIAZEPIN : 2.1. Dc ng hc : + Bn cht base yu. Hp thu tt qua ng tiu ho, t Cmax. sau khi ung 1/2 - 8 h + Gn vo protein huyt tng : 70% ( alprazolam ) 99 % (diazepam). Qua c hng ro rau thai, sa m.

+ Chuyn ho ch yu gan. + Thi tr ch yu qua thn. Khng c chu kz gan - rut. Cmax. = maximum concentration 2.2. Tc dng dc l : 2.2.1. Trn thn kinh trung ng : + An thn, gii lo, chng hung hn. + Lm d ng ( ung v m gy mt gic ng nh nhng, d chu, t tc dng ph ) + Chng co git, chng ng kinh ( ng kinh cn b , ng kinh lin tc : cn tim IV ). Ring flurazepamgy co git mo. + Gin c. + 1 s BZD c tc dng gy m : diazepam, lorazepam, midazolam + Ngoi ra cn lm suy yu k c mi ( tr nh ngn hn ), tr ngi k c c ( tr nh di hn ). 2.2.2. Tc dng ngoi bin : + Gin mch vnh khi tim IV. Cn gy gim nh HA, chng lon nhp tht. + C th gy gim nh h hp khi tim IV. + Liu cao phong ta thn kinh - c, gy nhc c. 2.3. C ch tc dng : BZD gn trn cc Rp c hiu vi n trn h TKTW ( v no, vng c nga, th vn, vng di i, hnh no, c bit l h thng li, h vin v c ty sng ). Cc Rp ca BZD c lin quan cht ch v gii phu v chc phn vi Rp ca GABA. C 3 loi Rp GABA : Rp GABA-A, B v C. Trn cc BN suy nhc thn kinh, khi khng c BZD, cc Rp ca BZD b mt protein ni sinh chim gi, lm cho GABA( g-amino butyric acid ) khng gn c vo Rp ca h GABA-nergic, lm cho knh Cl0ca neuron khp li BN mt ng. Khi c mt BZD, do BZD c i lc vi Rp mnh hn protein ni sinh, nn BZD s y protein ni sinh v chim li c Rp?, do GABA mi gn c vo Rp ca n v lm m knh Cl0; Cl0 i t bn ngoi vo bn trong t bo gy hin tng u cc ha c ch TKTW. BZD lm i lc ca Rp GABA vi GABA v lm lng GABA trong no. BZD cn lm hot lc ca cc neuron noradrenalin lim en trn h adrenergic trung ng v lm tc ti to ca NA. 2.4. Tc dng khng mong mun : + Liu cao ( liu gy ng ) : gy gim tr nh, u oi, ng tc thiu chnh xc,

l ln, ming kh, ng, nhp th chm, gim trng lc c + i khi gy tc dng ngc v tm thn : hung hng, kch ng, c mng, lo lng, nhp tim nhanh, v m hi, sng khoi, tht iu, o gic, chng mt, suy nhc, mun t t + Gim ham mun tnh dc, au khp, mt mi + C th gy quen thuc, nghin thuc, hi chng cai thuc ( khi ct thuc t ngt ngi nghin thuc ). 2.5. Ch nh lm sng : + Cc trng thi lo lng, cng thng ( bnh nhn suy nhc thn kinh, lo lng trc m, kch thch sau m) : alprazolam, clordiazepoxid, diazepam, oxazepam + Cc trng thi co git ( do thuc, sn git, st cao tr em ), ng kinh cn b lin tc : clorazepam, diazepam, lorazepam + Cc chng mt ng, trc khi gy m : flunitrazepam, diazepam, nitrazepam, triazolam. + Cc chng au, co cng c do co tht ( trong tng huyt p, nhi mu c tim): diazepam, tetrazepam 2.6. Chng ch nh : + Suy h hp, nhc c. + Suy gan, suy thn, suy nhc ton thn. + Ph n c thai hoc cho con b, tr em < 6 thng tui ( c ch h hp ) ( hoc tr em < 16 tui : i vi nordazepam) + Tng nhn p (glaucoma ), try tim mch ( i vi flunitrazepam ) + Thn trng : lm vic trn cao, li xe, ng my chuyn ng 2.7. Nguyn tc chung khi s dng cc BZD : + Liu lng thuc ph thuc tng c th, khng c liu chung cho mi ngi. + Phn chia liu trong ngy cho ph hp. + Dng thuc gii hn tng t (1 tun - 3 thng) trnh l thuc thuc. + Trnh phi hp vi cc thuc c ch TKTW khc. Bng 2a : Cc ch phm BZD hay dng Bng 2b : Cc ch phm BZD hay dng Bng 2c : Cc ch phm BZD hay dng Bng 2d : Cc ch phm BZD hay dng Bng 2e : Cc ch phm BZD hay dng

2.9. Mt s dn cht BZD khc : + Bromazepam ( BD : lexomil, lexotan, liketam..) + Clobazam ( BD : frisin, urbanol, urbanyl) + Cloxazolam ( TK: cloxazolazepam )( BD: betavel, elum, enadel, lubalix ) + Clotiazepam ( BD : rise, rize, veratran); + Medazepam ( BD : ansilan, benson, diepin, metonas, raporan ) + Flurazepam ( apo-flurazepam, fluzepam) + Lormetazepam ( loramet, minias ); + Midazolam ( hypnovel, versed ). + Medazepam + Nordazepam ( TK : desmethyldiazepam ), ( BD : nordax, praxadium, vegesan ). + Oxazolam ( BD : convertal, hializan, quiadon, serenal ) + Pinazepam ( BD : domar, duna ) + Prazepam ( BD : demetrin, reapam) 3. MEPROBAMAT : 3.1. Tn khc : meprotanum, procalmadiol 3.2. Bit dc : andaxin, arcoban, bamo, equanil, palpipax, pax, protran 3.3. c im tc dng : Tc dng gia barbbiurat v BZD. Cc ch nh, chng ch nh, tc dng? khng mong mun : nh BZD. Nay t dng. 4. THUC AN THN KHNG HISTAMIN : 4.1. i din : Hydroxyzin. 4.1.1. Bit dc: atarax, durax, lenopax, masmoran, vistaril 4.1.2. Tc dng dc l : - An thn. - Gin c trung ng - Gin ph qun - Gim au - Chng ri lon nhp tim. 4.2. Cc thuc khc : cc thuc khng histamin th h I

PHNG PHP K N ( Da theo Quy ch k n thuc v bn thuc theo n, ban hnh km theo Quyt nh s 1847/2003/Q-BYT ngy 28/5/2003 ) 1. I CNG : 1.1. Khi nim v n thuc : n thuc l mt vn bn chuyn mn mang tnh cht php l ca ngi thy thuc, quy nh ch iu tr, n ung, sinh hot cho ngi bnh v quy nh ch pha ch, cp pht, bn thuc cho cn b dc. 1.2. Nhm thuc phi k n v bn theo n : + Thuc gy nghin. + Thuc hng tm thn, tin cht dng lm thuc. + Thuc c bng A, B. + Thuc khng sinh. + Thuc ni tit ( tr thuc trnh thai ) + Thuc tim mch. + Dch truyn. 1.3. Yu cu ca mt n thuc : + Cn phi ghi y tt c cc mc trong n. n thuc phi c vit bng bt mc hoc bt bi, khng c vit bng bt ch. + Cn phi vit r rng, d c, d hiu. Khng c vit tt hoc vit cng thc ha hc trong n. + n vit sai phi vit li n khc, khng c ty xa hoc vit ln. + n thuc phi c in sn phn th tc hnh chnh trong n trn giy tt bo m r rng, mch lc. 2. THNH PHN N THUC : 2.1. Th tc hnh chnh : 2.1.1. Tn v a ch ca c s y t, bnh vin qun l n thuc ( km theo s in thoi nu c ) : 2.1.2. Mu s, s th t ca n thuc : 2.1.3. H v tn bnh nhn, tui, gii tnh : Bnh nhi 24 thng tui : cn phi ghi r s thng tui v phi ghi thm tn b ( hoc m ) sau tn bnh nhn. 2.1.4. a ch ngi bnh : + Thnh ph : s nh, ng ph, tn thnh ph. + Nng thn : thn ( xm ), x, huyn, tnh. 2.1.5. Chn on :

+Chn on xc nh: x gan khong ca giai on mt b. + Chn on s b : theo di lot hnh t trng. + Ghi triu chng, hi chng chnh : st cao cha r nguyn nhn + Vi nhng bnh c nh hng ln ti tm l ca bnh nhn v nhng ngi xung quanh th ghi cc k hiu ca bnh : V d : Ung th: K ( cancer ); Giang mai: siphylis, e ( ep-si-lon ); Lao : tbc, j 2.1.6. Ngy thng k n :2.1.7. H v tn, ch k ca ngi thy thuc : 2.2. Phn chuyn mn : 2.2.1. Tn thuc : * Phi ghi tn thuc theo danh php quc t ( INN, DCI ) vi thuc c mt thnh phn hoc tn bit dc ang lu hnh trn th trng nu thuc c nhiu thnh phn. Khng c vit tt, vit cng thc ha hc. + Thuc c mt thnh phn : amoxicilin, cimetidin, omeprazol + Tn bit dc nu thuc c nhiu thnh phn : becozym, homtamin, thalamonal * Mi tn thuc phi ghi vo m cer t dng, ch ci u tin vit in hoa. * Nu trong n thuc c nhiu loi thuc th cn ghi theo th t : - V thuc chnh c tc dng cha bnh. - Thuc lm tng tc dng ca thuc chnh. - Thuc iu tr triu chng ( nu c ). - Thuc bi dng ton thn. 2.2.2. Hm lng thuc : * Hm lng thuc : l lng thuc nguyn cht c trong mt n v thnh phm. Trong n thuc, hm lng thuc c ghi ngay bn cnh tn thuc trn cng mt dng. * V d : - Gentamicin 80 mg - Atropin 0,25 mg. - Penicilin G 1.000.000 IU 2.2.3. Liu lng thuc ( tng liu ) : * L lng thuc dng trong c t iu tr. * V d : - Amoxicilin 0,50 g - 50 vin. - Vitamin C 0,10 g 100 vin.

2.2.4. Cch dng thuc : + ng dng : ung hay tim, tht hu mn, bi, t hu mn + Liu lng thuc cho mt ln dng v s ln dng trong ngy. * Ch { khi k n thuc hng tm thn, tin cht dng lm thuc th phi vit thm s 0 pha trc nu s lng thuc ch c mt con s. VD: Diazepam 5 mg 05 vin + Nhng ch dn c bit : ngm di li; nut, khng c nhai vin thuc; ung lc no; ung trc khi i ng; tim bp su; tim tnh mch chm; th phn ng trc khi tim 2.2.5. Li dn ca thy thuc : * V d : k n cho bnh nhn thp tim n nh. Aspirin pH8 0,50 g 50 vin. Ung mi ln 2 vin, ngy 3 ln, sau ba n. Li dn : ngh min lao ng ng nng mt thng. 3. MT S QUY NH KHI K N : 3.1. n v : 3.1.1. Trng lng : * Hay dng : gam. V d : 0,5 gam vit l 0,5 g hoc 0,50. * n v nh qu : miligam ( mg ), microgam ( mcg, mg ) * Ch : khng vit dng phn s ( 1/4 mg ) m vit 0,25 mg. 3.1.2. Th tch : mililit ( ml ). * V d : siro nutroplex 120 ml. * Nu s lng nhiu : tha c-ph hoc tha canh ( nay t dng ) - 1 tha c-ph 5 ml; - 1 tha canh 15 ml. * Nu th tch qu nh th dng git ( ghi bng ch s La M hoc ghi bng ch ). 3.2. Trong trng hp c bit, cn phi k n liu cao hn liu bnh thng, thy thuc phi vit liu lng thuc bng ch ( ch ci u tin vit in hoa ), km theo ch Ti cho liu ny v k tn bn cnh. + V d : k n cho mt bnh nhn b nhim c Wofatox : Atropin 1 mg Nm mi ng ( Ti cho liu ny ) ( K tn ) Tim tnh mch Hai ng, sau c 10 ph tim nhc li Mt ng cho ti khi c

biu hin gin ng t, kh ming. * Ch : khi sa cha n thy thuc cng phi k tn xc nhn bn cnh 3.3. Khi k n cho bnh nhn cp cu, thy thuc phi ghi thm ch Cp cu v ngy, gi cp cu vo gc trn bn tri ca n thuc ri k tn bn cnh. Cp cu 21h00 ngy 10/2/2005 Bc s ( K tn ) 3.4. Thi gian dng thuc : - Khng c k n s lng thuc dng qu mi ( 10 ) ngy i vi thuc hng tm thn. 4. PH LC : 4.1. Ph lc 1 ( Ban hnh km theo Quyt nh s 1847/2003/Q-BYT ngy 28/5/2003 ) : * H?ng dn ph lc 1 : +K/thc : 1/2 trang giy A4 ngang. + Giy trng, ch in en. + Mc bc s khm bnh : k tn, ghi r hc v, h tn, ng du n v khm bnh. + n c s dng k n thuc thng, thuc c bng A, B v thuc hng tm thn, tin cht dng lm thuc. PHNG PHP K N THUC C V THUC GY NGHIN 1. n thuc phi ghi theo mu quy nh : + Thuc c A, B :dng mu MS : 17D/BV-01 ( ph lc 1 ). + Thuc gy nghinphi c k n ring ( ph lc 2 : MS : 20D/BV-01 ), mt n 2 bn ngi bnh gi 01 bn, ni bn thuc lu 01 bn, c s khm cha bnh lu phn gc ca n. + n thuc c ng thnh quyn, mi t u c ghi s th t. 2. Ni dung n cn tun theo cc quy nh sau : + Vi cc thuc c bng A v thuc gy nghin th liu lng thuc phi vit bng ch v ch ci u tin phi vit in hoa. + Liu lng thuc c bng B phi vit thm s 0 pha trc nu s lng thuc ch c mt con s. + Thi gian dng thuc : - Khng c k n thuc c A, B qu mi ( 10 ) ngy.

- Cc thuc gy nghin khng c k n qu by ( 07 ) ngy. Ring morphin hydroclorid dng ng 10 mg/1 ml khng qu nm ( 05 ) ngy cho bnh nhn ung th s dng liu 30 mg/24h. CC DNG THUC HAY DNG TRONG LM SNG 1- PHNG PHP K N CC DNG THUC UNG : 1.1. Dng thuc lng : 1.1.1. Dung dch ( solutiones ) : V d hydrosol polyvitamin, camphosol, nikethamid Ch s git phi ghi bng ch s La M ( XX git)( hoc ghi bng ch ) khng c ghi bng ch s Rp. 1.1.2. Poxio ( potio ): + V d : poxio cn qu : - Cn qu : 4 ml. - Cn 90o : 20 ml. - Sir n : 20 ml. - Nc ct va : 100 ml. Ha cn qu vi cn, thm sir, khuy u. Thm nc va 100 ml. Trn u, ng chai, dn nhn poxio cn qu . 1.1.3. Siro ( sirup ): V d siro nutroplex l 60 - 120 ml, siro ventolin ( salbutamol sulfat ) 40 mg/100 ml 1.1.4. Hn dch ( huyn dch - suspensiones ). V d hn dch teldan ( terfenadin ), l 720 mg/120 ml. 1.2. Dng thuc rn : 1.2.1. Thuc bt ( pulveres ) : V d : n s 12, gi 100 g; glucose, gi 100 g 1.2.2. Thuc nang ( capsule ) : * Da theo bn cht v nang, ngi ta phn bit 2 loi : + Nang tinh bt ( vin nhn ) : iu ch bng tinh bt. Ngy nay t dng do d ht m, nang to kh nut, cha c t thuc. + Nang gelatin : v nang c iu ch bng gelatin dc dng. Tuz theo th cht v nang m chia lm hai loi : - Nang mm : V d homtamin, pharmagel

- Nang cng ( vin nhng ) : V d nang doxycyclin 1.2.3. Vin nn ( tablet ) : + Vin ngm, vin t di li : vin nitroglycerin, vin bc h + Vin pha thnh dung dch : + Vin si bt : V d vin supradyn, berocca + Vin pha thnh hn dch : + Vin nn ph khoa : klion-D ( 100 mg metronidazol + 100 mg miconazol nitrat ) + Vin tc dng ko di ( k hiu LA, LP, SR, CR ) : profenid LP 200 mg, voltaren LP 100 mg * pht huy y tc dng ca vin nn, nn ung thuc cch xa ba n ?( khong 1 gi trc ba n hoc 2 gi sau khi n, tr nhng thuc kch ng d dy ) vi mt cc nc ( khong 200 ml ). i vi ngi c tui v tr em, nn dng vin pha thnh dung dch, vin pha hn dch, vin si bt 2- PHNG PHP K N CC DNG THUC TIM, THUC NH MT, THUC DNG NGOI, THUC T : 2.1. Thuc tim : V d : spartein, morphin, gentamicin, terneurin H 5.000, tilcotil * Tuz theo liu dng, chia 2 loi : + Loi c tim vi liu lng nh ( 1 - 2 - 5 - 10 - 20 ml ) iu tr hoc chn on. V d : strychnin 1 mg, morphin 10 mg + Loi c tim vi liu lng ln ( 500 - 1.000 - 2.000 ml ) ti lp thng bng kim toan, thng bng in gii hoc cung cp nng lng cho c th. Loi ny cn gi l dung dch tim truyn. V d : moriamin 500 ml, dextrose 5 %/500 ml * Ch { khi k n : V d 1 : Penicilin G 1.000.000 IU 20 l. Pha 1 l Penicilin vi 5 ml nc ct, tim bp tht; ngy tim 2 ln, cch nhau 8 gi. Trc khi tim ln u, th phn ng ni b. V d 2 : Chlorpromazin 25 mg 05 ng. Tim bp tht 01 ng/ngy. Tim xong nm ti ging 30 pht. 2.2. Thuc dng cho mt :

* Gm thuc nh mt dng lng ( dung dch, hn dch ) dng theo git v thuc tra mt dng mm hay rn ( thuc bt, thuc m ). * Ngoi dng thuc nh mt qui c, ngy nay cn c cc mng nhn khoa, cc h iu tr. Vd : h ocusert cha pilocarpin gii phng u n DC lin tc 7 ngy lin ( iu tr Glaucoma ). * Cch k n : Tobradex 5 ml Nh vo mt I git/ln, ngy 4 ln, cch nhau 4 - 6 gi. 2.3. Thuc dng ngoi : * Thuc dng ngoi gm nhiu dng thuc khc nhau : thuc bt, thuc lng ( dung dch, hn dch, nh tng ), thuc m, kem bi da Phn ny ch trnh by thuc m. Thuc m l dng thuc c th cht mm, dng bi ln da hay nim mc bo v da, cha bnh ngoi da hoc a thuc thm qua da vo cc c quan trong c th. * Cch k n: Profenid gel 2,5 %/60 g 1 tub. Thoa nh 2 ln/ngy trn vng da b vim. * Ngoi dng thuc m qui c, ngy nay ngi ta cn dng h iu tr qua da TTS ( transdermal therapeutic system ). y l dng thuc tc dng ko di trong DC ho tan trong mt ct polyme c gii phng c kim sot qua mt mng bn thm. Vd : TTS cha nitroglycerin, gii phng DC ko di 5 - 10 ngy. TTS thng c dn vng da mng theo kiu bng dnh. Ch { dn bnh nhn ch lt ming thuc khi thuc ht tc dng. 2.4. Thuc t : * Thuc t l nhng dng thuc c th cht mm hoc cng nhit thng, c hnh dng thch hp t vo cc hc t nhin ca c th ( hu mn, m o, niu o, l mi, l tai hoc ci l r ) * Thuc t thng s dng cho cc bnh nhn l tr nh, ngi gi, bnh nhn hn m, nn nhiu hoc khng th ung c * Phn loi : + Thuc n ( t trc trng ) + Thuc trng ( t m o ). Ngoi ra cn c dng vin nn v nang mm t m o.

+ Thuc bt ch ( hnh li bt ch mt u vt nhn ) dng t niu o, t cung, l m?i , l tai hoc cc l r ca c th. * trnh phin phc cho bnh nhn, thuc thng c t trc khi i ng ( bui tra, bui ti ), v vy khi k n cn ghi r cch dng. V d : k n cho BN nhim Trichomonas vaginalis Klion-D 10 vin. Bui ti trc khi i ng, t 1 vin thm t vo m o. * Ch : - Phi iu tr c 2 v chng. - Khng ung ru. - Khng giao hp trong thi gian dng thuc. BI 13. THUC NG V RU 1. I CNG Gic ng l nhu cu rt cn thit cho c th. nhng ng vt bc cao, cho qu trnh sng c th din ra bnh thng phi c s lun phin ca hai trng thi thc v ng. Do c ch thn kinh trung ng, thuc ng to mt gic ng gn gic ng sinh l. Khi dng liu thp, thuc gy tc dng an thn, vi liu cao c th gy m. Thuc c th gy ng c v ch t khi dng liu rt cao. chng mt ng, lm gim trng thi cng thng thn kinh trc y thng dng barbiturat v mt s thuc ng khc nh dn xut piperidindion, carbamat, ru, paraldehyd, dn xut benzodiazepin. Ngy nay, hay dng thuc an t hn- gy ng loi benzodiazepin v t gy quen thuc v t tc dng khng mong mun. 2. BARBITURAT Cc barbiturat u l thuc c bng B, hin nay t dng. 2.1. Cu trc Acid barbituric (2, 4, 6 - trioxohexahydropyrimidin) c to thnh t acid malonic v ure. Ur acid malonic acid barbituric V l acid mnh, d b phn ly nn acid barbituric cha khuch tn c qua mng sinh hc v cha c tc dng. Khi thay H C 5 bng cc gc R 1 v R2, c cc barbiturat (l acid yu, t phn ly) c tc dng c ch thn kinh

trung ng. 2.2. Lin quan gia cu trc v tc dng Khi thay i cu trc, s nh hng n ion ha v kh nng tan trong lipid ca thuc, do mc khuch tn ca thuc vo no v i lc ca thuc i vi lipid ca c th cng b hay i, nn cng tc dng cng thay i. Tc dng s rt yu khi ch thay th mt H C 5. Nu thay hai H C 5 bng cc chui R 1 v R2 s tng tc dng gy ng. Tc dng c ch thn kinh trung ng s mnh hn khi R 1 v R2 l chui nhnh hoc gc carbua hydro vng hoc cha no. Khi mt H C5 c thay bng mt gc phenyl, s c phenobarbital c tc dng chng co git. Thay O C2 bng S, c thiobarbiturat (thiopental) gy m nhanh v ngn. Khi thay H N1 hoc N3 bng gc methyl ta c barbiturat c ch thn kinh trung ng mnh v ngn (hexobarbital). 2.3. Tc dng dc l 2.3.1. Trn thn kinh Barbiturat c ch thn kinh trung ng. Tuz vo liu dng, cch dng, tuz trng thi ngi bnh v tuz loi barbiturat m c tc dng an thn, gy ng hoc gy m. Barbiturat to ra gic ng gn ging gic ng sinh l, lm cho gic ng n nhanh, gim lng ton th ca gic ng nghch thng (pha ng nhanh, in no c sng nhanh, ng rt say nhng c hin tng vn ng nhn cu nhanh nn pha ny cn c gi l pha ng c vn ng nhn cu nhanh), gim t l ca gic ng nghch thng so vi gic ng sinh l. Vi liu gy m, barbiturat c ch ng. Barbiturat (v d phenobarbital) cn chng c co git, chng ng kinh, do lm gim tnh b kch thch ca v no. Barbiturat i lp vi cn co git do strychnin, picrotoxin, cardiazol, c t un vn C ch tc dng: Gia hnh no v c no sinh t c h li ca no gia gm phn trc (phn i ln) hot ha v phn sau (phn i xung) c tnh c ch. Barbiturat tc ng bng cch c ch chc phn ca h li m vai tr l dn dt, chn lc nhng thng tin t ngoi bin vo v no. Thuc c th ngn cn xung tc thn kinh qua cc trc h li - v no, ngoi bin - i no- v no, h li c nga, v noi no Barbiturat tc dng gin tip thng qua GABA, lm tng thi lng m knh

Cl -. Vi liu cao, barbiturat tc dng trc tip trn knh Cl -, gip m knh, Cl - tin o t vo trong t bo thn kinh, gy u cc ha. Picrotoxin i lp vi barbiturat knh Cl -, c ch vn chuyn Cl -, gy co git. Barbiturat c kh nng tng cng hoc bt chc tc dng c ch synap ca GABA, tuy nhin tnh chn lc km cc benzodiazepin. 2.3.2. Trn h thng h hp Do c ch trc tip trung tm h hp hnh no nn barbiturat lm gim bin v tn s cc nhp th. Liu cao, thuc hu hoi trung tm h hp, lm gi m p ng vi CO 2, c th gy nhp th Cheyne- Stockes. Ho, ht hi, nc v co tht thanh qun l nhng du hiu c th gp, khi dng barbiturat gy m. Cc barbiturat lm gim s dng oxy no trong lc gy m (do c ch hot ng ca neuron). 2.3.3. Trn h thng tun hon Vi liu gy ng barbiturat t nh hng n tun hon. Liu gy m, thuc lm gim lu lng tim v h huyt p. Barbiturat c ch tim liu c. 2.4. c tnh Trong bi ny chng ti ch cp n c tnh ca phenobarbital, mt b arbiturat cn c dng nhiu trn lm sng. 2.4.1. Tc dng khng mong mun Khi dng phenobarbital, t l ngi gp cc phn ng c hi chim khong 1%. - Ton thn: bun ng - Mu: c hng cu khng l trong mu ngoi vi. - Thn kinh: rung git nhn cu, mt iu ha ng tc, b kch thch, lo s, l ln (hay gp ngi bnh cao tui). - Da: ni mn do d ng (hay gp ngi bnh tr tui). Him gp hi chng au khp, ri lon chuyn ha porphyrin do phenobarbital. 2.4.2. Ng c cp Ng c cp pheno barbital phn ln do ngi bnh ung thuc vi mc ch t t. Vi liu gp 5- 10 ln liu ng, thuc c th gy nguy him n tnh mng. T vong thng xy ra khi nng phenobarbital trong mu cao hn 80 microgam / ml. 2.4.2.1. Triu chng nhim c - Ngi bnh bun ng, mt dn phn x. Nu ng c nng c th mt ht phn x gn xng, k c phn x gic mc.

- ng t gin, nhng vn cn phn x vi nh sng (ch mt nu ngi bnh ngt th do tt li hoc suy h hp). - Gin mch da v c th h t hn nhit (v thuc lm gim chuyn ha chung nn gy gim sinh nhit). - Ri lon h hp, nhp th chm v nng, gim lu lng h hp, gim thng kh ph nang. - Ri lon tun hon: gim huyt p, try tim mch. Cui cng, ngi bnh b hn m v cht do lit h hp, ph no, suy thn cp. 2.4.2.2. X tr X tr cp cu ph thuc vo mc nng khi bnh nhn vo vin: loi b cht c trc hay hi sc trc. - m bo thng kh: t ng ni kh qun, ht m, h hp nhn to, m kh qun nu c ph thit hu, thanh mn. - Hn ch ng c: . Ra d dy bng dung dch NaCl 0,9% hoc KMnO 4 0,1%, ngay c khi ng c t lu v khi ng c barbiturat, nhu ng d dy b gim nn thuc li lu trong d dy. Ly dch ra d dy ln u xt nghim c c ht. . Ung than hot tng o thi thuc v rt ngn thi gian hn m hoc thuc ty sorbitol 1 - 2 g/kg. - Tng o thi: . Gy bi niu cng bc: truyn dung dch mn ng trng hoc dung dch glucose 5% (4 - 6 lt/ ngy) Dng thuc li niu thm th u (truyn tnh mch chm dung dch manitol 100 g/ lt) tng thi barbiturat. . Base ho huyt tng: truyn tnh mch dung dch base natribicarbonat 0,14% (0,5 - 1 lt) . Lc ngoi thn: l bin php thi tr cht c rt c hiu qu nhng khng phi t uyn no cng c th lm c, gi thnh cao. . Khi bnh nhn ng c nng, nng barbiturat trong mu cao nn chy thn nhn to (phi m bo huyt p bng truyn dch, dopamin hay noradrenalin). . nhng bnh nhn c tt huyt p, suy vnh hoc suy t im, lc mng bng s c hiu qu hn thn nhn to. - m bo tun hon. . Hi phc nc in gii, thng bng acid base.

. Nu try mch: chng sc, truyn noradrenalin, plasma, mu. - Chng bi nhim, ch ti cng tc h l{ v chm sc c bit trong t rng hp bnh nhn b hn m. 2.4.3. Ng c mn tnh Ng c mn tnh barbiturat thng gp cc bnh nhn lm dng thuc dn n nghin thuc. Biu hin ca ng c gm cc triu chng: co git, hong lon tinh thn, m sng 2.5. Tng tc thuc - Barbiturat gy cm ng mnh microsom gan, do s lm gim tc dng ca nhng thuc c chuyn ha qua microsom gan khi dng phi hp, v d nh dng phenobarbital cng vi sulfamid chng i tho ng, thuc chng th thai, estrogen, griseofulvin, cort ison, corticoid tng hp, diphenylhydantoin, dn xut cumarin, aminazin, diazepam, doxycyclin, lidocain, vitamin D, digitalin - C mt s thuc c th lm thay i tc dng ca barbiturat nh ru ethylic, reserpin, aminazin, haloperidol, thuc chng i tho ng, thuc c ch microsom gan (cimetidin, cloramphenicol) lm tng gic ng barbiturat. 3. DN XUT BENZODIAZEPIN c tng hp t 1956, ngy nay c dng nhiu hn barbiturat v t c, t tng tc vi thuc khc. Benzodiazepin c tc dng an thn, gii lo, lm d ng, gin c v chng co git. Thng dng cha mt ng hoc kh i vo gic ng do u t lo lng (xem biThuc bnh thn). 4. RU 4.1. Ru ethylic (ethanol) 4.1.1. Tc dng - Thn kinh trung ng: ru c ch thn kinh trun g ng. Tc dng ca ru trn thn kinh trung ng ph thuc vo nng ru trong mu: n?ng thp ru c tc dng an thn, lm gim lo u, nng cao hn ru gy ri lon tm thn, mt iu ha, khng t ch c hnh ng v c th b hn m, c ch h hp, nguy him n tnh mng khi nng ru trong mu qu cao. C ch tc dng: Trc y ngi ta cho rng tc dng c ch thn kinh trung ng l do ru lm tan r lp lipid ca mng, nn nh hng n hot ng ca cc knh ion v cc prote in tc ng trn cc knh. Nhng nghin cu gn y cho thy ru lm tng kh nng gn ca GABA trn receptor GABAA. Ru cn tc ng trn receptor NMDA glutamat (N -

methylD- aspartat), c ch kh nng m knh Ca ++ ca glutamat. - Ti ch: khi bi ngo i da ru c tc dng st khun, tt nht l ru 70 0. Ru 900 lm ng protein da, lm hp cc l tit m hi, do ru khng thm su vo trong da c. - Tim mch: ru nh t nh hng n tim mch. Dng ru mnh trong thi gian di c th gy gin c tim, ph i tm tht v x ha. - Tiu ha: ru nh (di 10 0) lm tng tit dch v, dch v c nhiu acid v t pepsin, tng nhu ng rut, tng kh nng hp thu thc n nim mc rut. V vy, dng ru nh c iu s lm tng th trng. Ngc li, ru 20 0 c ch s bi tit dch v. Ru mnh (40 0) gy vim nim mc d dy (do nh hng ti lp cht nhy d dy), nn, co tht vng h v, lm gim s hp thu ca mt s thuc qua rut. - C trn: do c ch trung tm vn mch nn ru gy g in mch. Tc dng gin mch ca ru cn do kh nng lm gin c trn ca acetaldehyd (cht chuyn ha ca ru). Do , ngi ng c ru d b h thn nhit v khi gp lnh d b cht cng. Ru cn lm gin c t cung. 4.1.2. Dc ng hc Ru hp thu nhanh qua ng tiu ha. Sau khi ung 30 pht, ru t nng ti a trong mu. Thc n lm gim hp thu ru. Sau khi hp thu, ru c phn phi nhanh vo cc t chc v dch ca c th (qua c rau thai). Nng ru trong t chc tng ng v i nng trong mu. Trn 90% ru c oxy ha gan, phn cn li c thi tr nguyn vn qua phi v thn. C 2 con ng chuyn ha ru thnh acetaldehyd. - Chuyn ha qua alcool dehydrogenase (ADH): (l con ng chnh). ADH l mt enzym cha km, c nhiu gan. Ngi ta cn tm thy ADH no v d dy. ADH chuyn ru thnh acetaldehyd vi s tham gia ca NAD + (nicotinamid adenin dinucleotid). - Chuyn ha qua h microsomal ethanol oxidizing system (MEOS) khi nng ru trong mu trn 100 mg/ dL (22 mmol/ L), ru c chuyn ha qua h MEOS. nhng ngi nghin ru, hot tnh ca cc enzym tng ln, lm tng chuyn ha ca chnh ru v mt s thuc c chuyn ha qua h ny nh phenobarbital, meprobamat, carbamazepin, diphenylhydantoin. .. 4.1.3. ng dng ca ru - Ngoi da: dng st khun

- Gim au: c th tim ru vo dy thn kinh b vim gim au. 4.1.4. Ng c mn nhng ngi dng ru lu di, mt s c quan nh gan, thn kinh, d dy, tim mch s b tn thng. - Gan d b vim, nhim m gan, x gan. Ph n d nhy cm vi? c tnh ca ru hn nam gii. - Ru lm tng s bi tit dch v, dch ty, nh hng ti lp cht nhy nim mc dn ti vim d dy. Ngi nghin ru hay b tiu chy (ru gy thng tn ru t non), chn n, gy yu v thiu mu. - Vim dy thn kinh, ri lon tm thn, co git, gim kh nng lm vic tr c, m sng thng gp ngi nghin ru nng. - Ung ru mnh v k o di, c tim d b tn thng v x ha. 5% ngi nghin ru b tng huyt p. - Ru c nh hng ti h thng min dch (thay i s ha ng ng bch cu, s lng t bo limpho T, hot tnh ca NK (natural killer cell) do ngi nghin ru d mc cc bnh nhim khun nh vim phi, lao Kh nng b ung th mi ng, thc qun, thanh qun v gan ngi nghin ru thng cao hn ngi bnh thng. 4.1.5. iu tr ng c 4.1.5.1. Ng c cp - Ra d dy nu bnh nhn mi b ng c - m bo thng kh trnh suy h hp - Gii quyt tnh trng h ng mu, tn g ceton mu bng truyn glucose. - Bnh nhn nn nhiu, c th dng thm kali (nu chc phn thn bnh thng) - Vitamin B1 v mt s vitamin khc nh acid folic, vitamin B 6 c th lm gim bt cc thng tn thn kinh do ru gy ra. 4.1.5.2. Ng c mn tnh Dng disulfiram cha nghin ru Disulfiram (tetraethylthiuram) c ch aldehyd dehydrogenase, lm tng nng acetaldehyd (gp 5 n 10 ln) nn gy c. Sau khi ung, khong 80% disulfiram c hp thu nhanh qua ng tiu ha nhng nng thuc trong mu thp v disulfiram b chuyn ha thnh

diethyldithiocarbamate (cht chuyn ha cn tc dng). Liu thng dng: 250 mg/ ngy (ti a 500 mg/ ngy) trong 1 - 2 tun, sau chuyn sang liu duy tr 125 mg/ ngy (tuz thuc vo mc nhy cm ca b nh nhn). Sau khi dng disulfiram 1 gi, ngi nghin ung ru s b bng mt, nhc u d di, bun nn, nn, v m hi, tt huyt p v bi ri. Cc du hiu ny c th ko di t 30 pht n vi gi, sau bnh nhn ng thip i. Mt s thuc nh metronidazol, cephalosporin, sulfamid chng i tho ng, khi phi hp vi ru ethylic cng gy nhng phn ng nh disulfiram. Cc nghin cu gn y cho thy c th phi hp Naltrexon (cht i khng trn receptor opioid) vi disulfiram cha nghi n ru. S phi hp ny s lm gim c c tnh ca thuc i vi gan. Naltrexon c dng 50 mg/ ln/ ngy. 4.1.6. Tng tc thuc - Cc thuc an thn, thuc ng, chng co git, thuc c ch tm thn, thuc gim au loi opioid lm tng tc dng ca r u trn thn kinh trung ng. - Ru lm tng tc dng ph trn ng tiu ha nh vim, lo t, chy mu ca cc thuc chng vim phi steroid (aspirin), ung ru cng vi paracetamol lm tng nguy c vim gan. - Khi ung k o di, ru gy cm ng mt s enzym chuyn ha thuc microsom gan, lm tng chuyn ha v gim hiu qu iu tr ca mt s thuc: sulfamid h ng huyt, thuc chng ng mu loi cumarin, meprobamat, diphenylhydantoin, carbamazepin - Do tc dng gin mch ngoi vi ca ru, nu ung ng thi ?vi cc thuc chng tng huyt p, c th c nguy c gy tt huyt p t ngt qu mc cn thit. - Cc thuc h ng huyt nhm biguanid c th gy tng acid lactic mu nu ung nhiu ru trong thi gian iu tr. 4.2. Methanol (ru met hylic) Loi ru ny dng trong cng nghip, khng dng trong y t v c. Trong c th, di s xc tc ca alcool dehydrogenase, methanol c oxy ha thnh formaldehyd rt c (gy au u, bun nn, nn, da lnh, hemoglobin niu v c th dn n m n u khng c iu tr kp thi). CH3OH H2CO HCOO- CO2+ H2O 4.3. Ethylen glycol (CH 2OHCH2OH) c s dng nhiu trong cng nghip, trong my iu kh ca xe t

Khng dng trong y t. Khi ng c, ethylenglycol c th gy acid chuyn ha v suy thn (do lng ng cc tinh th oxalat ng thn). BI 14. THUC T 1. TNH CHT CHUNG CA THUC T 1.1. nh ngha Thuc t lm mt cm gic (au, nhit ) ca mt vng c th, ti ch dng thuc, trong khi chc phn vn ng khng b nh hng. Carl Koller (1884) dng dung dch cocain gy t gic mc, m u thi kz ca cc thuc t. Ngy nay, v tnh cht c v gy nghin ca thuc, cocain dn dn b b. Vi vic tm ra procain (novocaine), Einhorn (1904) m u thi kz th hai, rt quan trng v dng tim gy t. 1.2. c im ca thuc t tt Nhiu thuc c tc dng gy t, nhng mt thuc t tt cn t c cc tiu chun sau: - Ngn cn hon ton v c hiu s dn truyn cm gic. - Sau tc dng ca thuc, chc phn thn kinh c hi phc hon ton. - Thi gian khi t ngn, thi gian tc dng thch hp (thng l khong 60 pht). - Khng c, khng kch thch m v khng gy d ng. - Tan trong nc, vng bn di dng dung dch, kh khun xong vn cn hot tnh. 1.3. Lin quan gia cu trc v tc dng Cc thuc t u c cu trc gn ging nhau, tng t lidocain, gm ba phn chnh: cc a m, cc a nc v chui trung gian:

- Cc a m l nhn thm, c nh hng n s khuch tn v hiu lc ca tc dng gy t. Tnh a m lm tng i lc ca thuc vi receptor nn lm tng cng t; ng thi lm chm thu phn ca cc esterase nn lm ko di thi gian t. Tuy nhin, c tnh ca thuc li tng. - Cc a nc l nhm amin bc 3 ( N ) hoc bc 2 ( NH ) quy nh tnh tan trong nc v s ion ha ca thuc. Nhm amin l cht nhn H + theo phn ng: R NH2 + H2O R NH3 + OH - Chui trung gian: c 4 -6 nguyn t (di 6 -9nm) nh hng n c tnh

ca thuc, chuyn ha v thi gian tc dng ca thuc. Ngoi gii hn , tc dng s km dn. Trong chui ny c th c : . Nhm mang ng ni ester ( COO, nh procain) b thu phn nhanh gan v mu do cc esterase, nn c thi gian tc dng ngn. . Nhm mang ng ni amid ( NHCO, nh lidocain), kh b thu phn, tc dng di. 1.4. C ch tc dng Cc thuc t tng hp lm gim tnh thm ca mng t bo vi Na + do gn vo receptor ca knh Na+ mt trong ca mng, khc vi cc c t thin nhin nh ttrodotoxin gn mt ngoi ca knh. Nh vy, thuc t c tc dng lm n nh mng, ngn cn Na + i vo t bo, lm t bo khng kh cc c. Ngoi ra, thuc t cn lm gim tn s phng xung tc ca cc si cm gic. Hu ht cc thuc t u c pKa l 8,0 - 9,0, v vy, pH ca dch c th u phn ln dng cation, l dng c hot tnh gn vo c receptor, nhng li khng qua c mng t bo nn khng c tc dng, v receptor ca thuc t nm mt trong mng t bo. Qu trnh thm nhp qua mng t bo ti c receptor din bin nh s :

Hnh 7.1. Qu trnh thm nhp ca thuc t qua mng t bo gn vo receptor Thuc t t c hiu qu m nhim khun v pH thp nn ch c t l rt thp thuc t qua c mng. Mun lm t nhanh th cn tng nng ca thuc. Nhng khi s c hi cho m v d dn ti nhim c ton thn, cho n n trong thc hnh, cn chn nng ti u. 1.5. Tc dng dc l 1.5.1. Tc dng ti ch: Thuc t tc dng trn tt c cc si thn kinh trung ng (cm gic, vn ng) v thn kinh thc vt, ln lt t si b n si to tuz theo nng ca thuc. Th t mt cm gic l au, lnh, nng, xc gic nng, ri n xc gic su. Khi ht thuc, tc dng hi phc theo chiu ngc li. Tuz theo mc ch lm sng m s dng cc ng a thuc khc nhau: - Gy t b mt: bi hoc thm thuc ti ch (0,4 -4%).

- Gy t thm nhim = tim di da thuc ngm c vo tn cng thn kinh (dung dch 0,1 - 1%). - Gy t dn truyn: tim thuc vo cnh ng dn truyn ca thn kinh (gy t thn thn kinh, phong ta hch, gy t ngoi mng cng, gy t tu sng (xem s ).

1.5.2. Tc dng ton thn Ch xut hin khi thuc t thm c vo vng tun hon vi nng hiu dng: - Tc dng c ch thn kinh trung ng xut hin sm nht vi trung tm c ch nn gy cc du hi kch thch: bn chn, lo u, run c, cn co g it (iu tr bng diazepam), mt nh hng. - c ch dn truyn thn kinh - c gy nhc c, lit h hp. - Lm gin c trn do tc dng lit hch v tc dng trc tip trn c trn. - Trn tim - mch: do tc dng lm n nh mng, thuc t lm gim tn h kch thch, gim dn truyn v gim lc co bp ca c tim. C th gy lon nhp, thm ch rung tm tht. Trn mch, hu ht gy gin mch, h huyt p (tr cocain). - Trn mu: liu cao (trn 10 mg/ kg) prilocain tch t cht chuyn ha O toluidin gy oxy ha, bin Hb thnh metHb. 1.6. Tc dng khng mong mun v c tnh 1.6.1. Loi tc dng do thuc ngm vo vng tun hon vi nng cao, gy nhng biu hin thn kinh (bun nn, nn, mt nh hng, ng tc git rung, lit h hp), hoc tim mch (ri lon dn truyn, bloc nh tht). 1.6.2. Loi tc dng c hiu, lin quan n k thut gy t: h huyt p, ngng h hp do gy t tu sng, tn thng thn kinh do kim tim m phi hoc do thuc chn p. 1.6.3. Loi phn ng qu mn hay d ng ph th uc vo tng c th.? Thng gp vi cc dn xut c thay th v tr para ca nhn thm (ester ca acid para aminobenzoic), loi ng ni ester (procain). Rt t gp vi loi c ng ni amid (lidocain). 1.7. Dc ng hc Cc thuc t u l base yu, t tan trong nc, nhng khi kt hp vi acid (nh HCl) s cho cc mui rt tan v hon ton n nh (dung dch c pH

acid). Khng thm qua da lnh. Cc thuc t tng hp kh thm qua nim mc. Ging ha v thi tr ph thuc ch yu vo cu trc. Cc thu c t c chc amid (nh lidocain) hoc chc ether ( O), (nh quinisocain) ch b chuyn ho rt t gan bi cyt P 450, phn ln thi tr nguyn cht qua thn. Tc chuyn ho t nhanh n chm l prilocain >etidocain>lidocain>mepivacain>bupivacain. ngi bnh thng, t/2 ca lidocain l 1,8 gi; ngi suy gan nng c th ti >6gi. Cc thuc t c chc ester (procain) b thu phn bi cc esterase ca c gan v huyt tng, nn ging ho v mt tc dng nhanh, t/2 vi procain ch khong 1 pht. Loi ester b chuyn ho thnh para amino benzoic acid (PABA) nn d gy d ng. Cn loi amid khng b chuyn thnh PABA nn rt him gy d ng. 1.8. Tng tc thuc - khc phc tc dng gy gin mch ca thuc t (tr cocain gy co mch), thng phi hp vi adrenalin, nht l khi gy t thm nhim. Adrenalin lm co mch, c tc dng ngn cn s ngm thuc t vo tun hon chung v k o di c thi gian gy t. - Cc thuc lm tng tc dng ca thuc t: cc thuc gim au loi morphin, cc thuc an thn kinh (clopromazin). - Cc thuc d lm tng c tnh ca thuc t: quinidin, thuc phong to adrenergic (lm ri lon dn truyn c tim). - Thuc t hip ng vi tc dng ca cura. Sulfamid i khng 2 chiu vi cc thuc t dn xut t acid para amino b enzoic (nh procain). 1.9. p dng lm sng 1.9.1. Ch nh - Gy t b mt: Vim ming, vim hng, chun b ni soi, s dng trong nhn khoa. - Gy t dn truyn: Mt s chng au, phu thut chi trn, trong sn ph khoa (gy t ngoi mng cng). - Cc ch nh khc: Lon nhp tim (xem bi thuc cha lon nhp tim). 1.9.2. Chng ch nh - Ri lon dn truyn c tim - C d ng (tm nhm thuc khc). 1.9.3. Thn trng khi dng thuc - Dng ng tng liu v chn ng nng ti u. Khng dng thuc qu lo ng v khng vt qu 1% nu tim tu sng.

- Tim ng vng cn gy t. Khng tim vo mch hoc trc tip vo thn kinh. - Ngng ngay thuc nu c bt kz mt biu hin bt thng no. 2. CC LOI THUC T THNG DNG 2.1. Cocain Bng A-nghin. V vy ng y cng t dng. L thuc t duy nht c ngun gc thc vt (l cy Erythroxylon coca) c nhiu Nam M. 2.1.1. Tc dng - Gy t: thm qua c nim mc, dng trong tai mi hng (dung dch 10 20%) hoc khoa mt (dung dch 1-2%). - Trn thn kinh trung n g: gy kch thch, sng khoi, o gic, gim mt mi (d gy nghin). Liu cao gy run chi v co git. - Trn thn kinh thc vt: cng giao cm gin tip do ngn cn ti thu hi noradrenalin ngn dy giao cm, lm tim p nhanh, co mch, tng huyt p. 2.1.2. c tnh - Cp: co mch mnh (tm ti, hi hp, lo s, d b ngt), kch thch thn kinh trung ng (o gic, co git). - Mn: d gy quen thuc v nghin, mt nht nht, ng t gin, hoi t vch mi. 2.2. Procain (novocaine) Bng B. Tng hp (190 5) - L thuc t mang ng ni este, tan trong nc. - Tc dng gy t km cocain 4 ln, t c hn 3 ln. - Khng thm qua nim mc, khng lm co mch, ngc li, do c tc dng phong ta hch li lm gin mch, h huyt p. Khi gy t nn phi hp vi a drenalin lm co mch, tng thi gian gy t. - Dng lm thuc gy t dn truyn, dung dch 1% -2% khng qu 3mg/kg cn nng. - c tnh: d ng, co git ri c ch thn kinh trung ng. - Hin c nhiu thuc tt hn nn ngy cng t dng. 2.3. Lidocain (xylocain): Tng hp (1948). Hin dng rt rng ri. - L thuc t mang ng ni amid, tan trong nc.

- L thuc gy t b mt v gy t dn truyn tt. Tc dng mnh hn procain 3 ln, nhng c hn hai ln. - Tc dng nhanh v ko di do b chuyn ha c hm. Hai cht chuyn ha trung gian l monoethylglycin xylidid v glycin xylidid vn cn tc dng gy t. V khng gy co mch nn nu dng cng vi adrenalin, thi gian tc dng s lu m c tnh li gim. - c tnh: + Trn thn kinh trung ng: lo u, vt v, bun nn, nhc u, run, co git v trm cm, c ch thn kinh trung ng. + Trn h hp: th nhanh, ri kh th, ngng h hp. + Trn tim mch: tim p nhanh, tng huyt p, tip theo l cc du hiu c ch: tim p chm, h huyt p, do tc dng c ch trung ng. 2.4. Bupivacain (Marcain) L nhm thuc t c ng ni amid nh lidocain. Dng t 1963. - c im gy t: thi gian khi t chm, tc dng gy t lu, cng mnh gp 16 ln procain, nng cao phong ta cn ng kinh vn ng. - Dng gy t tng vng, gy t thn thn kinh, m ri thn kinh v gy t tu sng. Dung dch gy t ty sng c t trng 1,020 37 0 (ng 4ml = 20mg bupivacain clohydrat): tim tu sng 3ml t th ngi, tc dng t v mm c (c bng, c chi di ko di 2-2,5 gi). - D tan trong m, gn vo protein huyt tng 95%, hon ton chuyn ha gan do Cyt.P 450 v thi tr qua thn. - c tnh: c tnh trn tim mnh hn lidocain: gy lon nhp tht nng v c ch c tim, do bupivacain gn mnh vo knh Na + ca c tim v c ch c trn trung tm vn mch. - Gy t tng vng, tuz thuc mc ch, tuz thuc tui ca ngi bnh, dng dung dch 0,25 - 0,50% (c th km theo adrenalin gy co mch), tim t vi ml ti 20 ml. Tng liu cho 1 ln gy t khng vt q u 150mg. 2.5. Ethyl clorid (Klne) C2H5Cl L dung dch khng mu, si nhit 12 0C. C tc dng gy m nhng c ch mnh h hp, tun hon nn khng dng. Do bc hi nhit thp, nn c tc dng lm lnh rt nhanh vng da c phun thuc, gy tc dng t mnh, nhng rt ngn. - Ch nh: trch p xe, mn nht, chn thng th thao.

- Thuc ng trong l thy tinh, c van kim loi, tin s dng khi phun vo ni cn gy t. BI 15. THUC AN THN KIN?H V THUC BNH THN 1. THUC AN THN KINH (thuc an thn ch yu) Cc thuc loi ny c 3 c im c bn : - Gy trng thi th , lnh m, ci thin c cc triu chng ca bnh tm thn phn lit. - C thm tc dng c ch thn kinh thc vt, gy h huyt p, gim thn nhit. - C th gy ra hi chng ngoi b thp (hi chng Parkinson). Khc vi thuc ng, cc thuc loi ny d dng vi liu cao cng khng gy ng, ch c tc dng gy m mng, lm d ng. 1.1. Dn xut phenothiazin v thioxanthen: clopromazin Clorpromazin (Largactil, plegomazin, Aminazin): thuc c bng B. Bt trng xm, rt tan tro ng nc, ru, cloroform. c tm ra t nm 1952 trong khi nghin cu cc thuc khng histamin tng hp dn xut ca vng phenothiazin. L thuc m u cho lnh vc dc l tm thn. 1.1.1. Tc dng dc l 1.1.1.1. Trn h thn kinh trung ng - Clopromazin gy trng thi c bit th v tm thn vn ng: thuc khng c tc dng gy ng, tr vi liu gn c, nhng n lm gim cc hot ng vn ng v cc s bn tm, u t m vn gi c tng i cc hot ng v tr tu v s cnh gic. Liu rt ca o cng khng gy hn m. Ngi dng thuc t ra khng quan tm n mi trng xung quanh, khng biu l xc cm, trong khi phn x tu v phn x khng iu kin vi kch thch au vn gi c. - Thuc lm gim c o gic, thao cung, vt v. Do , thuc c tc dng vi bnh tm thn phn lit. - Cloprozamin gy hi chng ngoi b thp, ging bnh Parkinson biu hin bng ng tc cng , tng trng lc. - H thn nhit do c ch trung tm iu nhit h khu no. - Chng nn do c ch trung tm nn sn no tht 4. - c ch trung tm trng lc giao cm iu ha vn mch.

- Trn vn ng, liu cao gy trng thi gi nguyn th (catalepsia). 1.1.1.2. Trn h thng thn kinh thc vt Va c tc dng hu ph giao cm va c tc dng phong ta receptor 1 adrenergic ngoi bin. Tc dng hu ph giao cm th hin bng nhn m (ng t gin), to bn, gim tit dch v, gim tit nc bt, m hi. Tc dng ny rt t xy ra vi cc dn xut c nhn piperazin. Tc dng hu 1 - adrenergic tng i c ngh a, c th phong ta tc dng tng p ca noradrenalin. V loi piperazin c tc dng an tm thn vi liu thp nn tc dng hu giao cm rt yu. 1.1.1.3. Trn h ni tit - Lm tng tit prolactin, gy chy sa v chng v to n ng. - Lm gim tit F SH v LH, c th gy c ch phng non v mt kinh. 1.1.1.4. C tc dng khng histamin H 1, nhng yu. 1.1.2. Tng tc thuc - Clopromazin lm tng tc dng ca thuc ng, thuc m, thuc t, thuc gim au loi morphin, thuc h huyt p (nht l guaneth idin, thuc c ch enzym chuyn angiotensin), ru. - Clopromazin i khng tc dng vi cc thuc kch thch thn kinh tm thn, c bit vi amphetamin v cc cht gy o gic. - Gia cc thuc an thn kinh, khng c tc dng hip ng tng mc, nhng v mt iu tr cc triu chng ca bnh tm thn, c th dng phi hp trong thi g?ian ngn. 1.1.3. C ch tc dng Sinh l hc ca hot ng thn kinh trung ng v sinh bnh hc ca ri lon tm thn (bnh tm thn phn lit) cn cha c bit r. Tuy nh in, ngi ta nhn thy rng s cn bng gia h dopaminergic trung ng v h serotoninergic trung ng c vai tr quyt nh n cc triu chng ca bnh tm thn phn lit. H dopaminergic (DA) trung ng Cc thuc cng h DA (amphetamin, cocain, DOPA) u lm tng triu chng bnh. Cc thuc hu h DA, c bit l cc receptor thuc nhm D 2 (gm D2, D3, D4) nh thuc an thn kinh u lm gim cc biu hin ca bnh tm thn. H serotoninergic (5HT) trung ng C ti 15 loi receptor 5HT, nhng vi bnh tm thn th receptor 5HT 2 (c

bit l 5 HT 2A) c vai tr quan trng hn c. Trong no, nhn tng hp 5HT nhiu nht (c th l duy nht) l cc nhn Raphe (Raphe nuclei). Cc nhn ny kim sot s tng hp DA c thn t bo v s gii phng DA tr c xinap ca cc nron h DA. Nhn chung, 5HT c ch gii phng DA. Gi thuyt sinh ha v bnh tm thn phn lit cho rng cc triu chng dng tnh (hoang tng, o gic, kch ng, a nghi, { tng t cao) l do tng hot h DA h vin v mt c ch iu ha ngc trung ng. Cn cc triu chc m tnh (cm xc cn mn, quan h km, v cm, t duy tru tng kh khn) l do ri lon chc phn vng trn trc, gim hot h DA no gia - v no do tng hot h 5HT 2. Cc thuc an thn kinh c in (clorpr omazin, haloperidol) c ch mnh D 2 hn 5HT nhiu nn tc dng trn triu chng dng tnh mnh, t tc dng trn triu trng m tnh, mt khc, gy tc dng ph ngoi b thp. Cc thuc an thn mi (c nghin cu nhiu t thp k 80 ca th k 20 tr l i y) u c c hai tc dng phong ta D 2 v 5HT2A v c ch 5HT2A mnh hn D2 (risperidon) do ci thin c c triu chng m tnh v t gy triu chng ngoi b thp, cn vi triu chng dng tnh th tc dng nh thuc c in. Hin c olanzapin, risperidon 1.1.4. Dc ng hc - Hp thu tt qua ng tiu ho. Nng cao hn 400mg/ml mu thng l c. - Thuc rt a m, gn nhiu vo protein huyt tng, tp trung no v t chc m, qua nhau thai d dng. Thi gian bn thi 20 -40gi. Hiu lc sinh hc ca liu mt ln thng tn ti t nht l 24gi nn ch cn dng liu 1 ln mi ngy. - Chuyn ho ch yu gan qua qu trnh oxy ho, to cc cht chuyn ho hon ton mt hoc ch cn mt phn hot tnh. - Thi tr: ch yu qua nc tiu (dng tan trong nc, khng c hot tnh), phn khc qua mt (c chu kz gan- rut) v ra phn. Thuc tn ti lu trong c th, sau khi ngng thuc 6 -12 thng vn cn tm thy vt trong cht thi. 1.1.5. Tc dng khng mong mun 1.1.5.1. Loi thng gp, li n quan n tnh cht dc l ca thuc: - Ri lon tm l: chng mt mi, suy ngh chm chp, trng thi trm cm, l ln (nht l ngi c tui). - Tt huyt p khi ng v nhp tim nhanh, nht l khi tim.

- Kh ming, nut kh, b i, ri lon iu ti t th lc, cn tng nhn p cp, to bn l nhng du hiu hu ph ng giao cm. - Ri lon iu tit v sinh dc: c ch phng non, v kinh, chy sa, gim tnh dc, tng cn. - Hi chng ngoi b thp: thay i tuz thuc vo thi gian iu tr, vo liu lng, vo thuc phi hp, vo tui, gii 1.1.5.2. Loi khng ph thuc vo tc dng dc l. - Gim bch cu. - Vng da tc mt, xut hin gia tun th 2 n th 4. Gim dn khi ngng thuc. C th do ph n cc ng dn mt do phn ng qu mn v khng ph thuc vo liu. - Phn ng ngoi da: d ng, mn cm vi nh nng, ng sc t trong tin phng ca mt. - Lon nhp tim: nhp nhanh xoang (iu tr bng propranolol), nh tht phn ly. - Hi chng st cao c tnh: st cao, da ti nht, m hi nh nhi, trng thi sc. Phi lm hi sc cp cu: gi thng bng nc v in gii. - Tai bin cht t ngt, thng xut hin sau khi tim. Cha r nguyn nhn.C th lin quan n huyt khi, vim tc mch. 1.1.6. p dng lm sng Do c nhiu tc dng a dng, clopromazin c dng nhiu khoa: - Khoa tm thn: lon thn kinh, tm thn phn lp, thao cung, hoang tng, o gic. - Khoa sn: sn git (ch thuc qua c rau thai) - Khoa gy m: tin m, gy m h th nhit, h huyt p. - Khoa ni: chn g nn, chng au, an thn, chng rung tim. - Khoa da liu: chng nga. - Ung 10- 25 mg/ ln 2- 4 ln/ ngy. Tim bp 25 - 50 mg/ ln 2- 3 ln/ ngy. 1.2. Dn xut butyrophenon: Haloperidol Haloperidol (Haldol) l tiu biu cho nhm an thn kinh a nn g (polyvalent neuroleptics) hay an thn kinh chng triu chng dng tnh (antiproductive), chng thao cung. V cu trc ho hc, haloperidol gn ging vi acid gamma -amin- butyric (GABA) l cht trung gian ho hc ca cc qu trnh c ch trong thn kinh trung ng. Tc dng an tm thn mnh l

do c ch receptor dopaminergic trung ng v cng v vy tc dng khng mong mun, hi chng Parkinson cng r. 1.2.1. Ch nh - Cc trng thi thao cung, hoang tng - Cc trng thi hong lon tm thn cp v mn, tm thn phn lp, paranoid (hoang tng c h thng). - Chng nn. Nn do dng thuc chng ung th, sau chiu x. 1.2.2. Cn thn trng - Khng dng chung vi thuc cng h dopaminergic (levodopa) v cc receptor ca h dopaminergic b halope ridol phong ta. Nu khi ang iu tr bng haloperidol m c du hiu ngoi b thp th dng thuc hu ph giao cm trung ng. - Dng cng vi thuc h huyt p c th gy tt huyt p khi ng. - Thn trng vi ngi li xe, ng my, v lc u iu t r c th gy ng g. 1.2.3. Tc dng khng mong mun Ging nh vi clopromazin, hay gp ng g, hi chng ngoi b thp, ri lon ni tit. 1.2.4. Liu lng ng 5mg/ml x 1-4 ng/ngy. Tim bp; Vin 5mg x 1 -8 vin/ngy. 1.3. Dn xut benzamid: Sulpirid (Dogmatil) 1.3.1. Tc dng Sulpirid l i din cho nhm benzamid, l thuc an tm thn c tc dng lng cc (bipolar): - Liu 600mg c tc dng gii c ch chng triu chng m tnh, kch thch receptor sau xinap ca h dopaminergic trung ng. - Liu > 600mg c tc dng? chng triu chng dng tnh (antiproductive), chng hoang tng v thuc kch thch receptor trc xinap ca h dopaminergic, lm gim gii phng dopamin. V vy, liu thp l cng v liu cao l hu h dopaminergic (trn cc receptor D4 trung ng). 1.3.2. Ch nh - Liu thp (di 600mg): tnh trng mt ngh lc, lon thn. - Liu cao (liu trn 600mg): cc ri lon tm thn cp tnh: tm thn phn lp, thao cung, o gic. 1.3.3. Tc dng khng mong mun

- Ri lon ni tit v chuy n ha: tng tit sa, tng cn. - Thn kinh: + Lon vn ng: vo c, cng hm, xoay mt (oculogyre). + Hi chng ngoi b thp. + Ng g. - Tim mch: tt huyt p khi ng. 1.3.4. Ch phm v liu lng Dogmatil vin 200mg, ng 2ml = 100mg - Chng suy sp, triu chng m tnh: 1 -3 vin/ngy. - Chng triu chng dng tnh: 4 -8 vin/ngy. - Trong lon thn cp v mn tnh, tim bp 200 - 800mg mt ngy, trong 2 tun lin. 1.4. Nhm benzisoxasol: Risperidon c im tc dng: i khng vi 5 HT 2 vng trn trc ca v no nn c hiu qu iu tr cc triu chng m tnh ca tm thn phn lp. ng thi c tc dng i khng D 2 vng no gia - h vin nn c hiu qu iu tr cc triu chng dng tnh. Risperidon gn vo 5HT 2A khong 20 ln mnh hn vo D2. Vi liu iu tr (4 -6 mg/ngy) rt t gy triu chng ngoi b thp. 2. THUC BNH THN (thuc an thn th yu) C nhiu tn gi: minor tranquillizers, anxiolytics, sedatives hoc thuc an thn th yu, thuc bnh thn. Nhm thuc quan trng hn g u l benzodiazepin. c im chung l c ch c bit trn h thng li hot ha i th h vin v cc nron kt hp ca tu sng. Do : - C tc dng an du (sedative), lm gim cnh gic, lm chm cc hot ng vn ng v lm du s bn chn. - C tc dng an thn gii lo (anxiolytic effects): lm gim cc phn ng xc cm thi qu v gim cng thng tm thn. - Ch c tc dng gy ng khi mt ng c lin quan n s lo u, bn chn. - t nh hng n h thn kinh thc vt nh nhm thuc an thn ch yu (loi clopromazin). - Chng co git. - Gin c lm gim trng lc c do tc dng trung ng. Benzodiazepin (BZD): l thuc i din cho nhm ny v rt thng dng.

2.1. Tc dng dc l 2.1.1. Trn thn kinh trung ng c 4 tc dng chnh - An thn, gii lo, gim hung hn. - Lm d ng: gim thi gian tim tng v tng thi gian gic ng nghch thng. Khc vi barbiturat l phn ln BZD khng c tc dng gy m khi dng liu cao. - Chng co git: clonazepam, nitrazepam, lorazepam, diazepam: do t nh cm th khc nhau ca cc vng, cc cu trc thn kinh v s cm th khc nhau ca cc loi vi cc dn xut m tc dng c khc nhau: c dn xut cn lm tng vn ng chut nht, chut cng, kh. Ring flurazepam li gy co git, nhng ch trn mo. - Lm gin c vn. Ngoi ra cn: . Lm suy yu k c c (retrograde amnesia) v lm tr ngi k c mi (anterograde amnesia). . Gy m: mt s t BZD c tc dng gy m nh diazepam, midazolam (tim tnh mch) . Liu cao, c ch h trung tm h hp v vn mch. 2.1.2. Tc dng ngoi bin - Gin mch vnh khi tim tnh mch - Vi liu cao, phong ta thn kinh - c. 2.2. C ch tc dng BZD gn trn cc receptor c hiu vi n trn thn kinh trung ng. Bnh thng, khi khng c BZD, cc receptor ca BZD b m t protein ni sinh chim gi, lm cho GABA (trung gian ha hc c tc dng c ch trn thn kinh trung ng) khng gn vo c receptor ca h GABA - ergic, lm cho knh Cl ca nron kh p li. Khi c mt BZD, do c i lc mnh hn protein ni sinh, BZD y protein ni sinh v chim li receptor, do GABA mi gn c vo receptor ca n v lm m knh Cl -, Cl- i t ngoi vo trong t bo gy hin tng u cc ha (hnh 12.1). Cc receptor ca BZD c lin quan v gii phu v chc phn vi receptor ca GA B

Hnh 12.1: C ch tc dng ca Benzodiazepin (BZD) Cc receptor ca BZD c nhiu trn thn kinh trung ng: v no, vng c

nga, th vn, h khu no, hnh no, nhng c bit l h thng li, h vin v c tu sng. BZD tc dng gin tip l lm tng hiu qu ca GABA, tng tn s m knh Cl 2.3. Cc tc dng khng mong mun Khi nng trong mu cao hn liu an thn, t ti liu gy ng, c th gp: u oi, ng tc khng chnh xc, l ln, ming kh ng, gim tr nh. c tnh trn thn kinh tng theo tui. V tm thn, i khi gy tc dng ngc: c mng, bn chn, lo lng, nhp tim nhanh, v m hi, sng khoi, o gic, hoang tng, mun t t. Quen thuc c th l do c ch tng chuyn ha hoc iu ha gim s lng cc receptor ca BZD trong no. t gy ph thuc v lm dng thuc, nhng sau mt t dng BZD ko di, c th gy mt ng tr li, lo lng, bn chn hoc co git. Mc du vy BZD vn l mt thuc an thn tng i an ton v ang c xu hng thay th dn thuc ng loi b arbiturat. Thuc c t/2 cng ngn (triazolam t/2 = 3 gi), cng d gy nghin. 2.4. Dc ng hc Hp thu hu nh hon ton qua tiu ha, t nng ti a trong mu sau 30 pht n 8 gi. Gn vo protein huyt tng t 70% (alprazolam) n 99% (diazepam) . Nng trong dch no tu gn tng ng nng dng t do trong mu. Thuc qua c rau thai v sa. c chuyn ho bi nhiu h enzym trong gan, thnh cc cht chuyn ho vn cn tc dng ri li b chuyn ho tip, nhng tc chm hn cho nn t c dng t lin quan n thi gian bn thi. Th d flurazepam c t/2 trong huyt tng l 2 -3gi, nhng cht chuyn ho cn tc dng l N-desalkyl flurazepam cn tn ti trn 50 gi. Da theo t/2, cc Bzd c chia lm 4 loi: - Loi tc dng cc ngn, t/ 2 <3 gi c midazolam,triazolam. - Loi tc dng ngn, t/2 t 3 -6 gi c, zolpidem (non -benzodiazepin) v zopiclon. - Loi tc dng trung bnh, t/2 t 6 -24 gi c estazolam v temazepam. - Loi tc dng di, t/2 >24 gi c flurazepam, quazepam, diazepam. 2.5. p dng 2.5.1. An thn : liu trung bnh 24gi: Diazepam (Valium): 0,005 -0,01g. Ung 2.5.2. Chng co git Diazepam (Valium): 0,010 -0,020g. Tim bp, tnh mch

Clorazepam (Tranxene): 0,010 -0,020g. Ung 2.5.3. Gy ng, tin m Triazolam (Halcion): 0,125 -0,250g. Ung: Mt ng u gic. Ung Midazolam (Versed): 0,025 - 0,050. Tim bp, tnh mch - tin m. 2.5.4. Gin c, gim au do co tht: thp khp, ri lon tiu ho Diazepam (Valium): 0,010 0,020g. Ung, tim bp, tim tnh mch. Tetrazepam (Myolastan): 0,0500,150g. Ung, tim bp, tim tnh mch. * Nguyn tc chung khi dng thuc: - Liu lng tuz thuc tng ngi. - Chia liu trong ngy cho ph hp. - Dng gii hn tng thi gian ngn (1tun -3 thng) trnh ph thuc vo thuc. - Trnh dng cng vi cc thuc c ch thn kinh trung ng, ru, thuc ng, khng histamin. 2.6. Chng ch nh - Suy h hp, nhc c: do tc dng c ch thn kinh v gin c. - Suy gan: do thuc chuyn ho to cc cht c tc dng ko di, c th tng c tnh hoc gy c cho gan b suy. - Nhng ngi li t, lm vic trn cao, ng my chuyn ng. 2.7. Nhm thuc mi Do BZD cn mt s tc dng ph nn ang nghin cu mt nhm thuc an thn mi khng tc dng qua h GABA: buspirone, zolpidem (nhm imidazopiridin). Buspiron i din cho mt nhm thuc an thn mi: - c im dc l: . Lm mt lo u nhng khng gy an du, ng g hoc mt tr nh. . Khng i khng hoc hip ng vi cc thuc an thn hoc barbiturat khc. . Dng liu cao cng khng gy c ch thn kinh trung ng r. . Tc dng mnh trn cc triu chng tm l{ nh lo u, k m tp trung t tng. Cn diazepam li c tc dng lm gin c v chng mt ng tt hn. . Nhc im: khi pht tc dng chm, km tc dng trn cn hong s. - C ch tc dng L cht ng vn vi receptor 5 - HT 1A c nhiu h vin, hi hi m, no gia, i th, hnh - cu no, th vn, h khu no v tiu no. C ch cn

ang nghin cu, nhng khng tc dng trn knh Cl- qua GABA nh BZD. - Tc dng khng mong mun: Chng mt, mt ng, bun nn, nhc u, au ngc, tai, lo u. Cn iu chnh liu. V l thuc mi, cn theo di thm. - ng hc Hp thu nhanh qua ng ung nhng c chuyn ha qua gan ln th nht do hydroxy ha v mt alkyl, tuy nhin li to ra nhiu cht ch uyn ha cn hot tnh vo c thn kinh trung ng, c cht c tc dng phong ta c receptor 2. Thi gian bn thi l 2 - 4 gi. Liu lng: vin 5 - 10 mg (Buspar), dng t liu thp, 3 ln/ ngy. BI 16. THUC AN THN CH YU 1. I CNG : 1.1. c im c bn : - Gy trng thi th lnh m, ngi dng thuc khng phn ng vi bn ngoi, ci thin c cc triu chng ca bnh tm thn phn lit. C thm tc dng c ch thn kinh thc vt, gy h huyt p, gim thn nhit. - C th gy ra hi chng ngoi b thp ( hi chng Parkinson ) - Khc vi thuc ng, cc thuc an thn d dng liu cao cng khng gy ng, ch c tc dng lm m mng, d ng. 1.2. Phn loi :gm c : + Cc dn xut phenothiazin v thioxanthen + Cc dn xut butyrophenon : haloperidol, droperidol + Cc dn xut d vng khc : - Dn xut benzamid : sulpirid ( dogmatil ), amisulprid. - Dn xut dibenzodiazepin : olanzapin. - Dn xut benzisoxa?zol : risperidol 2.1. Lin quan gia cu trc ho hc v tc dng dc l 2.2. Chlorpromazin HCl : 2.2.1. Tn khc : aminazin.2.2.2. Bit dc : chloractil, largactil, plegomazyn, propaphenin, protran 2.2.3. Dc ng hc : + Hp thu tt qua ng tiu ho v rt tt khi tim IM ( tng 4 - 10 ln ). + Thuc rt a m, gn nhiu vo protein huyt tng, tp trung no v m

m. Qua c nhau thai d dng. t1/2 = 20 40 h ( ch cn dng 1 ln/24 h ). + Chuyn ho ch yu gan ( oxy ho, glucuro-hp, kh methyl ) + Thi ch yu qua nc tiu, c chu kz gan-rut, thi 1 phn qua phn. 2.2.4. Tc dng dc l : a- Trn h thng TKTW : + Gy trng thi c bit th v tm thn vn ng ( gim cc hot ng vn ng, gim s bn tm, u t, khng biu l xc cm b mt aminazin), tuy nhin tuy nhin cc hot ng v tr tu v s cnh gic vn c duy tr gn bnh thng. Thuc khng c tc dng gy ng ( tr vi liu gn c ). Liu rt cao cng khng gy hn m. + Gim thao cung, o gic, vt v ( dng iu tr tm thn phn lit ) . + Gy hi chng ngoi b thp. + H thn nhit do c ch trung tm iu nhit vng di i. + Chng nn : c ch vng nhn cm ha hc sn no tht 4. + Gim trng lc e do c ch trung tm trng lc e iu ha vn mch. + Trn vn ng, liu cao gy trng thi gi nguyn th ( catalepsia ). b- Trn h thng TKTV : + Hu ph e : gy nhn m ( do gin ng t ), gim tit dch v, nc bt, m hi, to bn + Hu a1 - adrenergic ngoi bin : phong to tc dng gy tng huyt p ca noradrenalin. Tc dng ny nhm c nhn piperazin rt yu do liu an thn thp. c- Trn h ni tit : + Tng tit prolactin : gy chy sa, chng v to nam. + Gim titFSH v LH, c th gy c ch phng non, mt kinh, gim ham mun tnh dc. 2.2.6. Tc dng khng mong mun : a- Loi thng gp, lin quan n tc dng dc l ca thuc : + Ri lon tm l : chng mt mi, suy ngh chm chp, trm cm, l ln ( nht l ngi gi ). + Tt huyt p th ng, nhp tim nhanh ( nht l khi tim ). + Du hiu hu ph e : kh ming, kh nut, ri lon iu tit th lc, cn tng nhn p cp, b i, to bn + Ri lon ni tit v sinh dc : c ch phng non, v kinh, chy sa, gim ham mun tnh dc, tng cn.

+ Hi chng ngoi b thp : thay i ph thuc vo loi thuc, liu lng, thi gian iu tr, thuc phi hp, tui, gii b- Loi khng lin quan n tc dng dc l ca thuc : + Gim bch cu. + Vng da tc mt ( c th do ph n cc ng dn mt do phn ng qu mn ). + Phn ng ngoi da : d ng, mn cm vi nh sng, ng sc t trong tin phng ca mt. + Ri lon nhp tim : nhp xoang nhanh, nh tht phn ly + Hi chng st cao c tnh : st cao, da ti nht, m hi nh nhi, trng thi shock ( cn cp cu : gi thng bng nc v in gii ) + t t, thng xy ra sau khi tim ( c l do hu?yt khi gy tc mch ) 2.2.7. Ch nh lm sng : + Khoa tm thn : cc chng lon thn kinh ( cp hoc tin trin ), tm thn phn lit, thao cung, hoang tng, o gic + Khoa sn : sn git ( ch thuc qua c rau thai ). + Khoa gy m : tin m, gy m kiu h thn nhit, h HA. + Khoa ni : cc chng lo lng, cc chng nn, au, ri lon nhp tim. + Khoa da liu : cc chng nga ( t dng ). 2.2.8. Chng ch nh : + Ng c cp do ru, thuc ng barbiturat + Suy gan, suy thn, glaucoma gc ng, nc tiu do ri lon niu qun tin lit tuyn. 3. D/XUT BUTYROPHENON: 3.1. Haloperidol : l tiu biu cho nhm an thn kinh a nng ( neuroleptiques polyvalents ) hay thuc an thn kinh chng triu chng dng tnh ( antiproductive ), chng thao cung. 3.1.1. Tn khc : aloperidolo.3.1.2. Bit dc : aloperidin, haldol, haloperidin, halopidol, peridol 3.1.3. Dc ng hc : + Hp thu d qua ng tiu ha, t Cmax. sau 4 - 6 h. + C tnh kim, rt tan trong lipid. Gn vo protein huyt tng 90%; + Chuyn ho ch yu gan ( kh alkyl - oxy ho ) + Thi tr qua thn v mt; t1/2 = 24h. Khng c chu kz gan - rut. 3.1.4. Tc dng dc l :Gn vo receptor D2 khong 16 ln mnh hn gn vo 5HT2.

+ c ch mnh trng thi kch thch tm thn vn ng, thao cung. + c ch mnh hoang tng, lm mt o gic nhanh. + An thn, chng lo u, chng nn, iu ha cc ri lon TKTV ( liu thp ) + Khng c hoc rt t tc dng hu e, hu ph e v gy ng, rt t tc dng trn tim mch ( do khng gn vo receptor a1 v H1 ). + c ch cc phn x t nhin v phn x c iu kin ca ng vt th nghim ging nh chlorpromazin 3.1.5. C ch tc dng : Haloperidol c cng thc ha hc gn ging vi cng thc ca GA BA ( l cht TGHH ca cc qu trnh c ch trong TKTW ). Thuc c ch receptor dopaminergic trung ng nn c tc dng an thn kinh mnh, ng thi tc dng khng mong mun ( h/c Parkinson ) cng r. 3.1.6. Tc dng khng mong mun : nh vi clorpromazin. Hay gp : + Ng g ( thn trng vi ngi li xe, ng my, lm vic trn cao ) + Hi chng ngoi b thp, ri lon ni tit, kh vn ng mm, li, hm 3.1.7. Ch nh : + Cc trng thi thao cung, hoang tng + Cc trng thi lon tm thn cp v mn, tm thn phn lit, hoang tng c h thng ( paranoid ) . + Cc chng nn ( do dng thuc chng ung th, chiu x ). Tin m. + Liu thp : cc ri lon chc nng ng tiu ha, tim mch, h hp. 3.1.8. Chng ch nh : Trm cm, bnh Parkinson, suy gan, x cng ri rc, bnh tim mch nng, ph n c thai, 3.1.9. Tng tc thuc : + Khng dng chung vi thuc cng dopaminergic ( levodopa ) v haloperidol phong to cc receptor ca h ny, gy hi chng ngoi b thp ( iu tr bng thuc hy ph e trung ng : artan, lepticur ). + Lm tng tc dng ca thuc ng, gy h thn nhit. + Dng cng lithi c th gy l ln, tng lithi niu + Dng vi thuc h p : tt huyt p th ng. ? 3.2. Mt s dn xut khc ca haloperidol :3.2.1. Trifluperidol : 3.2.2. Droperidol : 3.2.3. Mopiperon : 4. Dn xut benzamid :

4.1. Sulpirid :4.1.1. Bit dc: abilit, dogmatil, dolmatil, sulpiren, synedil, vipral 4.1.2. Dc ng hc : + Hp thu tt qua ng tiu ho, t C max. sau khi ung 4 - 5h. + Gn vi protein huyt tng 40% + Khuych tn nhanh vo cc m gan thn, tuyn yn, qua nhau thai, sa + Chuyn ha ch yu gan. Khng c chu kz gan - rut. + Thi tr ch yu qua thn (90% di dng cn hot tnh) 4.1.3. Tc dng dc l : Sulpirid l thuc an thn c tc dng lng cc ( bipolar ) : + Liu 600 mg/24hc tc dng gii c ch, kch thch receptor sau sinap ca h dopaminergic trung ng ( tc dng cng h dopaminergic trn cc receptor D4 trung ng ) + Liu > 600 mg/24h c tc dng chng triu chng dng tnh, chng hoang tng do thuc kch thch receptor trc sinap ca h dopaminergic, lm gim gii phng dopamin ( tc dng hy h dopaminergic trn cc receptor D4 trung ng ). 4.1.4. Tc dng khng mong mun : + Ri lon ni tit, chuyn ho: gim ham mun tnh dc ( bt lc hoc lnh cm ), v kinh, tng tit sa, n ha tuyn v ( nam ), tng cn. + Thn kinh : - Lon vn ng : vo c, cng hm, xoay mt. - Hi chng ngoi b thp - Ng g + Tim mch : tt huyt p th ng 4.1.5. Ch nh : + Liu thp ( 600mg/24h ) : tnh trng mt ngh lc, lon thn, lot d dy t trng, vim lo t i trng. + Liu cao ( > 600mg/24h ) : cc ri lon tm thn cp tnh nh tm thn phn lit, thao cung, o gic 4.1.7. Ch phm v liu lng: + Ch phm : vin 50 - 200 mg, nang tr 50 mg; dung dch ung 5 mg/ml; ng IM 100 mg/2 ml + Liu lng : - Chng suy sp, triu chng m tnh : 200 - 600 mg/24h.

- Chng triu chng dng tnh: 800 - 1.600 mg/24h - Lon thn cp v mn tnh : tim IM 200 - 800 mg/24h x 2 tun lin. - Vim lot d dy, i trng mn tnh : ung 150 mg/24h x 4 - 6 tun. 4.2. Amisulprid : 4.2.1. Bit dc : solian.4.2.1. Tc dng, tc dng ph, ch nh, chng ch nh: tng t sulpirid. 4.1.6. Chng ch nh : + U tu thng thn ( gy cn tng HA kch pht ) + Bnh nhn ng kinh ( gy cn ng kinh do gim ngng sinh ng kinh ). + Ph n c thai ( gy qui thai ), cho con b ( thuc qua sa ), ngi c tui, tr s sinh ( d nhy cm ), suy thn nng, mn cm vi thuc + Phi hp vi ru, levodopa, cc thuc c ch TKTW ( gy tt HA ) 1. Olanzapin : 1.1. Bit dc : zyprexa1.2. Ch nh : tm thn phn lit v cc th lon thn khc1.3. Chng ch nh : glaucoma gc ng, mn cm vi thuc1.4. Tc dng khng mong mun: tng t nh chlorpromazin song mc v t l thp hn 1.5. Ch phm v liu lng: + Vin nn2,5 - 5 - 7,5 - 10 mg ( v 7 vin ). + Liu dng : - Liu khi u : ung 10 mg/24 h ( khng ph thuc n ung ), sau thay i liu tuz theo s p ng ca BN. Duy tr : 5 - 20 mg/24? h. - Ti a : 20 mg/24 h. - Ngi gi > 65 tui, suy gan, suy thn: liu khi u 5 mg/24 h. 2. Zuclopenthixol : 2.1. Tn khc : chlopenthixol.2.2. Bit dc : clopixol-acuphase, clopixol, clopixoldepot2.3. Ch nh : tm thn phn lit, ri lon lng cc, cc chng lon tm thn nht l trng thi kch ng 3. Risperidon : thuc dn xut benzisoxazol. 3.1. Bit dc : risperdal. 3.2. Ch nh : tm thn phn lit v cc th lon thn khc 3.3. Chng ch nh : mn cm vi thuc

3.4. Tc dng khng mong mun : tng t nh olanzapin. 3.4. Ch phm v liu lng : + Vin nn ( HCl ) 10 - 25 - 40 mg; ng tim ( acetat ) 50 mg/ml ( 1 - 2 ml ); ng tim ( decanoat ) 200 mg/ml ( 10 ml ). + Liu dng : ung liu khi u 20 - 30 mg/24 h ( chia lm 2 - 3 ln ), sau tng dn cho ti khi t hiu qu iu tr. Liu ti a 150 mg/24h. Duy tr 20 75 mg/24h. - Tim IM : dng acetat : 50 - 100 mg, c th nhc li 3 - 4 ngy. Liu ti a 400 mg/24h. Dng decanoat : tim IM su 100 mg, sau cch 1 - 4 tun tim nhc li 100 - 200 mg. Liu ti a : 600 mg/tun. BI 17. THUC CHA NG KINH 1. I CNG Thuc cha ng kinh l nhng thuc c kh nng loi tr hoc lm gim tn s, mc trm trng ca cc cn ng kinh, hoc cc triu chng tm thn km theo bnh ng kinh, m khng gy ng. Thuc m v thuc ng cng c tc dng chng co git, nhng tc dng ny ch xut hin sau khi ngi bnh ng. Thuc chng ng kinh cng khng cng ngha vi thuc chng co git. 1.1. Phn loi cn ng kinh Cc cn ng kinh lun xut pht t v no v c phn loi thnh: - Cn ng kinh cc b: bt u t 1 trn v no v tuz theo vng chc phn m th hin ra triu chng. Th d, v tr tn thng vng v n o vn ng, s c triu chng git rung phn c th do vng v no y kim tra. Trong loi ny cn phn ra: . Cn cc b n gin, bnh nhn vn cn thc ko di khong 30 -60 giy. . Cn cc b phc hp, c km theo mt thc, ko di khong 30 giy n 2 pht. - Cn ng kinh ton th: ngy t u lan rng ton b 2 bn cu i no. C th gp: . Khng c cn co git: bt cht mt thc khong 30 giy trong lc ang lm vic (ng kinh cn nh - petit mal). . Cn git rung c: co tht bt ng, ng n (khong 30 giy) c th gii hn mt chi, mt vng, hoc ton th. . Cn co cng - git rung ton c th (ng kinh cn ln - grand mal). 1.2. Phn loi thuc iu tr theo cn

1.3. Cch tc dng ca thuc cha ng kinh Cc thuc cha ng kinh c th tc ng theo mt trong ba c ch sau: - Lm tng dn truyn c ch ca h GABA - ergic - Lm gim dn truyn kch thch, thng l h glutamatergic. - Lm thay i s dn truyn ion qua mng nron do tc ng trn knh Na + ph thuc in th, hoc knh Ca++ typ T. V c ch bnh sinh ca ng kinh cha c hon ton bit r cho nn cc thuc cha ng kinh ch c ch c cc triu chng ca bnh ch khng d phng v iu tr c bnh. Thuc phi c s d t ch ng lu di, d c nhiu tc dng khng mong mun. Do cn c g im st nghim ngt. 2. CC THUC CHNH Sau y ch trnh by nhng thuc c trong danh mc thuc thit yu Vit Nam ln th 5 (2005) 2.1. Dn xut hydantoin: Diphenylhydantoin (Phenytoin, Dilantin) Diphenylhydantoin l mt trong nhng thuc c tc dng t t cha mi th ng kinh, tr ng kinh th khng c cn co git. 2.1.1. Tc dng v c ch Phenytoin c tc dng chng cn ng kinh nhng khng gy c ch ton b h thn kinh trung ng. Liu c cn gy kch thch. Tc dng trn cn co git ng kinh cng ging phenobarbital, nhng khng gy an thn v ng. Phenytoin c tc dng n nh mng t bo thn kinh v c tim, lm gim lung Na + trong hiu th hot ng trong kh cc do cc cht ha hc (c ch knh Na + cm ng vi in th). 2.1.2. Dc ng hc Phenytoin l acid yu, c pKa = 8,3 tan trong nc km. Hp thu qua ng tiu ha chm v i khi khng hon ton. Nng ti a trong mu khi ung l t 3 - 12 gi. Gn vo protein huyt tng 90%. Nng trong thn kinh trung ng tng ng nng trong huyt tng. Phn ln chuyn ha gan v thi tr qua thn di dng lin hp, ch 5% di dng khng chuyn ha. Thi gian bn thi t 6 -24 gi. 2.1.3. Tc dng khng mong mun - Da v nim mc: vim li qu sn, mn da, lupus ban . - Mu: thiu mu hng cu to do thiu acid folic (do thuc phong ta s hp thu acid folic ti rut), gim bch cu

- Tiu ha: nn, cn au bng cp. - Thn kinh-tm thn: lin quan n nng thuc trong mu: 20 g/ml c tc dng iu tr. = 30 g/ml lm rung git nhn cu. = 40 g/ml gy mt phi hp ng tc. > 40 g/ml gy ri lon tm thn. - Xng: ci xng hoc mm xng, c th l do ri lon chuyn ha vitamin D, nht l khi phi hp vi phenobarbital. 2.1.4. Tng tc thuc Cloramphenicol, dicumaro l, isoniazid, cimetidin c th lm tng nng ca phenytoin trong huyt tng do lm gim chuyn ha. Tri li, carbamazepin lm tng chuyn ha nn lm gim nng phenytoin trong huyt tng. Salicylat, tolbutamid, sulfisoxazol tranh chp vi phenytoi n v tr gn vo protein huyt tng. 2.1.5. p dng iu tr Phenytoin (Dihydan, Dilantin): vin nn 30 -100mg; ng tim 50mg/ml. Liu u 3-5mg/kg (300mg/ngy). Theo di nng thuc trong mu, khi t c nng c tc dng, ngh 1 tun. Liu cao 30 0mg/ngy th khong cch gia cc t iu tr l 2 tun. C th dng liu 1 ln/ngy. Phenytoin tim tnh mch khng vt qu 50mg/pht, pha long trong NaCl 0,9% v thuc c pH base, kch thch. Khng tim bp, gy tn thng t chc. 2.2. Phenobarbital (Gardenal, Luminal) Phenobarbital thuc nhm barbiturat (xem bi thuc ng), l thuc u tin dng iu tr ng kinh (1912). Khc vi barbiturat khc, phenobarbital c tc dng chng cc cn co git ca ng kinh ngay c vi nhng liu cha gy an thn hoc ng. Thuc gii hn c s lan truyn ca cn co git v nng c ngng kch thch gy co git. Phenobarbital v c pentobarbital tc dng trn receptor GABA -A lm tng qu trnh c ch. Ngoi ra ?cn chn knh Ca ++ trc xinap nn lm gim gii ph ng cc cht dn truyn thn kinh, c bit l glutamat nn lm gim mnh cc qu trnh kch thch trn thn kinh trung ng. V t c v gi r nn tng i c dng rng ri, nhng c nhc im l gy an thn, ng g v c xu hng lm ri lon hnh vi ca tr em nn cn thn trng.

Liu lng: ung 0,1 - 0,3 g/ngy (1 - 5 mg/kg). Khng ngng thuc t ngt trnh trng thi ng kinh lin tc. 2.3. Dn xut Iminostilben: Carbamazepin 2.3.1. Tc dng v c ch Tuy trn ng vt thc nghim v ngi, carbamazepin c nhiu im ging nh phenytoin, nhng: - Tc dng chng cn co git gy ra bi pentylentretazol li mnh hn. - C tc dng iu tr bnh nhn b hng trm cm, k c nhng trng hp lithium khng cn tc dng. - C tc dng chng bi ni u do lm gim nng ADH huyt tng. Cc c ch ny u cha r. Cc dn xut iminostilben cng c ch knh Na + nh phenytoin. 2.3.2. Dc ng hc Carbamazepin c hp thu chm qua ng tiu ha, nng ti a trong mu t c sau 4 -8 gi v gi c ti 24 gi. Gn vo protein huyt tng 75% v phn phi vo mi m. Nng trong dch no tu tng ng vi dng t do trong huyt tng. B chuyn ha gan, cho 10 - 11 epoxid vn cn hot tnh. Di 3% thi qua thn di dng khng i. Thi gian bn thi t 10 n 20 gi. Dng cng vi phenobarbital hoc phenytoin, thi gian bn thi gim cn 9 -10 gi. 2.3.3. Tc dng khng mong mun - Thng gp: ng g, chng mt, nhn la, mt ng tc, bun nn, nn. - Ngoi ra, c th gp: ri lon to mu, t n thng nng ngoi da, vim gan mt, suy thn cp, suy tim. V vy, trong qu trnh iu tr cn kim tra cc chc phn trn. - Phn ng d ng. 2.3.4. p dng lm sng - Ch nh: . Cn ng kinh th tm thn vn ng. . Cn co git cng hoc git run g cc b hoc ton thn. . Tc dng gim au c hiu trong vim dy thn kinh tam thoa. - Ch phm: Carbamazepin (Tegretol) vin nn 100 -200mg. Liu u 200mg x2 ln/ngy. Tng dn liu ti 600 -1200mg. Tr em 20 30mg/kg. Nn chia liu hng ngy lm 3 4 ln gi c nng hng nh trong mu. 2.4. Acid valproic

2.4.1. Tc dng dc l{ v c ch - Tc dng trn mi loi ng kinh. - Rt t tc dng an thn v tc dng ph. - Cc gi thit hin nay u cho rng valproat c ch knh Na + nhy cm vi i n th (MacDonald, 1988) v lm tng tch lu GABA (L scher, 1985). Nhng tc dng ging vi tc dng ca phenytoin v carbamazepin. Ngoi ra cn lm gim dng Ca ++ qua knh. 2.4.2. Dc ng hc Hp thu nhanh v hon ton qua tiu ha. Nng ti a tr ong huyt tng t c sau 1 -4 gi. Gn vo protein huyt tng 90%. Nng trong dch no tu tng ng trong huyt tng. Hu nh hon ton b chuyn ha gan, trong c mt cht chuyn ha 2 -propyl-2-pentanoic acid vn cn hot tnh nh cht m. Thi gian bn thi l 15 gi. 2.4.3. Tc dng khng mong mun - Khong 16% c cc triu chng chn n, bun nn, nn, au vng thng v. - Khi dng liu cao 7 -30 mg/kg c th gp vi g. T m gan cp, vim tu, an thn, run, hi, gim prothrombin. 2.4.4. p dng lm sng - Ch nh: ng kinh cc loi, c bit l th khng c cn co git. - Ch phm: Acid valproic (Depakin): vin bc ng 250mg; sir 5ml c 250mg hot cht. Liu u 15mg/kg, tng dn hng tun 5 - 10mg/kg cho ti 60mg/kg. Nng iu tr trong mu t 30 n 100g/ml. 3. NHNG VN TRONG S DNG THUC 3.1. Nguyn tc dng thuc - Ch dng thuc khi c chn on lm sng chc chn. - Lc u ch dng mt thuc. - Cho liu t thp tng dn, thch ng vi cc cn. - Khng ngng thuc t ngt. - Phi m bo cho bnh nhn ung u hng ngy, khng qun. - Cm ung ru trong qu trnh dng thuc. - Ch i thi hn nh gi hiu qu ca iu tr: . Vi ngy vi ethosuximid, benzodiazepin

. Hai ba tun vi phenobarbital, phenytoin . Vi tun vi valproic acid. - Hiu r cc tc dng ph, tc dng khng mong mun ca tng thuc theo di kp thi. - Nu c th, kim tra nng ca thuc trong mu khi cn. 3.2. iu tr ng kinh v thai nghn T l thai nhi c d dng hoc t vong ngi m c ng kinh c iu tr cao hn ngi bnh thng 2 - 3 ln. Cc cn ng kinh cng thng tng ln khi c thai, c th do nng thuc trong huyt tng gim. Khi c thai vn khng c ngng thuc, tuy nhin, tuz theo tng trng hp, c th gim liu, nht l trong 3 thng u. Tr mi nhng ngi m iu tr bng phenobarbital, primidon hoc phenytoin c th gp tai bin chy mu do thiu vitamin K, cn b sung d phng trc bng vitamin K. BI 18. THUC CHNG LAO - THUC IU TR PHONG 1. THUC CHNG LAO Lao l bnh nhim khun ph bin do trc khun lao gy nn v c th cha khi hon ton. Trc khun lao gy bnh lao phi v cc c quan khc l loi vi khun khng cn, khng acid, sng trong mi trng a kh, pht trin chm (chu kz ph n chia khong 20 gi). Mng t bo ca trc khun lao c cu to bi 3 lp: phospholipid trong cng, polysACharid lin kt vi peptidoglycan. Cc peptidoglycan c gn vi arabingolactose v acid mycolic lp gia. Acid mycolic lin kt vi cc lipid p hc tp nh myosid, peptidoglycolipid, phenolglycolipid ngoi cng. dy, mng v s cha nhiu hay t lipid ca mng t bo nh hng r rt n s khuych tn ca cc thuc chng lao vo trong t bo v sc khng ca vi khun vi cc tc nhn ha hc v l hc t bn ngoi. Trong c th, vi khun lao c th tn ti di 4 dng qun th nhng vng tn thng khc nhau. Cc qun th ny chu s tc ng ca thuc chng lao mc rt khc nhau. - Qun th trong hang lao cn gi l qun th A. Trong hang lao c pH trung tnh, lng oxy di do, vi khun nm ngoi t bo v pht trin nhanh, mnh nn s lng vi khun nhiu, d xut hin t bin khng thuc. Qun th ny

b tiu dit nhanh bi rifampicin, INH v streptomycin. - Qun th trong i th c bo cn gi l qun th B. Trong i thc bo pH acid, s lng vi khun t v pht trin chm nhng c kh nng sng st cao nn tn t?i dai dng gy nguy c ti pht bnh lao. Pyrazinamid c tc dng tt nht vi qun th ny. Rifampicin c tc dng, I NH rt t tc dng cn streptomycin khng c tc dng vi loi qun th ny. - Qun th nm trong b u gi l qun th C. b u l vng rt t oxy, c pH trung tnh, vi khun chuyn ha tng t ngn nn pht trin rt chm, ch c rifampicin c t c dng vi qun th vi khun ny. - Qun th nm trong cc tn thng x, vi ha gi l qun th D. S lng vi khun lao khng ln khng pht trin c gi l trc khun ng. Cc thuc chng lao khng c tc dng trn qun th vi khun ny. Mc tiu quan trng trong iu tr lao l dng cc thuc tiu dit tt c cc qun th, c bit l qun th B, C. Ngoi ra, tuz theo th bnh c th dng mt s phng php iu tr thch hp nh phu thut, ct lc, b bt hoc chc ht v.v Hin nay thuc chng lao c chia thnh 2 nhm: Nhm I: L cc thuc chng lao chnh thng dng, c ch s iu tr cao, t tc dng khng mong mun : isoniazid (INH, Rimifon), rifampicin, ethambutol, streptomycin v pyrazinamid. Nhm II: L nhng thuc t dng hn, d ng thay th khi vi khun lao khng thuc, c phm vi iu tr hp, c nhiu tc dng khng mong mun: ethionamid, para aminosalicylic (PAS), cycloserin, amikacin, kanamycin, capreomycin, thiacetazon, fluorquinolon v azithromycin, clarythromycin. 1.1. Cc thuc chng lao thng dng 1.1.1. Isoniazid (Rimifon, INH, H) L dn xut ca acid isonicotinic, va c tc dng km khun, va c tc dng dit khun. Nng c ch ti thiu i vi trc khun lao 0,025 - 0,05 mcg/ml. Khi nng cao trn 500mcg/ml, thuc c tc dng c ch s pht trin ca cc vi khun khc. Thuc c tc dng trn vi khun ang nhn ln c trong v ngoi t bo, k c trong mi trng nui cy. 1.1.1.1. C ch tc dng: Mc d isoniazid c s dng iu tr lao vi thp k v n nay vn c coi l thuc s mt trong iu tr tt c cc th lao nhng c ch tc

dng ca thuc vn cn cha c gii thch y . Theo Takayama v cng s (1975), acid mycolic l mt thnh phn quan trng trong cu trc mng ca trc khun lao. Giai on u ca qu trnh tng hp mycolic l s ko di mch ca acid nh desaturase. Vi nng rt thp ca INH, enzym ny b c ch lm ngn cn s ko di mch ca acid mycolic dn dn gim s lng lipid ca mng vi khun, vi khun khng pht trin c. Ngoi ra, mt s tc gi cn cho rng, INH to chelat vi Cu 2+ v c ch cnh tranh vi nicotinamid v pyridoxin lm ri lon chuyn ha ca trc khun lao. 1.1.1.2. Dc ng hc Thuc c hp thu nhanh qua ng tiu ha. Sau khi ung 1 -2 gi, nng thuc trong mu t ti 3-5mcg/ml. Thc n v cc thuc cha nhm lm gim hp thu thuc. Isoniazid khuch tn nhanh vo cc t bo v cc dch mng phi, dch c trng v nc no tu, cht b u, nc bt, da, c. Nng thuc trong dch no tu t ng ng vi nng trong mu. Thuc c chuyn ha gan nh phn ng acetyl ha, thu phn v lin hp vi glycin. S acetyl ha ca isoniazid thng qua acetyltransferase c tnh di tru?yn. ngi c hot tnh enzym mnh, thi gian bn thi ca thuc khong 1 gi, nhng ngi c hot tnh enzym yu thi gian bn thi ca thuc khong 3 gi. Thuc c thi tr ch yu qua thn. Sau dng thuc 24 gi, thuc thi tr khong 75 - 95% di dng chuyn ha. Gn y, mt s tc gi cho rng dng acet yl ha ca INH c kh acetyl trong c th to thnh dng cn hot tnh. 1.1.1.3. Tc dng khng mong mun - D ng thuc, bun nn, nn, chng mt, to bn, kh ming, thoi ho bch cu ht, thiu mu. - Vim dy thn kinh ngoi vi chim 10 - 20%, c bit hay gp bnh nhn dng liu cao, ko di, nghin ru, suy dinh dng v tng glucose mu. Vitamin B6 c th lm hn ch tc dng khng mong mun ny ca isoniazid. - Vim dy thn kinh th gic. - Vng da, vim gan v hoi t t bo gan thng hay g p ngi trn 50 tui v nhng ngi c hot tnh acetyltransferase yu. C ch gy tn thng gan ca isoniazid n nay vn cha c gii thch y . C gi thuyt cho rng, acetylhydrazin cht chuyn ha ca isoniazid b chuyn ha qua cytocrom - P450 sinh ra gc t do gy tn thng t bo gan.

Mt s thuc gy cm ng cytocrom - P450 nh phenobarbital, rifamycin gy tng tn thng gan ca INH. - Isoniazid c ch s hydroxyl ha ca phenytoin, c th gy ng c phenytoin khi iu tr phi hp thuc. 1.1.1.4. p dng iu tr - Rimifon: vin nn 50 - 100 - 300 mg; ng tim 2ml cha 50mg hoc 100mg/ml; Siro 10 mg/ml. - Phi hp vi cc thuc chng lao khc iu tr tt c cc th lao. Ngi ln dng 5mg/kg th trng, tr em 10 -20mg/kg th trng, t i a 300mg/24 gi. - Thuc c th dng d phng cho nhng ngi c test tuberculin dng tnh hoc bnh nhn sau iu tr tn cng bng cc thuc chng lao. Ngi ln dng 300mg/ 24 gi, tr em 10mg/kg th trng, ti a 300mg/24 gi ko di 3 - 6 thng. Khi iu tr, cn dng km vitamin B 6 10- 50mg /24 gi gim bt tc dng khng mong mun ca INH. 1.1.2. Rifampicin (RMP,R) Rifamycin l t ch c mt h khng sinh c cu trc ging nhau c chit xut t Streptomyces mediterranei. Rifampicin l khn g sinh bn tng hp t rifamycin B c tc dng dit khun c trong v ngoi t bo, chuyn ha v thi tr chm so vi cc cht cng nhm. 1.1.2.1. Tc dng Thuc khng ch c tc dng dit trc khun lao, phong, m cn dit c cc vi khun gram m, E-coli, trc khun m xanh , Haemophilus influenzae , Nesseria meningitis . Rifampicin dit vi khun c trong v ngoi t bo. Trong mi trng acid, tc dng ca thuc mnh gp 5 ln. 1.1.2.2. C ch tc dng Rifampicin gn vo chui ca ARN - polymerase ph th uc ADN ca vi khun lm ngn cn s to thnh chui ban u trong qu trnh tng hp ca ARN. Thuc khng c ch ARN - polymerase ca ngi v ng vt liu iu tr. Khi dng liu cao gp nhiu ln liu iu tr, thuc c th gy c ch ARN polymerase ty th t bo ng vt. 1.1.2.3. Dc ng hc Thuc c hp thu tt qua ng tiu ha. Sau khi ung 2 - 4 gi, t c nng ti a trong mu. Acid amino salicylic lm chm hp thu thuc.

Trong mu, thuc gn vo protein huyt t?ng khong 75 - 80%. ng thi tr ch yu ca thuc l qua gan v thn. Ngoi ra, thuc cn thi tr qua nc bt, m, nc mt, lm cho cc dch ny c mu da cam. Thi gian bn thi ca thuc khong 1,5 - 5 gi. Khi chc nng gan gim, thi gian bn thi ca th uc k o di. Ngc li, do t gy cm ng h enzym oxy ha thuc gan, sau iu tr khong 14 ngy thi gian bn thi ca thuc b rt ngn li. Thuc c chu kz gan - rut. Rifampicin lm tng chuyn ha mt s thuc thng qua tc dng gy cm ng cytoc rom - P450 nh: thuc trnh thai, phong ta - adrenergic, chn knh calci, diazepam, quinidin, digitoxin, prednisolon, sulfonylurea, mt s thuc chng ng mu 1.1.2.4. Tc dng khng mong mun: Thuc t c tc dng khng mong mun, song c th gp mt s ngi: - Pht ban 0,8%; bun nn, nn (1,5%); St (0,5%); ri lon s to mu. - Vng da, vim gan rt hay gp ngi c tin s bnh gan, nghin ru v cao tui. Tc khng mong mun ny tng ln khi dng phi hp vi isoniazid. 1.1.2.5. p dng iu tr - Ch phm Rifampicin (Rifampin, Rimactan, Rifadin) vin nang hoc vin nn 150 - 300 mg, siro 100mg/Ml, dung dch tim truyn 300 - 600 mg/l. - Phi hp vi cc thuc chng lao khc iu tr cc th lao, khng dng n c rifampicin trong iu tr lao. Ngoi ra thuc cn c ch nh trong mt s bnh nhim khun do cc vi khun cn nhy cm gy nn. - Liu dng cho ngi ln 1 ln trong 1 ngy 10 - 20mg/kg th trng, ti a 600mg/24 gi. -Khng dng thuc ngi gim chc nng gan v khi iu tr cn theo di chc nng gan thng xuyn. 1.1.3. Ethambutol (EMB, E) 1.1.3.1. Tc dng L thuc tng hp, tan mnh trong nc v vng bn nhit cao, c tc dng km khun lao mnh nht khi ang kz nhn ln, khng c tc dng trn cc vi khun khc. 1.1.3.2. C ch tc dng: Theo Takayama v cng s (1979), ethambutol c tc dng km khun l do

c ch s nhp acid mycolic vo thnh t bo trc khun lao, lm ri lon s to mng trc khun lao. Ngoi ra, mt s tc gi cn cho rng ethamb utol gy ri lon s tng hp acid nhn thng qua c ch cnh tranh vi cc polyamin v to chelat vi Zn 2+ v Cu2+. 1.1.3.3. Dc ng hc: Thuc c hp thu tt qua ng tiu ha, sau khi ung 2 - 4 gi, t c nng ti a trong mu. Trong c th, thuc tp trung cao trong cc m cha nhiu Zn 2+, Cu2+, c bit l thn, phi, nc bt, thn kinh th gic, gan, ty v.v Sau 24 gi, mt na lng thuc ung vo c thi ra ngoi qua thn, 15% di dng chuyn ha. 1.1.3.4. Tc dng khng mong mu n: Khi iu tr lao bng ethambutol c th gp mt s tc dng khng mong mun nh: ri lon tiu ha, au u, au bng, au khp, pht ban, st, vim dy thn kinh ngoi vi, nhng nng nht l vim dy thn kinh th gic gy ri lon nhn bit mu sc. Ct ngha cho tn thng th gic, c tc gi cho rng dy thn kinh th gic cha nhiu Zn 2+, ethambutol to chelat vi Z 2+gy vim. 1.1.3.5. p dng iu tr: Ethambutol vin n n 100 n 400mg c phi hp vi cc thuc chng lao iu tr cc th lao, ngi ln ung liu khi ?u 25mg/kg/ngy trong 2 thng sau gim liu xung 15mg/kg/ngy. Tr em ung 15mg/kg/ngy. Khng dng cho ngi c thai, cho con b, tr em di 5 tui v ngi c vim thn kinh th gic v gim th lc. 1.1.4. Streptomycin (SM , S). L khng sinh thuc nhm aminoglycosid c tc dng dit khun lao mnh c bit vi khun trong hang lao v mt s vi khun Gram (+) v Gram ( -). Nng 10mcg/ml c tc dng dit trc khun lao. c phi hp vi cc thuc chng lao khc iu tr lao. Tim bp hng ngy hoc cch ngy liu 15mg/kg th trng, ti a khng vt qu 1g/ngy. i vi ngi cao tui, liu dng 500 - 750mg/ngy. Dc ng hc, c ch tc dng, tc dng khng mong mun v chng ch nh ca thuc xin c bi khng s inh nhm aminoglycosid. 1.1.5. Pyrazinamid(Z, PZA) 1.1.5.1. Tc dng: L thuc c ngun gc tng hp, t tan trong nc, tc dng mnh trong mi trng acid c tc dng km khun lao c cu trc tng t nh nicotinamid. Thuc dit trc khun lao trong i thc bo c pH acid v t bo n nhn

vi nng 12,5mcg/ml, c bit khi vi khun ang nhn ln. C ch: cha bit d cu trc gn ging acid nicotinic v INH. 1.1.5.2. Dc ng hc: Thuc hp thu nhanh qua ng tiu ho. Ung sau hai gi t c n ng ti a trong mu v khuch tn nhanh vo m dch c th. Thuc i qua hng ro mu no tt nn c hiu qu iu tr cao trong lao mng no. Thi gian bn thi ca thuc khong 10 n 16 gi. 1.1.5.3. Tc dng khng mong mun: Thuc c th gy mt s tc dng khng mong mun nh: au bng, chn n, bun nn, nn, st, nhc u, au khp. c bit lu {, thuc c th gy tn thng t bo gan, vng da 15% s bnh nhn. Do vy, khi iu tr cn kim tra chc nng gan trc v trong iu tr. Nu c d u hiu gim chc nng gan phi ngng thuc. Do cnh tranh vi acid uric h vn chuyn tch cc ti ng thn, pyrazinamid c th gy tng acid uric mu. Pyrazinamid lm gim tc dng h acid uric ca probenecid, aspirin, vitamin C v lm tng tc dng h glucose mu ca cc thuc nhm sulfonylure. 1.1.5.4. p dng iu tr: Vin nn 500mg. Pyrazinamid thng phi hp vi cc thuc chng lao khc iu tr lao trong 6 thng u, sau thay bng thuc khc. Liu trung bnh ngi ln 1,5 -2,0 g/ngy v tr em 35mg/kg/ngy. 1.2. Cc thuc chng lao khc 1.2.1. Ethionamid - L thuc va km khun va dit khun (do c ch tng hp acid mycolic). Ung hp thu t t qua ng tiu ha, sau 3 gi t nng ti a trong mu v thi tr ch yu qua thn di dng chuyn ha. - Thuc c ch nh khi vi khun lao khng vi cc thuc nhm I. Ngoi ra, ethionamid cn c dng phi hp vi dapson, rifampin iu tr phong vi liu 10mg/kg th trng. - Mt s tc dng khng mong mun c th gp nh: chn n, bu n nn, nn, i lng, ri lon thn kinh trung ng (au u, co git, mt ng), vim dy thn kinh ngoi vi. Ethionamid c th gy ri lon chc nng gan, cn phi theo di chc nng gan trc v trong khi iu tr. - Thuc c dng vi liu tng dn. Kh i u 500mg cch 5 ngy tng 125mg n khi t 15 - 20mg/kg th da trng v khng vt qu

1gam/24gi. 1.2.2. Acid paraaminosalicylic (PAS) L thuc km khun lao c c ch tc dng ging sulfonamid, nhng khng c tc dng trn cc vi khun khc. Liu dng: 200- 300mg/kg/ngy, ti a 14 16g/ngy. PAS c th gy a lng, nn, au bng. hn ch tc dng khng mong mun, cn ung vo lc no. 1.2.3. Mt s khng sinh khc c tc dng chng lao - Kanamycin v amikacin c nng v c ch ti thiu vi trc k hun lao 10 g/ ml. Liu iu tr lao 1g/ 24 gi. - Capreomycin l 1 peptid vng c tc dng chng lao vi liu 15 - 30 mg/ kg/ 24 gi. - Ofloxacin v ciprofloxacin l 2 khng sinh nhm fluorquinolon c nng trong t chc phi cao hn trong huyt tng c nng c ch ti thiu trn trc khun lao rt thp t 0,25 - 3 g/ ml. Trong iu tr lao ciprofloxacin ung 1,5g chia 2 ln/ngy; ofloxacin ung 600 800 mg/ ngy. - Azithromycin v clarythromycin l 2 macrolid mi cng c tc dng trn trc khun la o c ch nh khi trc khun lao khng cc thuc chng lao chnh. - Cycloserin c ch nh iu tr lao vi liu 15 - 200 mg/ kg/ ngy. Chi tit xin xem bi Thuc khng sinh. 1.2.4. Thiacetazon (Amithiozon) L thuc km khun. C hot tnh chng lao v i nng c ch ti thiu (MIC) l 1 g/ml. Trong lm sng c th phi hp vi INH iu tr lao. Liu dng hng ngy 150mg. 1.2.5. Clofazimin Thuc c dng cho nhng bnh nhn c trc khun lao a khng thuc vi liu dng 200mg/24 gi. (Chi tit xin c bi thuc iu tr phong). 1.3. S khng thuc ca vi khun lao T l vi khun lao khng thuc ngy cng tng, nguyn nhn ch yu l do dng thuc khng ng phc phi hp, liu lng v thi gian dng thuc hoc cht lng thuc km. S khng thuc c th xp thnh 3 loi: - Khng thuc tin pht: l s khng thuc xy ra bnh nhn cha c dng thuc chng lao ln no. Nguyn nhn l do vi khun lao khng thuc lan truyn t bnh nhn khc sang. - Khng thuc mc phi hay cn gi l khng t huc th pht l s khng

thuc sau khi dng cc thuc chng lao t nht mt thng. Nguyn nhn do dng thuc khng ng liu lng v phi hp thuc khng ng gy nn s chn lc vi khun khng thuc. - a khng thuc l hin tng vi khun lao khng li t nht 2 loi thuc chng lao trong c khng rifampicin v INH v khng cng vi cc thuc chng lao khc. i ph vi s khng thuc ca vi khun lao, ngn nga s chn lc to ra chng khng thuc v s lan truyn cc chng khng thuc trong cng ng, cn phi p dng ng nguyn tc iu tr lao. 1.4. Nguyn tc dng thuc chng lao v mt s phc iu tr lao 1.4.1. Nguyn tc dng thuc chng lao - gim t l khng thuc v rt ngn thi gian iu tr, cc thuc chng lao lun dng cng mt lc (vo thi gian nht nh trong ngy) t nht 3 loi thuc trong 24 gi v c th phi hp 4-5 thuc trong giai on tn cng 2 - 3 thng u, sau chuyn sang iu tr duy tr. - Cn phi cy vi khun v lm khng sinh chn khng sinh thch hp. - Phi hp thuc theo tnh nng tc dng nhm nng cao hiu qu iu tr v gim tc dng khng mong mun. Thng phi hp thuc va dit khun trong t bo v ngoi t bo cng vi thuc dit khun th ang pht trin v th bnh. - iu tr lin tc, khng ngt qung, t nht 6 thng v c th ko di 9 - 12 thng. - Tr liu ngn ngy c kim sot trc tip (DOTS =directly observed treatment short course). - Liu php d phng bng INH trong 6 thng cho nhng ngi tip xc vi bnh nhn c k h nng b lao, nhng cha c du hiu nhim khun v ngi c test tuberculin rng trn 10mm v ngi trc kia b lao nhng hin nay th khng hot ng v hin ang dng thuc c ch min dch. - Thng xuyn theo di tc dng khng mong mun ca thuc. - Trong trng hp trc khun lao khng vi cc thuc chng lao chnh thng dng hoc c tc dng khng mong mun m bnh nhn khng th chp nhn c th la chn cc thuc chng lao khc. 1.4.2. Mt s phc iu tr lao hin nay Vit Nam

Da trn phc iu tr lao ca t chc Y t Th gii, chng trnh chng lao Quc gia xut mt s phc p dng cho iu tr lao hin nay Vit nam. 1.4.2.1. Ngi bnh cha cha lao bao gi: 2SRHZ / 6HE - iu tr tn cng 2 thng lin tc dng 4 l oi thuc S (SM); H (INH); R (RMP); Z (PZA) hng ngy. - iu tr duy tr hng ngy lin tc trong 6 thng vi 2 thuc l H v E (EMB). 1.4.2.2. Ngi bnh c lao ti pht hoc tht bi iu tr: 2SHRZE/1HRZE/5H 3 R3 E3 * - iu tr tn cng hng ngy lin tc trong hai thng vi 5 loi thuc SHRZE, mt thng tip theo dng hng ngy 4 loi thuc HRZE. - Sau iu tr duy tr 3 loi thuc H, R, E mt tun dng ba ln cch qung trong 5 thng lin tc. * H: Isoniazid Z: pyrazinamid S: Streptomycin R: Rifampicin E: Ethambutol S trc ch ci ch thi gian iu tr tnh bng thng; ch s di sau ch ci ch s ngy dng thuc trong 1 tun, nu khng c cc ch s ny th dng thuc hng ngy. 2.THUC IU TR PHONG Bnh phong l bnh nhim khun Myc obacterium leprae. Nu c iu tr sm v ng, bnh phong c th khi, khng li di chng. Hin nay, ba thuc ch yu iu tr phong l: dapson, rifampicin v clofazimin. 2.1. Dapson (DDS) L dn xut 4-4 diamino diphenyl sulfon cu trc gn ging pa ra-aminobenzoic acid c tc dng km trc khun phong. Mc d, c tng hp t nhng nm 1940, nhng n nay DDS vn c coi l thuc quan trng nht trong iu tr phong. 2.1.1. Dc ng hc Thuc c hp thu gn hon ton qua ng tiu ha. Ung 1 00mg, sau 24 gi t c nng trong mu gp 50 - 100 ln nng c ch ti thiu. Trong mu, thuc gn vo protein huyt tng khong 50% v khuch tn nhanh vo cc t chc: da, c, gan, thn v dch no tu. Dapson c chuyn ha gan nh phn ng acetyl ha to thnh monoacetyl DDS khng c tc dng km khun. S chuyn ha ca DDS

mang tnh di truyn. Thn v mt l ng thi tr ch yu ca thuc. Do c chu kz gan - rut, nn thuc tn ti rt lu trong c th, thi gian bn thi ca thuc khong 28 gi. 2.1.2. Tc dng v c ch tc dng Dapson ch c tc? dng km khun phong, khng dit khun. C ch tc dng ging sulfonamid. C ch chi tit xin c bi Thuc khng sinh, phn sulfamid. 2.1.3. Tc dng khng mong mun Dng Dapson c th g p mt s tc dng khng mong mun sau: - Bun nn, nn, au u, pht ban da. - Ri lon tm thn, vim dy thn kinh ngoi vi. - Thiu mu, tan mu, c bit hay gp ngi c thiu ht G 6PD. - Methemoglobin - Hi chng sulfon hay Jarish - Herxheimer. Hi chng ny thng xut hin sau khi dng thuc 5-6 tun. Biu hin: st, vng da, hoi t gan, vim da, met Hb v thiu mu.y l hi chng rt nng, cn phi ngng thuc ngay v hi sc tch cc trnh t vong. 2.1.4. p dng iu tr Do t l trc khun phong khng thuc ngy cng cao, nn t nm 1982 Vit Nam khng dng ring dapson iu tr m thng phi hp vi clofazimin hoc rifampin. Thuc dng vin nn 25mg, 100mg ung khi u liu thp 50mg/24 gi. Nu bnh tin trin khng tt, tng liu ln 100 mg/24 gi v duy tr t nht trong 2 nm. Trong iu tr cn theo di cng thc mu thng xuyn. nhng bnh nhn c d ng vi thuc, suy gim chc nng gan, thiu ht G6PD hoc methemoglobinreductase, chng ch nh dng thuc. 2.2. Rifampicin L khng sinh khng ch dit khun lao v cc vi khun Gram (+), Gram ( -) khc, m cn c kh nng dit trc khun phong mnh. So vi dapson, thuc khuch tn vo m thn kinh km nn khng lm gim c triu chng tn thng thn kinh do trc kh un phong gy nn. Thuc c phi hp vi cc thuc iu tr phong khc vi liu 600mg/24 gi. Chi tit v rifampicin xin c bi Thuc khng sinh v bi Thuc chng lao. 2.3. Clofazimin (Lampren) Thuc c tc dng km khun phong v mt s vi khun g y vim lot da (Mycobacterium ulcerans) v gy nn vim ph qun mn tnh (Mycobacteri-

um avium). Ngoi ra, clofazimin cn c tc dng chng vim v ngn chn s pht trin ca cc nt sn trong bnh phong. Theo Morrison v Marley (1976), clofazimin c tc dng km khun l do thuc gn vo AND ca trc khun lm c ch s nhn i ca ADN. Ung hp thu nhanh v tch ly lu trong cc m. Thn l ng thi tr ch yu ca thuc. Ngoi ra, thuc cn c thi qua m hi. Trong qu trnh dng thuc, c th g p mt s tc dng khng mong mun nh: mt mu da, vim rut, tng bch cu a acid. Vin 100mg - phi hp vi dapson v rifampin iu tr mt s th phong vi liu 50mg/24 gi hoc 100-300mg/24 gi/tun. Khi iu tr, cn theo di chc nng gan v thn. 2.4. Cc thuc iu tr phong khc 2.4.1. Sulfoxon Thuc c cu trc tng t nh dapson, nhng hp thu khng hon ton qua ng tiu ha v thi tr ch yu qua mt v qua phn. C ch tc dng v tc dng khng mong mun ca thuc ging dapson. Thuc c th dng thay dapson iu tr phong vi liu 330mg/24 gi. 2.4.2. Thalidomid L thuc an thn, nhng c tc dng iu tr phong, c bit th phong c. Liu dng 100 - 300mg/24 gi. Do gy qui thai, c bit giai on 24 - 36 tun u ca kz thai nghn, nn thuc t c dng. 2.4.3. Ethionamid C tc dng v chn a km khun va dit khun lao v phong c th thay th clofazimin trong nhng trng hp khng clofazimin. Liu dng hng ngy 250 375mg. Chi tit xin c thm bi Thuc chng lao. 2.5. Nguyn tc v mt s phc iu tr phong hin nay Nhm tng hiu qu iu tr, rt ngn thi gian dng thuc v hn ch s khng thuc ca trc khun phong t 1982, T chc Y t Th gii khuyn co mt s nguyn tc iu tr phong nh sau: - a ha tr liu, kh ng dng mt loi thuc iu tr phong v thng dng 3 thuc dapson, rifampicin v clofazimin. - Phi hp ha tr liu vi vt l liu php v th dc liu php trnh tn ph. - Ung thuc ng liu lng, ng phc , thi gian v nh kz theo di

tc dng trn lm sng, xt nghim vi khun v tc dng khng mong mun. - Thi gian iu tr ko di tuz thuc vo mc nhim trc khun. 2.5.1. Phc iu tr nhm c nhiu trc khun

BI 19. THUC DIU TR NG C Ng c thuc thng l do nhm ln (ca thy thuc, ca ngi bnh) hoc do c (t t, u c). Nhng trng hp nhm ln thng khng nng lm, v c chn on ng v sm nn x l kp thi. Cn nhn g trng hp c th thng rt nng v nn nhn che giu tn thuc dng, liu thuc nhim c li qu ln v lc a n iu tr thng mun, cho nn chn on kh khn, x tr nhiu khi phi m mm. Ch c rt t thuc c triu chng ng c c hiu v cch iu tr c hiu. V vy, cc x tr ng c thuc ni chung l loi tr nhanh chng cht c ra khi c th, trung ha phn thuc c hp thu v iu tr cc triu chng nhm hi sc cho nn nhn. 1. LOI TR CHT C RA KHI C TH 1.1. Qua ng tiu ha - Gy nn: Apomorphin hin khng dng v nhiu tc dng ph - Ipeca: Dng di dng siro t 15 - 20 ml, pha long trong 250 ml nc. Nu sau 15 pht khng nn, c th dng li. Thng dng cho tr em trn 1 tui. Trong trng hp khng c thuc, nn nhn cn tnh, c th ngoy hng hoc dng mn tht cho ung. - Ra d dy bng nc m hoc thuc tm (KMnO 4) dung dch mt phn nghn (1: 1000 )cho n khi nc ra tr thnh trong. Vi cc thuc hp thu nhanh nh aspirin, cloroquin, meprobamat, bar bituric, colchicin, thuc chng rung tim, ra d dy v gy nn ch c tc dng trong 6 gi u, khi cht trng c cn d dy. i vi loi benzodiazepin, thuc chng rung tim, hoc nhim c hn hp, hoc nhng cht khng r, c th ra trong vng 24 g i. Dng thn trng khi nn nhn hn m v d a nhm ng cao su vo kh qun, hoc cht nn quay ngc ng v ph. Tuyt i trnh ra d dy cho nhng ngi b trng

c cc cht n mn nh acid mnh, base, v ng cao su c th lm rch thc qun. Sau ra d dy, cho than hot, v c nhiu u im: Hon ton khng c, ngn cn c chu kz gan- rut i vi cc thuc thi theo ng mt, do tng thi theo phn. Liu 50- 100g. Mt trm gam than hot c th hp ph c 4 g thuc chng trm cm loi tricyclic. Thng cho 30- 40 g, cch 4 gi 1 ln. 1.2. Qua ng h hp Ng c cc thuc thi qua ng h hp nh cc thuc m bay hi, ru, kh t, xng, aceton, cn lm tng h hp bng cc thuc kch thch nh cardiazol (tim tnh mch ng 5 ml, dung dch 10%), lobelin (tim tnh mch ng 1 ml, dung dch 1%), hoc h hp nhn to. 1.3. Qua ng tit niu 1.3.1. Thng dng cc thuc li niu thm thu Nh manitol (10%; 25%), glucose u trng (10%; 30%), dung dch Ringer. Phi chc chn rng chc phn thn cn tt. Khng c dng khi c suy thn, suy tim, ph phi cp, huyt p cao, try tim mch nng. Khi dng cc thuc li niu ny th cc khng sinh cng b tng thi, cho nn cn phi nng liu cao hn. 1.3.2. Kim ho nc tiu Trong trng hp ng c cc acid n h (barbituric, salicylat, dn xut pyrazolol). Thngdng hai th: - Natri bicarbonat (NaHCO 3): Dung dch 14%0, truyn nh git tnh mch 2 - 3 lt mt ngy. Nhng c nhc im l a thm Na + vo c th, v vy khi chc phn thn khng c tt, d gy t ai bin ph no. - T.H.A.M. (trihydroxymetylaminmetan), truyn tnh mch 300 - 500 ml.

T.H.A.M. (trihydroxymetylaminmetan) THAM c u im l khng mang Na + v d thm vo c trong t bo. 1.3.3. Acid ha nc tiu lm tng thi cc base hu c nh cloroquin, dn xut quinolein, imipramin, mecamylamin, dn xut acridin, nicotin, procain, quinin, phenothiazin. Cc thuc lm acid ha nc tiu thng dng l amoni alorid

ung 3,0 - 6,0g hoc acid phosphoric 15- 100 git mt ngy. Acid ha kh thc hin hn kim ha v c th chu ng tnh trng toan km hn trng thi nhim kim, cho nn cng d gy nguy him. 2. TRUNG HA CHT C Thng dng cc cht tng k ngn cn hp thu cht c, lm mt hot tnh hoc i khng vi tc dng ca cht c. 2.1. Cc cht tng k ha hc ti d dy ngn cn hp th cht c, thng dng ra d dy bng cc dung dch: - Tanin 1- 2%: 100- 200 ml (c th thay th bng nc ch c), c tc dng lm kt ta mt s alcaloid v kim loi nh strychnin, calcaloid ca cy quinquina, apomorphin, cocain, mui km, coban, ng, thu ngn, ch - Sa, lng trng trng (6 qu cho 1 lt nc) ngn cn hp thu cc mui thy ngn, phenol. - Than hot (nh dch 2%), hoc bt go r ang chy, kaolin c tc dng hp ph cc cht c nh HgCl2 (sublim ), strycnin, morphin Than hot cn hp ph mnh c cc cht mang in tch dng cng nh m, cho nn c th dng c trong hu ht cc trng hp nhim c ng tiu ha. 2.2. Cc cht tng k ha hc dng ng ton thn - To methemoglobin (bng natri nitrit 3% - 10ml) khi b ng c acid cyanhydric (thng gp trong ng c sn). Acid cyanhydric rt c i lc vi cytocrom oxydase (c Fe +++) l cc enzym h hp ca m. Khi b ng c, c c enzym ny b c ch. Nhng acid cyanhydric li c i lc mnh hn vi Fe +++ ca methemoglobin, nn khi gy c methemoglobin, acid cyanhydric s hp vi methemoglobin to thnh cyanomethemoglobin v gii phng cytochrom - oxydase. - Dng B.A.L. khi b ng c cc kim loi nng nh Hg, As, Pb. - Dng EDTA hoc mui Na v calci ca acid ny khi b ng c cc ion ha tr 2: Ch, st,? mangan, crm, ng v digitalis ( thi tr calci). 2.3. S dng cc thuc i khng dc l{ c hiu Dng naloxon tim tnh mch khi b ng c morphin v cc opiat khc; dng vitamin K liu cao khi ng c dicumarol; truyn tnh mch dung dch glucose khi b ng c insulin Phng php ny dng iu tr c hiu qu nhanh v tt, nhng ch c rt t thuc c tc dng i khng d c l{ c hiu, cho nn phn ln phi iu tr theo triu chng. 3. IU TR TRIU CHNG V HI SC CHO NGI BNH

3.1. p dng i khng sinh l Dng thuc kch thch thn kinh khi ng c cc thuc c ch (dng bemegrid, amphetamin khi ng c barbiturat), dng thuc lm mm c khi ng c cc thuc co git (dng cura khi ng c strrynin), hoc ngc li, dng barbiturat khi ng c amphetamin, long no, cardiazol. Phng php ny khng tt lm v thuc i khng cng phi dng vi liu cao, thng l liu c, cho nn c hi i vi nn nhn. 3.2. Hi sc cho ngi bnh - Tr tim, gi huyt p, chng try tim mch: Dng cc thuc tr tim thng thng, noradrenalin 1- 4 mg ha trong 500 - 1000ml dung dch glucose ng trng, truyn nh git tnh mch. C th dng D.O.C dung dch du 1 - 5 mg tim bp. - Tr h hp: Cc thuc kch thch h hp (cardiazol, cafein), h hp nhn to, th oxy. - Thm phn phc mc hoc thn nhn to: Ch dng trong trng hp nhim c nng, thn suy, cc phng php iu tr thng th ng khng mang li kt qu, hoc cc trng hp chng ch nh dng cc thuc li niu thm thu. Thng gp ng c kim loi nng, sulfonamid liu cao, barbiturat liu cao. - Thay mu c ch nh trong cc trng hp: . Nhim c phospho trng: Phi l m trc 8 gi mi c kh nng cu c nn nhn. . Nhim c vi liu cht: Cc thuc chng st rt, cht c t bo, isoniazid, dn xut salicylat (nht l vi tr em). . Cc cht lm tan mu: Saponin, sulfon . Cc cht gy methemoglobin: Phenacetin, anilin, nitrit, cloroquin C th iu tr bng xanh methylen ng 1% - 10 ml ha trong 500 ml dung dch glucose ng trng truyn nh git tnh mch; hoc tim tnh mch vitamin C 4,0 - 6,0g trong 24 gi. Khi khng c kt qu th thay mu. Cn phi sm v khi lng mu thay th phi c nhiu (t nht l 7 lt). Nu hm sau mu cn cha nhiu hemoglobin ha tan th c th phi truyn li. 3.3. Cng tc chm sc ngi bnh - Ch dinh dng: Cho n cc thuc n nh, d tiu, calo, hoc truyn hu mn n u

c tn thng thc qun (nhim c acid). Cn cho thm nhiu vitamin, c bit l vitamin B, C; cho thm insulin khi phi truyn nhiu ng (ose): - Cc khng sinh phng nhim khun th pht. - Lm tt cng tc h l{: Ht m, ri, v sinh chng lot 3.4. Bng k mt s thuc trng c thng gp v cch iu tr Trong bng ny ch k mt s thuc thng gy c v cc thuc c tc dng iu tr c hiu. Ngoi nhng thuc iu tr ny cn phi hp thm cc thuc v phng php hi sinh tng hp tuz the o tnh trng trng c. Nhng thuc khng k trong bng ny, khi trng c phn nhiu l ch iu tr triu chng kt h?p vi hi sc.

4. MT S THUC C HIU DNG TRONG NHIM C 4.1. Dimercaprol Trong chin tranh th gii th hai, Anh nghin cu cc cht chng li cht c ha hc cha hi asen, tm ra dimercaprol. Do dimercaprol cn gi l British- anti Lewisite (vit tt l B.A.L). 4.1.1. Cu trc ha hc v l ha tnh Dimercaprol l 2, 3 - dimercaptopropanol: L cht lng snh, khng mu, mi kh chu, tan trong du thc vt, trong ru v cc cht ha tan hu c khc. 4.1.2. Tc dng v c ch Dimercaprol ngn nga c tnh ca nhng phc hp thiol - kim loi, bng cch phn ng vi kim loi hnh thnh phc hp dimercaprol - kim loi, ng thi gii phng h enzym c thiol; nh trong ng c asen, dimercaprol tc dng vi asen theo cch sau:

Kh nng to chelat ca dimercaprol thay i tuz tng kim loi, mnh nht vi thu ngn, mui vng v na kim loi nh asen. Ngoi tc dng ln h enzym cha nhm - SH, dimercaprol cn tc dng trc

tip ln cc enzym c hot ha bi cc ion kim loi nh: Catalase, anhydrase carbonic, peroxydase. 4.1.3. Tc dng ph ca dimercaprol - Nhc u, bun nn, nn, au bng - Tng huyt p, tim p nhanh. - Bong tm thi cc nim mc, vim kt mc, chy nc mi, tng tit nc bt. - au c v vng sau xng c - Kh chu im tim, i khi p xe. - tr em, st, gim bch cu, i khi co git - c ch chc nng ca tuyn gip trong trng h p dng ko di. - Thiu mu tan mu trong trng hp thiu G 6PD. 4.1.4. Ch nh, liu lng Dng trong iu tr ng c asen, thu ngn, mui vng. N cng c gi tr nh mt cht b tr cho CaNa 2 EDTA trong ng c ch v cho penicilamin trong bnh Wilson. t hiu lc trong nhim c bismuth, tali, ng, crm v nicken. - Tm tnh cm th ca ngi bnh: Ln tim u tin 50 mg. - Ng c cp: cch 4 gi tim 4 mg/ kg cho 48 gi u, ri 3 mg/ kg 2 ln mt ngy trong 8 ngy (liu ti a 5 mg/ kg/ ngy). - Ng c mn: cch 4 gi tim 2,5 mg/ kg cho 48 gi u, ri 2,5 mg/ kg 1 ln mt ngy trong 10- 15 ngy. - Tim bp su, mi ln tim, chuyn ch tim; dng bm tim bng thu tinh. - Kim ha nc tiu trong thi gian iu tr ( bo v thn i vi tc dng c ca nhng kim loi c gii phng). 4.2. EDTA calci dinatri v EDTA dinatri 4.2.1. EDTA dinatri (Na 2 EDTA) 4.2.1.1. Tc dng Tc nhn chelat khng c calci, khi vo c th to phc d dng vi calci. Thi qua thn di dng chelat ca calci: 72% thi qua nc tiu trong 2 4 gi. 4.2.1.2. Ch nh: Dng iu tr nhng trng hp qu ti calci: - Da: Bnh cng b, hi chng Thibierge - Weissenbach. - Mu: Tng calci - mu. 4.2.1.3. Chng ch nh: Suy thn nng

4.2.1.4. Cch dng v liu lng: ng tim 10 ml, dung dch tim 5%. Ch dng trong nhng t rng hp cp, 1 - 2 ng tim c ha long trong dung dch huyt thanh mn hay ngt ng trng, truyn nh git tnh mch rt chm trong ngy ( trnh him ha bnh tetani). Mt t iu tr trong 5 ngy v gia nhng ngy phi c theo di, c thi gian ngh 7 ngy. Vin bc ng: 0,25g Dng ch?o iu tr ngoi tr v liu duy tr t 6 - 8 vin bc ng/ ngy. Liu dng: 5 ngy/ tun l. 4.2.2. EDTA calci dinatri 4.2.2.1. Tc dng EDTA l ethylendiamin tetra acetic acid. Thng dng mui dinatra (Na 2EDTA, dinatri edetat) lm tan nc, c kh nng gp (chelate) calci. Nhng Na 2EDTA gy tetani do h calci mu, nn khi ng c kim loi ha tr 2 hoc 3 (ch, ng, st, coban, cadimi, cht phng x) th dng dinatri calci edetat (CaNa 2EDTA) s to thnh nhng ph c bn, mt ton b hot tnh ion v c tnh ca n v khng b tai bin h calci mu: c thi qua thn: trong 24 gi, 72% thuc c tm thy di dng chelat trong nc tiu, thi gian na thi tr huyt tng l 40 pht. Khng khuch tn qua dch n oty. 4.2.2.2. Ch nh - Ng c ch - Ng c kim loi nng: Crm (eczma ca ximang), st (chng nhim hemosiderin), coban, ng, cht phng x 4.2.2.3. Chng ch nh Suy thn nng 4.2.2.4. Tc dng ph - c tnh vi thn: Thng tn ng thn, al bumin- niu, gim niu, suy thn (thng thng c hi phc). - Bun nn, i lng, chut rt c, st, au c. - Ko di thi gian prothrombin. - iu tr ko di c th gy mt magnesi (ngng iu tr v dng mt mui magnesi). - Vim tnh mch huyt khi t rong trng hp dng nhng dung dch qu c

c. 4.2.2.5. Cch dng v liu lng ng tim 10 ml, c 0,50g. - ng tnh mch: 15 - 25 mg/ kg c th, truyn nh git tnh mch trong 250 500 ml dung dch huyt thanh ngt ng trng trong 1 - 2 gi, 2 ln/ ngy; liu ti a 50 mg/ kg/ ngy; chu kz iu tr trong 5 ngy lin, vi khong cch ti thiu 2 ngy gia nhng chu kz iu tr. Kim tra nc tiu hng ngy v ngng iu tr trong trng hp bt thng. - ng tim bp (dung dch 20%): c ch nh tr ong bnh no do ng c ch, vi tng p lc ca dch no tu; 4 - 6 gi tim 12,5 mg/ kg (ti a 50 mg/ kg/ ngy). Dung dch c ha thm vi procain 1% tim. 4.3. Penicilamin Penicilamin (D - bta, bta- dimethylcystein) l cht thu phn ca penicilin, c th tng hp. To chelat vi kim loi nng, hp vi nhng cht ny thnh nhng phc ha tan v c thi qua nc tiu. Trong cystein niu, penicilamin hp thnh vi cystein mt phc hp ho tan. Hp thu tt qua ng tiu ha; thi gian na thi tr l 2 - 3 gi, thi qua nc tiu di dng disulfid. 4.3.1. Ch nh v liu lng - Bnh Wilson: 500 mg/ ngy vi 25 mg/ pyridoxin; iu tr cn c theo ui sut i. - Ng c ch v thu ngn: 500 mg - 1,5g/ ngy trong 1 - 2 thng. Tr em 30 40 mg/ kg cn nng. - Cystein- niu mn ( phng bnh si): 250 mg/ ngy, liu c tng dn ti 500 mg, 4 ln/ ngy tuz theo s chu thuc. - Vim nhiu khp mn tin trin: Thng u 300 mg/ ngy; thng th hai, th ba: 600 mg/ ngy, nu sau 3 thng iu tr khng thy c kt qu th ngng thuc. - Ung thuc lc i, 2 gi trc hoc 3 gi sau khi n. 4.3.2. Chng ch nh - C thai, bnh mu, bnh thn, chng nhc c - D ng vi penicilin. 4.3.3. Tc dng ph - D ng, protein niu, mt v gic, khu gic.

- Vim nhiu dy thn kinh - Vng da mt -? c ch tu xng: Thiu mu, gim bch cu, tiu cu. 4.4. Pralidoxim (2- PAM) Xin xem bi Thuc tc dng trn h cholinergic, phn iu tr ng c hp cht phospho hu c. BI 20. THUC KHNG VIRUS (NHM KHNG VIRUS SAO CHP NGC) Virus gm c loi 1 hoc 2 chui ADN hoc ARN c bc trong mt v protein gi l capsid. Mt s virus c c v lipoprotein, v ging nh capsid, v ny c th cha cc protein khng nguyn. Virus b t buc phi sng k sinh trong t bo vt ch, s sao chp ca chng ph thuc ch yu vo cc qu trnh tng hp ca t bo vt ch. - Loi ADN virus nh poxvirus (gy bnh u ma), herpesvirus (gy thu u, herpes, zona), adenovirus (vim kt mc, vi m hng), hepa AND virus (vim gan B) v papillomavirus (ht cm). Sau khi thm nhp c vo nhn t bo vt ch, ADN virus c sao m sm vo ARN mbi ARNm polymerase ca t bo vt ch, ARN m c dch m theo cch thng thng ca t bo vt ch thn h cc protein c hiu ca virus. Ring virus u ma, do c ARN polymerase ring nn c th sao ch p ngay trong bo tng ca t bo vt ch. - Loi ARN virus gm rubellavirus (gy bnh si c [German measles], rubeon), rhabdovirus (bnh di), picoARNvir us (bnh bi lit, vim mng no, cm lnh), arenavirus (vim mng no, st Lassa), arbovirus (st vng), orthomyxovirus (cm), paramyxovirus (si, quai b). Vi ARN virus, vic sao chp trong t bo vt ch s da vo hoc l cc enzym trong virion (ht virus) tng hp ARN m cho n, hoc l ARN virus c dng nh chnh ARN m ca n. ARNmc dch m thnh cc protein virus, k c ARN polymerase, enzym chi phi s tng hp nhiu ARNm virus. Mt nhm ARN virus trong loi ny l retrovirus c cha enzym re verse transcriptase (enzym sao m ngc), to ADN t ARN virus. Sau , bn sao ADN tch hp vo genom (b gen) ca vt ch (lc c coi nh provirus) v c sao m thnh c ARN genom v ARN m dch m thnh cc protein virus (HIV). Trong nhiu bnh nhim virus, nh im ca s sao chp ca virus l vo

ngay trc lc triu chng lm sng xut hin. V vy, hiu qu iu tr lm sng ti u l phi bt u iu tr sm. Cc thuc khng virus cn phi: ngn cn s xm nhp ca virus vo t bo v phi c hot tnh vi virus trong t bo, ngha l phi c tnh c hiu. Da vo cc bc trong qu trnh sao ch p, nhn i ca virus m nghin cu cc thuc khng virus, theo bng 15.1 Thuc khng virus sao chp ngc (Antiretroviral agents): thuc chng HI V. HIV (human immunodeficiency virus) l virus sao ch p ngc. ARN tn cng vo cc t bo lympho CD4, i thc bo v t bo thn kinh si nhnh (dendritic cells). Nghin cu vng i ca HIV trong t bo chnh l tm mc tiu tc ng ca thuc. Bng 15.1: Cc giai on sao chp ca virus v mc tiu tc ng ca thuc chng virus

Hnh 15.1. Qu trnh pht trin ca HIV trong t bo vt ch 1) Virus gn vo cc receptor CD 42) Ha mng v thot v ca virus 3) Sao ch p ngc t ARN ADN 4) Tch hp ca ADN virus vo ADN vt ch 5) Sao m mun hay s tng hp protein ca virus 6) Lp rp hay t hp li ca virus v ny chi; j: ARN virus; j. ARN v enzym reverse transcriptase. Qua hnh trn, v l thuyt, c th nghin cu cc thuc tc ng vo cc khu sau: - Ngn cn virus gn vo cc receptor t bo (1) - Ngn cn s ha mng v thot v ca virus (2) - Km hm s sao ch p ngc t ARN (3) - Ngn cn s tch hp ca ADN virus vo ADN ca t bo vt ch (4). - Ngn cn s sao m mun hay s tng hp protein ca virus (5) - Km hm s lp rp hay s t hp li ca virus v s ny chi (6). mi giai on trn u c nhn g c ch c hiu v nhng enzym c hiu ring cho HIV, v nh vy c th tm ra cc thuc c ch thch hp cho tng giai on. Tuy nhin, do nhiu kh khn, cc nghin cu hin nay phn ln tp trung vo cc loi thuc c ch enzym sao ch p ngc (reverse transcriptase- RT), protease v integrase. RT l enzym c tc dng chuyn mch n ARN ca HIV thnh mch kp ADN (giai on 3 trn s ) trc khi xm nhp vo nhim sc th ca t

bo vt ch. Thuc c ch RT c 2 loi: - Thuc c ch nucleosid revers e transcriptase (NRTI): tc dng rt sm giai on sao chp ca HIV, ngn cn nhim khun cp tnh ca t bo, rt t tc dng trn t bo nhim HIV. Cc thuc ny u l tin thuc, c cu trc tng t nh mt thnh phn cu to ca ADN nhng phi c enzym bo tng ca t bo vt ch phosphoryl ha mi tr nn c hot tnh l nhm thuc quan trng nht trong cng thc phi hp thuc iu tr HIV. - Thuc c ch non - nucleosid reverse transcriptase (NNRTI): Thuc c ch enzym sao ch p ngc khng phi nucleosid l thuc tng hp c kh nng gn vo cnh v tr tc ng ca RT, lm thay i hnh dng ca v tr ny nn enzym b mt hot tnh. Thuc khng cn qua giai on phosphoryl ha nh NRTI v ch c tc ng trn HIV - 1. Tt c u chuy n ha gan qua Cyt. P450, gy cm ng enzym nn lm tng chuyn ha ca chnh n (phi tng liu khi dng ko di) v mt s thuc dng cng. Integrase l enzym c tc dng gm ADN ca provirus vo nhim sc th ca t bo vt ch. Nu c ch c enzym n y s lm HIV khng nhn ln c trong t bo k sinh v s b tiu dit. Hin cn l bc nghin cu phng th nghim. Cc protease l cc enzym tham gia trong qu trnh tng hp nhiu protein cu trc ca li virus v cc enzym ch yu, trong c c RT v chnh bn thn protease. c ch protease th HIV ch l cc virion (ht virus) khng trng thnh v khng gy bnh c. V vy, hng nghin cu ny rt hp dn. Cc thuc ny phn ln cn ang c nghin cu v nh gi trn lm sng. Di y l mt s thuc i din, hin c Vit Nam. 1. THUC C CH NRT 1.1. Zidovudin (azidothymidin, AZT) Zidovudin l cht tng hp tng t thymidin, lc u chng ung th (Horwitz - 1964), sau thy c tc dng chng virus (Ostertag, 1974) v n 1985 th Mitsuya ln u tin thy c tc dng c ch c HIV -1 in vitro 1.1.1. C ch tc dng Sau khi nhp vo t bo, zidovudin cng phi c phosphoryl ha 3 ln thnh zidovudin 5 - triphosphat mi c hot tnh. Trong t bo, dng hot tnh c t/2 3 gi. Zidovudin 5 - triphosphat c ch tranh chp vi deoxythymidin triphosphat ca RT. Ngoi ra cn tranh chp vi thymidin

triphos?phat tch hp vo ADN provirus, lm kt thc sm chui ADN, to ra ADN provirus khng hon chnh. In vitro, zidovudin chng c HIV - 1, HIV- 2 v cc virus hng lympho T (T cell lymphotropic viruses) ca ngi. 1.1.2. Dc ng hc Hp thu nhanh qua tiu ha v phn b vo mi m, nng trong dch no tu bng 60% trong huyt tng. Sinh kh dng khong 65%; t/2 huyt tng l 1,1 gi, nhng dng hot tnh trong t bo c t/2 3 gi. Thi tr 90% qua thn di dng chuyn ha v khng chuyn h a. 1.1.3. Tc dng khng mong mun - c tnh chnh l thiu mu thng xy ra trong 4 tun u (7%), gim bch cu (37%), gim tiu cu. - Cc tc dng khng mong mun khc l nhc u, mt ng, chn n, bun nn, mt mi, au c xy ra trong vi tun u. Dng thuc cha triu chng. - Tc dng ph xut hin chm hn, sau 6 - 17 thng l t sc t cc mng, cn co git, hi chng ging vim nhiu c. - Cc thuc c ch phn ng glucuronyl transferase gan (phn ng ging ha AZT) nh acetaminophen, aspirin, in dometacin, probenecid s lm tng tai bin c tnh v mu ca AZT nn cn trnh dng chung. 1.1.4. Ch nh v liu lng Ung 200 mg, cch 8 gi/ ln; hoc 100 mg 5 ln/ ngy. Dng lin tc. C th phi hp vi thuc c ch RT khc hoc thuc c ch protease. Ch phm: AZT, Retrovir vin nang 100 mg; l 200 mg/20 mL. 1.2. Didanosin (ddI) Didanosin (2, 3 dideoxy inosin - ddI) l cht tng t nucleosid purin, c nghin cu t 1989 v dng iu tr t cui nm 1991. Tc dng c trn HIV - 1 v HIV- 2. 1.2.1. C ch tc dng Sau khi thm nhp vo t bo, di tc dng ca enzym chuyn ha ni bo, didanosin c 3 ln phosphoryl ha thnh dng c hot tnh l dideoxyadenosin triphosphat (dd ATP), tranh chp vi dATP (deoxyadenosin triphosphat) c ch RT ca virus, ng t hi ngn cn ko di chui ADN, ngn cn tng hp ADN provirus. 1.2.2. Dc ng hc Didanosin b ph hu nhanh mi trng acid, v vy mi ch phm ung

u cha cht trung ha pH ca dch v. Cn ung lc i. Ung sau ba n, lm gim hp thu ti 50%. Nng nh huyt tng ca liu ung 300 mg l 1 g/ mL. Nng trong dch no tu bng 20% nng huyt tng. Thi gian bn thi l 0,6 - 1,5 gi, nhng t/2 trong t bo ca ddATP l 8 - 24 gi nn ch cn ung 2 ln/ ngy. Thi tr qua thn. 1.2.3. Tc dng khn g mong mun - Vim ty v vim thn kinh ngoi bin thng gp nht, lin quan n liu dng, nht l khi liu > 12,5 mg/ kg. T l thng gp l 6 - 28%. - Tiu chy: 17%, gn 2% l trng hp nng - Cc ri lon khc: khong 2% gm bun nn, nn, st, rt run, nhc u, au c, i acid uric - Mt s ri lon sinh ha - huyt hc gim bch cu, gim tiu cu, thiu mu, tng transaminase. Khng lin quan n liu iu tr. 1.2.4. Ch nh, liu lng Dng cho tr em trn 6 thng tui v ngi ln b nhim HIV k hng dung np vi AZT hoc dng AZT 4 thng nhng bnh t thuyn gim. Ngi ln: 200 mg 2 ln/ ngy. Gim liu nu nh cn. Tr em, da theo din tch c th: 0,8- 1,2 m2 : 75 mg 2 ln/ ngy 0,5- 0,7 m2 : 50 mg 2 ln/ ngy Phi ung lc i, tr c ba n 1 gi. Nhai nt vin thuc hoc ha vo nc cho tht tan ri ung ngay. Didanosin (Videx) vin nn 25, 50, 100, 150 mg; bt ho tan dng cho tr em: 100, 200 mg. 2. THUC C CH NNRT Nevirapin 2.1. C ch tc dng: Nevirapin khuch tn vo trong t bo , gn vo RT, lm thay i hnh dng v bt hot enzym. Tc ng mnh trn HIV - 1, k c cc virion ngoi t bo. 2.2. Dc ng hc. D hp thu qua ng tiu ha, thm c qua rau thai v sa. Nng trong dch no tu bng 45% nng huyt tng. Thi gian bn thi l 25 - 30 gi. Chuyn ha gan qua cytocrom P 450. 2.3. Tc dng khng mong mun: pht ban, st, nhc u ng g v tng transaminase. 2.4. Liu lng: Nevirapin (Viramune) vin 200 mg 1- 2 vin/ ngy. 3. THUC C CH PROTEASE

3.1. Indinavir c ch c hiu HI V- 1 protease Dng kt hp vi mt thuc c ch RT lm chm khng thuc. Ung 800 mg, cch 8 gi ung 1 ln; c hp thu tt, nn ung cch ba n 2 gi. Vin 200, 400 mg. Tc dng khng mong mun: tng bilirubin mu, si thn (nn ung nhiu nc), bun nn, tiu chy, gim tiu cu. Indinavir c ch mnh cytochrom P 450 nn c tng tc vi nhiu thuc chuyn ha qua cytochrom ny. 3.2. Ritonavir c ch c hiu HIV - 1 protease Sinh kh dng 60 - 80%. Ung liu 600 mg 12 gi/ ln. Tc dng khng mong mu n: ri lon tiu ha, t b, tng transaminase, tng triglycerid mu. Cng c ch mnh cytochrom P 450 nh indinavir nn c tng tc vi nhiu thuc. Ritonavir (Norvir): vin nang 100 mg, dung dch ung 80 mg/mL. Nguyn tc s dng thuc chng HIV Sau nhiu nm theo di iu tr, WHO a ra mt s khuyn co sau: - Cc liu php iu tr phi theo hng dn ton quc. Liu php hng u c th l: AZT + 3 TC + Nevirapin AZT + 3 TC + Nelfinavir AZT + 3 TC + Lopinavir/ indinavir/ Saquinavir - S dng 2 thuc khng cn c coi l thch hp. - S tun th c { ngha quan trng hn s la chn thuc. - Ph n mang thai v tr nh cng phi c iu tr phi hp thuc ti u. BI 21. THUC KHNG SINH KHNG KHUN 1. I CNG 1.1. nh ngha K nguyn hin i ca ha tr liu khng khun c bt u t vic tm ra sulfonamid (Domagk, 1936), Thi kz vng son ca khng sinh bt u t khi sn xut penicilin dng trong lm sng (1941). Khi , khng sinh c coi l nhng cht do vi sinh vt tit ra (vi khun, vi nm), c kh n ng km hm s pht trin ca vi sinh vt khc. V sau, vi s pht trin ca khoa hc, ngi ta

- C th tng hp, bn tng hp cc khng sinh t nhin (cloramphenicol) - Tng hp nhn to cc cht c tnh khng sinh: sulfamid, quinolon - Chit xut t vi sinh vt nhng cht dit c t bo ung th (actinomycin) V th nh ngha khng sinh c thay i: Khng sinh l nhng cht do vi sinh vt tit ra hoc nhng cht ha hc bn tng hp, tng hp, vi nng rt thp, c kh nng c hiu km hm s pht trin hoc dit c vi khun 1.2. C ch tc dng ca khng sinh S di y ?ch r v tr v c ch tc dng chnh ca cc khng sinh trn vi khun:

Hnh 14.2. Cc khng sinh c ch qu trnh tng hp protei 1. c ch to cu peptid ( Cloramphenicol) 2. Ngn cn chuyn ng chuyn on ca ribosom theo ARN m (Erythromycin) 3. Ngn cn s gn kt ca ARN t vo phc hp ribosom ARN m (Tetracyclin) 4. Lm thay i hnh dng 30S m ha trn ARN m nn c nhm (Streptomycin)

Hnh 14.3. V tr tc dng c a khng sinh c ch tng hp protein 1.3. Ph khng khun Do khng sinh c tc dng theo c ch c hiu nn mi khng sinh ch c tc dng trn mt s chng vi khun nht nh, gi l ph khng khun ca khng sinh 1.4. Tc dng trn vi khun Khng sinh c ch s pht trin ca vi khun, gi l khng sinh km khun ; khng sinh hu hoi vnh vin c vi khun gi l khng sinh dit khun . Tc dng km khun v dit khun thng ph thuc vo nng Nng dit khun ti thiu (MBC) T l Nng km khun ti thiu (MIC) Khi t l > 4, khng sinh c tc dng km khun. Kh t l gn bng1, khng sinh c xp vo loi dit khun. 1.5. Phn loi Cc khng sinh c phn loi theo cu trc ha hc, t chng c chung

mt c ch t c dng v ph khng khun tng t. Mt khc, trong cng mt h khng sinh, tnh cht dc ng hc v s dung np thng khc nhau, v c im v ph khng khun cng khng hon ton ging nhau, v vy cng cn phn bit cc khng sinh trong cng mt h Mt s h (hoc nhm) khng sinh chnh: - Nhm lactam (cc penicilin v cc cephalosporin) - Nhm aminosid hay aminoglycosid - Nhm cloramphenicol - Nhm tetracyclin - Nhm macrolid v lincosamid - Nhm quinolon - Nhm 5- nitro- imidazol - Nhm sulfonamid 2. CC KHNG SINH CHNH 2.1. Nhm lactam V cu trc u c vng lactam (H ) V c ch u gn vi transpeptidase (hay PBP: Penicilin Binding Protein), enzym xc tc cho s ni peptidoglycan to vch vi khun. Vch vi khun l b phn rt qua n trng m bo s tn ti v pht trin. Thnh phn m bo cho tnh bn vng c hc ca vch l mng li peptidoglycan, gm cc chui glycan ni cho vi nhau bng chui peptid. Khong 30 enzym ca vi khun tham gia tng hp peptidoglycan, trong c transpeptidase (hay PBP). Cc lactam v khng sinh loi glycopeptid (nh vancomycin) to phc bn vng vi transpeptidase, c ch to vch vi khun, lm ly gii hoc bin dng vi khun. Vch vi khun gram (+) c mng li peptidoglycan dy t 50 - 100 phn t, li ngay b mt t bo nn d b tn cng. Cn vi khun gram (-) vch ch dy 1 - 2 phn t nhng li c che ph lp ngoi cng mt v bc lipopolysaccharid nh 1 hng ro khng thm khng sinh, mun c tc dng, khng sinh phi khuch tn c qua ng dn (pores) ca mng ngoi nh amoxicilin, mt s cephalosporin. Do vch t bo ca ng vt a bo c cu trc khc vch vi khun nn khng chu tc ng ca lactam (thuc hu nh khng c). Tuy nhin vng lactam rt d gy d ng. Cc khng sinh lactam c chia thnh 4 nhm da theo cu trc ha hc

- Cc penam: vng A c 5 cnh bo ha, gm cc penic?ilin v cc cht phong ta Cc lactam. - Cc cephem: vng A c 6 cnh khng bo ha, gm cc cephalosporin. - Cc penem: vng A c 5 c nh khng bo ha, gm cc imipenem, ertapenem. - Cc monobactam: khng c vng A, l khng sinh c th tng hp nh aztreonam.

2.1.1.1. Penicilin G L nhm thuc tiu biu, c tm ra u tin. * Ngun gc v c tnh l ha Trong sn xut cng nghip, ly t Penicillium notatum, 1 mL mi trng nui cy cho 300 UI; 1 n v quc t (UI)= 0,6 g Na benzylpenicilin hay 1.000.000 UI = 0,6g. Penicilin G l dn g bt trng, vng bn nhit thng, nhng dung dch nc, phi bo qun lnh v ch vng bn pH 66,5, mt tc dng nhanh pH < 5 v > 7,5 * Ph khng khun - Cu khun Gr (+); lin cu (nht l loi tan huyt), ph cu v t cu khng sn xu t penicilinase. - Cu khun Gr (-): lu cu, mng no cu - Trc khun Gr (+) i kh (than, subtilis, bch cu) v ym kh (clostridium hoi th sinh hi) - Xon khun, c bit l xon khun giang mai (treponema pallidum) * Dc ng hc - Hp thu: b dch v ph hu nn khng ung c. Tim bp, nng ti a t c sau 15 - 30 pht, nhng gim nhanh (cn tim 4h/ ln). Tim bp 500.000 UI, pic huyt thanh 10 UI/ mL. - Phn phi: gn vo protein huyt tng 40 - 60%. Kh thm vo xng v no. Khi mng no vim, nng trong dch no tu bng 1/ 10 huyt tng. Trn ngi bnh thng, t/2 l khong 30 - 60 pht. - Thi tr: ch yu qua thn di dng khng hot tnh 60 - 70%, phn cn li vn cn hot tnh. Trong gi u, 60 - 90% thi tr qua nc tiu, trong 90% qua bi xut ng thn (mt s acid hu c nh probenecid c ch qu trnh ny, lm chm thi tr penicilin)

* c tnh Penicilin rt t c, nhng so vi thuc khc, t l gy d ng kh cao (1 10%), t phn ng rt nh n t vong do cho ng phn v. C d ng cho vi mi lactam v cephalosporin. * Ch phm, liu lng - Penicilin G l bt, pha ra dng ngay. Liu lng tuz theo tnh trng nhim khun, t 1 triu n 50 triu UI/ 24h chia 4 ln, tim bp hoc truyn tnh mch (pH dch t ruyn 6- 7). Tr em trung bnh cho 100.000 UI/ kg/ 24 h - Penicilin c ph G, tc dng ko di: kt hp vi cc mui t tan v chm hp thu s k o di c tc dng ca penicilin G: . Bipenicilin (natri benzylpenicilinat + procain benzylpenicilinat): mi n gy tim 1 ln, khng dng cho tr em. . Extencilin (benzathin penicilin): tim bp 1 ln, tc dng ko di 3 - 4 tun. Dng iu tr lu, giang mai v d phng thp khp cp ti nhim - l 600.000, 1.000.000 v 2.400.000 UI - Penicilin c ph G, ung c Penicilin V (Oracilin, Ospen): khng b dch v ph hy, hp thu t trng, nhng phi dng liu gp i penicilin G mi t c nng huyt thanh tng t. Cch 6h/ ln. 2.1.1.2. Penicilin khng penicilinase: Methicilin L penicilin bn tng hp Ph khng khun v thi gian tc dng tng t penicilin G, nhng cng tc dng th yu hn. Tim bp hoc tnh mch 2 - 8 g/ 24h chia lm 4 ln. Khng ung dc Mt s thuc khc vng bn vi dch v, ung c: oxacilin (Bristopen), cloxacilin (Orbenin): ung 2- 8g mt ngy chia lm 4 ln Ch nh tt trong nhim t cu sn xut penicilinase (t cu vng) C th gp vim thn k, c ch ty xng liu cao 2.1.1.3. Penicilin c ph rng Ampicilin, amoxicilin L penicilin bn tng hp, amino - benzyl penicilin c mt s c im: - Trn cc khun Gr (+) tc dng nh penicilin G, nhng c thm tc dng trn mt s khun gram (-): E. coli, salmonella, Shigella, proteus, hemophilus influenzae - B penicilinase ph hu

- Khng b dch v ph hy, ung c nhng hp thu khng hon ton (khong 40%). Hin c nhiu thuc trong nhm ny c t l hp thu qua ng ung cao (nh amoxicilin ti 90%) nn nhiu nc khng cn dng ampicilin na - Liu lng: Amoxicilin (clamoxyl, Oramox) Ung: 2- 4 g/ ngy. Tr em 50 mg/ kg/ ngy. Chia 4 ln - Ch nh chnh: vim mng no m, thng hn, nhim khun ng mt, tit niu, nhim khun s sinh. 2.1.1.4. Cc penicilin khng trc khun m xanh: Carboxypenicilin v ureidopenicilin. L nhm khng sinh quan trng c dng iu tr cc nhim khun nng do trc khun gram ( -) nh trc khun m xanh, Proteus, Enterobacter, vi khun khng penicilin v ampicilin. Thng l nhim khun mc phi ti bnh vin, nhim khun sau bng, nhim khun tit niu, vim phi. Cc khng sinh ny u l bn tng hp v vn b penicilinase ph hu. - Carbenicilin, ticarcilin: ung 2 - 20g/ ngy. - Ureidopenicilin: . Mezlocilin: 5- 15g/ ngy. Tim bp, truyn tnh mch. . Piperacilin: 4- 18g/ ngy. Tim bp, truyn tnh mch. 2.1.2. Cc cephalos porin c chit xut t nm cephalosporin hoc bn tng hp, u l dn xut ca acid amino - 7- cephalosporanic, c mang vng lactam. Tuz theo tc dng khng khun, chia thnh 4 th h 2.1.2.1. Cephalosporin th h 1: C ph khng khun gn vi metici lin v penicilin A. Tc dng tt trn cu khun v trc khun gram (+), khng c penicilinase ca t cu. C tc dng trn mt s trc khun gram ( -), trong c cc trc khun ng rut nh Salmonella, Shigella. B cephalosporinase ( lactamase) ph h u. Ch nh chnh: sc nhim khun, nhim khun huyt do t cu, nhim khun khng penicilin. Cc ch phm dng theo ng tim (bp hoc tnh mch) c: cefalotin (Kezlin), cefazolin (Kefzol), liu 2- 8g/ ngy Theo ng ung c cefalexin (Keforal), cefaclor (Alfatil), liu 2g/ngy. khc phc 2 nhc im: t tc dng trn vi khun gram ( -) v vn cn b

cephalosporinase ph, cc th h cephalosporin tip theo v ang c nghin cu sn xut. 2.1.2.2. Cephalosporin th h 2: Hot tnh khng khun tr n gram (-) tng, nhng cn k m th h 3. Khng c cephalosporinase. S dung np thuc cng tt hn. Ch phm tim: cefamandole (Kefandol), cefuroxim (Curoxim) liu 3 - 6 g/ ngy. Ch phm ung: cefuroxim acetyl (Zinnat) 250 mg 2 ln/ ngy. 2.1.2.3. Cephalosporin th h 3 Tc dng trn cu khun gram (+) km th h 1, nhng tc dng trn cc khun gram ( -), nht l trc khun ng rut, k c chng tit lactamase th mnh hn nhiu. Cho ti nay, cc thuc nhm ny hu ht u l dng tim: Cefotaxim (Claforan), ceftizoxim (Cefizox), ceftriaxon (Rocephin), liu t 1 n 6g/ngy, chia 3 4 ln tim. 2.1.2.4. Cephalosporin th h? 4. Ph khng khun rng v vng bn vi lactamase hn th h 3, c bit dng ch nh trong nhim trc khun gram ( -) hiu kh khng vi th h 3. Ch phm: cefepim, tim t/ m 2g 2 ln/ ngy. 2.1.3. Cc cht c ch lactamase (cu trc Penam) L nhng cht c tc dng khng sinh yu, nhng gn khng hi phc vi lactamase v c i lc vi lactam, cho nn khi phi hp vi khng sinh nhm lactam s lm vng bn v tng cng hot tnh khng khun ca khng sinh ny. Hin c cc ch phm sau: 2.1.4. Cc penem Imipenem Thuc nhm carbapenem, trong cng thc vng A thay S bng C. Ph khng khun rt rng , gm cc khun i kh v k kh: lin cu, t cu (k c chng tit penicilinase), cu khun rut (enterococci), pseudomonas. c dng trong nhim khun sinh dc - tit niu, ng h hp di, m mm, xng - khp, nhim khun bnh vin. Khng hp thu qua ng ung. Ch tim tnh mch liu 1 - 2g/ ngy. Er-

tapenem Ph khng khun nh imipenem, nhng mnh hn trn gram ( -). Tim bp hoc truyn tnh mch 1g/ ngy. 2.1.5. Monobactam Aztreonam Km tc dng trn khun gram (+) v k kh. Tri li, tc dng mnh trn khun gram ( -), tng t cephalosporin th h 3 hoc aminoglycosid. Khng lactamase. Khng tc dng theo ng ung. Dung np tt, c th dng cho bnh nhn d ng vi penicilin hoc cephalosporin. Tim bp 1- 4 g/ ngy. Trng hp nng, tim tnh mch 2g, cch 6 - 8 gi/ ln. 2.1.6. Thuc khc cng c ch tng hp vch vi khun: Vancomycin Khng sinh c ngun gc t Streptococcus orientalis. C ch tc dng : c ch transglycosylase nn ngn cn ko di v to li peptidoglycan. Vi khun khng to c vch nn b ly gii. Vancomycin l khng sinh dit khun. Tc dng: ch dit khun gram (+): phn ln cc t cu gy bnh, k c t cu tit lactamase v khng methicilin. Hip ng vi gentamycin v streptomycin trn enterococcus. ng hc: c hp thu rt t qua ng tiu ha nn ch c dng iu tr vim rut kt gi mc cng vi tetracyclin, clindamycin. Tim truyn tnh mch, gn vi protein huyt tng khong 55%, thm vo dch no tu 7 30% nu c vim mng no, trn 90% thi qua lc cu thn (khi c vim thn phi gim liu). Thi gian bn thi khong 6 h. Ch nh chnh : vim mng trong tim do t cu khng methicilin, cho bnh nhn c d ng penicilin. Liu lng 1g 2 ln/ ngy. Tc dng khng mong mun: ch khong 10% v nh. Thng gp l kch ng vim tnh mch ti ch tim truyn, rt run, st, c vi dy VIII. Nng truyn nn gi t 5 - 15 g/ mL (di 60 g/ mL) th trnh c tc dng ph. Ch phm: Vancomycin (Vancocin, Vancoled): l bt ng kh pha dch tim truyn 500 mg v 1,0g. 2.2. Nhm aminosid hay aminoglycosid u ly t nm, cu trc ha hc u mang ng (ose) v c chc amin nn c tn aminosid. Mt s l bn tng hp. C 4 c tnh chung cho c nhm: - Hu nh khng hp thu qua ng tiu ha v c P M cao.

- Cng mt c ch tc dng - Ph khng khun rng. Dng ch yu chng khun hiu kh gram ( -). - c tnh chn lc vi dy thn kinh VIII v vi th?n (tng creatinin mu, protein niu. Thng phc hi) Thuc tiu biu trong nhm ny l streptomycin. Ngoi ra cn: Neomycin, kanamycin, amikacin, gentamycin, tobramycin. 2.2.1. Streptomycin 2.2.1.1. Ngun gc v c tnh Ly t nm streptomyces griseus (1944). Thng dng di dng mui d tan, vng bn nhit di 250C v pH = 3- 7. 2.2.1.2. C ch tc dng v ph khng khun Sau khi nhp vo vi khun, streptomycin gn vo tiu phn 30 s ca ribosom, lm vi khun c sai m thng tin ARN m, tng hp protein b gin on. C tc dng dit khun trn cc vi khun phn chia nhanh, ngoi t bo hn l trn vi khun phn chia chm. pH ti u l 7,8 (cho nn cn alcali (kim) ha nc tiu nu iu tr nhim khun tit niu) Ph khng khun rng, gm: - Khun gram (+): t cu, ph cu, lin cu (c tc dng hip ng vi khng sinh nhm lactam) - Khun gram (-): Salmonella, Shigella, Haemophilus, Brucella. - Xon khun giang mai - L khng sinh hng u chng trc khun lao (BK) Vi khun khng streptomycin: khun k kh, trc khun m xanh v mt s nm bnh. 2.2.1.3. Dc ng hc - Hp thu: ung, b thi t r hon ton theo phn. Tim bp, hp thu chm hn penicilin, nhng gi c lu hn nn ch cn tim mi ngy 1 ln. Gn vo protein huyt tng 30 - 40%. - Phn phi: do tan nhiu trong nc v b ion ha pH huyt tng, streptomycin kh thm ra ngoi mch. Gn nhiu hn vo thn, c, phi, gan. Nng trong mu thai nhi bng 1/2 nng huyt tng. t thm vo trong t bo (khng dit c BK trong i thc bo nh isoniazid). Khng qua c hng ro mu no. - Thi tr: khong 85 - 90% liu tim b th i tr qua lc cu thn trong 24h. 2.2.1.4. c tnh - Dy VIII rt d b tn thng, nht l khi iu tr ko di v c suy thn.

c tnh on tin nh thng nh v ngng thuc s khi, cn c on c tai c th gy ic vnh vin k c ngng thuc. Dihydrostreptomycin c t l c cho c tai cao hn nn khng cn c dng na. - c vi thn v phn ng qu mn t gp. C th thy vim da do tip xc y t (ngi tim thuc). - C tc dng mm c kiu cura nn c th gy ngng h hp do lit c h hp v dng streptomycin sau phu thut c gy m. Khng dng cho ngi nhc c v ph n c thai. 2.2.1.5. Cch dng: Do c tnh nn ch gii hn ginh cho cc nhim khun sau: - Lao: phi hp vi 1 hoc 2 khng sinh khc (xem bi thuc chng lao) - Mt s nhim khun tit niu, dch hch, brucellose: phi hp vi tetracyclin - Nhim khun huyt nng do lin cu: phi hp vi penicilin G. L sulfat streptomycin 1g. Liu thng thng tim bp 1g/ ngy. Trong iu tr lao, tng liu khng qu 80- 100g. 2.2.2. Cc aminosid khc - Kanamycin: Tc dng, dc ng hc v c tnh tng t nh streptomycin. Thng dng phi hp (thuc hng 2) trong iu tr lao. Liu 1g/ ngy (xem bi thuc chng lao) - Gentamycin: Ph khng khun rt rng. L thuc c chn la cho nhim khun bnh vin do Enterococcus v Pseudomonas aeruginosa. Dng phi hp vi penicilin trong st gim bch cu v nhim trc khun gram (-) nh vim ni ?tm mc, nhim khun huyt, vim tai ngoi c tnh. Gentamycin sulfat ng trong n g 160, 80, 40 v 10 mg. Liu hng ngy l 3 5 mg/ kg, chia 2 - 3 ln/ ngy, tim bp. - Amikacin: L thuc c ph khng khun rng nht trong nhm v khng c cc enzym lm mt hot aminoglycosid nn c vai tr c bit trong nhim khun bnh vin gram ( -) khng vi gentamycin v tobramycin. Liu lng mt ngy 15 mg/ kg tim bp hoc tnh mch 1 ln, hoc chia lm 2 ln. ng 500 mg. - Neomycin: Thng dng di dng thuc bi iu tr nhim khun da - nim mc

trong bng, vt thng, vt lot v cc bnh ngoi da bi nhim. Dng neomycin n c hoc phi hp vi polymyxin, bacitracin, khng sinh khc hoc corticoid. 2.3. Cloramphenicol v dn xut 2.3.1. Ngun gc v tnh cht l ha Phn lp t nm Streptomyces venezualae (1947) v ngay sau t ng hp c . L bt trng, rt ng, t tan trong nc, vng bn nhit thng v pH t 2 - 9, v th c th ung c. 2.3.2. C ch tc dng v ph khng khun Cloramphenicol c tc dng km khun, gn vo tiu phn 50s ca ribosom nn ngn cn ARN m gn vo ribosom, ng thi c ch transferase nn acid amin c m ha khng gn c vo polypeptid. Cloramphenicol cng c ch tng hp protein ca ty th t bo ng vt c v (v ribosom ca ty th cng l loi 70s nh vi khun), hng cu ng vt c v c bit nhy cm vi cloramphenicol. Ph khng khun rt rng: phn ln cc vi khun Gram (+) v Gram ( -), xon khun, tc dng c hiu trn thng hn v ph thng hn. 2.3.3. Dc ng hc - Hp thu: sau khi ung, nng ti a trong mu t c sau 2 gi, t/ 2 t 1,5 3 gi, khong 60% gn vo protein huyt tng. - Phn phi: thm d dng vo cc m, nht l cc hch mc treo, nng t c cao hn trong mu (rt tt cho iu tr thng hn). Thm tt vo dch no tu nht l khi mng n o b vim, c th bng nng trong mu. Qua c rau thai. - Chuyn ha: phn ln b mt hot tnh do qu trnh glycuro - hp gan hoc qu trnh kh. - Thi tr: ch yu qua thn, 90% di dng chuyn ha. 2.3.4. c tnh Hai c tnh rt nguy him: - Suy ty: . Loi ph thuc vo liu: khi liu cao qu 25 g/ mL c th thy sau 5 - 7 ngy xut hin thiu mu nng, gim mnh hng cu li, bch cu, hng cu non. Liu ung 0,5g s c pic huyt thanh 6- 10 g/ mL . Loi khng ph thuc liu, thng do c ng: gim huyt cu ton th do

suy tu thc s, t l t vong t 50- 80% v tn xut mc t 1: 150.000 n 1: 6.000 - Hi chng xm (grey baby syndrome) gp nh nhi sau khi dng liu cao theo ng tim: nn, au bng, tm ti, mt nc, ngi mm nh n, try tim mch v cht. l do gan cha trng thnh, thuc khng c kh c bng qu trnh glycuro - hp v thn khng thi tr kp cloramphenicol. - Ngoi ra, bnh nhn thng hn nng, dng ngay liu cao cloramphenicol, vi khun cht gii phng qu nhiu ni c t c th gy try tim mch v t vong. V vy, duy nht trong trng hp thng hn nng phi dng t liu thp. 2.3.5. Tng tc thuc Cloramphenicol c ch cc enzym chuyn ha thuc gan nn ko di t/2 v lm tng nng huyt tng ca phenytoin, tolbutamid, warfarin 2.3.6. Ch phm v cch dng V c c tnh nng nn phi cn nhc trc khi dng cloramphenicol. Ch dng cloramphenicol khi khng c thuc tc dng tng ng, k m c hn thay th. - Thng hn v nhim salmonel la ton thn trc y l ch nh tt ca cloramphenicol. Nay khng dng na v c thay bng cephalosporin th h 3 (ceftriaxon) hoc fluoroquinolon. - Vim mng no do trc khun gram ( -) (H. influenzae) l ch nh tt v cloramphenicol d thm qua mng no. Cng c th thay bng cephalosporin th h 3. - Bnh do xon khun Rickettsia: Tetracyclin l ch nh tt nht. Nhng khi tetracyclin c chng ch nh th thay bng cloramphenicol. Liu lng: ung t 25 - 50 mg/ kg/ 24h. Chia lm 4 - 6 ln. Khng dng cho ngi suy gan nng. - Thiophenicol (thiamphenicol): ch phm tng hp, nhm NO 2 trong cloramphenicol c thay bng CH3 - SO2 - . c tnh t hn, d dung np, nhng tc dng cng k m hn, v vy liu dng gp 2 ln cloramphenicol. Khng dng cho ngi suy thn nng. 2.4. Nhm tetracyclin 2.4.1. Ngun gc v tnh cht l ha u l khng sinh c 4 vng 6 cnh, ly t Streptomyces aureofaciens (clotetracyclin, 1947), hoc bn tng hp. L bt vng, t tan trong nc, tan trong base hoc acid.

2.4.2. C ch tc dng v ph khng khun Cc tetracyclin u l khng sinh km khun, c ph khng khun rng nht trong cc khng sinh hin c. Cc tetracyclin u c ph tng t, tr minocyclin: mt s chng khng vi tetracyclin khc c th vn cn nhy cm vi minocyclin. Tc dng km khun l do gn trn tiu phn 30s ca ribosom vi khun, ngn cn RNA t chuyn acid amin vo v tr A trn phc hp ARNm - riboxom to chui polypeptid. Tc dng trn: . Cu khun gram (+) v gram ( -): nhng k m penicilin . Trc khun gram (+) i kh v ym kh . Trc khun gram ( -), nhng proteus v trc khun m xanh rt t nhy cm . Xon khun (km penicilin), rickettsia, amip, trichomonas 2.4.3. Ch nh Do ph khng khun rng, tetracyclin c dng ba bi, d g y khng thuc. V vy ch nn dng cho cc bnh gy ra do vi khun trong t bo v tetracyclin rt d thm vo i thc bo. - Nhim rickettsia - Nhim mycoplasma pneumoniae - Nhim chlamidia: bnh Nicolas - Favre, vim phi, ph qun, vim xoang, psittacos is, bnh mt ht. - Bnh ly truyn qua ng tnh dc - Nhim trc khun: brucella, tularemia, bnh t, l, E.coli. - Trng c: do tc dng trn vi khun propionibacteria khu tr trong nang tuyn b v chuyn ha lipid thnh acid bo t do gy kch ng vi m. Dng liu thp 250 2ln/ ngy. 2.4.4. Dc ng hc - Cc tetracyclin khc nhau v tnh cht dc ng hc, cc dn xut mi c c im hp thu tt hn, thi tr chm hn v do c th gim c liu dng hoc ung t ln hn. - Hp thu qua tiu ha 60 - 70%. D to phc vi st, calci, magnesi v casein trong thc n v gim hp thu. Nng ti a trong mu t c sau 2 - 4 gi. - Phn phi: gn vo protein huyt tng t 30% (oxytetracyclin) n 50% (tetracyclin) hoc t?rn 90% (doxycyclin). Thm c vo dch no tu, rau thai, sa nhng t. c bit l thm c vo trong t bo nn c tc dng tt trong iu tr cc bnh do brucella. Gn mnh vo h li ni m ca gan,

lch, xng, rng. Nng rut cao gp 5 - 10 ln nng trong mu. - Thi tr: qua gan (c chu kz gan - rut) v thn, phn ln di dng cn hot tnh. Thi gian bn thi l t 8h (tetracyclin) n 20h (doxycyclin) Bng 14.1. Cc tetracyclin thng dng 2.4.5. c tnh - Ri lon tiu ha: bun nn, nn, tiu chy, do thuc kch ng nim mc, nhng thng l do lon khun - Vng rng tr em: tetracyclin lng ng vo rng trong thi kz u ca s vi ha (trong t cung nu ngi m dng thuc s au 5 thng c thai hoc tr em di 8 tui) - c vi gan thn: khi dng liu cao, nht l trn ngi c suy gan, thn, ph n c thai c th gp vng da gy thoi ha m, ur mu cao dn n t vong. - Cc ri lon t gp hn: d ng, xut huyt gim tiu cu, tng p lc ni s tr ang b, nhc u, ph gai mt V vy, phi thn trng theo di khi s dng v trnh dng: . Cho ph n c mang . Cho tr em di 8 tui 2.4.6. Ch phm, cch dng D sao, tetracyclin vn l khng sinh c ph rng, t g y d ng, t c, c bit l thm c vo trong t bo nn c dnh cho iu tr bnh do brucella, nhim khun ng mt, mi - hng, phi. Mt s dn xut chnh: - Tetracyclin: ung 1- 2 g/ ngy, chia 3 - 4 ln. Vin 250- 500 mg; dch treo 125 mg/ 5mL - Clotetracyclin (Aureomycin): ung, tim t/m 1 - 2 g. - Oxytetracyclin (Terramycin): ung 1 - 2 g; tim bp, t/m 200 mg - 1g. - Minocyclin (Mynocin): ung 100 mg 2 ln; tim bp hoc t/m 100 mg. Vin 50 100 mg; dch treo 50 mg/ 5 mL - Doxycyclin (Vibramycin): ung liu duy nht 100 - 200 mg. Vin 50- 100 mg; dch treo 25 50 mg/ mL 2.5. Nhm macrolid v lincosamid Hai nhm ny tuy cng thc khc nhau nhng c nhiu im chung v c ch tc dng, ph khng khun v c im s dng lm sng.

2.5.1. Ngun gc v tnh cht Nhm macrolid phn ln u ly t streptomyces, cng thc rt cng knh, i din l erythromycin (1952), ngoi ra cn clarithromycin v azithromycin. Cc lincosamid cng ly t streptomyces, cng thc n gin hn nhiu, i din l lincomycin (1962), clindamycin. Hai nhm ny c c tnh: - Tc dng trn cc chng khng penicilin v tetracyclin, c bit l staphylococus. - Gia chng c khng ch o do c ch tng t - Thi tr ch yu qua ng mt - t c v dung np tt 2.5.2. C ch t c dngv ph khng khun Gn vo tiu phn 50s ca ribosom vi khun, cn tr to chui a peptid (ngn cn chuyn v ca ARNt) ca vi khun. Ph tc dng tng t penicilin G: cu khun v rickettsia. Hon ton khng tc dng trn trc khun ng rut v pseudomonas. Tc dng km khun mnh, c tc dng dit khun, nhng yu. 2.5.3. Dc ng hc B dch v ph hu mt phn, nu dng dng bo ch thch hp, c th ung c tt. Nng ti a t c trong mu sau 1 - 4h v gi khng qu 6 ting nn phi ung 4 ln mi ngy. Gn vo ? protein huyt tng khong 70% (lincomycin) n 90% (erythromycin), t/2 t 1h 30 n 3 h. Thm mnh vo cc m, c bit l phi, gan, lch, xng, tuyn tin lit. Nng trong i thc bo v bch cu a nhn gp 10 - 25 ln trong huyt tng do c vn chuyn tch cc. Rt t thm qua mng no. Thi tr ch yu qua mt di dng cn hot tnh (nng trong mt gp 5 ln trong huyt tng). 2.5.4. Ch nh L thuc c chn la ch nh cho nhim corynebacteria (bch hu, nh im nm corynebacterium minutissimum - erythrasma); nhim clamidia ng h hp, sinh dc, mt, vim phi mc phi cng ng; thay th penicilin cho bnh nhn b d ng vi penicilin khi nhim t cu, lin cu hoc ph cu; d phng vim ni tm mc trong phu thut rng ming cho nhng bnh nhn c bnh van tim. 2.5.5. c tnh

Ni chung t c v dung np tt ch gp cc ri lon tiu ha nh (bun nn, nn, tiu chy) v d ng ngoi da. Tuy nhin, lincomycin v clindamycin c th gy vim rut kt mc gi, i khi nng, dn n t vong; erythromycin v Tri Acetyl Oleandomycin (TAO) c th gy vim da mt, vng da. 2.5.6. Ch phm, cch dng 2.5.6.1. Nhm macrolid - Erythromycin (Erythromycin, Erythrocin): ung 1 - 2g/ ngy, chia lm 4 ln - Spiramycin (Rovamycin): ung 1 - 3g/ ngy, truyn chm t/m 1,5 triu UI 3 ln/ ngy - Azithromycin: thm rt nhiu vo m (tr dch no tu), t nng cao hn huyt tng ti 10- 100 ln, sau c gii phng ra t t nn t/2 khong 3 ngy. V th cho php dng l iu 1 ln/ ngy v thi gian iu tr ngn. Th d vi vim phi cng ng, ngy u cho 500 mg ung 1 ln; 3 ngy sau ung 250 mg/ ln/ ngy ch dng trong 4 ngy. Vin nang 250 mg 2.5.6.2. Nhm lincosamid - Lincomycin (Lincocin): ung 2g/ ngy. Chia lm 4 ln. Vin nang 500 mg. tim bp, t/m: 0,6 - 1,8g/ ngy - Clindamycin (Dalacin): ung 0,6 - 1,2g/ ngy, chia lm 4 ln (0,15 - 0,3g/ ln) Khng sinh 2 nhm ny thng dng cho nhim cu khun gram (+), nht l trong tai mi hng, vim phi, nhim khun ng h hp. Nhm lincosamid do thm mnh c vo xng nn cn c ch nh tt cho cc vim xng ty. 2.6. Nhm Quinolon 2.6.1. Ngun gc v tnh cht l ha L khng sinh hon ton tng hp. Loi kinh in c aci d nalidixic (1963) l tiu biu. Loi mi, do gn thm fluor vo v tr 6, gi l 6 - fluoroquinolon (pefloxacin 1985) c ph khng khun rng hn, ung c. Tt c u l cc acid yu, cn trnh nh sng 2.6.2. C ch tc dng v ph khng khun Cc quinolon u c ch ADN gyrase, l enzym m vng xon ADN, gip cho s sao chp v phin m, v vy ngn cn s tng hp ADN ca vi khun. Ngoi ra cn tc dng c trn ARN mnn c ch tng hp protein vi khun. Cc quinolon u l thuc dit khun. Acid nalidixic (cn gi l quinolon th h 1) ch c ch ADN gyrase nn ch c

tc dng dit khun gram (-) ng tit niu v ng tiu ha. Khng tc dng trn trc khun m xanh (Pseudomonas aeruginosa). Cc fluoroquinolon c tc dng ln 2 enzym ch l ADN gyr ase v topoisomerase IV ca vi khun (Drlica, 1997) nn ph khng khun rng hn, hot tnh khng khun cng mnh hn t 10- 30 lt l n. Cc fluoroquinolon th h u, cn gi l quinolon th h 2 (pefloxacin, norfloxacin, ofloxacin, ciprofloxacin 1987 - 1997) c khc nhau tng i v tc ng trn gyrase v topoisomerase IV: trn vi khun gram ( ), hiu lc khng gyrase mnh hn; cn trn vi khun gram (+), li c hiu lc khng topoisomerrase IV mnh hn. Cc fluoroquinolon th h mi cn gi l quinolon t h h 3 (levofloxacin, trovafloxacin, t 1999) c tc ng cn bng trn c 2 enzym v vy ph khng m rng trn gram (+), nht l cc nhim khun ng h hp, v vi khun kh khng thuc hn v phi t bin 2 ln trn 2 enzym ch. Ph khng khun ca fluoroquinolon gm: E.coli, Salmonella, Shigella, Enterobacter, Neisseria, P.aeruginosa, Enterococci, ph cu, t cu (k c loi khng methicilin). Cc vi khun trong t bo cng b c ch vi nng fluoroquinolon huyt tng nh chlamidia, mycoplasma, brucella, mycobacterium 2.6.3.Dc ng hc Acid nalidixic d hp thu qua tiu ha v thi tr nhanh qua thn, v vy c dng lm khng sinh ng tit niu, nhng phn ln b chuyn ho gan, ch 1/4 qua thn di dng cn hot tnh. Cc fluorquinolon c sinh kh dng cao, ti 90% (pefloxacin), hoc trn 95% (gatifloxacin v nhiu thuc khc), t gn vo protein huyt tng (10% vi ofloxacin, 30% vi pefloxacin). Rt d thm vo m v vo trong t bo, k c dch no tu. B chuyn ho gan ch m t phn. Pefloxacin b chuyn ha thnh norfloxacin vn cn hot tnh v chnh n b thi tr qua thn 70%. Thi gian bn thi t 4h (Ciprofloxacin) n 12h (pefloxacin). Nng thuc trong tuyn tin lit, thn, i thc bo, bch cu ht cao hn trong hu yt tng. 2.6.4. Ch nh - Nhim khun ng tit niu v vim tuyn tin lit, acid nalixilic, norfloxacin, ciprofloxacin, ofloxacin, tc dng ging nhau, tng t nh

trimethoprim sulfamethoxazol - Bnh ly theo ng tnh dc: .Bnh lu: ung liu du y nht ofloxacin hoc ciprofloxacin . Nhuyn h cam: 3 ngy ciprofloxacin . Cc vim nhim vng chu hng: ofloxacin phi hp vi khng sinh chng vi khun k kh (clindamycin, metronidazol) - Nhim khun ng tiu ha: do E. coli, S.typhi, vim phc mc trn bnh nhn phi lm thm phn nhiu ln. - Vim ng h hp trn v di, vim phi mc phi ti cng ng, vim xoang: cc fluoroquinolon mi nh levofloxacin, trovafloxacin, gatifloxacin. - Nhim khun xng - khp v m mm: thng do trc khun gra m (-) v t cu vng, liu lng phi cao hn cho nhim khun tit niu (500 - 750 mg 2 ln/ ngy) v thng phi ko di (7- 14 ngy, c khi phi ti 4 - 6 tun) 2.6.5. c tnh Khong 10%, t nh n nng: bun nn, nn, tiu chy, d ng ngoi da, tng p lc ni s (chng mt, nhc u, l ln, co git, o gic). Trn tr nh, c acid chuyn ha, au v sng khp, au c. Thc nghim trn sc vt cn non thy m sn b hu hoi cho nn khng dng cho tr em di 18 tui, ph n c mang v ang nui con b. Khng dng cho ngi thiu G 6PD. 2.6.6. Ch phm v cch dng 2.6.6.1. Loi quinolon kinh in , acid nalidixic (Negram): nhim khun tit niu do trc khun gram (-), tr pseudomonas aeruginosa. Ung 2g/ ngy, chia 2 ln. ng tim t/m ch c dn?g trong bnh vin khi tht cn thit. 2.6.6.2. Loi fluorquinolon: dng cho cc nhim khun bnh vin do cc chng a khng khng sinh nh vim phi, nhim khun huyt, vim mng no, mng tim, nhim khun xng cn iu tr ko di. Mt s ch phm ang dng : Pefloxacin (Peflacin) : ung 800 mg/ 24h chia 2 ln Nor floxacin (Noroxin): ung 800 mg/ 24h chia 2 ln Ofloxacin (Oflocet) : ung 400 - 800 mg/ 24h chia 2 ln Ciprofloxacin (Ciflox) : ung 0,5 - 1,5g/ 24 h chia 2 ln Levofloxacin (Levaquin): ung 500 mg Gatifloxacin (Tequin): ung liu duy nht 400 mg/ 24h Hin nay fluoroquinolon l thuc khng sinh c dng rng ri v:

- Ph rng - Hp thu qua tiu ha tt, t nng huyt tng gn vi truyn tnh mch. - Phn phi rng, c cc m ngoi mch - t/2 di, khng cn dng nhiu ln - D dng nn c th iu tr ngoi tr - R hn so vi iu tr bng khng sinh tim truyn khc. - Tng i t tc dng khng mong mun V vy sinh ra lm dng thuc. Nn trnh dng cho cc nhim khun thng thng. H y ginh cho cc nhim khun nng, kh tr nh: Pseudomonas aeruginosa, t cu vng khng methicilin, E. coli v khun gram ( -) khng trimethoprim - sulfamethoxazol. 2.7. Nhm 5- nitro- imidazol 2.7.1. Ngun gc v tnh cht L dn xut tng hp, t tan tro ng nc, khng ion ha pH sinh l, khuch tn nhanh qua mng sinh hc. Lc u (1960) dng chng n bo (trichomonas, amip) (xem bi thuc cha amip), sau (1970) thy c tc dng khng khun k kh. 2.7.2. C ch tc dng v ph khng khun Nitroimidazol c c tnh chn lc trn cc vi khun k kh v c cc t bo trong tnh trng thiu oxy. Trong cc vi khun ny, nhm nitro ca thuc b kh bi cc protein vn chuyn electron c bit ca vi khun, to ra cc sn phm c, dit c vi khun, l m thay i cu trc ca ADN. Ph khng khun: mi cu khun k kh, trc khun k kh gram ( -), trc khun k kh gram (+) to c bo t. Loi trc khun k kh gram (+) khng to c bo t thng khng c thuc (propionibacterium). 2.7.3. Dc ng hc Hp thu nhanh qua tiu ha, t gn vo protein huyt tng, thm c vo mi m, k c mng no, t/2 t 9h (metronidazol) n 14h (ornidazol). Thi tr qua nc tiu phn ln di dng cn hot tnh, lm nc tiu c th b xm mu. 2.7.4. c tnh Bun nn, sn da, ri lon thn kinh, gim bch cu, h huyt p. 2.7.5. Ch phm, cch dng Thng c dng trong vim mng trong tim, apxe no, d phng nhim khun sau phu thut vng bng- h chu C tc dng hip ng vi khng sinh nhm lactam v aminosid. Metron-

idazol (Flagyl), ornidazol (Tiberal): ung 1,5g hoc 30 - 40 mg/ kg/ 24h. (Xin xem thm bi thuc chng amp) 2.8. Sulfamid Nm 1935 Domagk pht hin ra tnh khng khun ca mt phm nhum l sulfamidochrysoidin (Prontosil), t m r a kz nguyn ca cc thuc chng nhim khun trc khi c penicilin. 2.8.1. Ngun gc v tnh cht Sulfamid u l cc cht tng hp, dn xut ca Sulfanilamid do thay th nhm NH2 hoc nhm - SO2NH2. L bt trng, rt t tan trong nc, d tan hn tron g huyt thanh v mt. 2.8.2. C ch tc dng v ph khng khun PABA (para amino benzoic acid) l ngun nguyn liu cn thit cho vi khun tng hp acid folic pht trin. Do c cu trc ha hc gn ging vi PABA nn sulfamid tranh chp vi PABA ngn cn qu trnh tng hp acid folic ca vi khun.

Ngoi ra, sulfamid cn c ch dihydrofolat synthetase, mt enzym tham gia tng hp acid folic (xem s mc 2.9). V vy sulfamid l cht km khun. T bo ng vt c v v vi khun no c th s dng trc tip acid folic t mi trng th u khng chu nh hng ca sulfamid. V mt l thuyt, ph khng khun ca sulfamid rt rng, gm hu ht cc cu khun, trc khun gram (+) v (-). Nhng hin nay, t l khng thuc v khng cho gia cc sulfamid ang rt cao nn hn ch vic s dng sulfamid rt nhiu. Vi khun khng thuc bng cch tng tng hp PABA hoc gim tnh thm vi sulfamid. 2.8.3. Dc ng hc - Cc sulfamid c hp thu nhanh qua d dy v rut (tr loi sulfaguanidin), 70 - 80% liu ung vo c mu, gn vi protein huyt tng 40 - 80%, nng ti a t c sau 2 - 4h. - T mu, sulfamid khuch tn rt d dng vo cc m, vo dch no tu (bng 1/2 hoc tng ng vi nng trong mu), qua rau thai, gy c. - Cc qu trnh ch uyn ha ch yu gan ca sulfamid gm:

. Acetyl ha, t 10 - 50% tuz loi. Cc sn phm acetyl ha rt t tan, d gy tai bin khi thi tr qua thn. Cc sulfamid mi c t l acetyl ha thp (6 16%) v sn phm acetyl ha li d tan. . Hp vi acid glucu ronic (sulfadimethoxin), rt d tan . Oxy ha Thi tr: ch yu qua thn (lc qua cu thn v bi xut qua ng thn). Dn xut acetyl ha (25 - 60% trong nc tiu) khng tan, to tinh th c th gy i mu hoc v niu. V vy, cn ung nhiu nc (1g/ 0,5 lt). * Phn loi sulfamid : V tc dng ca sulfamid u ging nhau, vic iu tr da vo dc ng hc ca thuc cho nn ngi ta chia cc sulfamid lm 4 loi: - Loi hp thu nhanh, thi tr nhanh: nng ti a trong mu sau ung l 2 - 4h. t/2=6-8h, thi tr 95% trong 24h. Gm sulfadiazin, sulfisoxazol (Gantrisin), sulfamethoxazol (Gantazol). Dng iu tr nhim khun theo ng mu. - Loi hp thu rt t: dng cha vim rut, vim lo t i trng. Gm sufaguanidin (Ganidan), salazosulfapyridin (Salazopyrin). - Loi thi tr chm: duy tr c nng iu tr trong mu lu, t/2 c th ti 7 9 ngy nn ch cn ung 1 ln ngy. Hin dng sulfadoxin (Fanasil), phi hp vi pyrimethamin trong Fansidar d phng v iu tr st rt khng cloroquin . - Loi dng ti ch: t hoc kh tan trong nc. Dng iu tr cc vt thng ti ch (mt, vt bng) di dng dung dch hoc kem. C sulfacetamid, silver sulfadiazin, mafenid. 2.8.4. c tnh - Tiu ha: bun nn, nn, tiu chy. - Thn: do sulfamid t tan v cc dn xut acetyl ha kt ta trong ng thn gy cn au bng thn, i mu, v niu (iu tr, d phng bng ung nhiu nc v base ha nc tiu). Vim ng k thn do d ng. - Ngoi da: cc biu hin d ng t nh n rt nng nh hi chn g StevensJohnson, hi chng Lyell. Thng gp vi loi su?lfamid chm. - Mu: thiu mu tan mu (do thiu G 6PD), gim bch cu, gim tiu cu, mt bch cu ht, suy ty. - Gan: tranh chp vi bilirubin gn vo protein huyt tng, d gy vng

da, c. Khng dng cho ph n c thai v tr em mi . Khng dng cho ngi suy gan, suy thn, thiu G 6PD, a tng d ng. 2.8.5. Ch phm cch dng Do c nhiu c tnh v c khng sinh thay th, sulfamid ngy cng t dng mt mnh. Thng phi hp sulfameth oxazol vi trimethoprim (xin xem phn sau). Hin cn c ch nh trong cc trng hp sau: - Vim ng tit niu: . Sulfadiazin: vin nn 0,5g . Sulfamethoxazol (Gantanol): vin nn 0,5g Ngy u ung 2g 4 ln; nhng ngy sau 1g 4 ln. Ung t 5 - 10 ngy - Nhim khun tiu ha: . Sulfaguanidin (Ganidan): vin nn 0,5g ung 3 - 4g/ ngy . Sulfasalazin (Azalin): vin nn 0,5g ung 3 - 4 g/ ngy - Dng bi ti ch: . Bc sulfadiazin (Silvaden): 10mg/ g kem bi 2.9. Phi hp sulfamid v trimethoprim 2.9.1. C ch tc dng v ph khng khun S di y cho thy v tr tc dng ca sulfamid v trimethoprim trong qu trnh tng hp acid folic. Hai thuc c ch tranh chp vi 2 enzym ca vi khun 2 khu ca qu trnh tng hp nn c tc dng hip ng mnh hn 20- 100 ln so vi dng sulfamid mt mnh.

Hnh 14.5. V tr tc dng ca sulfamid v trimethoprim trong qu trnh tng hp acid folic Trimethoprim l mt cht ha hc tng hp c tc dng c ch dihydrofolat reductase ca vi khun 50.000- 100.000 ln mnh hn trn ngi, v c ch trn enzym ca k sinh trng st rt 2000 ln mnh hn ngi. Ph khng khun rng v chng khng li t hn so vi sulfamid. C tc dng dit khun trn mt s chng. Khng tc dng trn Pseudomonas, S.perfringens, xon khun. 2.9.2. Dc ng hc T l l{ tng cho hip ng tc dng ca nng thuc trong mu ca sulfamethoxazol (SMZ):

trimethoprim (TMP) l 20: 1. V TMP hp thu nhanh hn SMZ (pic huyt thanh l 2 v 4h) v t/ 2 10h, cho nn nu t l SMZ: TMP trong vin thuc l 5: 1 (800 mg sulfameth oxazol + 160 mg trimethoprim), sau khi ung, nng trong mu s t c t l 20: 1(40 g/ mL huyt tng sulfamethoxazol v 2 g/ mL trimethoprim). C 2 thuc c hp thu qua ng ung, phn phi tt vo cc m (dch no tu, mt, tuyn tin lit). Thi tr ch yu qua nc tiu vi nng cn hot tnh. 2.9.3. c tnh v chng ch nh Thuc phi hp ny c tt c cc c tnh ca sulfamid. Ngoi ra, trn nhng ngi thiu folat, TMP c th gy thiu mu nguyn hng cu khng l, t l b ban cng cao hn. Khng dng cho ph n c thai v tr em mi (nht l non) 2.9.4. Ch phm v cch dng Thuc kt hp c ch nh chnh trong nhim khun tit niu, tai - mihng, ng h hp, ng tiu ha (thng hn, t), bnh hoa liu (clamydia) - Phi hp trimethoprim + sulfamethoxazol: . Vin Bactrim, Cotrimoxazol, gm trimethoprim (80 hoc 160 mg) v sulfamethoxazol (400 hoc 800 mg). Liu thng dng l 4 - 6 vin (loi 80 mg TMP + 400 mg SMZ), ung trong 10 ngy . Dch treo: trong 5 mL c 400 mg TMP + 200 mg SMZ. Dng cho tr em. . Dch tim truyn: TMP 80? mg + SMZ 400 mg trong ng 5 mL. Ho trong 125 mL dextrose 5% truyn tnh mch trong 60 - 90 pht. 3. MT S VN V S DNG KHNG SINH 3.1. Nguyn tc dng khng sinh 1. Ch dng khng sinh cho nhim khun. Khng dng cho nhim virus (c loi ring). Dng cng sm cng tt. 2. Ch nh theo ph tc dng. Nu nhim khun xc nh, dng khng sinh ph hp. 3. Dng liu t c nng v n nh. Khng dng liu tng dn. 4. Dng thi gian: trn c th nhim khun, vi khun nhiu giai on khc nhau vi khng sinh. Nu sau 2 ngy dng khng sinh, st khng gim, cn thay hoc phi hp khng sinh. Khi iu tr ht st, vn cn cho

thm khng sinh 2 3 ngy na. Ni chung, cc nhim khun cp, cho khng sinh 5 - 7 ngy. Cc nhim khun c bit, dng lu hn, nh: vim ni tm mc Osler, nhim khun tit niu (vim b thn): 2 - 4 tun; vim tuyn nhip h: 2 thng; nhim khun khp hng: 3 - 6 thng; nhim lao: 9 thng 5. Chn thuc theo dc ng hc (hp thu, phn phi, chuyn ha, thi tr) ph thuc vo ni nhim khun v tnh trng bnh nhn. 6. Cn phi hp vi bin php iu tr khc: khi nhim khun c m, hoi t m, vt l (si) th cho khng sinh phi km theo thng m, phu thut. 3.2. Nhng nguyn nhn tht bi trong vic dng khng sinh 1. Chn khng sinh khng ng ph tc dng 2. Khng sinh khng t c ti ngng tc dng ti nhim khun, do liu lng khng hp l{, do dc ng hc khng thch hp, do tng tc thuc lm gim tc dng ca khng sinh 3. Do vi khun khng thuc. Cn thay khng sinh khc hoc phi hp khng sinh. 3.3. Vi khun khng khng sinh 3.3.1. Khng t nhin: vi khun c tnh khng t trc khi tip xc vi khng sinh, nh sn xut lactamase, cu trc ca thnh vi khun khng thm vi khng sinh. 3.3.2. Khng mc phi: vi khun ang nhy cm vi khng sinh, sau mt thi gian tip xc, tr thnh khng nhy cm na, do: * t bin hoc khng qua nhim sc th. Mi vi khun u c protein ch gn vi kh ng sinh c th ti ribosom, DNA gyrase, RNA polymerase Do t bin, cc protein ch thay i, khng gn khng sinh na. *Khng qua plasmid: c nhiu dng. Thng l sn xut cc enzym lm bt hot khng sinh, hoc gim i lc ca khng sinh vi protein ch, hoc thay i ng chuyn ha. Vi khun khng khng sinh c th pht trin s khng cho vi khng sinh trong cng h. Qua plasmid c th khng nhiu loi khng sinh mt lc. Ngi ln u nu nhim vi khun khng khng sinh, mc du ch a dng khng sinh bao gi c khng khng sinh ngay. Loi khng mc phi thng l do dng khng sinh khng ng liu hoc lm

dng thuc, ang gy mt tr ngi rt ln cho vic iu tr. 3.4. Phi hp khng sinh 3.4.1. Ch nh phi hp khng sinh 1. Nhim 2 hoc nhiu vi khun mt lc 2. Nhim khun nng m nguyn nhn cha r 3. S dng tc dng hip ng lm tng hot tnh khng sinh trong mt s nhim khun c bit: . Vim ni tm mc: penicilin + streptomycin . Trimethoprim + sulfamethoxazol . Khng sinh lactam + cht c ch lactama?se 4. Phng nga xut hin vi khun khng khng sinh. Ch phi hp khng sinh cho mt s t cc trng hp nhim khun trong bnh vin nh cu khun rut, mt s trc khun gram ( -) (trc khun m xanh, trc khun mt loi Serratia, Enterobacter, Citrobacter ). 3.4.2. Nhc im ca phi hp khng sinh Khi thy thuc khng hiu r v phi hp khng ng s: . D gy khng do s chn la ca vi khun . Tng c tnh ca khng sinh . Hip ng i khng . Gi thnh iu tr c ao Ni chung, nn hn ch phi hp v c khng sinh ph rng 3.4.3. Mt s nhim khun thng gp v cch chn khng sinh. Bng gii thiu mt s cch la chn khng sinh. Bng 14.2.La chn khng sinh trong iu tr nhim khun

BI 22. THUC ST KHUN - TY U 1. I CNG 1.1. nh ngha - Thuc st khun , thuc kh trng (antiseptics) l thuc c tc dng c ch s pht trin ca vi khun c in vitro v in vivo khi bi trn b mt ca m sng (living tissue) trong nhng iu kin thch hp. - Thuc ty u, cht ty u (disinfectants) l thuc c tc dng dit khun trn dng c, c, mi trng.

1.2. c im - Khc vi khng sinh hoc cc ha tr liu dng ng ton thn, cc thuc ny t hoc khng c c tnh c hiu. - Tc dng khng khun ph thuc nhiu vo nng , nhit v thi gian tip xc: nng rt thp c th kch thch s pht trin ca vi khun, nng c ao hn c th c ch v nng rt cao c th dit khun. - lm v khun, c th dng cc phng php khc: + Nhit + Dung dch khng chu nhit, c th lc qua mng c l d = 0,22 micron, hoc chiu tia cc tm c bc sng 254nm vi liu khong 20 0.000 microwatt sec/cm2, hoc chiu tia , hoc tit trng lnh (cho qua kh ethylen oxyd hoc ngm trong dung dch glutaraldelhyd, ru formaldehyd) 1.3. Cc thuc st khun l{ tng cn t c cc tiu chun sau - Tc dng nng long - Khng c vi m hoc lm hng dng c - n nh - Khng lm mt mu hoc khng nhum mu - Khng mi - Tc dng nhanh ngay c khi c mt protein l, dch d vim - R Hin cha c cht no t c! 1.4. Phn loi theo c ch tc dng - Oxy ha: H2O2, phc hp c clo, KMnO4 - Alkyl ho: Ethylenoxyd, Formaldehyd, Glutaraldehyd - Lm bin cht protein: cn, phc hp phenol, iod, kim loi nng - Cht din hot: cc phc hp amino bc 4 - Ion ho cation: cht nhum - Cht gy tn thng mng: clorhexidin 1.5. Nguyn tc dng thuc st khun 1.5.1. da lnh - Ra sch cht nhn - Bi thuc st khun 1.5.2. Trn vt thng - o pH ch cn bi. Xc nh vi khun (nu cn) - Lm sch vt thng

- Ra bng nc dit khun - Bi thuc tuz theo pH vt thng 2. CC THUC ST KHUN THNG THNG 2.1. Cn Thng dng cn ethylic (C 2H5OH) v isopropyl (isopropanol) [CH 3CH(OH)CH3] 60 70%. Tc dng gim khi cn <60% v >90%. C ch: gy bin cht protein Tc dng: dit khun, nm bnh, siu vi. Khng tc dng t?rn bo t. Dng ring hoc phi hp vi tc nhn dit khun khc. nng thp cn c th c s dng nh cc c cht cho mt s vi khun, nhng nng cao cc phn ng kh hydro s b c ch. 2.2. Nhm halogen 2.2.1. Iod - C ch: Iod lm kt ta protein v oxy ha cc enzim ch yu theo nhiu c ch: phn ng vi cc nhm NH, SH, phenol, cc carbon ca cc acid bo khng bo ho, lm ngn cn to mng vi khun. - Iod c tc dng dit khun nhanh trn nhiu vi khun, virus v nm bnh. Dung dch 1: 20.000 c tc dng dit khun trong 1 pht, dit bo t trong 15 pht v tng i t c vi m. - Ch phm v cch dng: Iod c dng nh thuc st khun v ty u. + Cn iod: c iod 2% + kali iodid 2,4% ( lm iod d tan) + cn 44 -50%. Nhc im l hi kch ng da, st v nhum mu da. + Povidon - iod, l cht dn iod (iodophore), ch to bng cch to phc iod vi polyvinyl pyrolidon. Iod s c gii phng t t. Hin c dng nhiu v vng bn hn cn iod nhit mi trng, t kch ng m, t n mn ki m loi. Tuy nhin gi thnh t. Vi vt thng m, do c vi nguyn bo si (fibroblast) nn c th lm chm lnh. Ch phm: - Betadin - Povidin 2.2.2. Clo

- Tc dng v c ch: clo nguyn t phn ng vi nc to thnh acid hypoclor (HOCl). C ch dit khun cn cha r. + C th HOCl gii phng oxy mi sinh ra oxy ha cc thnh phn ch yu ca nguyn sinh cht: 2HOCl = H2O + Cl2 + O + Hoc, Cl kt hp vi protein ca mng t bo to thnh phc hp N - Clo lm gin on chuyn ha mng t bo. + Hoc, oxy ha nhm - H ca mt s enzym lm bt hot khng hi phc. Tc dng pH trung tnh hoc acid nh (ti u l 5) nng 0,25 ppm (phn triu) Clo c tc dng dit khun trn nhiu chng, tr vi khun lao c sc khng 500 ln mnh hn. Clo khng cn c dng nh mt thuc st khun v c tc dng kch ng v b mt hot tnh bi cc cht hu c do chng d kt hp vi cc cht hu c. Tuy nhin, n cn c dng nhiu lm thuc ty u v kh trng nc v r. - Cc ch phm: . Cloramin: l cc dn xut Cl N ca sulfonamid, dn xut guanidin, phc hp N d vng, cha 25 - 29% Clo. Tc dng ko di, t kch ng m, nhng yu. Thng dng Cloramin T (Na -p-toluen sulfon cloramid), dung dch 1 2% ra vt thng. . Halazon (acid p -dicloro sulfamidobenzoic): vin 4mg st khun cho 1 lt nc, ung c sau 30 pht. 3. CC CHT OXY HA Thng dng peroxyd hydro (H 2O2, nc oxy gi), thuc tm (KM nO 4). Do c tc dng oxy ha, to gc t do, nn cc thuc ny lm tn hi mng vi khun, ADN v mt s thnh phn ch yu khc ca t bo. Nc oxy gi 3 - 6% c tc dng dit khun v virus, nng cao hn (10 25%) dit c bo t. Khi tip xc vi m s gii phng oxy phn t. Khng thm vo m nn ch dng sc ming v ra cc vt thng, c c b phn gi. Catalase lm bt hot thuc. Nc oxy gi c vi nguyn bo si nn c th lm chm lin so vt thng. Khng c dng H2O2 di p lc ra cc vt thng su c rch nt v c th to hi di da. - Thuc tm: v?i nng 1:10.000, c tc dng dit nhiu loi vi khun trong 1 gi. Nng cao hn d kch ng da. Thng dng ra cc vt thng

ngoi da c r nc. 4. CC KIM LOI NNG Mi kim loi nng u c tc dng dit khun. Thng dng l Hg, Ag. 4.1. Thu ngn - Tc dng v c ch: ion Hg++ lm kt ta protein v c ch cc enzym mang gc SH. V vy cc vi khun b c ch bi Hg, c th hot ng tr li khi tip xc vi cc phc hp c nhm SH. Thu ngn hu c c tc dng km khun v yu hn cn, k m c hn Hg v c. - Ch phm: Thuc (mercurochrom) dung dch 2%, ch dng bi ngoi da. Khng nn bi din rng vng mt da. Khng c ung, c th gy c cho ng thn. Dng thn trng tr s sinh. 4.2. Bc - Tc dng v c ch: Bc ion kt ta protein v ngn cn cc hot ng chuyn ha c bn ca t bo vi khun. Cc dung dch mui bc v c c tc dng st khun. - Cc ch phm: . Bc nitrat dung dch 1% dng nh mt cho tr mi , chng c bnh lu cu gy vim mt. Hin ang thay th bng pomat khng sinh. . Bc - Sulfadiazin 1% di dng kem bi cha bng, lm gii phng t t c bc v sulfadiazin, c tc dng dit khun tt v lm gim au. Bi din rng v ko di, i khi c th gy gim bch cu. . Cc ch phm bc di dng keo (collargol, protargol, arg yrol) c tc dng km khun tt, t gy thng tn cho m. Ch phm cha 20% bc dng st khun nim mc. Thuc b hu bi nh sng nn phi trong l mu. Mi ch phm bc dng lu gy chng nhim bc (argyrism). 5. X PHNG X phng l cht din hot l oi anion, thng l cc mui Na hoc K ca mt s acid bo. V NaOH v KOH l cc base mnh trong khi phn ln acid bo li l cc acid yu, v vy cc x phng khi tan trong nc u l cc base mnh (pH 8.0 - 10.0), d kch ng da (pH ca da = 5,5 - 6,5). Mt s x phng c sn xut vi pH = 7. Cc x phng loi b trn b mt da cc cht bn, cc cht xut tit, biu m trc vy v mi vi khun cha trong . lm tng tc dng st khun

ca x phng, mt s cht dit khun c cho thm vo nh hexaclorophan, phenol, carbanilid, l nhng cht s trnh by di. 6. CC HP CHT CHA PHENOL Phenol c Lister dng u tin t nm 1867 tit khun. Do lm bin cht protein v kch ng da nn c, ch dng ty u. Ngy nay dng cc cht thay t h. 6.1. Hexaclorophen L cht km khun mnh. X phng v cht ty u cha 3% hexaclorophen c tc dng km khun mnh v lu bn v gi li lp sng ca da. Nhng dng nhiu ln c th b nhim c, nht l tr nh. 6.2. Carbanilid v Salicylanilid Hin dng thay th hexaclorophen trong x phng st khun. Dng thng xuyn x phng ny c th lm gim mi ca c th do ngn nga c s phn hu ca vi khun vi cc cht hu c cho trong m hi. Cc loi x phng ny c th gy d ng hoc mn cm vi nh sng. 6.3. Clohexidin L dn xut ca biguanid, c tc dng lm ph v mng bo tng ca vi khun, c bit l chng gram (+). Dng trong x phng st khun, nc sc ming. Dung dch 4% d?ng ra vt thng. Thuc c th c gi li lu da n n tc dng km khun ko di. BI 23. THUC CHNG AMP TRICHOMONAS 1. THUC CHNG AMIP Amp k sinh ngi c nhiu loi, nhng ch c Entamoeba histolytica l loi duy nht thc s gy bnh cho ngi. Amp c th gy bnh rut (l amp, vim i trng mn tnh do amip) hoc cc m khc (p xe gan, amip phi, no, da) Ngi nhim E. histolytica l do n phi bo nang. Bo nang nhim vo ngi qua ng tiu ha bng nhiu cch: thc n, nc ung hoc do rui, gin vn chuyn mm bnh Cc bnh do amp ch yu l iu tr ni khoa, nu iu tr khng trit , bnh d tr thnh mn tnh. Th bo nang (th kn) l th bo v v pht tn amp nn rt nguy him v d lan truyn bnh (bo nang c thi ra theo phn v c th sng nhiu ngy trong nc). Amp th bo nang khi gp iu kin thun li s chuyn s ang th hot ng 1.1. Thuc dit amip m

Cc thuc ny rt c hiu qu i vi cc th n hng cu ca amp. 1.1.1. Emetin hydroclorid L alcaloid ca cy Ipeca. V c nhiu c tnh nn hin nay rt t dng 1.1.2. Dehydroemetin (Dametin, Mebadin) L dn xut tng hp c a emetin, c tc dng dc l{ tng t nhng t c hn emetin. 1.1.2.1.Tc dng Thuc c tc dng dit amp trong cc m, t c tc dng trn amip rut. Dehydroemetin c tc dng dit amp trc tip do cn tr s chuyn dch phn t ARN thng tin dc theo rib osom nn c ch khng phc hi s tng hp protein ca amp. 1.1.2.2.Dc ng hc Thuc hp thu k m qua ng tiu ha. Sau khi tim bp dehydroemetin c phn b vo nhiu m, tch lu gan, phi, lch v thn. Dehydroemetin thi tr qua nc tiu nhanh hn em etin nn t tch lu hn v do t c hn emetin. 1.1.2.3.Tc dng khng mong mun Tc dng khng mong mun ca thuc cng tng t nh khi dng emetin nhng nh v t gp hn. - Cc phn ng ti ch: ti vng tim thng b au, d to thnh p xe v trng. C th gp ban kiu eczema. - Tc dng trn thn kinh c: thng gp mt mi v au c, c bit chn tay v c. Cc triu chng ny ph thuc vo liu dng v l du hiu bo trc c tnh trn tim. - Tc dng trn tim: h huyt p, au vng trc tim, n hp tim nhanh v lon nhp l nhng biu hin thng gp khi b tn thng tim. Nhng thay i trn in tim (sng T dt hoc o ngc, ko di khong Q - T) l cc du hiu n sm hn. - Tc dng trn h tiu ha: bun nn, nn, au bng, tiu chy Cn c th gp cc triu chng: nga, run, d cm. 1.1.2.4.p dng iu tr Ch nh - L amp nng - p xe gan do amp

Ch nn dng dehydroemetin khi khng c cc thuc khc an ton hn hoc b chng ch nh Chng ch nh Ph n c thai khng c dng dehydroemeti n v thuc c vi thai nhi. Ht sc thn trng khi dng thuc bnh nhn c bnh tim, thn, thn kinh c, th trng chung qu yu hoc tr em. Khi dng dehydroemetin, ngi bnh phi lun lun c thy thuc theo di. Phi ngng luyn tp cng thng tro ng 4- 5 tun sau khi iu tr.? Liu lng - Ngi ln: 1 mg/ kg/ ngy, khng dng qu 60 mg/ ngy. Cn gim liu ngi cao tui v ngi b bnh nng (c th gim ti 50%). t iu tr 4 - 6 ngy. - Tr em: 1mg/ kg/ ngy, khng dng qu 5 ngy. Thuc nn dng qua ng tim bp su, khng tim tnh mch v d gy c cho tim, khng dng ng ung v kch ng gy nn. Cc t iu tr phi cch nhau t nht 6 tun. Trong iu tr l do amp, dng thm tetracyclin gim nguy c bi nhim. Khi iu tr p xe gan do amp phi ung thm cloroquin ng thi hoc ngay sau . Sau iu tr tt c cc bnh nhn nn ung thm diloxanid loi tr amip cn sng st kt trng, phng ti pht. 1.1.3. Metronidazol (Elyzol, Flagyl, Klion, Trichazol) L mt dn xut 5 - nitro- imidazol, c ph hot tnh rng, t tan trong nc, khng ion ha pH sinh l, khuch tn rt nhanh qua mng sinh hc. 1.1.3.1.Tc dng Metronidazol c hiu qu cao trong iu tr nhim amp ngoi rut (p xe gan, amp no, phi- lch) v amp thnh ru t. Thuc c tc dng dit amp th hot ng nhng t nh hng n th kn. Thuc cn c dng iu tr trichomonas ng niu - sinh dc, bnh do Giardia lamblia v cc vi khun k kh bt buc. C ch tc dng: trong cc vi khun k kh v ng vt nguyn sinh (n bo), nhm 5 - nitro ca thuc b kh thnh cc cht trung gian c vi t bo. Cc cht ny lin kt vi cu trc xon ca phn t DNA, lm v cc si DNA v cui cng lm t bo cht. Qu trnh kh nhm 5 - nitro ca thuc c s tham gia tch cc ca

ferredoxin mt protein xc tc c nhiu trong cc vi khun v n bo nhy cm vi thuc. Mt s nghin cu cho thy, cc chng khng metronidazol c cha t ferredoxin. 1.1.3.2.Dc ng hc Metronidazol hp thu nhanh v hon ton qua ng tiu ha. Sau khi ung 1 3 gi, thuc t nng ti a trong mu (6 - 40 g/ mL). Metronidazol gn rt t vo protein huyt tng (10- 20%) v c th tch phn phi ln (Vd 0,6- 0,8 lt/ kg) nn thuc khuch tn tt vo cc m v dch c th, c nng cao tro ng nc bt, dch no tu, sa m Thi gian bn thi l 7,5 gi. Trn 90% liu ung c thi tr qua thn trong 24 gi, ch yu l cc cht chuyn ha hydroxy (30 - 40%) v dng acid (10 - 22%). 10% metronidazol thi nguyn vn qua nc tiu, 14% qua ph n. 1.1.3.3.Tc dng khng mong mun Phn ng c hi thng ph thuc vo liu dng. Vi liu iu tr n bo, cc tc dng khng mong mun ca thuc thng nh, c phc hi v gp 4 - 5% bnh nhn c iu tr. Hay gp cc ri lon ng tiu ha: bun nn, c hn n, kh ming, li c v kim loi, au vng thng v v cc triu chng trn h thn kinh trung ng: au u, chng mt, bun ng. C th gp tiu chy, vim ming, phng rp da, pht ban, nga, d cm. Khi dng liu cao, ko di, thuc c th gy c n ng kinh, ri lon tm thn, vim a dy thn kinh ngoi bin, vim ty. Nc tiu c mu nu xm do cht chuyn ha ca thuc 1.1.3.4. p dng iu tr Ch nh - L amp cp rut - p xe gan do amp, amp trong cc m - Nhim trichomonas vaginalis : cn iu tr cho c ?v v chng. - Bnh do Giardia Lamblia - Nhim khun k kh; vim mng trong tim, nhim khun ton thn, p xe no, vim mng no c m, vim lot li cp, vim quanh thn rng Chng ch nh Khng nn dng Metronidazol cho ph n c thai (c bit trong 3 thng u), ph n cho con b, ngi c tin s qu mn vi thuc. Cn thn trng khi dng thuc bnh nhn c tin s ri lon th tng mu, bnh h thng thn kinh trung ng. Phi gim liu ngi b suy gan

nng. Liu lng Metronidazol c th ung di dng vin nn (250 mg, 500 mg) hoc dung dch treo metronidazol benzoat. Trng hp bnh nhn khng ung c, c th truyn tnh mch (dung dch 5 mg/ mL), tc truyn 5 mL/ pht. - iu tr l a mp cp: c th dng n c hoc tt hn nn phi hp vi iodoquinol hoc vi diloxanid furoat. Liu thng dng cho ngi ln l 750 mg, ngy ung 3 ln trong 5- 10 ngy, ung sau ba n. - p xe gan do amp: ngi ln ung 500 - 750 mg/ ln, ngy 3 ln trong 5 - 10 ngy. i vi tr em liu thng dng l 30 - 40 mg/ kg/ 24 gi, chia lm 3 ln, ung lin 5 10 ngy. - Bnh do Giardia: . Ngi ln: ung 250 mg, ngy 3 ln, trong 5 - 7 ngy hoc ung 1 ln 2g/ ngy, trong 3 ngy. . Tr em: ung 15 mg/ kg/ ngy, chia lm 3 ln, trong 5- 10 ngy. Tinidazol (Fasigyne): vin nn 500 mg. L dn xut th ca imidazol (C 8H13N3O4). Tc dng v c ch tc dng tng t metronidazol, ch khc nhau v dc ng hc: hp thu nhanh v hon ton qua ng tiu ha, nng ti a trong mu t c sau 2gi, t/2 = 12- 14 gi, gn vo protein huyt tng 8 12%, thm vo mi m, thi tr ch yu qua thn, phn nh qua phn (t l 5: 1). Liu lng: liu duy nht 2g. Hoc iu tr cc nhim khun k kh dng ngy u 2g; ngy sau 1g (hoc 500 mg 2 ln) trong 5- 6 ngy. 1.1.3.5.Tng tc thuc Metronidazol lm tng tc dng chng ng mu ca cc thuc khng vitamin K, c th gy chy mu nu dng ng thi metronidazol vi warfarin. Phenobarbital v cc thuc gy cm ng microsom gan lm tng chuyn ha metronidazol nn metronidazol thi tr nhanh hn. Metronidazol c tc dng kiu disulfiram (cai ru)v vy, khng nn ung ru trong thi gian dng thuc trnh tc dng c trn thn kinh: au u, bun nn, nn, chng mt, ri lon tm thn, l ln 1.2. Thuc dit amp trong lng rut (dit amp do tip xc) Thuc tp trung trong lng rut v c tc dng vi th minuta (sng hoi sinh trong lng rut) v bo nang (th kn). 1.2.1. Diloxanid (Furamid)

Diloxanid Furoat l dn xut dicloro acetamid c tc dn g ch yu vi amp trong lng rut. 1.2.1.1.Tc dng Thuc c tc dng dit trc tip amp trong lng rut nn c dng iu tr cc bnh amp rut. Diloxanid c hiu lc cao i vi bo nang amp. Khng c tc dng i vi amp trong cc t chc. C ch tc dng ca thuc cha c sng t. Diloxanid c cu trc gn ging cloramphenicol (u l dn xut dicloro acetamid) nn thuc c th c ch s tng hp protein ca vi sinh vt. 1.2.1.2.Dc ng hc Nhng nghin cu trn ng vt cho thy diloxanid hp thu rt chm nn nng thuc trong rut kh cao. Ti rut thuc (?Diloxanid furoat) b thu phn thnh diloxanid v acid furoic. Lng thuc hp thu c thi tr trn 50% qua thn di dng glucuronid trong 6 gi u tin. Di 10% liu dng thi tr qua ph n. 1.2.1.3.Tc dng khng mong mun Thuc dung np tt ngay c khi dng liu cao. Diloxanid t gy cc phn ng c hi nghim trng. Hay gp cc ri lon trn ng tiu ha: chng bng (87%), chn n (3%), nn (6%), tiu chy (2%), co cng bng (2%). t gp cc triu chng trn h thn kinh trung ng: nhc u, ng lm, chng mt, hoa mt, nhn i, d cm 1.2.1.4.p dng iu tr Ch nh Diloxanid c la chn iu tr amp th bo nang (khng c triu chng lm sng nhng vng khng c dch bnh lu hnh). Thuc cn c phi hp vi metronidazol dit amp th hot ng trong lng rut. Chng ch nh Khng nn dng thuc cho ph n c thai (3 thng u) v tr em di 2 tui. Liu lng Diloxanid ch dng theo ng ung - iu tr cho ngui bnh man g kn amp khng triu chng: . Ngi ln: mi ln ung 500 mg, ngy ung 3 ln trong 10 ngy. Nu cn, iu tr c th k o di n 20 ngy.

. Tr em: 20 mg/ kg/ ngy, chia lm 3 ln, ung lin 10 ngy. - iu tr l amp cp: cn iu tr bng metronidaz ol trc, sau tip theo bng diloxanid furoat liu nh trn. 1.2.2. Iodoquinol (Yodoxin, Moebequin) 1.2.2.1.Tc dng Iodoquinol (diiodohydroxyquin) l mt dn xut halogen ca hydroxyquinolein c tc dng dit amp trong lng rut nhng khng nh hng n amp th nh rut v trong cc t chc. C ch tc dng ca thuc cha c r rng. 1.2.2.2.Dc ng hc Thuc hp thu rt k m qua ng tiu ha (90% thuc khng c hp thu). Phn thuc vo c vng tun hon c thi gian bn thi khong 11 - 14 gi v thi tr qua n c tiu di dng glucuronid. 1.2.2.3.Tc dng khng mong mun Khi dng liu cao v ko di, iodoquinol c th gy nhng phn ng c hi trn h thn kinh trung ng. Thuc d gy phn ng c hi tr em hn ngi ln. Vi liu iu tr, iodoquinol c th gy m t s tc dng khng mong mun nh v thong qua nh: bun nn, nn, tiu chy (thng ht sau vi ngy), chn n, vim d dy, kh chu vng bng, au u, ban , nga 1.2.2.4.p dng iu tr Ch nh Phi hp iu tr cc trng hp nhim amp rut (t h nh v trung bnh) Chng ch inh Khng nn dng thuc cho nhng ngi c bnh tuyn gip, d ng vi iod, ph n c thai, tr em di 2 tui. Liu lng Ung 650 mg/ ln, ngy 3 ln, trong 10 - 20 ngy. Nn ung thuc sau ba n. 2. THUC DIT TRICHOMONAS Trichomonas k sinh ngi c 3 loi: Trichomonas hominis (Trichomonas intestinalis) Trichomonas bucalis (Trichomonas tenax) Trichomonas vaginalis Trichomonas vaginalis k sinh ch yu m o, trong nc tit m o, cc np nhn ca da b phn s inh dc ngi. Khi k sinh m o, Trichomonas chuyn pH t acid sang base, nn to iu kin cho vi khun trong m o sinh sn, gy vim m o cp v mn tnh. Thuc dit T.vaginalis gm c cc dn xut ca 5 - nitroimidazol

nh metronidazol (Flagyl), tinidazol (Fasigyn), ornidazol (Tibr?al, Secnidazol, Flagentyl), nimorazol (xin xem bi khng sinh) Trong iu tr bnh do Trichomonas cn m bo cc nguyn tc sau: - V sinh b phn sinh dc thng xuyn l rt cn thit v tng cng v sinh s gim mc vim nhim ca b phn sinh dc - iu tr cho c v v chng (v y l mt bnh ly truyn t v sang chng v ngc li) - Trong thi gian ang iu tr khng c giao hp bnh khi truyn t v sang chng hoc ngc li. - Phi phi hp di t Trichomonas vi dit vi khun v nm men (Candida albicans) v thuc khng dit trc khun D derlein (l vt ch bnh thng v cn ca m o), khng tc ng vi candida albicans. V vy, nn dng km acid boric trong iu tr Trichomonas chng s p ht trin ca nm men v phi hp vi khng sinh dit vi khun. Liu lng: ung 1 liu duy nht 2 g hoc dng 7 ngy, mi ngy 3 ln, mi ln 250 mg. BI 24. THUC CHNG GIUN SN 1. I CNG L mt nc vng nhit i, kh hu nng m nn Vit nam c t l nhim giun sn kh cao. nc ta, bnh do giun thng trm trng hn do sn. Cc loi giun c t l nhim cao Vit nam l giun a, giun tc, giun kim, giun mc (m) v giun ch. Bnh sn thng do sn l v sn dy gy ra. Cc loi sn l gy bnh cho ngi l sn l gan nh, sn l phi v sn l rut. nc ta bnh sn dy b thng gp hn sn dy ln. Thuc chng giun sn c nhiu loi, c sp xp da theo hnh th chung ca k sinh trng. a s thuc u hiu qu cao, t tc dng khng mong mun v d s dng. 2. THUC CHNG GIUN 2.1. Mebendazol (Fugacar, Vermox, Mebutar, Nemasole) L dn xut benzimidazol, t tan trong nc v dung mi hu c. Khng ht m, n nh khng kh. 2.1.1. Tc dng Thuc c hiu qu cao trn cc giai on trng thnh v u trng ca giun a, giun kim, giun tc, giun mc, giun m. Mebendazol cn dit c trng

ca giun a v giun tc. Vi liu cao, thuc c tc dng i vi nang sn. C ch tc dng ca mebendazol ging nh cc dn xut benzimidazol khc: thuc lin kt vi cc tiu qun ca k sinh trng, c ch s trng hp tiu qun thnh cc vi tiu qun (l thnh phn thit yu cho s hot ng bnh thng ca t bo k{ sinh trng), do lm gim hp thu glucose, cn d tr glycogen, gim ATP (ngun cung cp nng lng cho k sinh trng). Cui cng k sinh trng b bt ng v cht. 2.1.2. Dc ng hc Thuc t hp thu qua ng tiu ha, sinh kh dng qua ng ung di 20%. S hp thu s tng ln khi ung mebendazol cng vi thc n c cht bo. Sau khi ung 4 gi, thuc t c nng ti a trong mu. Khong 95% thuc gn vi protein huyt tng. Chuyn ha ch yu gan thnh cc cht hydroxy v amino ha mt hot tnh. Thi tr qua phn, ch mt lng nh (5 - 10%) thi qua nc tiu. 2.1.3. Tc dng khng mong mun Thuc dung np tt, t tc dng ph. i khi gp ri lon tiu ha (au bng, tiu chy), au u nh. Dng liu cao iu tr nang sn, thuc c th gy c ch tu xng, rng tc, vi m gan, vim thn, st v vim da trc vy. V vy, khi dng liu cao,? phi theo di u n nng transaminase trong huyt thanh, bch cu v tiu cu. 2.1.4. p dng iu tr 2.1.4.1.Ch nh iu tr nhim mt hoc nhiu loi giun nh giun a, giun kim, giun tc, g iun mc, giun m Khi khng c albendazol, c th dng mebendazol trong bnh nang sn. 2.1.4.2.Chng ch nh Khng dng mebendazol cho nhng ngi mn cm vi thuc, ph n c thai, tr em di 2 tui, suy gan. 2.1.4.3.Liu lng Ngi ln v tr em trn 2 tui dng li u nh nhau - Nhim giun a, giun tc, giun mc, giun m: ung mi ln 100 mg, ngy 2 ln trong 3 ngy lin, hoc c th dng liu duy nht 500 mg. - Nhim giun kim: liu duy nht 100 mg, ung nhc li sau 2 tun v giun kim rt d b ti nhim. - Bnh nang sn: ung 40 mg/ kg/ ngy, trong 1 - 6 thng

2.1.5. Tng tc thuc - Cimetidin c ch chuyn ha mebendazol, c th lm tng nng mebendazol trong huyt tng. - Dng ng thi vi phenytoin hoc carbamazepin s lm gim nng mebendazol trong mu. 2.2. Albendazol (Albenza, Eskazole, Zeben, Zentel) Albendazol l mt dn xut benzimidazol carbamat, cu trc ha hc c nhiu lin quan vi mebendazol. 2.2.1. Tc dng Thuc c tc dng tt vi nhiu loi giun nh giun a, giun kim, giun tc, giun mc, giun m, giun l n, giun xon v sn dy. Albendazol c tc dng trn c giai on trng thnh v giai on u trng ca cc loi giun sn k sinh trong ng tiu ha, dit c trng giun a v giun tc. C ch tc dng tng t nh mebendazol. 2.2.2. Dc ng hc Sau khi ung, albendazol c hp thu rt km (5%). V chuyn ha ln u ti gan rt nhanh nn khng thy albendazol hoc ch thy dng vt trong huyt tng. Albendazol sulfoxid (cht chuyn ha vn cn hot tnh ca albendazol) gn 70% vi protein huyt tng, qua c hng ro mu no v c nng trong dch no tu bng 1/3 nng trong huyt tng. Thi tr phn ln qua thn, mt lng nh qua mt. Thi gian bn thi khong 9 gi. 2.2.3. Tc dng khng mong mun Khi iu tr trong thi gian ngn (1 - 3 ngy) khong 6 % bnh nhn gp mt vi tc dng khng mong mun nh, thong qua nh: au bng, tiu chy, chng mt, mt, mt ng. Dng liu cao, k o di iu tr bnh nang sn hoc bnh u trng sn ln c tn thng no, tc dng c hi thng gp nhiu v nng hn; au u, ri lon tiu ha (nn, bun nn, au bng), rng tc, ban , nga, gim bch cu 2.2.4. p dng iu tr 2.2.4.1.Ch nh - Nhim mt hoc nhiu loi giun nh giun a, giun kim, giun tc, giun mc, giun m, giun ln. - iu tr bnh nang sn v bnh u trng sn ln c tn thng no. 2.2.4.2.Chng ch nh Ph n c thai, tr em di 2 tui, ngi c bnh gan nng 2.2.4.3.Liu lng

Ngi ln v tr em trn 2 tui dng liu nh nhau. Khng cn phi nhn i hoc dng thuc ty. - Nhim giun a, giun kim, giun tc, g iun mc: ung liu duy nht 400 mg. Giun kim thng hay b ti nhim, c th dng nhc li sau 2 - 4 tun. - Nhim giun ln, sn dy; mi ngy ung 400 mg, trong 3 ngy - Bnh nang sn: dng 4 t, mi t 28 ngy, mi ngy 10 - 15 mg/ kg chia lm 3 ln. Cc t cch nhau 14 ngy. Tuy nhin thi gian ?iu tr cn tuz thuc vo tnh trng bnh v s dung np ca ngi bnh. - Nhim u trng sn ln c tn thng no: mi ngy 15 mg/ kg chia lm 3 ln, trong 28 ngy. 2.2.5. Tng tc thuc Dexamethason, cimetiin, p raziquantel lm tng nng albendazol sulfoxid trong mu khi dng phi hp 3. THUC CHNG SN 3.1. Niclosamid (cestocid, Yomesan, tredemine, niclocide) L dn xut salicylanilid c clor, bt mu vng nht, khng mi, khng v, khng tan trong nc. 3.1.1. Tc dng Thuc c hiu lc cao i vi sn b, sn ln, sn c (Diphyllobothrium latum), sn dy rut (Hymenolepis nana) khng c tc dng trn u trng sn ln. Thuc c tc dng ti ch, khi tip xc vi thuc, u v thn sn b git ngay v niclosamid c ch s o xy ha. Thuc cn nh hng n chuyn ha nng lng ca sn do c ch s sn sinh ra adenosin triphos phat (ATP) ty lp th. Niclosamid cng c ch s thu nhp glucose ca sn. Sn khng bm c vo rut, b tng ra ngoi theo phn thnh cc on nh. 3.1.2. Dc ng hc Thuc hu nh khng hp thu qua ng tiu ha. Thm vo thn sn qua tn thng m niclosamid to v sn, sn b dit ngay ti rut ca vt ch. 3.1.3. Tc dng khng mong mun Thuc dung np tt, t gy tc dng khng mong mun. C th gp cc ri lon nh ng tiu ha nh bun nn, nn, au bng, tiu chy. Cc triu chng: au u, hoa mt, ban v nga him gp hn v c th do gii phng cc khng nguyn t k sinh trng b phn hu. 3.1.4. p dng iu tr

3.1.4.1.Ch nh Niclosamid c dng khi b n him sn b, sn c v sn ln (nn dng praziquantel khi b nhim u trng sn ln) Dng iu tr sn dy rut khi khng c praziquantel 3.1.4.2.Chng ch nh Trng hp nhim sn b, sn c, sn ln: ung liu duy nht vo sau ba n sng, nn nhai k vin thu c. - Ngi ln: 2,0 g - Tr em 11- 34 kg: 1,0 g - Tr em > 34 kg: 1,5 g - Tr em < 11 kg: 0,5 g Trng hp nhim sn dy rut (Hymenolepis nana): dng trong 7 ngy lin tip - Ngi ln: mi ngy 2g ung 1 ln. - Tr em 11- 34 kg: ngy u ung 1 g, 6 ngy sau mi ngy 0,5 g ung 1 ln - Tr em > 34 kg: ngy u ung 1,5g, 6 ngy sau mi ngy 1g, ung 1 ln Khi b to bn, cn lm sch rut trc khi iu tr. Sau khi dng thuc, nu mun tng sn ra nhanh hn v nguyn con, nn dng thuc ty mu i c tc dng mnh nh magnesisulfat (ung 2 - 4 gi sau khi dng niclosamid) 3.1.5. Tng tc thuc Ru lm tng kh nng hp thu ca niclosamid qua ng tiu ha, gy c. V vy, khng c dng ru trong khi iu tr. 3.2. Praziquantel (Biltricid, Cysticid, Dronci t, Cesol) L dn xut isoquinolein - pyrazin tng hp, c ph tc dng rng, thng c la chn iu tr cc bnh sn l, sn dy. 3.2.1. Tc dng Thuc c hiu qu cao i vi giai on trng thnh v u trng ca sn mng, cc loi sn l (sn l gan nh, sn l phi, sn l rut) v sn dy (sn c, sn ch, sn mo, sn b, sn ln) Praziquantel khng dit c trng sn, khng phng c bnh nang sn. C ch tc dng: thuc lm tng tnh thm ca mng t bo sn vi ion calci, lm sn co cng v cui c n b ng lm lit c ca sn. Khi tip xc vi praziquantel, v sn xut hin cc mn nc, sau v tung

ra v phn hu. Cui cng sn b cht v b tng ra ngoi. 3.2.2. Dc ng hc Thuc c hp thu nhanh khi ung (ngay c khi ung trong ba n), trn 80% liu d ng c hp thu. Sau khi ung 1- 3 gi, thuc t nng ti a trong mu. Gn vi protein huyt tng khong 80%. Nng thuc trong dch no tu bng 15 - 20% nng trong huyt tng. Thi gian bn thi l 1 - 1,5 gi. Thi tr ch yu qua nc tiu, di dng chuyn ha (60 - 80%). 3.2.3. Tc dng khng mong mun Cc phn ng c hi thng nh, xy ra mt vi gi sau ung thuc v c th ko di ti 1 ngy, hay gp: au u, chng mt, chong vng, bun nn, nn, au bng, nga, m ay, st nh, au c - khp, tng nh enzym gan. Cc du hiu st nh, nga, pht ban i khi i cng vi tng bch cu a acid c th do gii phng protein ngoi lai t sn cht. Cc phn ng c hi thng gp nhng bnh nhn nhim sn nng, mc v tn sut ca phn ng c h i tng theo liu lng thuc dng. 3.2.4. p dng iu tr 3.2.4.1.Ch nh - Nhim cc loi sn mng gy bnh ngi, bnh sn l gan nh, sn l phi, sn l rut, sn dy ln, sn dy b. - Bnh do u trng sn ln (bnh go sn) no 3.2.4.2.Chng ch nh - Bnh go sn trong mt, bnh go sn tu sng - Nn thn trng khi dng praziquantel ngi b suy gan (phi gim liu), ph n c thai, ph n cho con b (ngng cho b trong nhng ngy iu tr v 72 gi sau iu tr v thuc qua c sa m) Khng c li xe, iu khin my mc trong khi dng thuc v praziquantel gy chng mt, chong vng. 3.2.4.3. Liu lng - Nhim sn mng: liu thng dng cho ngi ln v tr em trn 4 tui l 60 mg/ kg, chia lm 3 ln, cch nhau 4 - 6 gi trong ngy. - Nhim sn l gan nh , sn l phi, sn l rut: ung 75 mg/ kg, chia lm 3 ln, trong 1 - 2 ngy. - Nhim sn dy ln, sn dy b, sn dy ch dng liu duy nht 10 mg/ kg cho c ngi ln v tr em.

i vi bnh u trng sn ln no: ung 50 mg/ kg/ ngy, chia lm 3 ln , trong 14 n 15 ngy (c th n 21 ngy i vi mt s ngi bnh). Praziquantel thng ung ngay sau ba n, nut nguyn vin thuc, khng c nhai (thuc c v kh chu, c th gy bun nn) C th dng phi hp praziquantel vi dexamethason (6 - 24 mg/ ngy) hoc prednisolon (30- 60 mg/ ngy) gim tc dng ph trn thn kinh trung ng nhng ngi bnh mc u trng sn ln no. 3.2.5. Tng tc thuc Carbamazepin, phenytoin v corticoid lm gim ng k nng praziquantel trong huyt tng trong khi cimetidin c tc dng ngc li. 3.3. Metrifonat (Bilarcil) L mt phc hp phospho hu c, c dng trong iu tr t 1960, tc dng ch yu vi cc loi sn mng gy tn thng bng quang. 3.3.1. Tc dng Thuc c tc dng dit sn mng gy bnh bng quang c giai on trng thnh v u trng, khng c hiu lc i vi trng sn l do trng vn tn ti trong nc tiu mt vi thng sau khi sn trng thnh b dit. C ch tc dng c?a thuc cha hon ton bit r, c th do metrifonat c ch enzym cholinesterase, lm lit tm thi sn trng thnh. Cui cng sn b y t m ri mch bng quang n cc tiu ng mch ca phi, mc li v cht. 3.3.2. Dc ng hc Thuc hp thu nhanh qua ng tiu ha, nng ti a trong mu t c sau khi ung 1- 2 gi. Thi gian bn thi khong 1,5 gi. Metrifonat v dichlorvos (cht chuyn ha cn hot tnh ca metrifonat) c phn phi vo nhiu t chc v thi tr hon ton qua nc tiu trong vng 24 - 48 gi. 3.3.3. Tc dng khng mong mun Metrifonat c th gy ra c c triu chng cng h cholinergic nh: bun nn, nn, au bng, tiu chy, co tht ph qun, au u, hoa mt, chng mt, v m hi Cc du hiu ny c th bt u 30 pht sau khi ung thuc v ko di ti 12 gi. 3.3.4. p dng iu tr 3.3.4.1.Ch nh - Nhim sn mng gy tn thng bng quang. Thuc c gi thnh r nn c th p dng rng ri cho cng ng trong chng trnh iu tr sn mng bng quang. - Phng bnh cho tr em nhng vng c t l nhim bnh cao.

3.3.4.2.Chng ch nh Ph n c thai khng c dng m etrifonat. Sau giai on tip xc vi cht dit cn trng loi phospho hu c hoc cc thuc c ch cholinesterase khng nn dng metrifonat Trong 48 gi sau khi ung metrifonat khng c dng cc thuc gin c. 3.3.4.3.Liu lng Mi ln ung 7,5 - 10 mg/ kg, ng y 3 ln, trong 14 ngy. 3.3.5. Tng tc thuc Metrifonat hip ng vi tc dng gin c ca succinylcholin 3.4. Triclabendazol (Egaten) 3.4. Triclabendazol (Egaten) methylthiobenzimidazol. 3.4.1. Tc dng Triclabendazol c hiu lc cao vi sn l gan ln (Fasciola) v sn l phi (paragonimus). Thuc c a vo danh mc thuc thit yu iu tr sn l gan ln t 1997. C ch tc dng: thuc gn c chn lc vi cc tiu qun ca sn l, ngn cn s trng hp tiu qun thnh cc vi tiu qun, lm gim hp thu glucose v cn d tr glycogen ca sn. 3.4.2. Dc ng hc Thuc c hp thu nhanh qua ng tiu ha. S hp thu s tng ln khi ung triclabendazol sau ba n. Thi tr ch yu qua phn (90%), mt phn qua nc tiu (10%). Thi gian bn thi khong 11 gi. 3.4.3. Tc dng khng mong mun Thuc c th gy mt s tc dng khng mong mun nh v thong qua: au bng vng h sn phi, v m hi, chng mt, nhc u, st nh, ho, bun nn, nn, ni m n, nga. 3.4.4. p dng iu tr 3.4.4.1. Ch nh Triclabendazol c ch nh trong nhim sn l gan ln cp v mn tnh. 3.4.4.2. Chng ch nh Ph n c thai, ph n ang cho con b, bnh nhn qu mn vi thuc; ngi ang vn hnh my mc, tu xe. 3.4.4.3. Liu lng Ngi ln dng liu duy nht 10 mg/ kg, ung sau khi n no.

BI 25. THUC KHNG NM Thnh cng ca khng sinh chng vi khun v virus dn n s tng ng k t l nhim nm. Nhim nm thng c chia lm 2 loi, nhim nm ton thn v nhim nm ngoi da, nim mc. Cc thuc chng nm v th cng c chia lm 2 loi, ton thn v ti ch. Nhng thc ra thuc ton thn cng c tc d?ng ti ch v ngc li. 1. THUC CHNG NM TON THN 1.1. Amphotericin B 1.1.1. c im: Amphotericin c tm ra t nm 1956 (Gold) l mt trong s 200 cht thuc h khng sinh polyen macrolid, khng tan trong nc, v vy thuc tim dng di dng dch treo. 1.1.2. Tc dng v c ch Tc dng trn cc loi Candida albicans v Cryptococcus neoformans, Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis, Aspergillus. Amphotericin B gn vo ergosterol ca vch t bo nm, to nn cc ng dn lm r r cc ion v cc phn t nh t trong t bo nm ra ngoi, gy cht t bo. Sterol ca vch t bo nm l ergosterol, cn sterol chnh ca vch vi kh un v t bo ngi li l cholesterol, v vy amphotericin B khng c tc dng dit khun v khng c vi ngi. 1.1.3. Dc ng hc Khng hp thu qua ng ung. Gn vo protein huyt tng ti 95%, ch yu vo -lipoprotein. Ch dng ng truyn tnh mch, thm nhiu vo cc m gan, lch phi, thn. Nng trong dch bao khp bng khong 2/3 nng huyt tng, nhng ch 2 -3% vo c dch no tu. Thi gian bn thi khong 15 ngy. Thi tr chm qua thn trong vi ngy. 1.1.4. c tnh - c tnh lin quan n vic truyn thuc: run, st, nn, nhc u, h huyt p. Cn gim tc truyn hoc gim liu. C th lm test bng tim 1mg vo tnh mch. Dng thuc h st, khng histamin hoc corticoid trc khi truyn. - c tnh mun: Tn thng ng th n, tng ur-huyt (80%), toan huyt, tng thi K +, Mg++. Truyn dung dch NaCl 0,9% c th lm gim c tnh cho thn. Ngoi ra c th thy bt thng test chc phn gan, thiu mu do gim sn

xut erythropoietin ca thn. 1.1.5. Ch phm v liu lng - Amphoterincin B (Fungizon) tim, truyn tnh mch. L 50 mg bt ng kh pha thnh dch treo trong glucose 5%, truyn 0,5 -0,6mg/kg trong 4gi. - Vin nn 100 mg. Ngm (nm ming) hoc ung (nm rut) 1 - 4 vin/ ngy. - Kem bi 3%. 1.2. Flucytosin 1.2.1. c im Flucytosin (5-FC) c tm ra nm 1957 trong khi nghin cu cc thuc chng ung th (gn ging 5-FU). Flucytosin d tan trong nc, ph khng nm hp hn amphotericin B v khng c tc dng chng ung th. 1.2.2. Tc dng v c ch Ch c tc dng trn Cryptococcus neoformans v vi loi candida. V c tc dng hip ng vi thuc chng nm khc nn thng c dng phi hp trnh khng thuc. Flucytosin c nhp vo t bo nm nh enzym cytosin permease. Trong t bo, 5 -FC c chuyn thnh 5 -FU (5 fluorouracil), sau thnh 5 fluorodeoxyuridin monophosphat (F -dUMP) c ch tng hp DNA, v thnh fluorouridin tri phosphat (FUTP) c ch tng hp RNA. T bo ngi v t bo ng vt c v khng chuyn c 5 -FC thnh 5-FU, v th 5-FC c tc dng chn lc trn nm. 1.2.3. Dc ng hc Hp thu d dng qua ng tiu ha (>90%), t pic huyt tng sau 1 -2gi, t gn vo protein huyt tng, thm d vo cc dch trong c th, vo dch no tu vi nng bng 65 -90% nng huyt tng. Thi qua thn 80% di dng khng chuyn ho. Thi gian bn thi l 3 -6gi, ngi suy thn, c th k c, o di ti 200 gi. 1.2.4. c tnh C kh nng l vi khun rut chuyn ho flucytosin thnh hp cht c, gy c ch tu xng, dn n thiu mu, gim bch cu , gim tiu cu, ri lon chc nng gan (5%) ri lon tiu ho (nn, tiu chy). 1.2.5. Ch phm Ancobon: vim nang 250 -500mg. Ung 100-150mg/kg/ngy chia lm 4ln. Dng phi hp vi amphotericin B (0,3mg/kg/ngy) cha nm Candida.

Khng dng dng tim . 1.3. Nhm azol: Imidazol v Triazol 1.3.1. c im Imidazol v triazol u thuc nhm azol chng nm, c cng c ch v cng ph tc dng. Triazol dng ng ton thn chm b chuyn ho v t tc dng trn tng hp sterol ca ngi hn l imidazol. V vy, cc dn xut mi u phn ln l t triazol ch khng phi t imidazol. Vic tm ra azol (1980) l mt bc tin quan trng trong nghin cu thuc chng nm. 1.3.2. Tc dng v c ch X = C: Imidazol: ketoconazol, miconazol, clotrrimazol X = N: Triazol; itraconazol, fluconazolPh tc dng rng, gm: cc loi Candida, Cryptococcus neoformans, Blastomyces dermatitidis, cc bnh nm da. Cc azol c ch enzym cytochrom P 450 ca nm nn lm gim tng hp ergosterol ca vch t bo nm, km hm s ln ln v pht trin ca nm. 1.3.3. Dc ng hc, c tnh v p dng Ba thuc thng dng ca nhm azol l: 1.3.3.1. Ketoconazol (Nizoral) - Ung d hp thu, nhng cn mi trng acid (nu dng cng khng H 2 s lm gim hp thu mnh). Gn vo protein huyt tng 84%, vo hng cu 15%, cn 1% dng t do. Thi gian bn thi tng theo liu, ung 800mg th t/2 = 7 -8gi. Vo dch no tu bng 1% liu dng. - c tnh: Km fluconazol v itraconazol l c ch c cytocrom P450 ca ng vt c v nn dn n 2 hu qu: . Lm cn tr sinh tng hp hormon thng thn, sinh dc, n ng gy chng v to, gim tnh dc; ph n gy lon kinh nguyt, v sinh. . Lm tng c tnh ca thuc kt hp cng chuyn ho qua P450. Ngoi ra cn gp bun nn, chn n (20%), d ng (4%) tng transferase (5 10%). V th khng dng liu cao. - Ch nhv liu dng: Vin 200mg, kem bi 2%. Candida m o: ung 400mg/ngy 5 ngy Candida thc qun: ung 400mg/ngy 10-14 ngy Histoplasmosis, blastomycosis: 400mg/ngy 6-12 thng. Khng dng khi c thai v ang nui con bng sa m. 1.3.3.2. Itraconazol (Sporanox, Sporal) Ph rng, t c hn ketoconazol v ch c ch cytochro m P450 c hiu ca nm.

- Hp thu qua ng ung khong 30%, hp thu ti a ngay sau khi n. Pic huyt tng sau 3 -4 gi, t/2 khong 1 -1,5 ngy. Gn vo protein huyt tng ti 99,8%. Gn vo cc m sng (da, mng) vi nng cao hn huyt tng 4ln v gi rt lu t vi tun n vi thng sau ngng iu tr. Nng trong m mm (phi, thn, gan, lch) cng cao hn huyt tng 2 -3 ln. - Ch nh v liu lng: Vin nang 100mg, ung ngay sau ba n. . Candida m o: Ung 1 ngy duy nht 400mg chia 2 l n, hoc 200mg/ngy 3 ngy. . Nm da, lang ben: ung 200mg/ngy 7 ngy. . Candida ming: 100mg/ngy 15 ngy. . Nm mng: ung 2 t cch nhau 3 tun. Mi t 7 ngy. Mi ngy ung 400mg chia 2 ln. 1.3.3.3. Fluconazol (Flunaz, Diflucan, Triflucan) C gn thm 2 nguyn t Fluo. - Ung hp thu hon ton, khng chu nh hng ca thc n hay acid dch v. Rt tan trong nc nn c th tim tnh mch. Nng trong huyt tng ca ng ung gn bng ng tim tnh mch. Gn vo protein huyt tng 11 12%, t/2 = 25 gi, khong 90% thi qua thn di dng khng i. Thm vo mi dch ca c th, nng trong dch no tu t 50 - 90% nng huyt tng. - Thuc d dung np. C th gp phn ng d ng. - Ch nh v cch dng: Vin nang 50, 100, 150 mg. Li u 100 - 400mg/ngy. L 200 - 400 ml, cha 2mg/ml. Candida nim mc (ming, m o), nm da, nm mng, nm Cryptococcosis (mng no, phi, da), nhim nm trong AIDS (lm tng sinh kh dng ca Zidovudin khong 20% v lm gim chuyn ha Zidovudin). Thi gian iu tr tuz tng loi nm, tng t itraconazol. Khng dng cho ph n c thai hoc ang cho con b. Khng dng cho tr di 16 tui v l thuc mi, cha s liu theo di. 1.4. Griseofulvin 1.4.1. c im Khng sinh ly t nm Penicillium griseof ulvum, khng tan trong nc, vng bn vi nhit. 1.4.2. Tc dng v c ch

Tc dng trn nm da, biu b, tc, mng: Microsporum, Epidermophyton v Trichophyton. Khng c tc dng trn vi khun. Griseofulvin gn vo protein tiu qun, lm gy thoi phn bo nn km hm s pht trin ca nm. 1.4.3. Dc ng hc Hp thu qua tiu ha thay i theo dng thuc v thc n. Ch phm siu vi tinh th (ultramicrocristalline preparation) c sinh kh dng gp ri loi bt vi tnh th. Thc n c m s d hp thu v thuc khng tan trong nc. t pic sau 4 gi v t/2 = 24 gi. Thuc tch lu trong t bo tin thn ca keratin lm n khng li s xm nhp ca nm, do tc, mng mi mc s khng b bnh. 1.4.4. c tnh Thng nh: nhc u (15%), vim thn kinh, ng g, khng lm c vic kho lo, mt mi, nhn m, ri lon tiu ha 1.4.5. Ch phm, liu dng Griseofulvin (Fulvicin, Grisactin) vin nang 125 -250 mg; vin nn 250 -500mg. Liu tr em 10mg/kg; ngi ln 0,5 - 1,0 g. Thi gian iu tr t nht l 1 t hng cho bnh nm tc v 6 -9 thng cho bnh nm mng. 2. THUC CHNG NM TI CH 2.1. Nystatin Nystatin l khng sinh macrolid, tng t amphotericin B c v cu trc v c ch tc dng, nhng c hn nn ch dng ngoi v khng hp thu qua da hoc m o. Tc dng iu tr cc loi nm Candida nim mng v k da. Nystatin (Mycostatin, Nilstrat), dng pomat, kem bi, thuc bt, dng phun, cha 100.000 n v/g. Bi 2 - 3 ln/ngy 7 ngy. 2.2. Clotrimazol v miconazol Thuc nhm azol dng ngoi. Bi ngoi da ch hp thu 0,5%; bi m o, hp thu 3 - 10%. Dng thuc: Kem 1%, thuc ra, dung dch (Lotrimin, Mycelex), vin n n t m o 100 - 500 mg, thuc phun 2%. Nm da: bi 2 ln/ngy. Nm m o: t vin 500mg/ngy; kem 5g/ngy, dng trong 7 - 14 ngy. Nm ming: vin ngm 10mg 5 ln/ngy.

BI 26. THUC IU TR ST RT 1. I CNG Bnh st r t c Hypocrate m t cch y hn 2000 nm, l bnh truyn nhim, do plasmodium gy ra, plasmodium l mt loi k t sinh trng khng nhng gy bnh cho ngi m cho c sc vt. Bn loi k sinh trng st rt gy bnh cho ngi l: P. falciparum, P.vivax, P.malariae v P.ovale. Vit nam, st rt do P.falciparum chim khong 70 - 80%, do P.vivax 20 30%, P.malariae 1- 2% cn P.ovale hu nh khng c. Dch s t rt do P.falciparum thng xy ra t ngt, din bin nng, t vong cao nhng thi gian tn ti ca dch ngn. Ngi c th nhim bnh st r t theo 3 phng thc: - Do mui truyn: y l phng thc nhim ch yu v quan trng nht. - Do truyn mu. - Truyn qua rau thai. Vic iu tr st rt hin nay cn gp nhiu kh khn v k{ sinh trng st r t (c bit l P.falciparum) khng li nhiu thuc chng st r t. Hn na, Vit nam c khong 35 triu ngi sng trong vng st r t lu hnh (trong c 15 triu ngi sng trong vng st r t lu hnh nng), nn mun iu tr st rt c hiu qu phi trit tun th phc iu tr ca chng trnh phng chng st rt quc gia. 2. CHU K SINH HC CA K SINH TRNG ST RT 2.1. Chu kz pht trin trong c th ng i (chu kz sinh sn v tnh) 2.1.1. Giai on gan Khi mui t ngi, thoa trng ( trong tuyn nc bt mui) chui qua mch mu lu thng trong mu. Sau 30 pht, thoa trng vo gan pht trin trong t bo gan thnh th phn lit (10 - 14 ngy), sau p h v t bo gan v gii phng ra cc mnh trng. Giai on ny gi l giai on tin hng cu. Vi P.falciparum, tt c mnh trng u vo mu v pht trin . Cn P.vivax v P.ovale, ngoi s pht trin tc th ca cc thoa trng thnh th phn li t, cn c s pht trin mun hn ca mt s thoa trng khc. Nhng thoa trng ny khng pht trin ngay thnh th phn lit m to thnh cc th ng. Cc th ng pht trin tng t thnh phn lit, v ra v gii phng nhng mnh trng vo mu gy nn nh ng cn ti pht xa (th ngoi hng cu). 2.1.2. Giai on mu Cc mnh trng t gan xm nhp vo hng cu, lc u l th t dng ri

pht trin thnh phn lit non, phn lit gi. Th phn lit gi s ph v hng cu gii phng ra nhng mnh trng. Lc ny tng ng vi cn st xy ra trn lm sng. Hu ht cc mnh trng ny quay tr li k sinh trong cc hng cu mi, cn mt s bit ha thnh nhng th hu gii, l nhng giao bo c v giao bo ci. 2.2. Chu kz pht trin trong c th mui (chu kz sinh sn h u tnh) Giao bo c v ci c mui ht vo d dy s pht trin thnh nhng giao t c v ci, qua sinh sn hu tnh sinh ra thoa trng. Cc thoa trng n tp trung trong tuyn nc bt ca mui l tip tc truyn bnh cho ngi khc. Chu kz ca k sinh trng st rt v v tr tc dng ca cc thuc iu tr st rt

1a: Thoa trng vo t bo gan 2a,3a: Th phn lit pht trin trong t bo gan 4: Gii phng cc mnh trng 5: Mnh trng vo hng cu 6: Th t dng trong hng cu 7,8: Th phn lit pht trin trong hng cu 9: Ph v hng cu v gii phng cc mnh trng 10,11,12: Pht trin thnh giao bo c v giao bo ci 1b, 2b, 3b: Pht trin ca th ng. 3. CC THUC IU TR ST RT THNG DNG 3.1. Thuc dit th v tnh trong hng cu 3.1.1. Cloroquin (Aralen, Avloclor, Malarivon, Nivaquin) L thuc tng hp, dn xut ca 4 amino quinolein 3.1.1.1.Tc dng Cloroquin c hiu lc cao i vi th v tnh trong hng cu ca c 4 loi k sinh trng st rt, tc dng va phi vi giao bo ca P.vivax, P.malariae v P.ovale. Khng nh hng ti giao bo ca P.falciparum. C ch tc dng: tn ti, k sinh trng st rt nut hemoglobin ca hng cu vt ch vo khng bo thc n. , hemoglobin c chuyn thnh heme (ferriprotoporphyrin IX) l sn phm trung gian c c tnh gy ly gii mng. Heme c chuyn thnh sc t hemozoin t c hn nh enzym polymerase. Cloroquin c ch polymerase, lm tch ly heme, gy c vi k sinh trng st rt, lm ly gii k sinh trng.

Thuc tp trung trong khng bo thc n ca k sinh trng st r t, lm tng pH v nh hng n qu trnh ging ha hemoglobin, lm gim cc amino acid cn thit cho s tn ti ca k sinh trng. Cloroquin cn c th gn vo chui xon kp DNA c ch DNA v RNA polymerase, cn tr s tng hp nucleoprotein ca k sinh trng st rt. 3.1.1.2.Dc ng hc Cloroquin hp thu nhanh v gn nh hon ton ng tiu ha, sinh kh dng khong 90%. Sau khi ung 3 gi, thuc t c nng ti a trong mu, 50 65% thuc gn vi protein huyt tng. Khu ch tn nhanh vo cc t chc. Thuc tp trung nhiu hng cu, gan, thn, lch v phi. hng cu nhim k sinh trng st rt, nng thuc cao gp 25 ln hng cu bnh thng. Chuyn ha chm gan, cho desethylcloroquin vn dit c plasmodium. Thi tr chm, khong 50 - 60% qua nc tiu. Thi gian bn thi 3 - 5 ngy, c khi ti 12 - 14 ngy. 3.1.1.3.Tc dng khng mong mun Vi liu iu tr, thuc thng dung np tt, t gp cc tc dng khng mong mun: au u, chng mt, bun nn, nn, au bng, a chy, ri lon th gic, pht ban, nga (c bit lng). Ung thuc khi no c th lm gim cc tc dng ny. Khi dng liu cao v ko di thuc c th gy tan mu ( ngi thiu G 6PD), gim thnh lc, nhm ln, co git, nhn m, bnh gic mc, rng tc, bin i sc t ca tc, da xm nu en, h huyt p. 3.1.1.4.p dng iu tr Ch nh: - Cloroquin c dng trong iu tr v phng bnh st rt - Thng dng trong st rt th nh v trung bnh ( nhng vng v k sinh trng cn nhy cm vi thuc) khng dng khi st rt nng hoc c bin chng. iu tr d phng cho nhng ngi i vo vng c st r t lu hnh. - Thuc cn c dng dit amp gan, trong vim a khp dng thp, lupus ban . Chng ch nh: - Chng ch nh: bnh vy nn, ri lon chu yn ha porphyrin, tin s ng kinh v bnh tm thn, ph n c thai. - Thn trng: cn khm mt trc khi dng thuc di ngy v theo di trong

sut qu trnh iu tr. Ch ti nhng ngi c bnh v gan, thn, c bt thng v thnh gic v th gic, nghin ru, ri lon v mu v thn kinh, thiu ht G 6PD. Liu lng: Chng trnh phng chng st rt Vit nam dng vin cloroquin phosphat 250 mg 150 mg cloroquin base - iu tr st rt: ung cloroquin phosp?hat 3 ngy Ngy u: 10 mg cloroquin base/ kg, chia 2 ln Ngy th 2, 3: 5 mg cloroquin base/ kg - iu tr d phng; 5 mg cloroquin base/ kg/ tun cho c ngi ln v tr em. 3.1.1.5. Tng tc thuc - Cc thuc khng acid hoc kaolin c th lm gim hp thu cloroquin, v vy ch ung cloroquin sau khi dng thuc ny 4 gi - Cimetidin lm gim chuyn ha v thi tr, tng th tch phn b ca Cloroquin - Dng cloroquin kt hp vi proguanil lm tng tai bin lot ming. - Cloroquin lm gim kh nng hp thu ampicilin 3.1.2. Quinin L alcaloid chnh ca cy Quinquina, c dng iu tr st r t hn 300 nm (t 1630) 3.1.2.1.Tc dng Quinin c tc dng nhanh, hiu lc cao i vi th v tnh trong hng cu ca c 4 loi k sinh trng st rt. Thuc dit c giao bo ca P.vivax v P.malariae nhng t hiu lc i vi giao bo ca P.falciparum. C ch tc dng ca quinin tng t nh cloroquin. Ngoi tc dng dit k sinh trng st rt, quinin cn c mt s tc dng khc. - Kch ng ti ch: khi ung thuc kch ng d dy, gy bun nn, nn. Tim di da rt au, c th gy p xe v khun, v vy nn tim bp su. - Tim mch: liu cao quinin gy gin mch, c ch c tim, h huyt p (khi tim tnh mch nhanh). - C trn: lm tng co bp t cung u n trong nhng thng cui ca thi kz c thai, t tc dng trn t cung bnh thng hoc mi c thai. 3.1.2.2.Dc ng hc

Thuc c hp thu nhanh v hon ton qua rut, sau khi ung 1 - 3 gi thuc t c nng ti a trong mu, nng trong huyt tng thng gp 5 ln trong hng cu. Gn vi protein huyt tng khong 80%, qua c rau thai v sa, 7% vo dch no ty. 80% thuc c chuyn ha qua gan v thi tr phn ln qua thn. Thi gian bn thi 7 12 gi trn ngi bnh thng v 8 - 21 gi ngi b st rt. 3.1.2.3.Tc dng khng mong mun - Hi chng quinin; thng g p khi nng thuc trong mu trn 7 - 10 g/ mL vi cc biu hin: au u, nn, chng mt, tai, ri lon th gic. Phi ngng thuc khi cc triu chng tin trin nng hn. - c vi mu: thuc c th gy tan mu (hay gp ngi thiu enzym G 6PD). Gim bch cu, gim prothrombin, mt bch cu ht l nhng du hiu t gp hn. - H ng huyt c th gp khi dng quinin vi liu iu tr. - c tnh nghim trng (do qu liu hoc dng lu di): st, phn ng da (nga, pht ban), ri lon tiu ha , ic, gim th lc (nhn m, ri lon mu sc, nhn i), tc dng ging quinidin. - Khi dng liu cao quinin c th gy xy thai, d tt bm sinh thai nhi. - Trong mt vi trng hp, khi tim tnh mch quinin c th gy vim tnh mch huyt khi. 3.1.2.4.p dng iu tr Ch nh: - iu tr st rt nng do P.falciparum v st rt c tnh, hay dng nhng vng m P.falciparum khng cloroquin. Ung quinin sulfat kt hp vi cc thuc chng st r t khc nh tetracyclin (hoc doxycyclin), fancidar, mefloqui n hoc artemisinin. - Quinin cn c ch nh cho ph n c thai (thay th cloroquin khi b khng thuc). V hiu lc k m hn cloroquin nn quinin khng dng iu tr t cp do P.vivax, P.malariae v P.ovale; khng dng khi P.fa?lciparum cn nhy cm v i cloroquin. - Phng bnh: v c nhiu c tnh nn quinin t c dng phng bnh. Tuy nhin nhng vng P.falciparum khng cloroquin, khi khng c mefloquin v doxycyclin, c th phng bnh bng quinin. Chng ch nh, thn trng: - Chng ch nh: ngi nhy cm vi thuc, tin s c bnh v tai, mt, tim

mch. Khng dng quinin phi hp vi mefloquin bnh nhn thiu G 6PD. - Thn trng: bnh nhn suy thn phi gim liu thuc Liu lng: - iu tr st rt do P.falciparum khng cloroquin (th nh v trung bnh): ung quinin sulfat 30 mg/ kg/ ny, chia 3 ln. Mt t iu tr 7 ngy. - iu tr st rt nng v st rt c tnh: tim bp hoc truyn tnh mch quinin hydroclorid. Tim bp: 30 mg/ kg/ ngy, trong 7 ngy Truyn tnh mch: quinin hydroclo rid 10 mg/ kg mi 8 gi (vi 10 mL/ kg dch truyn) Theo di n khi bnh nhn tnh, chuyn sang tim bp hoc ung cho liu iu tr. 3.1.2.5.Tng tc thuc - Cc thuc khng acid cha nhm lm chm hp thu quinin - Quinin lm tng nng digoxin trong mu d o gim thanh thi ca thuc. - Lm tng tc dng ca warfarin v cc thuc chng ng mu khc khi dng phi hp. - Cimetidin lm chm thi tr quinin, acid ha nc tiu lm tng thi quinin. 3.1.3. Fansidar L thuc phi hp gia sulfadoxin 500 mg v pyrimet hamin 25 mg. 3.1.3.1.Tc dng Sulfadoxin thuc nhm sulfamid thi tr rt chm. Thuc c tc dng dit th v tnh trong hng cu ca P.falciparum, tc dng ch yu vi P.vivax, khng nh hng ti giao bo v giai on gan ca P.falciparum v P.vivax. Pyrimethamin l dn xut ca diaminopyrimidin, c tc dng chm i vi th v tnh trong hng cu ca bn loi k sinh trng st rt. Thuc cn c ch cc th hu tnh pht trin trong c th mui nn c tc dng ngn chn s lan truyn st rt trong cng ng. Sulfadoxin v pyrimethamin c ch 2 enzym ca 2 giai on khc nhau trong qu trnh tng hp acid folic ca k sinh trng. V vy, khi phi hp hai thuc ny s c tc dng hip ng tng mc, lm c ch s tng hp acid folic, nn k sinh trng khng tng hp c DNA v RNA.

3.1.3.2.Dc ng hc Fansidar hp thu tt qua ng tiu ha, sau khi ung 2 - 8 gi thuc t c

nng ti a trong mu, khong 90% gn vi protein huyt tng. Thi tr ch yu qua nc tiu. Thi gian bn thi l 170 gi i vi sulfadoxin v 80 - 110 gi i vi pyrimethamin. 3.1.3.3.Tc dng khng mong mun Khi dng Fansidar c th b d ng vi sulfamid (nga, m ay), ri lon v mu (tan mu, gim bch cu ht), ri lon tiu ha, ri lon ch c nng thn. Dng Fansidar phng bnh (di ngy) c th gy phn ng da nghim trng: hng ban, hi chng Stevens - Johnson, hoi t biu b 3.1.3.4.p dng iu tr Ch nh: - iu tr st r t do P.falciparum khng cloroquin, thng phi hp vi quinin (v tc dng ca fansidar chm) - D phng cho nhng ngi i vo vng st r t lu hnh nng trong thi gian di. Chng ch nh, thn trng - Chng ch nh: d ng vi thuc, ngi b bnh mu, bnh gan, thn nng, ph n c thai. - Thn trng: ph n cho con b, tr em ?di 2 thng tui, ngi thiu enzym G 6PD, c a d ng, hen ph qun. Liu lng: iu tr st rt: ung 25 mg sulfadoxin + 1,25 mg pyrimethamin/ kg D phng st r t: ngi ln: ung 1 vin/ tun hoc 3 vin/ thng 3.1.3.5.Tng tc thuc Sulfadoxin lm tng tc dng ca warfarin v thiopenton, lm gim hp thu digoxin qua ng tiu ha. 3.1.4. Mefloquin (Eloquin, Lariam, Mephaquin) L thuc tng hp, dn xut ca 4 - quinolin methanol. Cu trc ha hc c lin quan nhiu vi quinin. 3.1.4.1. Tc dng Mefloquin c tc dng mnh i vi th v tnh trong hng cu ca P.falciparum v P.vivax nhng khng dit c giao bo ca P.falciparum hoc th trong gan ca P. vivax. Mefloquin c hiu qu trn cc k{ sinh trng a khng vi cc thuc st rt khc nh cloroquin, proguanil, pyrimethamin Tuy nhin, vng ng Nam cng c chng P.falciparum khng mefloquin. Hin nay cn c nhiu gi thuyt khc nhau v c ch tc dng ca mefloquin.

Tc dng khng k sinh trng st rt lin quan nhiu ti kh nng c ch enzym polymerase ca thuc. 3.1.4.2. Dc ng hc Mefloquin c hp thu tt qua ng ung. Nng ti a trong huyt tng (0,2 - 1,4 g/ mL) t c khong 2 - 12 gi sau khi ung mefloquin vi liu duy nht 250 mg. Gn mnh vi protein huyt tn g (98%). Thuc tp trung nhiu trong hng cu, phi, gan, lympho bo v thn kinh trung ng. Thuc c chuyn ha gan, cht chuyn ha chnh l acid quinolin carboxylic khng cn hot tnh. Thi tr ch yu qua phn, c th c chu kz gan rut. Thi gian bn thi khong 21 ngy (t 13 n 33 ngy). 3.1.4.3. Tc dng khng mong mun Mc v tn sut ca cc phn ng c hi lin quan nhiu vi liu dng. Tc dng khng mong mun ph bin nht l chng mt (20%) v bun nn (15%). - liu phng bnh t c dng c hi thng nh v thong qua, bao gm ri lon tiu ha (bun nn, nn, au bng, tiu chy), au u, chng mt, ngoi tm thu. t gp cc triu chng thn kinh tm thn (co git, ng g, lon tm thn), tng bch cu, tng amino - transferase. - Khi dng liu cao (> 1000 mg) khong 1% bnh nhn thy bun nn, nn, au u, chng mt, tai, ri lon th gic, lon tm thn cp t gp: nga, pht ban, rng tc, au c. 3.1.4.4. p dng iu tr Ch nh: iu tr v d phng st rt do P.falci parum khng cloroquin v a khng thuc Chng ch nh, thn trng - Chng ch nh: Mefloquin khng s dng cho nhng ngi c tin s bnh tm thn, ng kinh, lon nhp tim, ngi nhy cm vi mefloquin hoc cc thuc c cu trc tng t nh cloroquin, quinin, quinidin, Tr em di 3 thng tui, ngi suy gan hoc suy thn nng khng c dng mefloquin - Thn trng: cn thn khi dng cho ngi li xe, vn hnh my mc v nguy c - Thn trng: cn thn khi dng cho ngi li xe, vn hnh my mc v nguy c 3 tun sau khi ngng thuc. Trong d phng st rt bng mefloquin, nu xut hin cc ri lon nh lo u, trm cm, kch ng hoc l ln phi ngng thuc v y l tin triu ca

nhng tc dng ph nghim trng hn. Khng nn dng cho tr em di 15 kg hoc di 2 tui, ph n c thai trong 3 thng u. Khng dng mefloquin lu qu? 1 nm. Nu dng lu, phi nh kz kim tra chc nng gan v mt (thuc c th lm gim chc nng gan v gy tn thng mt) Liu lng: - iu tr st r t: ngi ln v tr em; 15 mg/ kg, chia lm 2 ln, cch nhau 6 - 8 gi. Liu dng ti a ngi ln l 1000 mg Phng bnh Ngi ln: ung 1 vin mefloquin 250 mg/ tun, vo mt ngy c nh, bt u dng t trc khi i vo vng c st rt v ko di 4 tun sau khi ra kh i vng st r t lu hnh. i vi ngi i vo vng st rt nng trong thi gian ngn: tun u ung 1 vin 250 mg mi ngy, ung lin 3 ngy. Sau mi tun ung 1 vin Tr em: ung tuz theo tui. 3.1.4.5. Tng tc thuc - Phi ht sc thn trng khi d ng mefloquin cho ngi bnh ang dng cc thuc chn beta, chn knh calci, digitalis hoc cc thuc chng trm cm (c th xy ra tng tc bt li) - Dng mefloquin cng vi valproic acid lm gim nng valproat trong huyt thanh. - Phi hp mefloquin vi quinin s lm tng c tnh trn thn kinh (gy co git) v tim mch Mefloquin c th dng cho ngi sau khi tim quinin nhng phi cch 12 gi sau liu cui cng ca quinin trnh c tnh. 3.1.5. Artemisinin v cc dn xut Artemisinin c phn lp t c y Thanh hao hoa vng Artemisia annua L. h Asteraceae. Artemisinin t tan trong nc, ch dng ng ung hoc t trc trng. Cc dn xut nh artesunat tan c trong nc, c th ung hoc tim (bp, tnh mch), artemether v arteether tan trong du, c h dng tim bp. 3.1.5.1.Tc dng Artemisinin v cc dn xut c hiu qu cao trong iu tr st rt. Thuc c tc dng dit th v tnh trong hng cu ca c 4 loi k sinh trng st rt, k c P.falciparum khng cloroquin. Thuc khng c tc dng trn giai on gan, trn thoa trng v giao bo ca plasmodium.

Artemisinin l mt sesquiterpen lacton c cu ni endoperoxid, cu ni ny rt quan trng i vi tc dng chng st rt ca thuc. Hin nay, ngi ta cha hon ton hiu r v c ch tc dng ca thuc. Thuc tp trung chn lc vo cc t bo nhim k sinh trng v phn ng vi hemozoin trong k sinh trng. Phn ng ny to ra nhiu gc t do hu c c c th ph hu mng ca k sinh trng. Mt s cng trnh nghin cu cho thy bnh nhn dng artemisini n c thi gian ct st v thi gian sch k{ sinh trng trong mu nhanh hn dng cloroquin , quinin hoc mefloquin. Song t l ti pht cao. Artemisinin, artemether v arteether c tc dng mnh hn artemisinin. 3.1.5.2.Dc ng hc Artemisinin hp thu nhanh sau khi ung, t nng cao sau 1 gi, phn b vo nhiu t chc: gan, no, phi, mu, thn, c, tim, lch. Artemisinin gn 64% vo protein huyt tng, dihydroartemisinin 43%, artemether 76% v artesunat 59%. Chuyn ha ch yu qua gan, cho 4 cht chuyn h a: de oxyartemisinin v crystal- 7 khng cn hot tnh. 80% liu dng c thi qua phn v nc tiu trong vng 24. Thi gian bn thi khong 4 gi. 3.1.5.3.Tc dng khng mong mun Artemisinin v cc dn xut l nhng thuc c c tnh thp, s dng tng i an ton. Cc tc dng khng mong mun thng nh v thong qua nh ri lon tiu ha (bun nn, nn, au bng, tiu chy), nhc u, chng mt, hoa mt, c bit l sau khi ung?. Mt vi ngi dng artesunat, artemether c th b c ch nh tim, chm nhp tim. Sau t trc trng, artemisinin c th kch thch gy au rt, au bng v tiu chy. Trn sc vt, thuc gy c ch tu xng v c vi thn kinh trung ng. 3.1.5.4.p dng iu tr Ch nh - L thuc st r t c dng nhiu Vit nam, thng dng i u tr st rt th nh v trung bnh do c 4 loi plasmodium. - iu tr st rt nng do P.falciparum a khng thuc hoc st rt c tnh. Thuc c bit hiu qu trong st rt th no. Chng ch nh: Khng c chng ch nh tuyt i cho artemisinin v c c dn xut. Tuy vy,

khng nn dng cho ph n c thai 3 thng u tr khi b st rt th no hoc st rt c bin chng vng m P.falciparum khng nhiu thuc. Liu lng: Artemisinin: ngy u ung 20 mg/ kg ngy th 2 n ngy th 5: mi ngy 10 mg/ kg Artesunat: ngy u ung 4 mg/ kg ngy th 2 n ngy th 5 : mi ngy 2 mg/ kg 3.1.5.5.Tng tc thuc - Artemisinin hip ng tc dng vi mefloquin hoc tetracyclin trong iu tr st rt . - S phi hp gia artemisinin vi cloroquin v pyrimethamin c tc dng i khng. 3.1.6. Halofantrin (Halfan) Thuc tng hp, dn xut phenanthrenmethanol. 3.1.6.1. Tc dng Halofantrin c hiu lc i vi th v tnh trong hng cu ca P.falciparum. Thuc khng c tc dng trn giai on gan, th t hoa trng v giao bo ca k sinh trng st rt C ch tc dng ca halofantrin cn cha r, c th thuc tc ng nh cloroquin, quinin trn ferriprotoporphyrin IX v gy tn hi mng k sinh trng. 3.1.6.2. Dc ng hc Hp thu k m qua ng tiu ha, t huc t c nng ti a trong mu sau khi ung 6 gi. M trong thc n lm tng hp thu ca thuc Cht chuyn ha chnh l N - debutyl- halofantrin vn c tc dng dit k sinh trng st rt. Thi tr ch yu qua phn. Thi gian bn thi t 10 - 90 gi. 3.1.6.3. Tc dng khng mong mun Halofantrin t c, thnh thong bnh nhn c th b bun nn, nn, au bng, tiu chy, nga, ban . Tiu chy thng xy ra ngy th 2, th 3 sau dng thuc v lin quan ti liu dng. nh hng ca thuc trn tim p h thuc vo liu: liu iu tr, c th ko di khong QT v PR, khi dng liu cao halofantrin c th gy lon nhp tht. 3.1.6.4. p dng iu tr Ch nh: iu tr st r t do P.falciparum khng cloroquin v a khng thuc. Chng ch nh, thn trng : halofantrin khng c dng cho ph n c thai, ph n cho con b, ngi c tin s bnh tim mch, ngi dng mefloquin trc 2 - 5 tun.

Khng phi hp halofantrin vi nhng thuc c c tnh trn tim mch. Khng s dng halofantrin phng bnh st rt. Liu lng: vin nn 250 mg Ngi ln v tr em > 40 kg: ung 24 mg/ kg/ ngy, chia lm 3 ln, cch nhau 6 gi. 3.1.6.5. Tng tc thuc Phi hp halofantrin vi mefloquin , cloroquin, quinin, thuc chng trm cm loi 3 vng, dn xut phenothiazi n, thuc chng lon nhp tim (aminodaron, quinidin, procainamid), Cisaprid, khng histamin (astemizole, terfenadin), thuc li tiu, s lm tng c tnh trn tim. 3.2. Thuc dit giao bo: primaquin L thuc tng hp, dn xut 8 a?mino - quinolein 3.2.1. Tc dng Thuc c tc dng tt i vi th ngoi hng cu ban u gan ca P.falciparum v cc th ngoi hng cu mun (th ng, th phn lit) ca P.vivax v P.ovale, do trnh c ti pht. Primaquin dit c giao bo ca c 4 loi plasmodium trong mu ngi bnh nn c tc dng chng ly lan. C ch tc dng ca primaquin cha r rng. C th cc cht trung gian ca primaquin (quinolin- quinin) tc ng nh nhng cht oxy ha, gy tan mu v methemoglobin. 3.2.2. Dc ng hc Primaquin hp thu nhanh, sau khi ung 1-2 gi thuc t nng ti a trong mu, phn phi d vo cc t chc. Chuyn ha hon ton gan. Thi tr nhanh qua nc tiu sau 24 gi. Thi gian bn thi 3 - 8 gi. Carboxyprimaquin (cht chuyn ha chnh ca primaquin) c nng trong huyt tng cao hn nhiu so vi cht m v c tch ly v thi tr chm (thi gian bn thi 22 - 30 gi). 3.2.3. Tc dng khng mong mun Vi liu iu tr thuc dung np tt, tuy vy bnh nhn c th b au bng, kh chu vng thng v, au u nu ung primaquin lc i. Vi liu cao hn c th gy bun nn v nn. Him gp cc triu chng nng nh tng huyt p, lon nhp tim, mt bch cu ht. c tnh thng gp i vi primaquin l c ch tu xng, gy thiu mu tan mu (hay gp ngi thiu G 6PD) v methemoglobi n (hay xy ra ngi

thiu NADH bm sinh) 3.2.4. p dng iu tr Ch nh: iu tr st r t do P.vivax v P.ovale, thng dng phi hp vi cc thuc dit th v tnh trong hng cu - iu tr cho cng ng ct ng lan truyn ca k sinh trng st r t, c bit P.falciparum khng cloroquin. Chng ch nh: Khng dng primaquin cho ngi c bnh tu xng, bnh gan, tin s c gim bch cu ht, methemoglobin, ph n c thai, tr em di 3 tui. Trong qu trnh iu tr, phi ngng thuc ngay khi c cc du hiu tan mu hoc methemoglobin. Liu lng: Ung 0,5 mg primaquin base/ kg/ ngy iu tr st rt do P.vivax v P.ovale: ung 5 ngy lin trnh ti pht. Dit giao bo ca P.falciparum: ung 1 ngy 3.2.5. Tng tc thuc Primaquin lm tng thi gian bn t hi ca antipyrin khi dng phi hp. 4. K SINH TRNG KHNG THUC K sinh trng st rt khng thuc l vn ht sc nghim trng. Trong nhng thp k gn y c s gia tng nhanh chng v s lan rng k sinh trng P.falciparum khng li cc thuc st r t hin c, ch yu l s dng cho phng bnh, t iu tr khng ng phc , hoc dng khng liu 4.1. nh ngha Theo WHO, khng thuc l kh nng mt chng k sinh trng c th sng st v pht trin mc d bnh nhn c iu tr v hp thu mt lng thuc, hoc chnh xc trong mu bnh nhn c nng thuc m trc y vn ngn cn v dit c k sinh trng s r t . S khng nh vy c th l tng i (vi liu lng cao hn m vt ch dung np c vn dit c k sinh trng) hoc khng hon ton (vi liu lng ti a m vt ch dung np c nhng khng tc ng vo k sinh trng). Khng thuc st rt c th c chia lm hai nhm: - khng t nhin: K{ sinh trng c tnh kh la ng t trc khi tip xc vi thuc, do gen ca k sinh trng bin d t nhin, tnh khng thuc c di truyn qua trung gian nhim sc th. K sinh trng c th khng ch o nh P.falciparum khng cloroquin cng c th khng vi amodiaquin. - khng mc phi: K sinh trng nhy cm vi thuc, sau mt th i gian tip xc, tr thnh khng nhy cm na, do t bin nhim sc th, tip nhn gen

 khng t bn ngoi qua plasmid hoc transposon (gen nhy) ca k sinh trng. 4.2. C ch khng thuc Cho n nay cha c mt gii thch hon ton sng t v c ch khng thuc ca k sinh trng st rt, c mt s gi thuyt nh sau: 4.2.1. K sinh trng khng cloroquin - Do FPIX c i lc yu vi cloroquin, nn cloroquin khng to c phc FPIX cloroquin, v vy thuc khng hy c mng v dit k sinh trng. - chng k{ sinh trng khng cloroquin protein gn heme (hemin -bindingprotein), tng s lng v i lc vi FPIX, protein ny s cnh tranh vi cloroquin to phc vi FPIX, lm mt tc dng ca cloroquin. - P.falciparum c th c 2 gen m ha cht v n chuyn a khng thuc MDR (multi drug resistant) l Pfmdr 1 v Pfmdr 2, gen ny lm tng s vn chuyn P glycoprotein qu mc trn mng v gy tng thi tr cloroquin. Pfmdr 1 c trong chng k sinh trng khng vi mefloquin, halofantrin nhng khng tn g trong chng k sinh trng khng cloroquin. 4.2.2. K sinh trng khng fansidar Ging nh c ch vi khun khng bactrim. - K{ sinh trng tng tng hp PABA, tng sn xut dihydrosynthetase. - Gim tnh thm vi sulfonamid v pyrimethamin. 5. NGUYN TC IU TR ST RT - iu tr sm: iu tr cng sm cng tt, ngay sau khi cc triu chng bnh xut hin (tr em trong vng 12 gi, ngi ln trong vng 24 gi). - iu tr ng thuc, liu, thi gian (theo ng phc ). Phi m bo bnh nhn ung c v ung liu thuc cn thit. - Theo di cht ch kt qu iu tr c bin php x l kp thi v thch hp. BI 27. THUC H ST - GIM AU - CHNG VIM Cc thuc trong nhm ny rt khc nhau v cu trc ha hc, gm cc dn xut ca salicylat, pyrazolon, anilin, indol v mt s thuc khc. Tt c cc thuc, mc khc nhau, u c tc dng h st, gim au, v - tr dn xut anilin - cn c tc dng chng vim , chng thp khp, chng ng vn tiu cu. V vy cn c gi chung l thuc chng vim khng (mang nhn) steroid (CVKS) phn bit vi cc glucocorticoid, mang nhn sterol, c gi l thuc chng vim steroid. 1. TC DNG CHNH V C CH

C ch chung ca thuc CVKS: c ch sinh tng hp prostagladin Vane 1971 cho rng c ch tc dng chnh ca cc thuc CVKS l c ch enzym cyclooxygenase, lm gim tng hp cc prostaglandin l nhng cht trung gian ha hc c vai tr quan trng trong vic lm tng v k o di p ng vim m sau tn thng. Khi tn thng, mng t bo gii phng phospholipid mng. Di tc dng ca phospholipase A 2(l enzym b corticoid c ch), cht ny chuyn thnh acid arAChidonic. Sau , mt mt, di tc dng ca lipooxygenas e (LOX), acid arAChidonic cho cc leucotrien c tc dng co kh qun; mt khc, di tc dng ca cyclooxy?genase, acid arAChidonic cho PGE 2 (gy vim, au), prostacyclin (PGI2) v thromboxan A 2 (TXA2) tc ng n s lng ng tiu cu. Cc CVKS c ch COX nn c ch c cc phn ng vim (s )

Hnh 10.1: V tr tc dng ca CVKS v corticoid trong tng hp PG Tuy nhin, c ch trn cha gii thch c y nhng nhn xt lm sng trong qu trnh s dng CVKS, nh: - Hiu qu v tnh an ton ca cc thu c CVKS khng ging nhau. - Hiu qu c ch tng hp PG v TX ca cc thuc rt thay i. Nhiu thuc c ch mnh tng hp PG hn TX v ngc li. Aspirin c ch mnh v khng hi phc s kt t tiu cu vi liu thp, nhng phi liu rt cao mi c tc d ng chng vim. T mi nm gn y, cc nghin cu cho thy c 2 loi COX, c gi l COX - 1 v COX- 2 c chc phn khc nhau v cc thuc chng vim tc dng vi mc khc nhau trn COX - 1 v COX-2 (s ) - COX-1: hay PGG/ H synthetase - 1 c tc dng duy tr cc hot ng sinh l bnh thng ca t bo l mt enzym cu to . Enzym c mt hu ht cc m, thn, d dy, ni mc mch, tiu cu, t cung, tinh hon Tham gia trong qu trnh sn xut cc PG c tc dng bo v, do cn gi l enzym gi nh (house keeping enzyme) : . Thromboxan A2 ca tiu cu . Prostacyclin (PGI2) trong ni mc mch, nim mc d dy

. Prostaglandin E 2 ti d dy bo v nim mc . Prostaglandin E 2 ti thn, m bo chc phn sinh l. - COX- 2: hay PGG/ H synthetase 2 c chc phn thc y qu trnh vim. Thy hu ht cc m vi nng rt thp, cc t bo tham gia vo phn ng vim (bch cu 1 nhn, i thc bo, bao hot dch khp, t bo sn). Trong cc m vim, nng COX - 2 c th tng cao ti 8 0 ln do cc kch thch vim gy cm ng v hot ha mnh COX - 2. V vy COX- 2 cn c gi l enzym cm ng

Hnh 10.2: Vai tr sinh l ca COX - 1 v COX- 2 Ngoi tc dng c ch tng hp PG, cc CVKS cn c th c nhiu c ch khc. Cc CVKS l cc phn t a m, d thm nhp vo mng t bo hoc mng ti th, nht l vo cc bch cu a nhn, nn : . c ch tit cc enzym ca cc th tiu bo . c ch sn xut cc gc t do. . c ch lng ng v kt dnh cc bch cu a nhn trung tnh. . c ch cc chc phn mng ca i thc bo nh c ch NADPH, oxydase, phospholipasse C, protein G v s vn chuyn ca cc anion qua mng. 1.1. Tc dng chng vim Cc CVKS c tc dng trn hu ht cc loi vim khng k n nguyn nhn, theo cc c ch sau: - c ch sinh tng hp prostaglandin (PG) do c ch c hi phc cyclooxygenase (COX), lm gim PG E2 v F1 l nhng trung gian ha hc ca phn ng vim (Vane v cs. 1971). - Lm vng bn mng lysosom (th tiu bo): vim, trong qu trnh thc bo, cc i thc bo lm gii phng cc e nzym ca lysosom (hydrolase, aldolase, phosphatase acid, colagenase, elastase), lm tng thm qu trnh vim. Do lm vng bn mng lysosom, cc CVKS lm ngn cn gii phng cc enzym phn gii, c ch qu trnh vim. - Ngoi ra c th cn c thm mt s c ch khc nh i khng vi cc cht trung gian ho hc ca vim do tranh chp vi c cht ca enzym, h c ch di chuyn bch cu, c ch phn ng khng nguyn- khng th. Tuy cc CVKS u c tc dng gim au - chng vim, song li khc nhau gia t l l iu chng vim/ liu gim au. T l y ln hn hoc bng 2 vi hu ht

cc CVKS, k c aspirin (ngha l liu c tc dng chng vim cn phi gp i liu c tc dng gim au) nhng li ch gn bng 1 vi indometacin, phenylbutazon v piroxicam. 1.2. Tc dng gim au Ch c tc dng vi cc chng au nh, khu tr. Tc dng tt vi cc chng au do vim (au khp, vim c, vim dy thn kinh, au rng, au sau m). Khc vi morphin, cc thuc ny khng c tc dng vi au ni tng, khng gy ng, khng g y khoan khoi v khng gy nghin. Theo Moncada v Vane (1978), do lm gim tng hp PG F 2 nn cc CVKS lm gim tnh cm th ca cc ngn dy cm gic vi cc cht gy au ca phn ng vim nh bradykinin, histamin, serotinin. i vi mt s chng au s au m, CVKS c th c tc dng gim au mnh hn c morphin v m gy ra vim. Trong au do chn p c hc hoc tc dng trc tip ca cc tc nhn ha hc, k c tim trc tip prostaglandin, cc CVKS c tc dng gim au k m hn, cng chng t c ch quan trng ca gim au do CVKS l do c ch tng hp PG. Ngoi ra c th cn nhng c ch khc. 1.3. Tc dng h st Vi liu iu tr, CVKS ch lm h nhit trn nhng ngi st do bt kz nguyn nhn g, khng c tc dng trn ngi thng. Khi vi khun , c t, nm (gi chung l cc cht gy st ngoi lai) xm nhp vo c th s kch thch bch cu sn xut cc cht gy st ni ti (cc cytokin, interferon, TNF ). Cht ny hot ha prostaglandin synthetase, lm tng tng hp PG (c bit l PG E1, E2) t acid arAChidonic ca vng di i, gy st do lm tng qu trnh to nhit (rung c, tng h hp, tng chuyn ha) v gim qu trnh mt nhit (co mch da). Thuc CVKS do c ch prostaglandin synthetase, lm gim tng hp PG, c tc dng h st d o lm tng qu trnh thi nhit (gin mch ngoi bin, ra m hi), lp li thng bng cho trung tm iu nhit vng di i. Cc CVKS khng c ch c st do tim trc tip PG vo vng di i. V khng c tc dng n nguyn nhn gy st nn thuc h st ch c tc dng cha triu chng, sau khi thuc b thi tr, st s tr li.

Hnh 10.3. C ch gy st v tc dng ca thuc h st 1.4. Tc dng chng ngng kt tiu cu Trong mng tiu cu c cha nhiu thromboxan synthetase l enzym chuyn endoperoxyd ca PG G2/ H2 thnh thromboxan A 2 (ch tn ti 1 pht) c tc dng lm ng vn tiu cu. Nhng ni mc mch cng rt giu prostacyclin synthetase, l enzym tng hp PG I 2 c tc dng i lp vi thromboxan A 2. V vy tiu cu chy trong mch bnh thng khng b ng vn. Khi ni mch b tn thng, PGI2 gim; mt khc, khi tiu cu tip xc vi thnh mch b tn thng, ngoi vic gii phng ra thromboxan A 2 cn phng ra cc gi tc lm dnh cc tiu cu vi nhau v vi thnh mch, dn ti hin tng ngng kt tiu cu. Cc CVKS c ch thr omboxan synthetase, lm gim tng hp thromboxan A 2 ca tiu cu nn c tc dng chng ngng kt ?tiu cu (hnh 3.4) Tiu cu khng c kh nng tng hp protein nn khng ti to c cyclooxyganase. V th, mt liu nh ca aspirin (40 - 100 mg/ ngy) c th c ch khng hi phc cyclooxyganase sut cuc sng ca tiu cu (8 - 11 ngy)

Hnh 10.4. C ch c ch ng vn tiu cu 2. CC DN XUT Phn loi ha hc cc thuc CVKS Loi c ch COX khng chn l c Nhm acid salicylic . Aspirin Nhm pirazolon . Phenylbutazon Nhm indol . Indometacin, sulindac . Etodolac (ring thuc ny li c ch chn lc COX - 2) Nhm acid enolic . Oxicam (piroxicam, meloxicam) Nhm acid propionic . Ibuprofen, naproxen, ketoprofen, fenoprofen Nhm dn xut acid phenylacetic . Diclofenac

Nhm dn xut acid heteroarylacetic . Tolmetin, ketorolac Loi c ch chn lc COX - 2 Nhm furanon c nhm th diaryl . Rofecoxib Nhm pyrazol c nhm th diaryl . Celecoxib Nhm acid indol acetic . Etodolac Nhm sulfonanilid . Nimesulid 2.1. Dn xut acid salicylic 2.1.1. Acid salicylic (acidum salicylicum): Tinh th hnh kim, khng mu, n h, ng nh, khng mi, v chua v hi ngt, kh tan trong nc. Do kch ng mnh nim mc nn khng dng ung. Dng ngoi da, dung dch 10% cha chai chn, ht cm, nm da 2.1.2. Acid acetylsalicylic (aspirin): Kt tinh hnh kim trng, hi chu a, kh tan trong nc, d tan hn trong ru v cc dung dch base. L sn phm acetyl ha ca acid salicylic gim tnh kch ng nn ung c. 2.1.2.1. c im tc dng: - Tc dng h st v gim au trong vng 1 - 4 gi vi liu 500 mg/ln. Khng g y h thn nhit. - Tc dng chng vim: ch c tc dng khi dng liu cao, trn 3g/ngy. Liu thp ch yu l h st v gim au. - Tc dng thi tr acid uric: liu thp (1 -2g/ngy) lm gim thi tr acid uric qua nc tiu do lm gim bi xut cht ny ng ln xa. Liu cao (2 5g/ngy) lm i nhiu urat do c ch ti hp thu acid uric ng ln gn. - Tc dng trn tiu cu v ng mu: Aspirin vi liu thp (40 -325mg/ngy) c ch mnh cyclooxygenase ca tiu cu, lm gim tng hp thromboxan A 2 (cht lm ng vn tiu cu) nn lm gim ng vn tiu cu. Liu cao hn, c ch cyclooxygenase ca thnh mch, lm gim tng hp PG I 2 (prostacyclin) l cht chng kt dnh v lng ng tiu cu, gy tc dng ngc li. Nhng tc dng trn tiu cu mnh hn nhiu.

Liu cao aspirin cng lm gim tng hp prothrombin, c th l do i khng vi vitamin K. V vy, aspirin c tc dng chng ng mu. - Tc dng trn ng tiu ha: Nim mc d dy - rut sn xut ra PG, c bit l PG E 2, c tc dng lm tng to cht nhy v c th l c kch thch phn bo thay th cc t bo b ph hu. Nh vy, vai tr ca PGE l bo v nim mc ng tiu ha. Aspirin v cc thuc chng vim phi steroid ni chung, vi mc khc nhau, c ch cyclooxygenase, lm gim PG , to iu kin cho HCl v pepsin ca dch v gy tn thng cho nim mc sau khi hng ro bo v b suy yu. V vy, khng c dng thuc cho nhng ngi c tin s lot d dy v phi ung thuc sau ba n. 2.1.2.2. ?Dc ng hc pH ca d dy, cc dn xut salicylic t b ion ha cho nn d khuch tn qua mng, c hp th tng i nhanh vo mu ri b thu phn thnh acid salicylic, khong 50 - 80% gn vi protein huyt tng, b chuyn ha gan, thi gian bn thi khong 6 gi. Thi tr qua nc tiu 50% trong 24 gi di dng t do, glycuro - hp, acid salicylic v acid gentisic. Nu pH ca nc tiu base, thi tr salicylic tng. 2.1.2.3. c tnh: - Mc du cc dn xut salicylic u t c, d ung, nhng dng lu c th gy hi chng salicyle (salicylisme): bun nn, tai, ic, nhc u, l ln. - c ng: ph, m ay, mn, ph Quincke, hen. - Xut huyt d dy th n (c hng cu trong phn) hoc th nng (lot, nn ra mu). - Nhim c vi liu trn 10g. Do aspirin kch thch trung tm h hp, lm th nhanh v su (nn gy nhim alcali h hp), sau v p lc ring phn ca CO 2 gim, m gii phng nhiu acid lactic, a n hu qu nhim acid do chuyn ha (hay gp tr em v c ch iu ha cha n nh). Liu cht i vi ngi ln khong 20g. 2.1.2.4. Liu lng v ch phm: - Ung 1-6g/ngy, chia lm nhiu ln. Dng h st, gim au v chng vim (thp khp cp, thp khp mn, vim a khp, vim thn kinh) Vin nn aspirin 0,5g (bit dc: Acesal, Aspro, Polopyrin).

- Lysin acetyl salicylat (Aspgic): l dng mui ha tan, mi l tng ng vi 0,5g aspirin. Tim tnh mch hoc tim bp 1 -4 l/ngy. - Aspirin pH8: vin nn cha 0,5 g aspirin, c bao bng cht khng vi dch v, nhng tan trong dch rut, on 2 ca t t rng, t thuc c hp thu vo mu v b thu phn thnh acid salicylic. Nng ti a trong mu t c sau 7 gi, thi gian bn thi di hn aspirin bnh thng, do gim c s ln ung thuc trong ngy, rt tin li cho cc trng hp iu tr ko di. 2.1.3. Methyl salicylat Dung dch khng mu, mi hc lu, ch dng xoa bp gim au ti ch. Ngm qua da cho nn khi xoa bp, thy metyl salicylat trong nc tiu. 2.2. Dn xut pyrazolon Hin ch cn dng mt cch hn ch phenylbutazon. Cc dn xut khc nh phenazon (antipyrin), aminophenazon (pyramidon), metamizol (analgin), khng cn dng na v c nhiu c tnh vi mu (gim bch cu, suy tu), vi thn (i albumin, vim ng thn cp, v niu). Ch dng phenylbutazon cho vim cng khp v vim a khp mn tnh tin trin khi cc thuc CVKS khc khng cn tc dng v phi theo di cht ch cc tc dng khng mong mun ca thuc. Liu lng v ch phm: Ngy u ung 200mg chia lm 2 ln ung trong hoc sau ba n, tng dn liu ti 600 mg /ngy. Tuz theo tnh trng bnh v sc chu ng ca ngi bnh, c th gi liu trong 4 - 5 ngy, sau gim xung liu duy tr 100 - 200 mg. Ni chung, mt t thuc khng qu 15 ngy, sau ngh 4 - 5 ngy mi dng. Phenylbutazon vin 50 v 100 mg. Oxyphenbutazon (Tandery) vin 100 mg. Chngta s b thuc ny trong tng lai gn 2.3. Dn xut indol: 2.3.1. Indometacin

2.3.1.1. c im tc dng - Tc dng gim vim mnh hn phenylbutazon 20 - 80 ln v mnh hn hyd?rocortioson 2 - 4 ln. i khng r vi PG. Tc dng c trn giai on u

v giai on mun (mn tnh) ca vim. - Tc dng gim au lin quan mt thit vi tc dng chng vim (liu chng vim/liu gim au = 1). - C tc dng h st, nhng khng dng cha st n thun v c nhiu c tnh v c thuc h st khc thay th (paracetamol, aspirin). - Sinh kh dng gn bng 100%. Gn protein huyt tng 99%, thm c vo dch khp (bng khong 20% nng huyt tng). 2.3.1.2. c tnh: Xy ra cho khong 20 -50% ngi dng thuc. - C th gy chng mt, nhc u (v cng thc ca indomatacin tng t nh serotonin), ri lon tiu ha, lot d dy. V th khng c dng cho ngi c tin s d dy. 2.3.1.3. Ch nh: - Vim xng khp, h khp, thp khp ct sng, vim nhi u khp mn tnh tin trin, au lng, vim dy thn kinh - Ch phm v liu lng: Indometacin (Indocid; Indocin): vin nn hoc vin nang 25mg. Thuc n 50 100mg. Mi ngy ung 50 - 150 mg chia lm nhiu ln. 2.3.2. Sulindac Sulindac l tin cht ( prodrug): bn thn n khng c hot tnh, vo c th c chuyn ha thnh dn cht sulfat c hot tnh sinh hc mnh, c ch cyclooxygenase 500 ln mnh hn sulindac. V cu trc ha hc, sulindac l indometacin c thay methoxy bng fluor v thay Cl bng gc methylsulfinyl (CH 3SO). - Trong thc nghim, tc dng dc l ca sulindac bng 1/2 indometacin; trong thc t lm sng, tc dng chng vim v gim au ca sulindac tng t aspirin. - T l v mc c tnh km indometacin. - Ch phm: Arthro cin, Artribid, Clinoril vin 150 v 200 mg; mi ngy ung 1 -2 vin, liu ti a 400mg/ngy, l liu tng ng vi 4g aspirin hoc 125 mg indometacin. 2.3.3. Etodolac L thuc c tc dng c ch u tin COX - 2, hp thu nhanh qua tiu ha, 99% gn vo prot ein huyt tng, c chu kz gan - rut. Thi gian bn thi l 7 gi. Liu ung 200- 400 mg 2.4. Dn xut enolic acid: oxicam (piroxicam, meloxicam v tenoxicam) L nhm thuc gim vim mi, c nhiu u im:

- Tc dng chng vim mnh v ngoi tc dng c c h COX cn c ch proteoglycanase v collagenase ca m sn, liu iu tr ch bng 1/6 so vi cc thuc th h trc. Tc dng gim au xut hin nhanh, na gi sau khi ung. - Thi gian bn thi di (2 -3 ngy) cho php dng liu duy nht trong 24 gi. G n vo protein huyt tng ti 99%. V t/2 qu di, d c nguy c tch lu thuc. - t tan trong m so vi cc CVKS khc, cho nn d thm vo t chc bao khp b vim, t thm vo cc m khc v vo thn kinh, gim c nhiu tai bin. - Cc tai bin thng nh v t l thp hn so vi cc CVKS khc, ngay c khi dng thuc ko di ti 6 thng. - Thng ch nh trong cc vim mn v tc dng di. - Ch phm v liu lng: + Piroxicam (Feldene) 10 -40 mg/ngy. Vin nang 10 mg,20 mg;ng tim 20 mg/ ml T 2002 do thy tai bin trn tiu ha cao nn nhiu nc b. + Tenoxicam (Tilcotil) 20mg/ngy.Vin nn 20 mg, ng tim 20 mg/ ml. + Meloxicam (Mobic). Vin nn 7,5 mg v 15 mg. Liu bnh thng 7,5 mg/ ngy, ti a 15 mg/ ngy; t/2= 20 gi. Lc u, da vo k tqu th in vitro, meloxicam c coi nh thuc ?c ch chn lc COX - 2 (1999), nhng trn lm sng, in vivo, tc dng c ch COX - 2 ch mnh hn COX- 1 c 10 ln nn khng cn c xp vo nhm thuc ny na. 2.5. Dn xut acid propionic - Liu thp c tc dng gim au; liu cao hn, chng vim. - So vi aspirin, indometacin v pyrazolon c t tc dng ph hn, nht l trn tiu ha, v vy c dng nhiu trong cc vim khp mn . - Ch phm v liu lng: Ibuprofen: - Tc dng chng vim v gim au tn g t aspirin, nhng tc dng ph trn tiu ha th thp hn nhiu, d c dung np hn. - c hp thu nhanh qua ng tiu ha, nng ti a t c trong huyt tng sau 1 - 2 gi. Thuc b chuyn ha nhanh v thi tr qua thn, thi gian bn thi l 1,8- 2 gi. - Ch nh chnh trong vim khp dng thp, vim cng khp, iu tr cc chng au nh v va (nhc u, au rng, au do kinh nguyt).

- Tc dng khng mong mun: ngoi cc tc dng khng mong mun chung ca nhm thuc CVKS, cn thy nhn m, gim th lc, thay i nhn cm mu sc. Cn ngng dng thuc v khm chuyn khoa mt. - Liu lng v cch dng: . Vin nn 100, 150, 200, 300 v 400 mg . Vin nang 200 mg . n trc trng 500 mg Vim khp: thng dng 1,2 - 1,8g/ ngy, chia lm 4 ln. C th tng liu nhng khng vt qu 3,2g/ ngy. Sau 1 - 2 tun cn gim xung liu thp nht c tc dng (0,6 - 1,2g/ ngy). Gim au: ung 400 mg/ ln, cch 4 - 6 gi/ ln. Naproxen Vin 250mg. Ung 250mg x 2 ln/ngy. Thi gian bn thi l 14 gi. D dung np nn thng c dng nh ibuprofen 2.6. Nhm dn xut ca acid phenylacetic i din duy nht l diclofenac (Voltaren) - Tc dng c ch COX mnh hn indometain, naproxen v nhiu thuc khc. Ngoi ra c th cn lm gim nng acid arAChidonic t do trong bch cu do ngn cn gii phng hoc thu hi acid bo. - Hp thu nhanh v hon ton qua ng tiu ha, nhng ch 50% vo c tun hon v b chuyn ha trong qu trnh hp thu. T 1/2 = 1- 2 h, nhng tch lu dch bao khp nn tc dng vn gi c lu. - Ch nh trong vim khp mn. Cn dng gim au trong vim c, au sau m v au do kinh nguyt. - Tc dng ph t, ch khong 20%, c th lm tng aminotransferase gan gp 3 ln, nhng hi phc c. - Ch phm v liu lng: vin 50 - 100 mg ung 100- 150 mg/ ngy. 2.7.Nhm dn xut acid heteroarylacetic - Tolmetin: . Tc dng chng vim, gim au v h st tng t aspirin nhng d dung np hn. Thuc c gi li trong bao hot dch ti 8 gi sau 1 liu duy nht. . Tc dng ph: 25 - 40%. . Tc dng chng vim, gim au liu 0,8 - 1,6g/ ngy, tng ng vi aspirin 4 - 4,5g/ ngy hoc indometacin 100 - 150 mg/ ngy. Liu ti a l 2g/ ngy chia

lm 3 - 4 ln. - Ketorolac: . L thuc c tc dng gim au mnh hn chng vim. Khc opioid , tc dng gim au ca ketorolac khng gy quen thuc v du hiu cai thuc, khng c ch trung tm h hp. C tc dng chng vim ti ch, dng nh mt. . L mt trong s t thuc CVKS c th dng ng tim. . Tc dng ph gp 2 ln placebo, thng l n g g, chng mt, nhc u, chm tiu, nn, au ch ?tim. Thng dng cho gim au sau m, au cp tnh. Liu ung 5- 30 mg/ ngy; tim bp 30 - 60 mg/ ngy; Tim tnh mch 150 30 mg/ ngy, khng dng qu 5 ngy. . Ch nh gim au ngn hn, di 5 ng y nh au sau m: tim bp 30 60 mg; tim tnh mch 15- 30 mg v ung 5 - 30 mg. . Khng dng cho au trong sn khoa. Khng dng cho au nh v au mn tnh. 2.8. Thuc CVKS loi c ch chn lc COX - 2 Cc thuc loi ny, c nhng c im sau: - c ch chn lc trn COX -2 nn tc dng chng vim mnh, v c ch COX 1 yu nn cc tc dng ph v tiu ha, mu, thn, cn hen gim i rt r rt, ch cn t 0,1 - 1%. - Thi gian bn thi di, khong 20 gi cho nn ch cn ung mi ngy 1 ln. - Hp thu d dng qua ng tiu ha, d thm vo cc m v dch bao khp nn c nng cao trong m vim, ch nh tt cho vim xng khp v vim khp dng thp V kt t tiu cu ph thuc duy nht vo COX - 1, nn cc thuc nhm ny khng dng d phng c nh i mu c tim. Vn cn dng Aspirin. Qua thc t s dng, vn thy c tc dng ph do c ch COX - 1 cho nn nhiu tc gi ngh khng dng t c ch chn lc m nn thay bng t c ch u tin COX- 2 th ng hn. Rofecoxib (Vioxx) c ch COX- 2 mnh hn COX- 1 ti 800 ln. c dng t 1999. Qua nhiu th nghim lm sng dng lin tc trn 18 thng iu tr polip i trng, ung th tuyn tin lit, bnh Alzheimer, thy tai bin tim mch ca Vioxx cao hn placebo nn thng 10/ 2004 Hng sn xut (Merck) t nguyn xin rt khi th trng. Celecoxib (Celebrex) Thuc c ch COX - 2 mnh hn COX - 1 t 100 n 400 ln, c dng t 1998.

- Hp thu qua tiu ha, t nng ti a trong huyt tng sau 2 - 4 gi. Gn mnh vi protein huyt tng. Phn ln b chuyn ha gan. Thi gian bn thi l 11 gi. - Liu thng dng 100 mg 2 ln/ ngy. trong thp khp c th tng liu ti 200 mg 2 ln/ ngy. Etodolac: (xem 2.3.3) Cc thuc c ch chn lc COX - 2 c khng nh l lm gim r rt t ai bin chy mu tiu ha, nhng sau 5 nm s dng thy nguy c tim mch tng v thuc gy mt thng bng gia PGI2 v TXA2, lm gim mnh PGI 2, yu t bo v ni mc mch. Hin nay (2005) thuc vn c gim st cht ch khi dng ko di. 2.9. Dn xut para aminophenol : Acetaminophen, paracetamol 2.9.1 c im tc dng Paracetamol c cng v thi gian tc dng tng t nh aspirin v gim au v h st. Khng c tc dng chng vim nn nhiu tc gi khng xp vo nhm thuc CVKS. Thc ra, trn m hnh thc nghim, paracetamol vn tc dng chng vim, nhng phi dng liu cao hn liu gim au, v trong vim c nng cao cc peroxid, lm mt tc dng c ch COX ca paracetamol (Marshall v cng s 1987) v mt khc, paracetamol khng c ch s hot ha bch cu trung tnh nh cc CVKS khc (Abramson v cng s, 1989). Trong thc hnh, paracetamol c dng h st, gim au. Ch nh tt cho nhng ngi khng dng c aspirin (lot tiu ha, ri lon ng mu). 2.9.2. Dc ng hc Hp thu nhanh qua tiu ha, sinh kh dng l 80 -? 90%, t/2 = 2 gi, hu nh khng gn vo protein huyt tng. Chuyn ha phn ln gan v mt phn nh thn, cho cc dn xut glucuro v sulfo-hp, thi tr qua thn. 2.9.3. c tnh Vi liu iu tr thng th ng, hu nh khng c tc dng ph, khng gy tn thng ng tiu ha, khng gy mt thng bng base -acid, khng gy ri lon ng mu. Tuy nhin, khi dng liu cao (> 10g), sau thi gian tim tng 24 gi, xut hin hoi t t bo gan c th tin trin t i cht sau 5 - 6 ngy. Nguyn nhn l paracetamol b oxy ha gan cho N - acetyl parabenzoquinon -imin. Bnh thng, cht chuyn ha ny b kh c ngay bng lin hp vi glutathion ca gan. Nhng khi dng liu cao, N -acetyl parabenzoquinon -imin qu tha s

gn vo protein ca t bo gan v gy ra hoi t t bo. Biu hin bng au h sn phi, gan to, vng da, hn m gan (do tng amoniac), acid mu. V sinh ha, AST, ALT, LDH u tng. Bnh nhn thng cht sau 6 -7 ngy. Nu iu tr sm bng N -acetylcystein (NAC, Mucomyst, Mucosol), l cht tin thn ca glutathion, bnh nhn c th qua khi. Sau 36 gi, gan b tn thng, kt qu s km. Sau ng c di 10 gi, dng NAC c hiu qu hn: ung dung dch 5% - 140mg/kg, sau , cch tng 4 gi, ung 70 mg/kg 17 liu. NAC cng c tc dng ph: ban , my ay, nn, tiu chy, nhng khng cn ngng thuc. 2.9.4. Ch phm v liu lng - Paracetamol (Efferalgan; Dafalgan): vin 0,5g; gi bt 0,08g; vin n 80, 150, 300 mg. . Ngi ln: 0,5 -1,0g 1-3 ln/ngy. Khng c dng qu 4 g/ngy. . Tr em 13-15 tui: 0,5g 1-3 ln/ngy. . Tr em 7-13 tui: 0,25g 1-3 ln/ngy. - Propacetamol clohydrat (Pro - Dafalgan) (th h 1) V paracetamol kh tan trong nc nn tng hp tin cht ca paracetamol tan c trong nc, vo c th di tc dng ca esterase huyt tng s gii phng paracetamol: esterase Propacetamol Diethylglycin + PARACETAMOL (2g) huyt tng (1g) Trnh by: l thuc bt + dung mi. Pha ngay trc khi dng, khn g qu 30 pht. Tim bp su hay tim tnh mch chm trong vng 2 pht. C th truyn tnh mch trong vng 15 pht (pha trong 100 mL NaCl 0,9% hoc glucose 5%). Liu dng 1 -2g/ ln, cch 4 - 6 gi. Khng dng qu 8g/ ngy. Khng dng cho tr em d i 15 tui v ngi suy thn. - Perfalgan (th h 2) L paracetamol c lm tan hon ton trong nc (1g/ 100 mL). Perfalgan 1g c tng ng sinh hc vi propacetamol 2g v c tc dng gim au tng ng vi diclofenac 75 mg tim bp, hoc morphin 10 mg tim bp. - Rt nhiu ch phm khc c cha paracetamol kt hp vi cafein, ephedrin, codein, phenylpropanolamin (PPA) 3. NHNG VN CHUNG 3.1. Dc ng hc chung - Mi CVKS ang dng u l cc acid yu, c pKa t 2 n 5. - Hp thu d qua tiu ha d o t b ion ha d dy.

- Gn rt mnh vo protein huyt tng, ch yu l albumin, c thuc ti 99,7% (nhm oxicam, diclofenac), do d y cc thuc khc ra dng t do, lm tng c tnh ca thuc (sulfamid h ng huyt, thuc khng vitamin K ). Cc thuc CVKS d dng thm nhp vo cc m vim. Nng thuc trong bao hot dch bng khong 30- 80% nng huyt tng. Khi dng lu, s vt qu nng huyt tng. Do tc dng vim k?hp c duy tr. - B ging ha gan (tr acid salicylic), thi qua thn di dng cn hot tnh khi dng vi liu chng vim v liu c. - Cc thuc khc nhau v thi tr, t 1/2 huyt tng thay i t 1 - 2 gi (aspirin, nhm propionic) n vi ngy (pyrazol, oxicam). - Nhm salicylic dng cho au nh (rng) hoc cc vim cp. Cc CVKS c t 1/2 di c dng cho vim mn vi liu 1 ln/ ngy. Da theo thi gian bn thi ca thuc, c th chia cc CVKS lm 3 nhm (bng 3.3): - Cc thuc c thi gian bn thi ngn, di 10 gi, cn ung 3 ln/ ngy, bnh nhn kh tun th. Tuy nhin, c li l khi ngng thuc, tc dng s ht nhanh, nht l khi xy ra tc dng khng mong mun. An ton hn cho ngi cao tui v bnh nhn suy thn. - Cc thuc c thi gian bn thi di, trn 30 gi, ch cn dng 1 ln/ ngy, ngi b nh khng qun. Tuy nhin, d gy tch lu thuc, nht l vi ngi c tui v suy thn, d gy tai bin nng, khi ngng thuc tc dng c hi cn ko di. Phi 7 ln t/2 th thuc mi thi tr ht, nh vy, vi piroxicam c t/2 = 40 gi, phi ch 12 ngy . - Cc thuc c thi gian bn thi trung gian: tng i d dng v t tc dng ph hn. Bng 10.1: Phn loi thuc theo thi gian bn thi (t/2)

3.2. Cc tc dng khng mong mun Thng lin quan n tc dng c ch tng hp PG. - Lot d dy - rut: nim mc d dy rut sn xut PG, c bit l PG E 2 c tc dng lm tng cht nhy v c th l c kch thch phn bo thng xuyn thay th cc t bo nim mc b ph hu. Thuc CVKS c ch tng hp PG, to iu kin cho HCl ca dch v gy tn thng cho nim mc sau khi

hng ro bo v b suy yu. - Lm ko di thi gian chy mu do c ch ngng kt tiu cu. - Vi thn, PG c vai tr quan trng trong tun hon thn. c ch tng hp PG gy hoi t gan v sau l vim thn k mn, gim chc phn cu thn, d dn n tng huyt p. - Vi ph n c thai: + Trong 3 thng u, CVKS d gy qui thai + Trong 3 thng cui, CVKS d gy cc ri lon phi, lin quan n vic ng ng ng mch ca bo thai trong t cung. Mt khc, do lm gim PG E v F, CVKS c th ko di thi gian mang thai, lm chm chuyn d v PG E, PG F lm tng co gp t cung, trc khi vi gi, s tng hp cc PG ny tng rt mnh. - Mi CVKS u c kh nng gy cn hen gi (pseudo asthma) v t l nhng ngi hen khng chu thuc l cao v c th l CVKS c ch cyclooxygenase nn lm tng cc cht chuyn ha theo ng lipooxygenase (tng leucotrien). 3.3. Tng tc thuc Khng dng CVKS vi: - Thuc chng ng mu, nht l vi loi khng vitamin K. - Thuc li niu v h huyt p, v CVKS c ch tng hp c cc PG gy gin mch. - Lithium: CVKS lm gim thi tr lithi qua thn, gy tch lu. - CVKS lm tng tc dng ca phenytoin v sulfamid h ng huyt d o y chng ra khi protein huyt tng, lm tng nng thuc t do trong mu. 3.4. Ch nh 3.4.1. Gim au v h st thng thng: aspirin, paracetamol Gim au sau m: cho thuc trc khi rch dao, loi c t/2 trung bnh hoc di. 3.4.2. Cc bnh th p cp v m o d n - V t l c tnh tiu ha/hiu qu chng vim ging nhau cho mi loi CVKS, cho nn tiu chun chn thuc cn da trn: + p ng ca tng ngi bnh + S thun tin trong s dng + Tc dng nhanh. - Th d: + Vim a khp dng thp: dn x ut propionic, diclofenac (Voltaren). + Vim khp mn ca ngi tr: aspirin + Vim cng khp: indometacin

+ Thoi ha khp: loi c tc dng gim au vi liu thp v khi tng liu s t c tc dng chng vim: aspirin, dn xut propionic. Hoc mt thu c gim au n thun paracetamol. 3.4.3. Cc ch nh khc Cc thuc c ch chn lc COX - 2 ang c th dng d phng v iu tr bnh Alzheimer, polip i trng, ung th rut kt - trc trng, tuyn tin lit. Tuy nhin, do phi dng di ( 18 thng), thy nguy c tim mch tng. 3.5. Nguyn tc chung khi s dng CVKS - Vic chn thuc tuz thuc vo c th. C ngi chu ng c thuc ny nhng khng chu ng c thuc khc. - Ung trong hoc sau ba n trnh kch ng d dy. - Khng ch nh cho bnh nhn c tin s lot d dy. Trong trng hp tht cn thit, phi dng cng vi cc cht bo v nim mc d dy. Song, nhng tai bin tiu ha khng phi ch do tc dng kch thch trc tip ca thuc ln nim mc m cn do tc dng chung ca th uc. CVKS gy lot d dy do c ch tng hp PG E 2 , PG I2 nim mc d dy. Cc PG ny c vai tr c ch bi tit HCl, v kch thch bi tit dch nhy cng bicarbonat d dy, v th c tc dng bo v nim mc d dy. Hin tng hp c mt loi t ng t PG E1 l Misoprostol (Cytotec), tc 15 - deoxy- 16 hydroxy- 16 metylPG E1 c tc dng chng lot d dy tng t thuc khng H2. c bit c dng trong nhng ngi phi iu tr ko di bng CVKS. Tc dng ph: tiu chy (30%), au qun bng, x y thai. Liu lng: Vin 200 g x 4 ln/ ngy. ang nghin cu tng hp thuc tng t PGE 2 (Arboprostol, Enprostil, Trimoprostil). - Ch nh thn trng i vi bnh nhn vim thn, suy gan, c c a d ng, cao huyt p. - Khi iu tr ko di, cn ki m tra c nh kz (2 tun mt ln) cng thc mu, chc phn thn. - Nu dng liu cao tn cng, ch nn ko di 5 - 7 ngy. Nhanh chng tm c liu thp nht c tc dng iu tr trnh c tai bin. - Ch khi dng phi hp thuc: + Khng dng ph i hp vi cc CVKS vi nhau v lm tng c tnh ca nhau. + Khng dng CVKS cng vi thuc chng ng mu loi khng vitamin K

(dicumarol, warfarin), sulfamid h ng huyt, diphenylhydantoin, v CVKS s y cc thuc ny ra khi ni d tr (protein huy t tng), lm tng c. Nu vn cn phi hp th gim liu cc thuc . + Cc CVKS c th lm gim tc dng mt s thuc do lm tng ging ha hoc i khng ti ni tc dng, nh meprobamat, androgen, li niu furosemid. BI 28. THUC CHNG VIM STEROID 1. I CNG : 1.1. Khi nim chung : Corticoid l hormon v thng thn, xut pht t ch adrenal cortex. Do trong cng thc cu to c nhn steroid nn cn c gi l glucocorticoid (GC)( tn chung c ho cc hormon ca v thng thn ). 2.1. Ngun gc : + Thin nhin : phn lp t tuyn v thng thn cc ng vt ln. + Tng hp hoc bn tng hp : t acid desoxycholic mt, t thc vt ( t sarmentogenin ca cy Strophantus, t botogemis ca cy Dioscorea mexicana). Mi GC ang dng trong iu tr u l dn xut ca cortisol. 2.2. Dc ng hc : 2.2.1. Hp thu : + Hp thu tt qua ng tiu ho hoc ng tim ( F = 86-90 % ), sau 1 - 2 h t Cmax. trong mu. Ch yu dng ng ung, c bit iu tr cc bnh mn tnh. + Thuc hp thu km qua da, qua kt mc, mng hot dch. Dng nh dch c th tim IM v c tc dng ko di. Dng ester tan trong nc, dng tim IM hoc tim IV. 2.2.2. Phn phi :Sau khi hp thu, hn 90 % cortisol trong huyt tng c gn thun nghch vi protein l CBG ( corticosteroid - binding globuline ) hay transcortin ( 1 2-globulin do gan sn xut ). Sau, c phn phi u n cc t chc v gy tc dng sinh hc. Mc gn vi protein huyt tng ca cc GC rt khc nhau. 2.2.3. Chuyn ho : Ch yu gan bng phn ng lin hp v phn ng hydroxy ho ( kh ng ni 4-5 v kh ceton v tr 3 ). 2.2.4. Thi tr : Thi tr ch yu qua thn di dng glucuro-hp v sulfo-hp. t1/2 ca thuc khc nhau tuz loi corticoid ( = 90 300 ph ) Khong 15 % c bi xut

dng cha chuyn ho. * Loi tc dng trung bnh (12 - 36 h )cho ung cch nht. - Prednisolon hay hydrocortancyl: mnh hn hydrocortison 3 - 5 ln. - Prednison hay cortancyl. Vo gan b chuyn ha thnh prednisolon mi c hot tnh nn tc dng km prednisolon khong 20 %. - Metylprednisolon : tc dng mnh hn hydrocortison 5 ln. - Triamcinolon. + Loi tc dng trung bnh : prednison, prednisolon, triamcinolon acetonid, hydrocortison valerat, flucinolon acetonid. + Loi tc dng mnh v rt mnh : betamethason dipropionat, flucinolon acetonid, diflorason diacetat, halobetasol propionat. + Tng phn hy protid trong c th ( thnh glucose ) nhiu m b nh hng : m lin kt km bn vng ( vch rn da ), m lympho b teo ( tuyn c, lch, hch lympho ), tha xng do lm teo cc thm m lin kt, ni lng ng cc cht v c to nn khung xng ( xng di d gy, t sng b ln, hoi t v khun c xng i ). c- Trn chuyn ha lipid : + GC c ch tng hp acid bo c chui carbon di. + Lm tng phn hu lipid t cc t chc m, lm tng gii phng glycerol v acid bo vo mu. + ng thi cc GC c tc dng phn b li lipid trong c th, lm m ng nhiu mt ( mt trn nh mt trng ), c v na thn trn ( nh dng Cushing ), trong khi cc chi v na thn di th teo li. d- Trn chuyn ha nc, in gii : tc dng theo kiu aldosterol nhng k m hn rt nhiu. + Na+ : lm tng ti hp thu Na+ v nc ti ng thn, d gy ph v tng huyt p. + K+ : lm tng thi tr K+ ( v H+ ), d gy nhim base mu gim K+ ( c nhim base mu gim Cl ). + Ca2+ : l?m gim hp thu Ca2+ rut ( do i khng vi vitamin D ), tng thi tr Ca2+ qua thn gim Ca2+/mu, d dn ti cng tuyn cn gip trng phn ng ko Ca2+ t xng ra, cng lm xng b tha, lm tr em chm ln. + Nc : nc thng i theo cc ion. Khi c ph do cng aldosteron ( v d x gan ) th GC gy i nhiu do GC i khng vi aldosteron ti thn. 2.5.2. Trn cc m, c quan :

a- Trn thn kinh trung ng: + Lc u gy kch thch, lc quan, sng khoi ( c l do ci thin nhanh tnh trng bnh l ). + V sau lm bt rt, bn chn, lo u, kh ng ( c th do ri lon trao i ion Na+, K+ trong dch no tu ). Gy thm n ( do tc dng trn hypothalamus ). bTrn mu v qu trnh ng mu : Lm tng nhanh qu trnh ng mu, tng s lng hng cu, bch cu, tiu cuTuy vy, li lm gim s lng t bo lympho do hu cc c quan lympho. c- Trn ng tiu ha : GC va c tc dng gin tip, va c tc dng trc tip lm tng tit dch v, HCl v pepsin, lm gim sn xut cht nhy, gim tng hp PGE1, PGE2. V vy GC c th gy vim, lot d dy - hnh t trng. d- GC c ch cu to nguyn bo si, c ch cc m ht, lm chm lin so cc vt thng. e- Trn h ni tit : GC c tc dng c ch h HPA ( Hypothalamic pituilary adrenocortical system ) theo c ch feedback, lm gim hot ng ca tuyn yn, tuyn gip, tuyn thng thn 2.6. Tc dng dc l : C 3 tc dng dc l chnh : chng vim, chng d ng, c ch min dch. Tuy nhin, cc tc dng dc l ch t c khi lng GC trong mu cao hn nng sinh l{ v khi li xut hin cc tc dng khng mong mun. 2.6.1. Tc dng chng vim : a- c im tc dng : + GC l thuc chng vim mnh nht v thng c dng nht trong nhiu bnh vim cp v mn tnh. + GC c tc dng trn nhiu giai on khc nhau ca qu trnh vim, khng ph thuc nguyn nhn ( c hc, ha hc, nhim khun, bc x), v vy ngn cn c cc biu hin lm sng ca vim. b- C ch tc dng : + giai on sm ca vim : GC c ch cc yu t ha ng ng v cc cytokin thc y vim nh IL-1, IL-6, IL-8, TNF, do lm gim lung i thc bo v bch cu ht k o n vim. Hn na, GC cn lm gim tit cc cht vn mch nh serotonin, histamin v do i khng vi s tng tnh thm thnh mch. IL-1 : interleukin-1 TNF : tumor necrosis factor Cc GC c ch phospholipase A2, lm gim tng hp acid arachidonic, v vy c ch cc PG v LT do c tc dng chng vim, chng co tht kh ph qun.

Tc dng ny l gin tip v GC lm tng sn xut lipocortin, l protein c mt trong t bo, c tc dng c ch phospholipase A2. Khi phospholipase A2 b c ch, phospholipid khng chuyn c thnh acid arachidonic ( Hnh 2 ). GC c ch c c 2 con ng lipooxygenase v cyclooxygenase ( COX ), lm gim tng hp c 2 loi PG v LT. V th GC c tc dng tri hn hn thuc CVPS. Thuc CVPS ch c ch COX, ch lm gim tng hp PG ch khng c ch ?c cc LT. V vy, GC mnh hn hn thuc CVPS khi dng iu tr cc bnh l v vim. * Giai on ang vim :GC c ch mnh nitric oxyd ( NO ) synthetase, lm gim sn xut gc t do NOtrong i thc bo. Thuc cn c ch sn xut cc protease trung tnh nh elastase collagenase ( c th do c ch gii phng cc enzym thu phn ny t lysosom ). GC cn lm gim hot ng thc bo ca cc i thc bo, bch cu a nhn, gim sn xut cc cytokin. GC cng lm gim sn xut v gim hot tnh ca cc cht TGHH ca vim. HPETE HydroPeroxyEicosa TetraEnoic acid 2.6.2. Tc dng chng d ng : GC phong to s gii phng cc cht TGHH ca phn ng d ng bng cch c ch phospholipase C. Nh vy, IgE gn trn dng bo nhng khng hot ha c nhng t bo . GC l nhng cht chng d ng mnh. Ngoi ra GC cn c ch tc dng cacht phn ng chm ca shock phn v ( slow reacting substance of anaphylaxis) gin tip thng qua c ch LT. 2.6.3. Tc dng c ch min dch : GC tc dng ch yu c ch trn min dch t bo, t nh hng trn min dch th dch, c ch cc cytokin ( IL-1, IL-2) - Thuc c ch tng sinh cc t bo lympho T do lm gim sn xut IL-1 ( t i thc bo ) v IL-2 ( t T4 ) - Thuc c ch hot tnh gy c ca t bo ca lympho T ( T8) v cc t bo dit t nhin ( natural killer - NK ) do lm gim sn xut IL-2 v interferon gama. - Thuc c ch sn xut TNF v interferon, lm suy gim hot tnh dit khun, gy c t bo v nhn dng khng nguyn ca i thc bo. Mt s tc dng ny ng thi l tc dng chng vim. Do c ch tng sinh, GC

c tc dng tt trong iu tr bnh bch cu lympho cp, bnh Hodgkin c li l ngn cn s phn ng qu mc ca c th trc mt yu t ngoi lai ( stress, nhim khun, phu thut ) bo v c th, song n lm gim sc khng ca c th, lm cho c th d b nhim khun, nhim nm, virus v lan rng cc nhim khun c t trc. 2.7. c tnh ( tc dng khng mong mun ca GC ) : 2.7.1. c tnh do dng liu cao hoc dng lin tc ko di : a- Ri lon nc v in gii : Nhim kim, h K+/mu, ph do gi Na+ nn gi nc, tng huyt p. Cn kim tra nh kz, cho bnh nhn n ch n gim mui, b sung thm K+. Nn chn cc ch phm khng gi Na+ nhiu nh triamcinolon, betamethason bNhim khun : V GC c tc dng c ch min dch nn lm gim sc khng ca c th, lm tng nguy c nhim khun hoc lm bc l mt bnh lao tim tng. Ch dng GC khi bit chc chn bnh nhn khng c nhim khun, hoc nu cn th dng phi hp vi thuc khng sinh, khng nm thch hp. c- Vim lot ng tiu ha : GC c th gy chy mu, lm thng lot hin c hoc so lo t c ( c th gy lot mi ? ). Ch dng GC cho cc bnh nhn khng c tin s hoc khng b lot ng tiu ha. d- Nhc c v teo c : Thng xy ra vi cc c gn gc chi. c bit trn nhng bnh nhn cao tui, bnh nhn hen hoc c bnh phi tc nghn mn tnh, G?C lm nhc c h hp c th lm nng thm suy h hp. e- Thay i hot ng tm thn, tc phong : C th gp tnh trng kch ng, mt ng, thay i tm trng, sng khoi, c th lm bc l bnh tm thn tim n.f- c thu tinh th : g- Xp xng : Gp mi la tui khi dng GC liu cao hoc ko di ( 30 - 50 % BN ), d dn n gy xng t pht do xp xng ( c xng i v ct sng ).h- Chm ln v chm pht trin : tr em, d dng GC vi liu thp cng c th dn n chm pht trin. C th do gim tng hp protid hoc do c ch tuyn yn, lm gim tng hp GH ( growth hormone ) 2.7.2. c tnh do ngng iu tr :

ang iu tr bng GC di ngy, khi ngng thuc t ngt c th lm bnh bng pht tr li. Mt tai bin nng n khc l suy tuyn thng thn cp do c ch trc HPA. Ngoi ra c th gp : st, au c, au khp, kh chu v mt hi chng t gp l gi u no ( pseudotumor cerebri) ( tng p lc ni s + ph gai mt ). 2.8. Ch nh : Cn c vo tc dng c th sp xp cc ch nh thnh 3 loi : 2.8.1. Ch nh bt buc :thay th khi c thiu ht hormon : + Suy thng thn cp. + Suy thng thn mn (bnh Addison) + Bnh gan : vim gan t min mn tnh + Bnh c tnh : Hodgkin, bnh bch cu cp tr em, u lympho c tnh, u lympho non-Hodgkin, a u tu + Shock, c bit shock phn v. + Sau phu thut gh p cc c quan : chng thi ghp. + Tn thng tu sng 2.8.2. Ch nh cn thit:iu tr cc bnh m c ch bnh sinh lin quan n phn ng min dch, phn ng vim v phn ng d ng : + Bnh khp : vim xng khp, vim khp dng thp. + Bnh thp tim. + Bnh thn : hi chng thn h, bnh thn th pht sau lupus ban , vim cu thn tng sinh mng v x cng thnh . + Bnh d ng. + Bnh collagen : x cng b da, vim a c, vim nt quanh ng mch, luput ban + Hen ph qun. + Bnh mt. + Bnh ngoi da : vim da d ng, vy nn + Bnh mu : thiu mu tan huyt t min, xut huyt do gim tiu cu + Bnh ng tiu ha : vim rut kt mn tnh c lot, bnh Crohn ( ch dng GC khi cc phng php iu tr bo tn khc nh ngh ngi, dinh dng, sulfasalazin tht bi ). 2.8.3. Ch nh cn nhc : Loi ny gm cc bnh c nguyn nhn r rt, nhng c km theo phn ng min dch, cn thn trng: + Vim gan, x gan.

+ Lao phi. + Trn dch mng phi, mng bng + Vim rut, vim i trng + Vim cu thn. 2.9. Chng ch nh : + Lot d dy, lot hnh t trng tin trin. + Qu mn cm vi thuc. + Cc nhim khun hoc nhim nm cha c iu tr bng KS c hiu. + i tho ng. + Long xng. + Tng huyt p, ph + Vim gan virus A, B, non A non B 2.10. Nguyn tc iu tr : + V thuc c nhiu tc dng khng mong mun cho nn u tin cn cn nhc k gia nguy c v li ch khi dng thuc cho tng bnh nhn. + Vi bt c bnh nhn no v i v o ph i tng bnh nhn cn phi xc nh liu thch hp c hiu qu iu tr bng nh kz kim tra nh gi tin trin ca bnh v tc dng khng mong mun ca thuc thay i liu. Nu khng phi l chng ch nh th mt liu duy nht d hi cao hoc mt t iu tr ngn < 1 tun th thng l v hi. + Khi thi gian dng thuc ko di > 1 tun th cc tc dng khng mong mun s tng c v s lng v cng , thm ch c nguy c t vong. + Vic ngng thuc t ngt sau mt t iu tr di thng dn n nguy c suy tuyn thng thn cp rt nguy him cho bnh nhn. 2.11. Nhng im cn ch khi dng thuc : + Khi dng GC thin nhin ( cortisol, hydrocortison ) phi n nht. i vi cc thuc tng hp, n nht tng i. + Lun cho mt liu duy nht vo lc 8h sng. Nu phi dng liu cao th 2/3 liu ung vo bui sng, 1/3 liu cn li ung vo bui chiu. + Tm liu ti thiu c tc dng. + Khi dng thuc ko di cn kim tra nh kz glucose, K+/mu, nc tiu, Xquang d dy v ct sng, thm d chc phn trc HPA. + Dng thuc phi hp : tng liu insulin i vi bnh nhn i tho ng; phi hp khng sinh nu c nhim khun, nhim nm.

+ Ch n : nhiu protid, calci v kali; t mui, ng v lipid. C th dng thm vitamin D. + Phi tuyt i v khun khi tim GC vo khp. + Sau mt t dng GC ko di ( > 1 thng ) hoc vi liu cao, khi ngng thuc t ngt, bnh nhn c th t t do suy tuyn thng thn cp. Phi tim ACTH 50 mg/24 h 2 ngy. 2.12. Tng tc thuc : + Cc thuc lm tng chuyn ho GC : barbiturat, rifampicin, diazepam, diphenylhydantoin. + Cc thuc lm gim chuyn ho GC : cyclosporin, erythromycin, thuc trnh thai. + Cc thuc lm nng thm tai bin ca GC : cc CVPS 3. MT S CH PHM HAY DNG : 3.1. Nhm khng c delta : + Cortison ( BD : corton ). + Hydrocortison ( BD : acepolcort H, hydrocorton, microcort, polcort H, solucortef, unicort). 3.2. Nhm c delta : + Delta cortison ( BD : cortancyl, decortin, encorton, prednison, urtilon) + Deltahydrocortison ( BD : hydrocortancyl, prednisolon). + Triamcinolon (TK: fluoxyprednisolon ) ( BD : adcortyl, kenacort, kenalog, volon) + Dexamethason ( BD : decadron, dexon, deronil, dexadrol ) + Metylprednisolon ( BD : adlon, depoject, depo-medrol, depopred, D-med, duralon, medrol oral, solu-medrol). 4. MT S PHNG PHP S DNG GLUCOCORTICOID : 4.1. Liu cao, dng nhiu ln trong ngy : Thng dng khi c biu hin ca bnh l vim nng ( vim mch h thng, vim khp mc nng, t cp ca lupud ban h thng). 4.2. Liu dng cao v dng mt ln vo bui sng : Khi bnh nng ( hiu qu cao, khng c ch trc HPA ). 4.3. Liu cao, t ngn. 4.4. Dng liu nh, t ngn < 10 ngy. 4.5. Liu trung bnh cch ngy : Thng dng vo bui sng, c mt ngy dng thuc li ngh mt ngy. ( lm gim tc dng ph ). C th s dng cch ny khi cn dng GC ko di hoc khi gim liu thuc hoc chun b dng thuc. Nn

s dng cc loi corticoid tc dng ngn v trung bnh. 5. CCH S DNG CORTICOID TRONG IU TR : 5.1. Cch ngng corticoid : N c u s dng GC liu thp ( < 20 mg/24 h tnh theo liu prednison ) trong thi gian ngn ( < 3 tun ) th vic ngng thuc t ngt t gy tai bin v c th ngng ngay khi thy tc dng. Tuy vy nu dng liu cao th vic gim liu phi t t . 5.2. iu tr cch ngy : C mt ngy dng thuc li ngh mt ngy ( gim tc dng ph ). C th s dng cch ny khi cn dng corticoid ko di t vi tun tr ln iu tr cc bnh nh vim lo t rut kt, ghp thn, vim da mn tnh, nhc c nng, hen ph qun Nhng bnh khng nn iu tr cch ngy l vim khp dng thp, lupus ban . Nn s dng cc loi corticoid tc dng ngn v trung bnh v n cho php khi phc li hot ng ca trc HPA vo ngy ngng thuc. Nhng tc dng ph kiu Cushing ( bo mt, b o ph, tng glucose huyt, bnh c, bnh nhim khun, chm ln tr em) t gp hn khi iu tr theo kiu ny. * Cch iu tr cch ngy : Bt u t iu tr th dng thuc hng ngy - khi bnh i vo n nh th chuyn sang iu tr cch ngy. Thi gian iu tr ban u cng ngn cng tt, trnh cho h HPA b c ch. Vic quyt nh khi no ngng ch iu tr hng ngy chuyn sang iu tr cch ngy tuz thuc din bin ca bnh. Chun b : trc ht phi gim liu t t cho ti khi t liu 15 - 20 mg/24 h ( tnh theo prednison ). Liu ny c ung mt ln vo bui sng ( khong 7-8 h sng ). Nu mc liu ny m bnh vn n nh, trng thi bnh nhn vn tt th quyt nh cho chuyn sang ch iu tr cch ngy. Cn nh rng khng c ct ngay thuc ngy nh ngng m phi gim t t liu ca ngy , mi ln 10 - 20 % liu ang dng cho ti khi ht. Mi ln gim cn duy tr liu trong 3 ngy thm d phn ng ca bnh nhn. Nu trong thi gian xut hin triu chng thiu nng thng thn nh mt mi, au khp, bun nn, h huyt p th phi tng liu tr li, bng mc liu ct gim; nu cc triu chng trn vn khng gim th c th phi quay li mc liu ban u. Tuy nhin nu trong thi gian ny m bnh ang iu tr ti pht tr li th tt

nht nn dng thuc c hiu iu tr bnh ( nu c th ) tt hn l tng liu corticoid. 6. Mt s phc chung v ch nh ca corticosteroid : ( Ly prednisolon lm chun ).6.1. Liu cao ( 80 - 1000 mg/24h ) : 6.1.1. Cho thi gian di mt tun l ( 7 ngy ) trong cc bnh - trng thi sau: + Vim phi khng nhim khun + Lot thc qun do ho cht n mn, bng + Bnh huyt thanh cp tnh + Phn ng d ng cp + Ph Quincke + Cn hen ph qun + Cc trng thi shock. + Phn ng thi mnh ghp cp trong ghp thn. 6.1.2. Cho nhiu tun - nhiu thng trong cc trng hp sau : + Bch cu cp + Vim da kiu Herpes. + Bnh ban a dng + Hoi sng c hnh thnh nang nc. + Cn kch pht ca lupud ban ri rc cch hi p ng vi iu tr, c km theo thn h + Bnh thp khp cp giai on sm + Vim khp dng thp + Xut huyt do gim tiu cu nguyn nhn do t?ng hu hoi tiu cu + Vim gan cp + Hn m gan + Vim no sau nhim khun + Vim no do lao + Ri lon thc, trng thi u m + Cn khng hong nhim c gip cp + i tho ng khng vi insulin + iu tr c ch min dch trong cc bnh : cc bnh t min, ghp tng. 6.2. Liu trung bnh duy tr ( 20-60 mg/24h ) trong cc nhm bnh sau : 6.2.1. Cc bnh huyt hc : + Thiu mu ( khng do bm sinh ) + Thiu mu do tan mu trong bnh t min + Chng gim tiu cu ( s lng )

+ Mt bch cu ht + Bnh bch cu ( mn v cp ) 6.2.2. Cc trng thi d ng : + Hen ph qun + Vim mi d ng + Cc bnh nga + Vim da d ng + Bnh huyt thanh. 6.2.3. Cc bnh t min : + Lupud ban h thng + Vim a c. + Vim khp dng thp + Vim mch mu + Vim nt quanh ng mch. + Vim ng mch thi dng 6.2.4. Cc bnh ng tiu ho : + Vim lo t i trng + Bnh gan : x gan c chng, vng da do thuc, vim gan mn tin trin 6.2.5. Cc bnh thn : + Bnh thn phi hp trn mt bnh collagen. + Vim cu thn cp th ko di + Vim cu thn mn t cp + Hi chng thn h. 6.2.6. Cc bnh c quan tun hon : + Vim c tim. + Vim mng ngoi tim. + Cc ri lon dn truyn. 6.2.7. Cc bnh ni tit : + Vim tuyn gip bn cp + Cc trng hp tr, tng keton khng n nh ( dao ng ) + H ng mu ( do u tu tuyn o b-Langerhans ) 6.2.8. Cc bnh thn kinh : + Bnh x cng mch lan to a dng + Vim no, vim no tu + Vim a r thn kinh

+ Vim dy thn kinh sau nhn cu. 6.2.9. Bnh truyn nhim : ( bn cnh iu tr khng sinh c hiu ) + Lao cc dng, cc trng hp c bit sau : - Lao phi - Lao sinh dc, tit niu. - Lao xng - Lao mng no - Lao mng phi. 6.2.10. Bnh nhit i : + Bnh hi + Giun ch 6.2.11. Mt s bnh hn hp khc + Gin ph nang + Cn Gout cp + Vim khp + Nhc c bm sinh + Sarcoidosis + Bnh Hodgkin + Hi chng Stevens- Johnson. BI 29. THUC GIM AU GY NGHIN 1. I CNG : 1.1. Khi nim chung : + au : l mt cm gic c bit rt kh nh ngha, thng lin quan n s tn thng thc th v lm tng s tin trin ca qu trnh bnh l, gy tht bi trong iu tr. + Hi nghin cu au quc t : au l mt cm gic hoc xc cm kh chu kt hp vi tn thng m hc hin din hoc tim n, hoc c m t nh c tn thng ( Merskey, 1986 ). + au l mt c ch bo v c th. Cm gic au xut hin ti mt v tr no khi b tn thng, to nn mt p ng nhm loi tr cc tc nhn gy au. + Nguyn nhn gy au l do cc ngn dy thn kinh cm gic b kch thch qu bi cc tc nhn vt l hay ho hc ( nhit, c, in, cc acid, base ). Di nh hng ca cc kch thch au, trong c th s gii phng ra mt hoc nhiu cht gy au : - Histamin

- Cht? P ( pain ) - Cc kinin huyt tng ( bradykinin, kallidin ) + Khng c nghim php thn kinh hoc sinh ha o lng, lng gi c au. Nh vy au l mt cm gic ch quan, ph thuc vo tng c th. + Thuc gim au : l nhng thuc lm gim cm gic au nhng khng lm ri lon thc, khng lm thay i cc cm gic khc. 1.2. Phn loi thuc gim au : + Thuc gim au gy nghin : morphin, fentanyl, tramadol + Thuc gim au phi steroid ( NSAIDs ) : aspirin, paracetamol, nimesulid + Thuc gim au h tr : lm tng hiu qu gim au ca thuc loi morphin v thuc NSAIDs, hoc lm gim nh cc TDKMM ca cc thuc trn. VD : - Thuc m : propofol, etomidat - Thuc t : procain, lidocain Thuc gim au tm thn : thuc chng trm cm cu trc 3 vng ( amitryptilin, imipramin), thuc chng co git ( carbamazepin, phenytoin), thuc an thn ( fluphenazin, haloperidol, dn xut benzodiazepin). - Thuc chng au na u:dihydroergotamin.. - Cc thuc chng vim steroid ( SAIDs ) dexamethason, prednisolon - Thuc chng au tht ngc : nitroglycerin, isosorbid 5-mononitrat. - Thuc khng histamin H1 : hydroxyzin Thuc gim au loi vitamin : vitamin B1, B6, B12 - Thuc chng co tht c trn : alverin, drotaverin Trn ng dn truyn cm gic au, t cc receptor ngoi bin n v no, c th dng cc thuc tc dng vo cc khu khc nhau ct t dn truyn, lm mt hoc gim au ( Hnh 1 ). 1.3. Cc c ch lm gim au C nhiu c ch gim au : + Lm gim nhn cm vi kch thch au : chm lnh, chm , xoa bp. + Lm gim dn truyn cm gic au : thuc t. + Lm gim hoc i lp vi cc cht trung gian ho hc ca au : NSAIDs. + Tc ng ln cc receptor c hiu ca au : cc opiat. + Kch thch gii phng morphin ni sinh : chm cu. 1.4. Cc receptor ca opiat :

+ 1973 : xc nh c receptor c hiu ca morphin. Nhng receptor ny nm ch yu h vin, vng di i, i no, nhn ui v th keo Rolando tu sng. c bit trc thn kinh, nhng vng dn truyn v tp hp cm gic au th receptor tp trung . + V mt iu tr, mi receptor c coi nh c chc phn ring : - Receptor muy ( m ) : gim au, gim h hp, co ng t, thay i cm xc, o th. - Receptor kappa ( k ) : gim au, xc cm, an thn. - Receptor delta ( d ) : gn chn lc vi enkephalin v cng c th c tham gia vo tc dng gim au ca opioid. - Receptor sigma ( g ) : cn bit t lin quan n iu tr. C quan h gin tip n nhn thc v tm thn vn ng. + C 3 loi receptor tr thnh kinh in l m, d v k. Gn y ( 1998 2000 ) mi pht hin ra mt loi receptor mi do pht hin c cc peptid opioid mi c gi l N/OFQ receptor. Do 2 nhm tc gi ring bit tm ra, mt nhm gi peptid mi l nociceptin ( N ), cn nhm kia gi l orphanin FQ ( OFQ ) Mi loi receptor c s phn b gii phu ring ti no, ty sng v m ngoi bin, v vy gi cho vic nghin cu chc nng ca chng. Cc nghin cu v dc l{ v hnh vi xut vic phn loi nh hn, v d nh vi cc receptor m, d, k th li c m1, m2, d1, d2, k1, k2, k3. Tuy nhin nhng ng?hin cu v gen cn cha thy r, ang cn c khng nh thm. Tc dng gim au ca opioid l tc dng kch thch trn receptor m v k Trong bi ny ch cp n thuc gim au loi opiat ( hoc opioid ). 2. THUC GIM AU GY NGHIN : 2.1. i cng : 2.1.1. Khi nim chung : a- Danh php : + Thuc gim au gy ng + Thuc gim au gy nghin. + Thuc gim au trung ng. + Thuc gim au loi morphin. Thuc gim au loi morphin hay cn gi l thuc gim au gy ng u c chung mt c tnh l gy nghin, v vy u c xp vo nhm Thuc gy nghin, khng c k n qu 7 ngy.

b- Phn loi : V thut ng, theo Howard v cs, cn phn bit : + Cc opioid : bao gm tt c cc hp cht c lin quan v tc dng vi opium. Opium bt ngun t ch opos ca Hy Lp l nha qu thuc phin Opium poppy Papaver somniferum. + Cc opiat : l cc thuc dn xut t opium ( thuc phin ), bao gm cc sn phm thin nhin nh morphin, codein, thebain v nhiu cht bn tng hp cng loi dn xut t cc cht trn. + Cc peptid opioid ni sinh ( endogenous opioid peptides ) : l cc peptid t nhin trong c th, gn c vo cc receptor opioid ( xem phn trn ). + Endorphin c dng ng ngha vi peptid opioid ni sinh nhng ch ring cho bendorphin. 2.1.2. Cc alcaloid ca thuc phin : Thuc phin l nha kh ca qu cy Anh tc ( Papaver somniferum Papaveraceae ). T gn 4.000 nm trc CN bit n tc dng ca thuc phin. Th k th XIX chit c mt alcaloid u tin t thuc phin c tc dng gy ng, ly tn thn ng Hy Lp ( Morphee ) t tn cho n l morphin. u th k XX mi tm ra cng thc ca morphin v tng hp ra morphin cng nh cc cht ging morphin. chit c 25 alcaloid t thuc phin v chia lm hai nhm : + Nhn piperidin-phenantren : morphin 10%, codein 0,5 %, narcein, thebain, narcotin C tc dng u tin trn TKTW. + Nhn benzyl-isoquinolein papaverin. Papaverin khng gy ng, m gy gin c trn, chng co tht c trn ( mch vnh, tiu ng mch, c trn kh, ph qun, rut, ng mt, niu qun) . 2.2. Morphin : 2.2.1. Tnh cht : Mui morphin hydroclorid d tan trong nc, cha 75 % morphin. 2.2.2. Lin quan gia cu trc v tc dng dc l :

+ Nhm phenol v tr C3 + Nhm ru v tr C6 2.2.3. Dc ng hc : + Bn cht base yu. Hp thu d qua ng tiu ha. t Cmax. sau khi ung 30 60 ph. SKD = 25 % khi ung. + D phn phi vo cc m ( no, gan, thn ). Thuc qua c hng ro mu no, nhau thai. Gn khong 30 % vi protein huyt tng. + Chuyn ho : ch yu l lin hp vi acid glucuronic c 2 v tr gn OH ( 3 v 6 ), cho morphin-3-glucuronid ( khng c tc dng ) v morphin-6-glucuronid ( c tc dng mnh gp 2 ln morphin nhng vo no rt t v kh tan trong lipid ). Thuc c chu trnh gan - rut. + Thi tr : ch yu qua thn ( 90 % ) di dng morphin-3-glucuronid; Mt phn nh thi qua mt, m hi, nc bt, qua sa m, qua d dy. t1/2 ca morphin l 2 - 3 h, ca morphin-6-glucuronid khong 4 h. 2.2.4. Tc dng dc l : 2.2.4.1. Tc dng trn TKTW : a- Tc d?ng gim au : * c im : + L tc dng quan trng nht. Morphin c tc dng gim au mnh, c ch chn lc v trc tip vi t bo TKTW, nht l v no. + Morphin lm gim nhng cn au ln, au su, au ni tng. Thuc t tc dng vi nhng cn au nh, au nng. Liu gim au ngi : 10 mg/70 kg/24 h. * C ch tc dng : Lin quan n receptor ca morphin. Tc dng gim au ca morphin l do thuc kch thch trn cc receptor m v k. + Khi morphin gn vo cc receptor, c ch dn truyn cm gic au, lm tng ngng au, lm thay i tnh cht ca cm gic au, lm bin i trng thi tm l bnh nhn ( lo s au, ch i au ). + Thuc cng c ch vng sau sinap ca cc neuron trung gian, lm mt tc dng gy au ca cht P, lm thay i s gn v thu hi ion Ca2+ vo ngn dy thn kinh. + Morphin c ch tt c cc im cht trn ng dn truyn cm gic au ca h TKTW nh : ty sng, hnh ty, i th v v no ( v tr tc dng ca morphin v cc opioid ch yu nm trong h TKTW, khc vi NSAIDs nm ngoi bin ). + ngoi bin, ngoi vic lm tng ngng nhn cm gic au, morphin

cn c ch trc sinap, lm gim gii phng cc cht dn truyn thn kinh ( do ng knh Ca2+ ). + Thuc cng c ch vng sau sinap ca cc neuron trung gian, lm mt tc dng gy au ca cht P ngoi lai khi tim. vng sau sinap, cc opioid cn lm m knh K+, lm thay i tnh thm ca mng neuron i vi K+, gy u cc ha, c ch tnh chu kch thch ca ca neuron v kt qu l lm bin i phn ln h thng dn truyn thn kinh ca cc h cholinergic, adrenergic, serotoninergic v dopaminergic trn h TKTW. + Do morphin c tc dng gy ng nn lm tng ngng au. b- Gy sng khoi, gy ng : + Vi liu iu tr, morphin gy cm gic lng lng d chu, thanh thn, khoan khoi, th gin nn d dn ti sng khoi, d gy nghin. Cc c quan nh thnh gic, xc gic c tng cng, nghe ting ng cm thy d chu, nhn ci g cng thy mu hng p. + Cm gic lo u, cng thng, bn chn s hi do au gim; morphin lm thay i t th, tng cng tr tng tng. Bnh nhn lun trng thi lc quan v mt cm gic i. + Morphin c th gy gim hot ng tinh thn v gy ng, bnh nhn dn dn i vo gic ng vi nhiu gic m p. Liu cao ( > 20 mg/24 h ) c th gy m v lm mt tri gic. Ngc li liu thp ( 1 3 mg/24 h ) c th gy hng phn, lm cho bnh nhn mt ng, nn, tng phn x ty. + Chnh do khoi cm m bnh nhn s thch dng v sau nhiu ln s b nghin. c- Tc dng trn h h hp : * c im tc dng : + Morphin tc dng trn Rp m2 v nh hng trc tip n trung tm h hp. Tc dng trn h h hp ph thuc r rt vo liu : liu thp ( 1 3 mg/24 h ) thuc kch thch h hp. liu iu tr, morphin gy c ch h hp. Morphin tc ng c ch trc tip ln cc trung tm h hp. Tc dng cng r trn bnh nhn ang b c ch h hp, b suy h hp, ang hn m hoc b gy m. + liu cao ( > 20 mg/24 h ), thuc c ch mnh trung tm h hp ( kiu th bnh l Cheyne Stockes ). C khi gy lit hon ton trung tm h ?hp. + thai nhi, tr mi , tr cn b, trung tm h hp rt nhy cm vi morphin v cc dn xut ca morphin. Morphin qua c hng ro nhau - thai, hng ro mu - no, v vy cm ch nh dng thuc cho ph n c thai (?), ang cho con

b v tr em. ( v lm gim sc ln, s trng thnh, s thch nghi ca tr s sinh, do tr thng b non, suy dinh dng. Mt khc, tr c th b ri lon v hnh vi, mt ng, nn, i lng do thuc tc ng trc di i tuyn yn, lm gim tit hormon hng thn ) + Morphin cn c ch trung tm ho, lm gim cc kch thch, gim phn x gy ho. Tuy nhin tc dng ny khng mnh bng cc dn xut nh codein, pholcodein, dextromethorphan + Gy co tht c trn kh ph qun. Cc thuc phong ta b ( propranolol) lm tng tc dng gy co tht c trn ph qun ca morphin. * C ch : + Liu cao morphin lm gim nhy ca trung tm h hp vi nng CO2 trong mu nn lm gim c bin v tn s h hp. + Do thiu O2, c bit thiu O2 no s gy hot ha cc receptor ca thnh mch, lm gin mch no, nhm lm tng cng lng mu ln no. Tuy nhin cc mch mu no gin to li gy chn p hnh no ( hin tng ci chm ) cng gy c ch thm trung tm h hp. d- T/dng trn vng di iMorphin v cc opioid ni chung lm mt thng bng c ch iu nhit, lm cho thn nhit gim nh. Tuy nhin, khi dng liu cao ko di, thuc c th gy tng thn nhit. e- Tc dng ni tit : + Morphin tc dng ngay ti vng di i, c ch gii phng GnRH ( Gonadotropin releasing hormone : hormon gii phng hormon hng sinh dc ) v CRF ( Corticotropin releasing factor : yu t gii phng hormon hng v thng thn ), do do lm gim tit LH ( Luteinizing hormone ), FSH ( Follicle stimulating hormone ), ACTH ( Adrenocorticotropic hormone ), TSH ( Thyroid stimulating hormone ) v bendorphin. + Cc opioid kch thch Rp m, lm tng tit hormon khng li niu ADH ( Anti diuretic hormone ), trong khi cht ch vn ca Rp k li lm gim tit ADH, gy li niu. f- Co ng t : Do kch thch cc Rp m v k trn trung tm dy thn kinh III ( dy vn nhn ), morphin v cc opioid c tc dng gy co ng t. Khi ng c morphin cp tnh, ng t co rt mnh, nh nh u inh ghim. Song khi c ngt th th ng t s gin ra.

g- Tc dng gy bun nn v nn : Do morphin kch thch trc tip vng nhn cm ha hc (Trigger zone, area postrema ) vng sn no tht IV, gy cm gic bun nn v nn. Vi liu cao thuc c th c ch trung tm nn. h- Phn x tu : tng phn x. 2.2.4.2. Tc dng ngoi bin : a- Tc dng trn tim mch : + liu iu tr morphin t tc dng trn tim mch, dng c cho bnh nhn suy tim ( nhi mu c tim ). Tuy nhin c th gy chm mch do kch thch dy X v lm tng gii phng histamin. + Liu cao gy gin mch vnh, h huyt p do c ch trung tm vn mch hnh no v cng do tng gii phng his tamin. b- Tc dng trn c trn : + C trn ca rut : trn thnh rut v m ri thn kinh c nhiu receptor vi morphin ni sinh. Morphin lm gim nhu ng rut, lm gim tit cc dch ngoi tit ( dch mt, ty, dch rut ) v v lm t?ng hp thu nc, in gii qua thnh rut, do gy to bn, v vy cn c s dng trong iu tr a chy. Morphin lm co cc c vng ( c Oddi, c tht mn v, c tht hu mn ), gy au qun bng, to bn. + Trn cc c trn khc : lm tng trng lc, tng co bp nn c th gy b i ( do co tht c vng bng quang ), lm xut hin cn kh th kiu hen trn ngi b hen ( do co tht c trn kh, ph qun ) + Khi dng iu tr gim au ng tiu ho ( cn au qun gan, qun thn) phi dng phi hp vi thuc gin c trn ( atropin). c- Tc dng trn bi tit Morphin lm gim tit dch mt, tu, d dy, ph qun, gim tit niu. Tuy nhin li lm tng tit m hi. d- Tc dng trn chuyn ho : Morphin lm gim oxy ho, gim d tr base, gy tch ly acid trong mu. V vy ngi nghin mt b ph, mi, mng tay v mng chn thm tm. e- Tc dng trn da : Vi liu iu tr morphin gy gin mch da v nga, gy da mt, c v na thn trn. Mt phn c th do thuc lm tng gii phng histamin v cc thuc

khng H1-histamin khng i lp c hon ton tc dng gin mch ca morphin trong khi naloxon i lp c. 2.2.5. Ch nh : + Cc chng au : nhng cn au ln d di, cp tnh hoc au khng p ng vi cc thuc gim au khc nh au sau chn thng, sau phu thut, au qun gan, au qun thn do si, K giai on cui ( dng morphin > 7 ngy ). + Shock : shock chn thng, sau , do thuc + Tin m hoc phi hp khi gy m. + Nhi mu c tim cp. + Hen tim. + Ph phi cp th nh v va. + Ho ( t dng ). + i lng ( t dng ). 2.2.6. Chng ch nh : + au bng ngoi khoa cp khi cha chn on xc nh r nguyn nhn. + Chn thng s no hoc tng p lc ni s ( nguy c lm tng HA, tng p lc hp s, co git ). + Hen ph qun. + Suy h hp. + Suy gan nng. + Tr em di 5 tui. + Ph n c thai, ang cho con b. + Ph phi cp th nng ( try mch, nhp th CheyneStockes ). + Ng c ru, thuc ng barbiturat, CO v cc thuc c ch h hp khc. * Thn trng : khi dng cho ngi cao tui, mc bnh gan, thn mn tnh, thiu nng tuyn gip, suy tuyn thng thn, * Thn trng : ngi c ri lon tit niu tin lit tuyn ( nguy c b i ), nhc c, ngi ang li xe, ng my chuyn ng, lm vic trn cao 2.2.7. TDKMM : + To bn : gp 100 % trng hp, do gim nhu ng, gim bi tit dch rut + Bun nn v nn ngay t liu u tin : gp 30 60 % s bnh nhn. D phng : haloperidol liu thp 0,5 1 mg/24 h. + An thn : 50 % trng hp. + Cc ri lon khc :

- Nga ( do lm tng gii phng histamin ). - Tot m hi. Ri lon tm thn ( l ln, c mng, o gic). - B i - Yu c. - Co tht ti mt, co tht kh qun 2.2.8. c tnh : 2.2.8.1. c tnh cp : a- Triu chng : + Liu c trn ngi ca morphin : > 0,06 g/ln. + Cc triu chng ca ng c morphin cp tnh xut hin rt nhanh. Bt u bng mt giai on kch thch ngn ( bun nn, nn, nng u, chng mt, m?ing kh, mch nhanh v mnh ); Tip theo l giai on c ch, bnh nhn ng su dn, ng t co nh nh u inh ghim v khng phn ng vi nh sng. Nhp th chm ( 2 4 ln/ph ), ri lon h hp ( kiu Cheyne Stockes ), hn m, da xanh tm, h thn nhit, nhp tim chm, h HA, gim hoc mt phn x, ngng th, gin ng t. Bnh nhn c th t vong trong vi pht sau khi tim hoc 1 4 h sau khi ung. Nu hn m ko di c th cht v vim phi. + Hn m, ng t co nh nh u inh ghim v suy gim h hp l 3 triu chng thng gp ca ng c cp tnh morphin. b- X tr cp cu : + Cp cu phi da vo tnh trng bnh nhn lc a vo bnh vin. - Hi sc h hp : phi bo m thng kh cho bnh nhn bng th oxy, h hp nhn to. Nu bnh nhn hn m phi cho th my. - Hi sc tim mch : truyn dch, duy tr n nh huyt p. - iu tr c hiu :naloxon ng 0,4 mg, tim IV 1 ng. Liu ban u c th ti 2 mg nu ng c nng. Sau 2 - 3 ph, nu bnh nhn khng tnh th cho nhc li mt ln 0,4 mg ( c th ti 4 liu ). V sau V sau dng naloxon qua ng tim IM. Tng liu naloxon c th ti 10 20

mg/24 h. Trong iu tr ng c cp tnh morphin nn dng naloxon truyn IV lin tc d phng suy h hp tr li v naloxon c t1/2 ngn. - iu tr triu chng. 2.2.8.2. Ng c mn tnh : Do dng lu ngy, thiu ch nh cht ch v khng c kim sot. a- Quen thuc ( tolerance ) : + Quen thuc ph thuc vo liu dng v s dng lp li. Khi dng morphin hoc opioid lp i lp li nhiu ln vi liu iu tr, th hiu qu s gim dn, i hi phi dng tng liu mi gi c hiu qu nh ban u. Ngi quen thuc c th dng liu cao gp 10 - 20 ln so vi bnh thng. Hin tng ny gi l quen thuc. Nu dng liu cao vi khong cch ngn, quen thuc s xut hin nhanh. lm gim thiu s quen thuc, phi dng liu thp v khong cch gia cc ln dng thuc di hn. S quen thuc thng xy ra nhanh vi tc dng gim au, sng khoi v c ch h hp. Vi ngi khng quen thuc th liu 60 mg c th lm ngng h hp; nhng vi ngi quen thuc, liu 2.000 mg dng trong khong 2 3 h vn cha gy du hiu c ch h hp c { ngha. Mc quen thuc xy ra khng ging nhau gia cc triu chng. Tc dng sng khoi v c ch h hp s tr li vi ngy sau khi ngng thuc, nhng tc dng gy nn th phi vi thng sau. Tc xut hin v mt i cng nh mc quen thuc c khc nhau gia cc thuc trong nhm opi oid : methadon lu quen v mc quen cng thp hn so vi morphin. C hin tng quen thuc cho gia cc thuc opioid. + C ch : t khi tm ra morphin ni sinh, ngi ta ct ngha c hin tng quen thuc. Cht ch vn ni sinh ca receptor morphin l enkephalin b ging ha qu nhanh, nn khng gy quen thuc. Enkephalin (v c morphin ) kch thch receptor, c ch gii phng mt s cht TGHH, c ch enzym adenylcyclase, lm gim sn xut AMPc ( cyclic adenosin monophosphate ) - cht truyn tin th hai. Khi dng thuc lp i lp li, c th phn ng bng cch tng tng hp AMPc, gim? cn bng sn xut adenylcyclase, v vy liu morphin sau i hi phi cao hn liu trc receptor p ng mnh nh c, dn n hin tng quen thuc. b- Nghin thuc : + Khi dng morphin ngoi sinh ko di s dn ti 2 hu qu :

- Receptor gim p ng vi morphin. - C th gim sn xut morphin ni sinh. S thiu ht morphin ni sinh lm cho ngi dng phi l thuc vo morphin ngoi lai, l nghin thuc. + Triu chng : ngi nghin morphin thng c biu hin ri lon v tm l, hay ni iu, li bing, t ch gi v sinh thn th. Bnh nhn hay b to bn, co ng t, mt ng, chn n nn st cn, thiu mu, run chn tay, gi trc tui Kh nng khng km, v vy h d b cht v cc bnh truyn nhim. cHi chng cai thuc : * Triu chng : khi dng morphin di ngy, c th phn ng bng cch tng hp morphin ni sinh (endorphin). Ngi nghin lun lun i morphin, khi thi thuc t ngt, morphin ni sinh khng , cc receptor morphin ang trong tnh trng chng li s tc ng thng xuyn ca morphin b ri vo trng thi mt thng bng; t l GMPc/AMPc b o ngc, dn n mt s ri lon lm sng : v m hi, chy nc mt, nc mi, ngi vt v, au c, run ry, ni da g, d cm, mch nhanh, tng HA, tng thn nhit, au qun bng, bun nn, nn, a lng, o gic, gin ng t, mt nc, st cn Ngoi ra cn c th gp mt s ri lon v thn kinh nh : bn chn, thao thc, chn n, ngp vt, u su Cc biu hin ny nng nht l 36 72 h sau khi dng liu thuc cui cng v mt dn sau 2 5 tun. Cc triu chng ny s mt ngay sau khi dng morphin. * Cai nghin morphin : + Ngi nghin cn c cch ly, kt hp lao ng chn tay v tm l liu php, dng mt s thuc. Trong thc t, rt d ti nghin d cai c. + Dng thuc loi morphin : phng php c in cai nghin morphin l dng methadon, mt loi thuc opioid c tc dng ko di. - iu tr tn cng : liu thng thng 1040 mg/24 h, ko di 3 5 ngy, sau bt u gim liu tng t, mi t gim 5 mg. - iu tr duy tr : ko di 9 12 thng, sau gim liu dn ri ngng hn. + Khng dng thuc loi morphin - iu tr triu chng : chng bn chn, vt v bng cc thuc an thn ( BZD, haloperidol ); chng au bng cc thuc gim au NSAIDs ( aspirin, paracetamol), chng nn ( metoclopamid ), chng a lng ( loperamid )

- Dng clonidin : ti vng nhn lc ( h vin, locus ceruleus ) c nhiu neuron ca noradrenalin, cc neuron ny bnh thng b cc opiat tc ng trn cc receptor m c ch. Khi cai thuc, cc neuron noradrenalin c thot c ch nn gy cc triu chng cng giao cm, v th s rt hiu qu nu dng clonidin, l thuc kch thch receptor a2-drenergic trc sinap, lm gim tit noradrenalin, c ch giao cm. - Ngoi ra c th dng cc thuc i khng vi morphin nh naloxon, naltrexon 2.2.9. Ch phm v liu lng : a- Ch phm : + Morphin sulfat : vin nn 10 15 30 mg; dung dch ung 10 20 100 mg/5 ml; vin LA 30 60 mg; thuc n 5 10 20 30 mg. + Morphin hydrochlorid : ng 10 mg. b- Liu l BZD ng : + ng ung : thng dng gim au. Liu u tin ( ngi ln ) thng l 30 mg/ln x 2 ln/24h ( cch nhau 12h ) i vi vin LA. Cng c th cho BN ung vin nn hoc dung dch 10 mg/ln x 6 ln/24 h ( cch 4 h/ln ). Khi cha t hiu qu gim au, c th tng liu dn. Khng c gii hn trn cho morphin khi cha c TDKMM ( m mng, bun nn, to bn ). To bn rt thng gp, nn dng thm thuc nhun trng. + ng tim : khi dng ng ung khng c hiu qu hoc bnh nhn khng th ung c th dng cch truyn morphin lin tc vo SC hoc IV. Liu truyn SC u tin bng 1/2 liu ung. C th thay bng tim SC, cch 4 h/ln. Liu truyn IV u tin bng 1/3 liu ung. Khng nn dng ng IM cho bnh nhn. 2.2.10. Tng tc thuc : + Cm phi hp morphin vi cc thuc c ch MAO ( MAO = monoaminooxydase ) v c th gy try tim mch, tng thn nhit, hn m v t vong. Ch c dng morphin sau khi ngng thuc IMAO t nht 15 ngy. + Cc cht va ch vn, va i khng vi morphin nh buprenorphin, nalbuphin, pentazocin lm gim tc dng gim au ca morphin ( do c ch cnh tranh trn receptor ). + Cc thuc chng trm cm loi 3 vng, thuc khng H1-histamin loi c in, thuc ng barbiturat, benzodiazepin, ru, clonidin lm tng tc dng c ch h TKTW ca morphin.

2.3. Cc dn xut ca morphin : Mt s dn xut ca morphin nh thebain, dionin, dicodid, dilaudid, eucodal, heroin c tc dng gim au, gy sng khoi, gy nghin nh morphin. Khng c u im g hn morphin. Ngi nghin morphin c th dng nhng dn xut ny thay th v ngc li. 2.4. Thuc phin ton phn: + Tc dng : gim au, cha a chy. + Cc ch phm : cao opi, bt opi, bt dover, ru opi, ru paregoric, siro opi, siro diacod, siro pectoral 2.5. Thuc gim au gy nghin bn tng hp v tng hp : Trong cng thc c gi li phn tinh ty, quyt nh tc dng dc l ca morphin l : - Nhn thm. - Nhn piperidin. - Nhn thm ni vi chc amin bc 3 bi chui 3 carbon. Cc thuc gim au gy nghin tng hp cng c tc dng gn ging morphin ( gim au, c ch h hp, gy ng v gy nghin). Khng c u im g hn morphin. iu tr ng c cp v mn tnh nh vi morphin. C hin tng quen thuc cho. 2.5.1. Pethidin : * Tn khc :petidina, meperidin. * Bit dc : dolargan, dolosal, dolsin, dolantin, lidol 2.5.2. Loperamid : 2.5 3. Methadon : * Bit dc : dolophin, amidon, phenadon 2.5.4. Fentanyl : * Tn khc : fentanil, phentanyl citrat. * Bit dc : actiq, fentanest, leptanal, pentanyl, sublimaze 2.5.5. Sufentanyl : + Tn khc : sufentanil. + Bit dc : sufenta Tc dng gim au mnh hn morphin 5.000 ln. 2.5.6. Alfentanil : + Bit dc : alfenta

2.5.7. Remifentanyl 2.5.8. Promedon ( hydroclorid ) : 2.5.9.Propoxyphen: * Bit dc : darvon 2.5.10. Tramadol : * Bit dc : topalgic, ultram 2.5.11. Cc opioid c tc dng hn hp : Va hip ng, va i lp, hoc hip ng mt phn ( agonist antagonist; partial agonist ). C n nhiu thuc gn trn receptor m, tranh chp vi morphin v cc opioid khc nhng khng gy tc dng g, c gi l thuc i lp tranh chp, v d naloxon, cyclazocin Ngc li, mt s thuc sau khi tranh chp c receptor cn c th gy ra mt s tc dng dc l, hoc trn receptor m, hoc trn cc receptor khc nh receptor d, k. Cc thuc c gi l thuc c tc dng hn hp hoc hip ng mt phn, v d pentazocin, nalbuphin, buprenorphin 2.6. Thuc i khng vi opiat : naloxon, nalorphin, pentazocin 2.6.1. Khi nim chung : + Bng cch thay i cng thc ha hc ca morphin, c bit v tr 17 mang nhm N-methyl, nhm c hiu kch thch receptor m, s c cc cht i khng. + Cc cht ny c i lc mnh vi cc receptor ca morphin, tranh chp receptor ca morphin nn c tc dng i lp vi morphin, cc dn cht ca morphin cng nh cc thuc opioid tng hp khc. Cc thuc ny lm mt c mt s tc dng do morphin gy ra, ch yu l nhng du hiu c ch nh gim au, c ch h hp, an thn, sng khoi, h huyt p, co ng t Ngoi ra chng cn lm mt nhng triu chng cai thuc phin, do c dng cai nghin morphin v cc opioid ni chung ( tr heroin ). Thi gian tc dng ni chung ngn hn morphin. + Ch { : nalorphin khng cn c dng trong lm sng v c ch h hp, lm chm nhp tim, co ng t, sng khoi. 2.6.2. Ch nh : + Ng c cp tnh morphin v cc opioid ni chung. + Chn on nghin morphin.

2.6.3. Cc thuc : a- Naloxon hydroclorid : + Bit dc : nalonee, nalon, narcan, narcanti, narcan neonatal b- Natrelxon : + Bit dc : depad, revia c- Levalorphan : + Bit dc : lorphan d- Cyclazocin : tc dng mnh hn nalorphin 4 5 ln. e- Cyprenorphin : tc dng mnh hn nalorphin 35 ln. 3. MORPHIN NI SINH : Hai nm sau khi tm ra receptor ca opiat, mt s cng trnh nghin cu cho thy receptor ca morphin cn c i lc rt mnh vi mt s peptid c hiu sn c trong c th ng vt, nhng peptid ny gy ra nhng tc dng ging morphin. Cc morphin ni sinh c chia thnh 3 h : + Cc enkephalin ( Met-enkephalin v Leu-enkephalin ). + Cc endorphin. + Cc dynorphin. Mi loi li c tin thn khc nhau v phn b nhng v tr khc nhau trn h TKTW. BI 30. THUC GIM AU LOI MORPHIN 1. I CNG au l mt c ch bo v c th. au l do cc ngn dy thn kinh cm gic b kch thch qu bi tc nhn vt l hay ha hc (nhit, c, in, cc acid hay base). Di nh hng ca cc kch thch au, c th gii phng ra mt hoc nhiu cht gy au nh histamin, cht P, cc cht chuyn ha acid, cc kinin huyt tng (brady kinin, kallidin). Thuc gim au c chia lm 3 loi: - Thuc gim au loi morphin. - Thuc gim au khng phi loi morphin: paracetamol v thuc chng vim khng steroid. - Thuc gim au h tr: l nhng thuc c tc dng lm tng hiu qu gim au hoc gim nh tc dng khng mong mun ca cc thuc trn. 2. THUC GIM AU LOI MORPHIN

Thuc gim au loi morphin c chung mt c tnh l gy nghin, v vy u thu?c bng A, gy nghin, khng k n qu 7 ngy. Nhm thuc ny bao gm: - Opiat: l cc dn xut ca thuc phin (opium), c tnh cht ging nh morphin. - Opioid: l cc cht tng hp, bn tng hp, c tc dng ging morphin hoc gn c vo cc receptor ca morphin. Nha kh ca qu cy thuc phin c cha khong 25 alcaloid, trong morphin chim 10%, codein gn 0,5%, papaverin 0,8% Da vo cu trc ha hc, cc alcaloid ca thuc phin c chia lm 2 loi: - Nhn piperidin- phenanthren: morphin, codein, tc dng u tin trn thn kinh trung ng. - Nhn benzyl- isoquinolein: papaverin Papaverin khng gy ng, tc dng ch yu l lm gin c trn (mch vnh, tiu ng mch ca tim, phi, no, si c trn ca ph qun, rut, ng mt v niu qun). 2.1. Morphin Trong lm sng dng mui morphin clohydrat d tan trong nc, cha 75% mo rphin. 2.1.1. Tc dng Morphin c tc dng chn lc vi t bo thn kinh trung ng, c bit l v no. Mt s trung tm b c ch (trung tm au, trung tm h hp, trung tm ho), trong khi c trung tm li b kch thch gy co ng t, nn, chm nhp tim . Tc dng ca thuc thay i theo loi, gy hng phn mo, chut nht, loi nhai li, c nhng c ch r ngi, ch, th, chut lang. 2.1.1.1. Receptor ca morphin (v cc opioid) Receptor c hiu ca morphin c tm thy t cui 1973, c 3 loi chnh v mi loi li c cc phn loi nh. Gn y, mt receptor mi c pht hin, c tn l N/ OFQ receptor. Cc receptor ny c rt nhiu sng sau tu sng ca ng vt c xng sng, nhiu vng trong thn kinh trung ng: i th, cht xm quanh cu no, no gia. Cc receptor ca morphin cn tm thy trong vng chi phi hnh vi (hnh nhn, hi hi m, nhn lc, v no), vng iu ha h thn kinh thc vt (hnh no) v chc phn ni tit (li gia). ngoi bin, cc receptor c tu thng thn, tuyn ngoi tit d dy, m ri thn kinh tng. V mt iu tr, mi receptor c coi nh c chc phn ring. Tc dng ca cc receptor

2.1.1.2. Tc dng trn thn kinh trung ng * Tc dng gim au Morphin l thuc gim au mnh do lm tng ngng nhn cm gic au, thuc cn lm gim cc p ng phn x vi au. Tc dng gim au ca morphin l do thuc kch thch trn receptor muy v kappa. Morphin c ch tt c cc im cht trn ng dn truyn cm gic au ca h thn kinh trung ng nh tu sng, hnh tu, i th v v no. Nh vy, v tr tc dng ca morphin v cc opioid ch yu nm trong h thn kinh trung ng. Khi dng morphin, cc trung tm v no vn hot ng bnh thng, nhng cm gic au mt, chng t tc dng gi m au ca morphin l chn lc. Khc vi thuc ng, khi tt c cc trung tm v no b c ch, bnh nhn mi ht au. Tc dng gim au ca morphin c tng cng khi dng cng thuc an thn kinh. Morphin lm tng tc dng ca thuc t. * Gy ng Morphin lm gim hot ng tinh thn v gy ng. Vi liu cao c th gy m v lm mt tri gic. * Gy sng khoi Cng vi tc dng gim au, morphin lm mt mi lo lng, bn chn, cng th g th ng do au gy ra nn ngi bnh cm thy thanh thn, th gin v d dn t i sng khoi. Morphin lm thay i t th, lm tng tr tng tng, ngi bnh lun trng thi lc quan v mt cm gic i. * Trn h hp Morphin tc dng trn receptor 2 v nh hng trc tip n trung tm h hp. Morphin c ch trung tm h hp hnh tu, lm trung tm ny gim nhy cm vi CO 2 nn c tn s v bin h hp u gim. Khi nhim c, nu ch cho th O 2 nng cao, c th gy ngng th. tr mi v tr cn b, trung tm h hp rt nhy cm vi morphin v cc dn xut ca morphin. Morphin qua c hng ro rau thai, hng ro mu no. V vy, cm dng morphin v cc opioid cho ngi c thai hoc tr em. Morphin cn c ch trung tm ho nhng tc dng ny khng mnh bng codein, pholcodin, dextromethorphan * Tc dng trn v ng di i Morphin lm mt thng bng c ch iu nhit lm thn nhit gim nh. Tuy

nhin, khi dng liu cao ko di, thuc c th gy tng nhit c th. * Tc dng ni tit Morphin tc ng ngay ti vng di i, c ch gii phng GnRH (Go nadotrop in- releasing hormone) v CRF (corticotropin - releasing factor) do lm gim LH, FSH, ACTH, TSH v beta endorphin. Cc opioid kch thch receptor muy, lm tng tit ADH (hormon khng niu), trong khi cht ch vn ca receptor kappa li lm gim tit ADH, gy li niu. * Co ng t Do kch thch cc receptor muy v kappa trn trung tm thn kinh III, morphin v opioid c tc dng gy co ng t. Khi ng c morphin, ng t co rt mnh, ch cn nh nh u anh ghim. * Tc dng gy bun nn v nn Morphin kch thch trc tip trung tm nn sn no tht IV, gy cm gic bun nn v nn. Khi dng liu cao thuc c th c ch trung tm ny. 2.1.1.3. Tc dng ngoi bin * Trn tim mch: liu iu tr morphin t tc dng trn tim mch. Liu cao lm h huyt p do c ch trung tm vn mch. * Trn c trn: - C trn ca rut: trn thnh rut v m ri thn kinh c nhiu receptor vi morphin ni sinh. Morphin lm gim nhu ng rut, lm gim tit mt, dch ty, dch rut v lm tng hp thu nc, in gii q ua thnh rut, do gy to bn. Lm co c vng (mn v, hu mn.) co tht c oddi ch ni rut t ng mt ch - Trn cc c trn khc: morphin lm tng trng lc, tng co bp nn c th gy b i (do co tht c vng bng quang), lm xut hin cn hen trn ngi c tin s b hen (do co kh qun). * Trn da: vi liu iu tr morphin gy gin mch da v nga, mt, c, na thn trn ngi bnh b . * Trn chuyn ha: lm gim oxy ha, gim d tr base, gy tch lu acid trong mu. V vy, ngi nghin mt b ph, mng tay v mi thm tm. 2.1.2. Lin quan gia cu trc v tc dng Hai nhm nh hng nhiu n tc dng ca morphin l: - Nhm phenol v tr 3: tc dng gim au gy nghin s gim i khi alkyl ha nhm ny, v d codein (methyl morphin). N gc li, tc dng ca morphin s

c tng cng nu nhm phenol v tr 3 b ha ester, nh acetyl morphin (acetyl ha). Cng thc:

- Nhm ru v tr 6: tc dng gim au v c tnh s tng ln nh?ng thi gian tc dng li gim i khi nhm ny b kh H cho nhm ceton (hydro morphin) hay b ha ester, ha ether. Tc dng gim au v gy nghin s tng mnh khi c 2 nhm phenol v ru u b acetyl ha, v d heroin (diacetyl morphin). 2.1.3.Dc ng hc 2.1.3.1. Hp thu Morphin d hp thu qua ng t iu ha, ch yu t trng, hp thu qua nim mc trc trng song v phi qua chuyn ha ban u gan nn sinh kh dng ca morphin dng ng ung thp hn ng tim (ch khong 25%). Morphin hp thu nhanh sau khi tim di da hoc tim bp v c th thm nhp tt vo tu sng sau khi tim ngoi mng cng hoc trong mng cng (trong ng sng). 2.1.3.2. Phn phi Trong huyt tng, khong 1/3 morphin gn vi protein. Morphin khng lu trong cc m. Mc d v tr tc dng ch yu ca morphin l h thn kinh tr ung ng, nhng ch c mt lng nh qua c hng ro mu - no v morphin t tan trong m hn cc opioid khc, nh codein, heroin v methadon. 2.1.3.3. Chuyn ha Con ng chnh chuyn ha morphin l lin hp vi acid glucuronic v tr gn OH (3 v 6), cho morphin - 3- glucuronid khng c tc dng dc l v morphin 6- glucuronid (cht chuyn ha chnh ca morphin) c tc dng gim au mnh hn morphin. Khi dng lu, morphin - 6- glucuronid cng c tch lu. Thi gian bn thi ca morphin khong 2 - 3 gi; morphin - 6- glucuronic c thi gian bn thi di hn. 2.1.3.4. Thi tr Morphin thi tr di dng nguyn cht rt t. Trn 90% liu dng c thi tr qua thn trong 24 gi u di dng morphin - 3- glucuronid. Morphin c chu kz gan - rut, v th nhiu ngy sau vn cn thy cht chuyn ha trong phn v nc tiu. 2.1.4. Tc dng khng mong mun

Khi dng morphin c th gp mt s tc dng khng mong mun: * Thng gp: bun nn v nn (khong 20%), to bn, c ch thn kinh, co ng t, b i * t gp: c ch h hp, nga, tot m hi, l ln, c mng, o gic, co tht ti mt, co tht ph qun Morphin tim ngoi mng cng t gy bun nn, nn, co tht ng mt hoc ng niu hn khi dng qua cc ng khc. 2.1.5. p dng iu tr 2.1.5.1. Ch nh - Gim au: dng trong nhng cn au d di cp tnh hoc au khng p ng vi cc thuc gim au khc (au sau chn thng, au sau phu thut, au thi kz cui ca bnh, au do ung th). gim au nhng bnh khng cha khi c (nh ung th thi kz cui), c th dng morphin qu 7 ngy. - Phi hp khi gy m v tin m 2.1.5.2. Chng ch nh - Tr em di 30 thng tui - Triu chng au bng cp khng r nguyn nhn - Suy h hp - Suy gan nng - Chn thng no hoc tng p lc ni s - Hen ph qun (morphin gy c o tht c trn ph qun) - Ng c ru cp - ang dng cc cht c ch monoaminoxidase 2.1.5.3. Thn trng Cn ch khi dng morphin ngi cao tui, suy gan, suy thn, thiu nng tuyn gip, suy thng thn, ngi c ri lon tit niu - tin lit (nguy c b i), bnh nhc c. - Thuc lm gim s tnh to, v vy khng nn li xe hoc vn hnh my khi dng morphin. - Khng nn dng morphin trong thi k?z mang thai v cho con b. 2.1.6. Tng tc thuc - Cm phi hp vi thuc c ch monoaminoxidase v c th gy try tim mch, tng thn nhit, hn m v t vong. Morphin ch c dng sau khi ngng thuc MAOI t nht 15 ngy.

- Cc cht va ch vn va i khng morphin nh buprenorphin, nalbuphin, pentazocin lm gim tc dng gim au ca morphin (do c ch cnh tr anh trn receptor) - Cc thuc chng trm cm loi 3 vng, khng histamin H 1 loi c in, cc barbiturat, benzodiazepin, ru, clonidin lm tng tc dng c ch thn kinh trung ng ca morphin. 2.1.7. c tnh 2.1.7.1. c tnh cp * Triu chng ng c: Cc biu hin ca ng c cp morphin xut hin rt nhanh: ngi bnh thy nng u, chng mt, ming kh, mch nhanh v mnh, nn. Sau ng ngy cng su, ng t co nh nh u anh ghim v khng phn ng vi nh sng. Th chm (2 - 4 nhp/ pht), nhp th Cheyne - Stokes, c th cht nhanh trong vi pht sau tim hoc 1 - 4 gi sau ung trong trng thi ngng th, mt tm xanh, thn nhit h, ng t gin v try mch. Nu hn m ko di c th cht v vim phi. Hn m, ng t co nh nh u anh ghim v suy gim h hp l 3 triu chng thng gp khi ng c cc opioid. * X tr Cp cu bnh nhn ng c cp morphin phi da vo tnh trng bnh nhn lc c a vo bnh vin. u tin phi m bo thng kh cho bnh nhn bng th oxy, h hp nhn to Truyn dch gi vng huyt p, nu bnh nhn hn m phi cho th my. Gii c bng naloxon (thuc i khng vi morphin). Tim tnh mch naloxon 1 mL = 0,4 mg cho c ngi ln v tr em, c th cho liu ban u 2 mg nu ng c nng. Hai - ba pht sau bnh nhn khng tnh, dng thm 0,4 mg (c th ti 4 liu), sau dng naloxon qua ng tim bp. Tng liu naloxon c th ti 10 20 mg/ 24 gi. Trong x tr ng c cp morphin nn dng naloxon qua ng truyn tnh mch lin tc d phng suy h hp t r li v naloxon c thi gian bn thi ngn. 2.1.7.2. c tnh mn * Quen thuc Quen thuc ph thuc vo liu dng v s dng lp li. Ngi quen thuc c th dng morphin vi liu gp 10- 20 ln liu ban u v cao hn nhiu so vi ngi bnh thng T khi tm ra morphin ni sinh, ngi ta ct ngha c hin tng quen thuc: cht ch vn ni sinh ca receptor morphinic l

enkephalin b ging ha qu nhanh, nn khng gy quen thuc. Enkephalin (v c morphin) kch thch receptor, c ch gii phng mt s cht trung gian ho hc, c ch adenylcyclase, lm gim sn xut AMP vng. Khi dng thuc lp i lp li, c th phn ng bng tng tng hp AMP vng, v vy liu morphin sau i hi phi cao hn liu trc receptor p ng mnh nh c, l hin tng que n thuc. * Nghin thuc Mt s tc gi cho rng khi dng morphin ngoi sinh lu s dn ti 2 hu qu: - Receptor gim p ng vi morphin - C th gim sn xut morphin ni sinh S thiu ht morphin ni sinh lm ngi dng phi l thuc vo morphin ngoi lai, l nghin thuc. Ngi nghin morphin thng c ri lon v tm l{, ni iu, li bing, t ch v sinh thn th. Hay b to bn, co ng t ng. Hai , mt ng, chn n nn st cn, thiu mu, run Kh nng khng km, v vy h d b cht v cc bn h truyn nhim. Ngi nghin lun i morphin, khi thi thuc t ngt, morphin ni sinh khng , cc receptor morphinic ang trong tnh trng chng li s tc ng thng xuyn ca morphin b ri vo trng thi mt thng bng ; t l GMPv/ AMPv b o ngc, dn n mt s ri lon lm sng: vt v, au c, au qun bng, v m hi, nn, a lng, chy nc mi, run, sn gai c, d cm, tng nhp tim, tng huyt p, tng thn nhit, gin ng t, mt nc, st cn. Ngoi ra, cn gp mt s du hiu v thn kinh nh: thao thc, bn chn, chn n, ngp vt, u su. Cc biu hin ny nng nht l 36 - 72 gi sau khi dng liu thuc cui cng v mt dn sau 2 - 5 tun. * Cai nghin morphin Ngi nghin cn c cch ly, kt hp gia lao ng chn tay vi tm l liu php v dng thuc. Trong thc t, d cai c cng d b nghin li. - Dng thuc loi morphin Phng php c in cai nghin morphin l dng methadon, mt opioid c tc dng ko di. Methadon c tc dng lm nh cn i ma ty, phong ta tc dng gy khoi cm ca cc cht dng thuc phin do lm cc triu chng ca hi chng cai xy ra m m hn, nh nhng hn v khng thi thc tm ma ty cp bch ngi nghin. Vic iu tr bng methadon c chia lm 2 giai on: iu tr tn cng: liu thng dng t 10 - 40 mg/ngy (khng qu 120

mg/ngy), ko di 3 - 5 ngy, sau bt u gim liu tng t, mi t gim 5 mg. iu tr duy tr: ko di t 9 - 12 thng, sau gim dn liu ri ngng hn. Hin nay, ang dng th levomethadyl aceta t (L - - acetylmethadon) trong cai nghin heroin v thuc c thi gian tc dng rt di, 3 ngy mi cn ung 1 ln. - Khng dng thuc loi morphin . iu tr triu chng: chng bn chn, vt v bng benzodiazepin hay thuc an thn kinh. Chng au bng cc thuc gim au phi steroid (aspirin, paracetamol). Dng loperamid (l opioid t tc dng trn thn kinh trung ng) chng tiu chy. Chng nn, chng mt ng . iu tr bng clonidin: ti vng nhn lc (locus ceruleus) c nhiu nron ca noradrena lin, cc nron ny bnh thng b cc opioid tc ng trn cc receptor muy c ch. Khi cai thuc, cc nron noradrenalin c thot c ch, gy nn cc triu chng cng giao cm, v th s rt hiu qu nu dng clonidin, thuc cng 2 adrenergic trc s ynap, c tc dng lm gim tit noradrenalin. Clonidin thng c dng 0,1 mg/ ln, mi ngy 2 ln (ti a 0,4 mg/ngy), trong 3- 4 tun. Ngoi ra c th dng cc thuc i khng vi morphin nh naloxon, naltrexon. 2.2. Dn xut ca morphin Mt s dn xut ca morphin nh thebain, dionin, dicodid, eucodal c tc dng gim au, gy sng khoi, gy nghin nh morphin. Ngi nghin morphin c th dng nhng dn xut ny thay th. c bit c heroin gy nghin mnh hn hn nhng dn xut khc nn khng dng l m thuc. Khng cai heroin c. 2.3. Cc opioid thng dng 2.3.1. Pethidin (meperidin, dolosal, dolargan) 2.3.1.1. Tc dng - Sau khi ung 15 pht, pethidin c tc dng gim au mc d khng mnh bng morphin (km 7- 10l n). t gy nn, khng gy to bn. Khng gim ho, pethidin cng gy an thn, lm du, c ch h hp nh morphin. - Pethidin lm gim huyt p, nht l t th ng, do lm gim sc cn ngoi vi v lm gim hot ng ca h giao cm. Khi dng qua ng tnh mch, pethidin lm tng lu lng tim, lm tim p nhanh, do c th nguy him cho ngi b bnh tim. - ng mt, thuc lm co tht c oddi, v vy khi au ng mt phi dng thm atropin. 2.3.1.2. Dc ng hc Hp thu d qua cc ng dng. Sau khi ung, khong 50% pethidin phi q ua

chuyn ha ban u gan. Thi gian bn thi l 3 gi. Gn vi protein huyt tng khong 60% Pethidin t tan trong lipid, nn c i lc vi thn kinh trung ng yu hn morphin. 2.3.1.3. Tc dng khng mong mun Pethidin t c hn morphin Thng gp: Bun nn, nn, kh ming. Him gp cc tc dng khng mong mun trn thn kinh trung ng nh bun ng, suy gim h hp, ngt. 2.3.1.4. p dng iu tr - Ch nh: gim au, tin m - Chng ch nh nh morphin - Liu lng: ung hoc t hu mn 0,05g m i ln, ngy dng 2 - 3 ln Tim bp 1 mL dung dch 1%, liu ti a: 0,05 g mi ln, 0,15g trong 24 gi. 2.3.1.5. Tng tc thuc - Dng pethidin cng MAOI gy nguy him: c ch mnh h hp, hn m, st cao, h huyt p, co git . - Clopromazin lm tng tc dng c ch h hp ca pethidin - Scopolamin, barbiturat v ru lm tng c tnh ca pethidin, do phi gim liu pethidin khi dng ng thi. 2.3.2. Methadon (dolophin, amidone, phenadon) L thuc tng hp, tc dng ch yu trn receptor muy 2.3.2.1.Tc dng Methadon c tc dng tng t morphin nhng nhanh hn v k o di hn, t gy to bn. Gy gim au mnh hn pethidin. D gy bun nn v nn. 2.3.2.2.Dc ng hc Hp thu tt qua ng tiu ha, 90% gn vi protein huyt tng. Nh c nhm c eton v amin trong cu trc nn methadon c lin kt ng ha tr bn vi protein no. Thuc c th tch lu nu dng lin tip. Chuyn ha qua gan vi phn ng N - kh methyl. Thi tr qua nc tiu v mt. Thi gian bn thi khong 15 - 40 gi. 2.3.2.3.Tc dng khng mong mun Tc dng khng mong mun v c tnh ging nh morphin. Khi dng k o di, methadon c th lm ra nhiu m hi, tng bch cu lympho, tng nng prolactin, albumin v globulin trong mu.

2.3.2.4.p dng iu tr Trn lm sng, metha don c dng gim au v cai nghin morphin, heroin Liu lng: ung mi ln 2,5 mg, ngy 2 - 3 ln, tuz thuc mc au v phn ng ca bnh nhn. 2.3.3.Fentanyl (Submimaze, Fentanest, leptanal) Thuc tng hp, tc dng ch yu trn receptor muy 2.3.3.1.Tc dng Fentanyl gim au mnh gp 100 ln morphin, tc dng nhanh (khong 3 - 5 pht sau khi tim tnh mch) v ko di 1 - 2 gi. 2.3.3.2.Dc ng hc Thuc ch dng tim bp hoc tnh mch. 80% fentanyl gn vi protein huyt tng; phn b mt phn trong dch no tu, rau thai v sa. Fentanyl b chuyn ha gan v mt hot tnh. Thi tr qua nc tiu (khong10% di dng cha chuyn ha). 2.3.3.3.Tc dng khng mong mun Khong 45% tr?ng hp iu tr vi fentanyl c th xut hin tc dng khng m ong mun. - Ton thn: chng mt, ng l m, l ln, o gic, ra m hi, bng mt, sng khoi. - Tiu ha: bun nn, nn, to bn, co tht ti mt, kh ming. - Tun hon: chm nhp tim, h huyt p thong qua, nh trng ngc, lon nhp . - H hp: th nhanh, suy h hp, ngt th - C xng: co cng c bao gm c lng ngc, git rung - Mt: co ng t 2.3.3.4.p dng iu tr * Ch nh - Gim au trong phu thut. - Phi hp vi droperidol gim au, an thn - Phi hp trong gy m. * Chng ch nh - Cc trng hp au nh (c th dng cc thuc gim au khc nh acetaminophen) - Nhc c - Thn trng trong cc trng hp: bnh phi mn tnh, chn thng s no v tng p lc s no, bnh tim, trm cm, ph n c thai.

Fentanyl c ch nh i v i ph n cho con b, mc d thuc c mt trong sa m nhng vi liu iu tr fentanyl khng nh hng n tr ang b. * Liu lng - Dng cho tin m: 50 - 100 g, c th tim bp 30 - 60 pht trc khi gy m. - Gim au trong phu thut: 0,07 - 1,4 g/ kg th trng, c th nhc li trong 1 2 gi nu cn. 2.3.3.5.Tng tc thuc - Cc thuc c ch thn kinh trung ng nh ru, thuc ng, thuc m, phenothiazin lm tng tc dng gim au ca fentanyl. - Fentanyl lm gim hp thu ca mt s thuc nh metoclopamid, mexiletin khi dng phi hp. - Huyt p gim mnh khi phi hp fentanyl vi thuc c ch - adrenergic v thuc chn knh calci. Sulfentanyl (Sufenta) - Tc dng v ch nh tng t fentanyl. Mnh hn fentanyl 10 ln, cng gy cng c. - Gn vi protein huyt tng trn 90%, thi gian bn thi 2 - 3 gi. - Thng tim tnh mch 8 g/ kg Alfentanil (Alfenta) Tc dng nhanh v ngn hn sufentanyl nn cn dng theo ng truyn tnh mch. Thng c dng khi m v gim au, phi hp vi thuc m loi barbiturat, nitoxyd. 2.3.4.Propoxyphen 2.3.4.1.Tc dng Propoxyphen c cng thc gn ging methadon, tc ng ch yu trn receptor muy. Tc dng gim au k m, ch bng 1/2 n 2/3 codein: 90 - 120 mg propoxyphen hydroclorid theo ng ung, c tc dng gim au tng t 60 mg codein hoc 60 mg aspirin. 2.3.4.2.Dc ng hc Sau khi ung 1 - 2 gi, thuc t c nng ti a trong mu. Chuyn ha ch yu qua gan, nh phn ng N - kh methyl. Thi gian bn thi t 6 - 12 gi. Cht chuyn ha l norpropoxyphen c thi gian bn thi di hn (khong 30 gi). 2.3.4.3. Tc dng khng mong mun Propoxyphen c th gy c ch h hp, co git, hoang tng, o gic, c vi tim khi dng.

2.3.4.4. p dng iu tr Dng gim au nh v trung bnh. Propoxyphen thng c phi hp vi aspirin hoc acetaminophen. 2.3.5.Cc opioid c tc dng hn hp : va hip ng- va i lp, hoc hip ng mt phn (Agonist- antagonist; partial agonist) C nhiu thuc gn trn receptor muy, tranh chp vi morphin v cc opioid khc nhng khng gy tc dng g, c gi l thuc i lp tranh chp, v d naloxon, cyclazocin Ngc li, mt s thuc sau khi tranh c?hp c receptor cn c th gy ra mt s tc dng dc l, hoc trn receptor muy, hoc trn cc recept or khc nh delta v kappa. Cc thuc c gi l thuc c tc dng hn hp hoc hip ng mt phn, v d: pentazocin, nalbuphin 2.3.5.1. Pentazocin Pentazocin l mt dn xut benzomorphan, cu trc c nhiu im ging morphin. * Tc dng Thuc c tc dng i khng ti receptor muy nhng li c tc dng hip ng ti receptor kappa 1, gy an thn , gim au v c ch h hp Tc dng gim au nh morphin nhng khng gy sng khoi. Khi dng liu cao, pentazocin lm tng huyt p v nhp tim. * Dc ng hc Hp thu d qua ng tiu ha. Sau khi ung 1 - 3 gi, thuc t c nng ti a trong mu. Thi gian bn thi khong 4 - 5 gi. V phi qua chuyn ha ln u gan nn ch 20% pentazocin vo c vng tun hon. Thuc qua c hng ro rau thai. * Tc dng khng mong mun Pentazocin c th gy ra mt s tc dng khng mong mun: an thn, v m hi, chng mt, bun nn v nn Thuc c ch h hp khi dng liu cao. * p dng iu tr Thuc c ch nh trong nhng cn au nng, mn tnh h oc khi ngi bnh khng dng c cc thuc gim au khc. Thng dng dung dch pentazocin lactat cha 30 mg pentazocin base/ 1 mL. Tim tnh mch hoc di da 30 mg mi ln, sau 4 gi c th tim li. Hin nay c nhng ch phm phi hp gia pentazocin vi aspirin hay acetaminophen. 2.3.5.2. Buprenorphin L thuc tng hp, dn xut ca thebain. Buprenorphin hip ng 1 phn trn

receptor muy, c tc dng gim au mnh hn morphin t 25 - 50 ln. Hp thu d qua cc ng dng: ung, di li, tim bp Gn vi protein huyt tng khong 96%, thi gian bn thi 3 gi. c dng gim au trn lm sng. Thng tim bp hoc tnh mch 0,3 mg mi ln, ngy dng 3- 4 ln. 2.4. Thuc i khng vi opioid Thay i cng thc ha hc ca morphin, c bit v tr 17 mang nhm N methyl, nhm c hiu kch thch receptor muy, s c cc cht i khng. V d: Morphin nalorphin Levorphanol levallorphan Oxymorphon naloxon, naltrexon Cc cht ny i lp c cc tc dng do morphin gy ra, ch yu l nhng du hiu c ch nh gim au, c ch h hp, an thn, sng khoi. Thi gian tc dng ni chung ngn hn morphin. Nalorphin khng c dng trn lm sng v c ch h hp, lm chm nhp tim, co ng t, sng khoi. 2.4.1. Naloxon (nalonee, narcan, nar canti) 2.4.1.1.Tc dng Khc vi levallorphan hoc nalorphin, naloxon t hoc khng c hot tnh ch vn. ngi dng liu ln opioid, naloxon i khng phn ln nhng tc dng khng mong mun ca opioid nh c ch h hp, an thn, gy ng Khi dng, naloxon c th gy ra hi chng thiu thuc sm ngi nghin opioid, tuy vy dng liu cao s ngn chn c triu chng suy h hp trong hi chng ny. 2.4.1.2. Dc ng hc Mc d c hp thu d qua ng tiu ha nhng naloxon b chuyn ha gan trc khi vo vng tun hon nn liu ung phi ln hn nhiu so vi liu tim. Thuc c tc dng nhanh (1 - 2 pht sau khi tim tnh mch) thi gian tc dng ph thuc vo liu v kc ng dng. Sau khi tim, naloxon phn b nhanh vo cc m v dch c th. Thi gian bn thi l 60 90 pht. 2.4.1.3. Tc dng khng mong mun - Tim mch: tng huyt p (c khi gim huyt p), nhp tim nhanh, lon nhp tht. - Thn kinh trung ng: mt ng, kch thch, lo u

- Tiu ha: bun nn, nn - Nhn m, ban ngoi da. 2.4.1.4. p dng iu tr Naloxon c dng iu tr ng c cp cc opiat v opioid, cai nghin opioid Phi ht sc thn trng khi dng naloxon cho ngi c bnh tim mch, ph n c thai v cho con b. Liu lng; ngi ln: 0,4 - 2 mg, tim tnh mch , 2 -3 pht tim nhc li nu cn. Tng liu 10 mg. V thi gian tc dng ca naloxon rt ngn (60 - 90 pht) nn cn truyn lin tc naloxon khi bnh nhn ng c opium nng. 2.4.2. Naltrexon i khng vi opioid mnh hn naloxon, thng dng ng ung. Nng ti a trong mu t c sau 1- 2 gi. Thi gian bn thi l 3 gi. Naltrexon c chuyn ha thnh 6 - naltrexon (c hot tnh sinh hc yu hn nhng thi gian bn thi di hn, khong 13 gi). Naltrexon c dng cai nghin opioid (ung 100 mg / ngy), cai nghin ru (phi hp vi disulfiram). 2.5. Morphin ni sinh Hai nm sau khi tm ra receptor ca opiat, mt s cng trnh nghin cu cho thy receptor ca morphin cn c i lc rt mnh vi mt s peptid c hiu sn c trong c th ng vt, nhng peptid ny gy ra nhng tc dng ging morphin. Cc morphin ni c chia thnh 3 h: - Enkephalins (Met - enkephalin v leu - enkephalin) - Endorphins - Dynorphins Mi loi c tin thn khc nhau v phn b nhng v tr khc nhau trn thn kinh tru ng ng. Cc morphin ni sinh hot ng nh mt cht dn truyn thn kinh, hoc cht iu bin ca dn truyn hoc l hormon thn kinh. V th, chng tham gia vo cc c ch gim au, cc cm gic thm mun (n ung, tnh dc), cc qu trnh cm xc, tm t hn, tr nh. tu sng, morphin ni sinh c ch gii phng cht P, l mt decapeptid (10 acid amin) c gii phng ti ngn dy cm gic sng sau tu sng. Cht P c vai tr kim tra ng cm gic truyn vo v kch thch cc nron vn ng ca sng trc gy phn x t v. Cc enkephalin l pentapeptid c tc dng gim au rt ngn v b ging ha

nhanh trong c th nh cc enzym: dipeptidyl amino peptidase, aminopeptidase v enkephalinase. Cc endorphin c 4 loi, nhng ch c beta endorphin c t c dng gim au mnh v lu (3 - 4 gi) v tng i vng bn. 3. THUC GIM AU KHNG PHI LOI MORPHIN : (xin xem bi thuc h st gim au- chng vim). 4. THUC GIM AU H TR Thuc gim au h tr c tc dng hip ng, lm tng tc dng gim au ca cc opioid v thuc gim au chng vim khng steroid. Cc thuc ny c bit hiu qu i vi au do nguyn nhn thn kinh. 4.1. Thuc chng trm cm: Tc dng gim au khng ph thuc vo tc dng chng trm cm. Thng dng trong cc trng hp au k o di, c lin quan n bnh l thn kinh. Nhm thuc c tc dng tt nht l thuc chng trm cm loi ba vng (xin xem thm bi thuc chng trm cm). 4.2. Thuc chng ng kinh gi?m au trong bnh thn kinh do i tho ng, au sau zona, au dy t hn kinh, d phng cn au na u (migraine) c th dng cc thuc: phenytoin, carbamazepin v valproat (xin xem thm bi thuc cha ng kinh). 5. NGUYN TC S DNG THUC GIM AU 5.1. Chn thuc Thuc gim au ch iu tr triu chng, thuc c th che lp cc du hiu ca bnh trong khi bnh vn tin trin nn phi ht sc cn nhc khi s dng thuc gim au. Khi la chn thuc cn ch { n cng v bn cht ca au. T chc Y t Th gii khuyn co nn ung thuc theo bc thang gim au: - Bc 1 (au nh): dng thuc gim au khng phi opioid nh paracetamol, thuc chng vim khng phi steroid. - Bc 2 (au va): phi hp thuc loi opioid yu (codein, oxycodon) vi paracetamol, thuc vim khng steroid hoc thuc gim au h tr. - Bc 3 (au nng): dng thuc gim au loi opioid mnh : morphin, hydromorphon, methadon phi hp vi thuc chng vim khng steroid. 5.2. ng dng thuc Thng thng nn dng ng ung. Tuy nhin, trong cc cn au nng, cp tnh hoc sau phu thut ln phi dng ngay cc thuc gim au mnh loi

opioid qua ng tim trnh sc vnh hng xu ca au n tin trin ca bnh . BI 31. THUC IU TR TNG HUYT P 1. HUYT P V BNH TNG HUYT P 1.1. Huyt p Vai tr ca thn trong kim tra th tch tun hon: Khi p lc ti mu cho thn b gim, s c s phn phi li mu trong thn, km theo lm gim p lc mao mch thn v hot tnh giao cm (thng qua receptor ) dn n sn xut renin t tng sn xut angiotensin, gy ra: - Co mch - Kch thch sn xut aldosteron lm gi Na + v nc Tng huyt p thng c chia thnh hai loi: - Tng huyt p th pht: khi huyt p tng ch l mt triu chng ca nhng tn thng mt c quan nh: thn, ni t it, tim mch, no iu tr nguyn nhn, huyt p s tr li bnh thng. - Tng huyt p nguyn pht: khi nguyn nhn cha r, lc c gi l bnh tng huyt p. C ch bnh sinh ca tng huyt p rt phc tp. Huyt p ph thuc vo lu lng ca tim v sc cn ngoi vi. Hai yu t ny li ph thuc vo hng lot cc yu t khc, nh hot ng ca h thn kinh trung ng v thn kinh thc vt, ca v v tu thng thn, ca hormon chng bi niu (ADH), ca h renin angiotensin - aldosteron, ca t nh trng c tim, tnh trng thnh mao mch, khi lng mu, thng bng mui v th dch v.v Mt yu t quan trng trong tng huyt p l lng cc ng mch nh v mao mch thu hp li. Phn ln khng tm c nguyn nhn tin pht ca tng huyt p, v vy phi dng thuc tc ng ln tt c cc khu ca c ch iu ha huyt p lm gin mch, gim lu lng tim dn n h huyt p (xem hnh). Tt c u l thuc cha triu chng v nhiu thuc c trnh by trong cc phn c lin quan (xem bng b). Bng 24.1: Phn loi cc thuc h huyt p theo v tr hoc c ch tc dng 1. Thuc li niu: lm gim th tch tun hon: - Nhm thiazid - Thuc li niu quai

2. Thuc hu g?iao cm: - Tc dng trung ng: methyldopa, clonidin - Thuc lit hch: trimethaphan - Thuc phong to nron: guanethidin, reserpin - Thuc chn : propranolol, metoprolol - Thuc hu : prazosin, phenoxybenzamin 3. Thuc gin mch trc tip: - Gin ng mch hydralazin, minoxidil, diazoxid - Gin ng mch v tnh mch: nitroprussid 4. Thuc chn knh calci :Nifedipin, felodipin, nicardipin, amlodipin. 5. Thuc c ch enzym chuyn angiotensin Captopril, enalapril, ramipril. 6. Thuc i khng ti receptor angiotesin II Losartan, Irbesartan 2. THUC CHN KNH CALCI 2.1. Khi nim v knh calci Nng Ca ngoi t bo 10.000 ln hn trong t bo (10 -3 M so vi 10-7 M) v khi ngh mng t bo hu nh khng thm vi Ca, ng thi c bm Ca cng vi s trao i Na + - Ca++ y Ca++ ra khi t bo. Ca vo t bo bng 3 ng (knh): 2.1.1. Knh hot ng theo in p (voltage operated chanel -VOC hoc cn gi l POC: potential operated channel): hot ng theo c ch tt c hoc khng c g (hoc hon ton m hoc hon ton khp kn) gy ra do s kh cc mng (t 90mV ln - 40mV). Thuc h knh loi ny cn c c knh Na+, K+. Tuz vo s dn (conductance) v s cm th (sensitive) vi in th, knh VOC cn c chia thnh 4 loi knh: - Knh L (long acting): c nhiu trong c tim v c trn thnh mch - Knh T (transient): c trong cc tuyn tit - Knh N (neuron): c trong cc nron - Knh P (purkinje): c trong purkinje tiu no v nron. Knh T, N v P t cm thu vi thuc chn knh Ca. 2.1.2. Knh hot ng theo receptor (receptor operated channel -ROC): p ng vi cc cht ch vn. 2.1.3. Knh d : Tri vi 2 knh trn, knh ny lun c m cho qua lung Ca nh, nhng lin tc. Ca t bo hoc vo li bo tng v t li bo tng ra, lm cho nng Ca trong bo tng t 10-7 M (nng gin c) tng ln 10 -5M (nng co c),

s kt hp c vi calci protein (troponin/calmodulin -CaM) v gy ra nhiu tc dng sinh l. 2.2. Vai tr sinh l ca Ca trn tim mch

Hnh 24.1: Vai tr c a Ca++ sau khi qua knh Trn c tim, Ca++ gn vo troponin, lm mt tc dng c ch ca troponin trn chc nng co bp, do cc si actin c th tng tc vi myosin, gy co c tim. Trn c trn thnh mch, khi calci ni bo tng s to phc vi calmodulin, phc hp ny s hot ha cc protein-kinase (phosphoryl ha myosin kinase chui nh), thc y s tng tc gia actin v myosin, gy co c trn thnh mch (Hnh 24.1) Sau khi tc ng, nng Ca 2+ ni bo s gim do Ca 2+ c bm li vo ti li ni bo hoc y ra khi t bo do bm v do trao i vi Na +. S trao i Na+/Ca2+ c th thc hin c hai chiu: Na + vo Ca2+ ra, hoc Na+ ra Ca2+ vo. Trong iu kin sinh l{ bnh thng Na + vo v Ca2+ ra, ngha l s trao i ny c vai tr chnh trong vic gi nng Ca 2+ thp trong t bo. Khi c tr Na + trong t bo (th d digitalis phong ta bm Na +) th hot ng theo chiu ngc li: Ca 2+ vo t bo trao i vi Na+ i ra, gy tc dng tng co bp tim. Khc vi knh Na +, knh calci chu n h hng rt mnh ca cc yu t ngoi lai (trung gian ha hc, hormon) v cc yu t ni ti (pH, ATP). Ni chung, cc knh Ca ch hot ng khi? trc c phos phoryl ha. S phosphoryl ha ph thuc vo hot tnh ca adenylcyclase. 2.2. Cc thuc chn k nh calci Fleckenstein (1964) ln u tin a ra khi nim chn knh calci khi m t tc dng ca verapamil trn t bo c tim, l thuc c tng hp phng theo cng thc cu to ca papaverin. Cc thuc thuc nhm ny gn c hiu trn knh v phong ta knh, tuy cu trc ha hc rt khc nhau. 2.2.1. Phn loi Theo cu trc ha hc v c im iu tr, c 3 nhm thng thng. Sau li chia thnh th h: th h 1 l thuc chn knh Ca mng t bo v mng ti li ni bo; th h 2 tc dng nh th h 1 nhng chn lc trn t bo c trn

thnh mch hoc tim hn. Tc dng ko di. Bng 24.2: Cc thuc chn knh calci

Thuc c tc dng trn ng mch mnh hn trn tim do lm gin mch nhanh v mnh, d gy h huyt p nhanh, dn n phn x lm tn g nhp tim, khng li, nht l trn c tim b thiu mu. Verapamil do c tc dng c ch trn tim mch hn trn ng mch nn thng c ch nh trong lon nhp tim (xin xem thm bi Thuc cha lon nhp tim). 2.2.2. Dc ng hc Cc thuc chn kn h calci tc dng theo ng ung v chu s chuyn ha qua gan ln th 1, v vy ngi ta nghin cu thay i cc nhm chc trong cng thc cu to, lm cho thuc chm b chuyn ha, chm b thi tr hoc n nh hn, c tnh chn lc hn. Do to ra cc thuc th h 2, 3. Bng 24.3: Dc ng hc mt s thuc chn knh calci

2.2.3. C ch tc dng Cc thuc chn knh Ca gn ch yu vo knh L, l knh c nhiu t bo c tim v c trn thnh mch. Nifedipin v cc thuc nhm dihydropyridin (DHP) gn vo mt v tr mt trong knh, trong khi verapamil v diltiazem gn vo tr tr khc. Knh L c nhiu di n v 2, , v . DHP gn ch yu vo . Ngoi ra, DHP c th cn c ch nucleotid phosphodiesterase vng nn lm tng nucleotid vng, gy gin c trn: thuc cng phong ta knh hot ng theo receptor, nhng mc k m hn. Knh T v N rt km nhy cm vi thuc nn nron v cc tuyn tit t chu nh hng ca cc thuc ny. 2.2.4. Cc tc dng trn c quan 2.2.4.1. Trn c trn Lm gin cc loi c trn: kh - ph qun, tiu ha, t cung, nhng c bit l thnh mch (mao ng mch nhy cm hn mao tnh mch). 2.2.4.2. Trn c tim Hot ng ca tim ph thuc nhiu vo dng Ca (xem in sinh l ca tim). Thuc chn knh Ca lm gim to xung tc, gim dn truyn v gim co bp c

tim, v th lm gim nhu cu oxy trn bnh nhn c co tht mch vnh. Mc tc dng gia cc thuc c khc nhau. 2.2.4.3. Mch no Nimodipin c i lc cao vi mch no, v vy c dng cho bnh nhn c tai bin mch no (chy mu di mng nhn gy co mch do chn p; t qu c vim tc mch). Nhng cn cha r kt qu iu tr l do gin mch no hay l do lm gim nhu cu oxy ca nron. 2.2.5. Tc dng khng mong mun v c tnh - Tc dng nh, khng cn ngng iu tr: cn nng bng, nhc u, chng m t (do phn x gin mch, tng nhp tim nn dng cng vi thuc chn giao cm), bu i n nn, to. - Tc dng nng hn, lin quan n tc dng iu tr do c ch qu mnh knh Ca: tim p chm, nghn nh tht, suy tim xung huyt, ngng tim. Him gp. 2.2.6. p dng lm sng trong iu tr THA - Do lm gim lc co bp c tim, gim nhu cu oxy ca c tim, gim trng lc v sc cn mch ngoi bin nn cc thuc ny c dng iu tr THA. Cho ti nay, cc thuc chn knh calci c coi l thuc iu tr THA an ton v c hiu qu. Verpamil, nifedipin, nicardipin v diltiazem u c hiu qu h p nh nhau. Tuy nhin, do c s khc nhau v hiu qu huyt ng hc nn vic chn la iu tr c khc nhau: Nifedipin c tc dng chn lc nht trn mch v tc dng c ch tim li yu nht. Phn x giao cm hi lm tng nhp tim v lm tng hiu sut tim. Verapamin c tc dng trn tim mnh nht, lm gim nhp tim v gim hiu sut tim. Diltiazem c tc dng trung gian - Ngn cn co tht mch vnh khu tr, c ch ch nh ca cn au tht ngc - Verapamil, diltiazem lm gim dn truyn nh tht, c ch nh trong nhp tim nhanh trn tht do ti nhp (xin xem bi Thuc chng lon nhp tim). 2.2.7. Ch phm - Amlodipin: vin nn 2,5- 5- 10 mg - Diltiazem: vin nn 30- 60- 90- 120 mg Vin nang gii phng chm: 60 - 90- 120- 180 mg Thuc tim 5 mg/ mL - Felodipin (Plendil): vin gii phng chm 2,5 - 5- 10 mg - Nifedipin (Adalat): vin nang 10- 20 mg Vin gii phng chm 30 - 60- 90 mg

- Nimodipin (Nimotop): vin nang 30 mg - Verapamil: vin nn 40- 80- 120 mg Vin gii phng chm 120 - 180- 200 mg Thuc tim 5 mg/ 2mL 3. THUC C CH ENZYM CHUYN ANGIOTENSIN (ECA) Enzym chuyn angiotensin (ECA) hay bradykinase II l mt peptidase c tc dng: - Chuyn angiotensin I (decapeptid khng c hot tnh) thnh angiotensin II (octapepetid c hot tnh) l cht c tc dng co mch v chng thi tr Na + qua thn. - Lm mt hot tnh ca bradykinin, l cht gy gin mch v tng thi Na + qua thn. Sau khi c hnh thnh, angiotensin II s tc ng trn cc receptor ring, hin c bit l AT1, AT2, AT3, AT4, trong ch c AT 1 l c bit r nht (s ).

Hnh 24.2: Tc dng ca ECA v thuc c ch ECA Cc receptor AT 1 c nhiu mch mu, no, tim, thn, tuyn thng thn. Vai tr sinh l : co mch, tng gi Na +, c ch tit renin, tng gii phng aldosteron, kch thch giao cm, tng co bp c tim v ph i tht tri. Cc receptor AT 2 c nhiu tuyn thng thn, tim, no, c t cung, m bo thai. Vai tr sinh l: c ch s tng trng t bo, bit ha t bo, sa cha m, kch hot prostaglandin, bradykinin v NO thn. 3.1. C ch v c im tc dng Cc thuc do c ch ECA nn lm angiotensin I khng chuyn thnh angiotensin II c hot tnh v ngn cn ging ha bradykin, kt qu l lm gin mch, tng thi Na + v h huyt p. Trong iu tr tng huyt p, cc thuc ny c cc c im sau: - Lm gim sc cn ngoi bin nhng khng lm tng nhp tim do c ch trng lc giao cm v tng trng lc ph giao cm. - Khng gy tt huyt p th ng, dng c cho mi la tui. - Tc dng h huyt p t t, m du, ko di.

- Lm gim c huyt p tm thu v tm trng. -? Lm gim thiu mu c tim do tng cung cp mu cho mch vnh. - Lm chm dy tht tri, gim hu qu ca tng huyt p. - Trn thn kinh trung ng: khng gy trm cm, khng gy ri lon gic ng v khng gy suy gim tnh dc. 3.2. Ch nh - Thuc c tc dng iu tr tt cho mi loi tng huyt p: . Trn ngi c tui, h huyt p khng nh hng n tun hon no v kh ng nh hng n phn x p lc. . Trn ngi c i tho ng: khng nh hng n chuyn ha glucid, lipid. Mt khc, insulin lm K+ vo t bo, gy h K + mu; thuc c ch ECA lm gim aldosteron nn gi li K+. . Trn ngi c bnh thn, do angiotens in II gim, lm lu lng mu qua thn tng nn lm gim bi tit - Suy tim sung huyt sau nhi mu c tim. 3.3. Tc dng khng mong mun - H huyt p mnh c th xy ra khi dng liu u trn nhng bnh nhn c th tch mu thp do ang s dng thuc l i niu, ch n gim mui hoc mt nc qua tiu ha. - Suy thn cp nht l trn bnh nhn c hp mch thn. - Tng Kali mu khi c suy thn hoc i tho ng. - Ho khan v ph mch l do bradykinin khng b ging ha, prostaglandin tch lu phi gy ho (nhiu khi lm bnh nhn phi b thuc).

- Khng dng cho ph n c thai 3 - 6 thng Enalapril, perindopril, benezepril u l tin thuc, vo c th phi c gan chuyn ha mi c tc dng. 3.4.2. Thuc c ch ti receptor ca angiotensin II Do vic chuyn an giotensin I thnh II cn c s tham gia ca cc enzym khc (nh chymase) khng chu tc ng ca thuc c ch ECA nn s to thnh angiotensin II vn cn. Mt khc, do thuc c ch ECA ngn cn s ging ha ca bradykinin nn bradykinin phi tng, kch ng gy cn ho khan rt kh tr. V vy kch thch vic nghin cu cc thuc c ch angiotensin II ngay ti receptor ca n: thuc c ch AT 1. Cc thuc ny cn ang c nghin cu,

nh gi trn cc th nghim lm sng. V nguyn tc, do c tc dng ch n lc trn AT1 nn trnh c tc dng ph ca bradykinin (ho, ph mch). Bng 24.4: Mt s c im dc ng hc ca cc thuc c ch AT 1

* t/2 ca loscartan l 2 gi, nhng ca cht chuyn ha cn hot tnh l 6-9 gi. 4. CC THUC H HUYT P KHC 4.1. Clonidin (2,6 diclorophenyl - amino - 2 imidazolin - catapres) L thuc kch thch receptor 2 ca h giao cm trung ng nn lm gim trng lc giao cm ngoi bin. 4.1.1. Tc dng - Lm h huyt p do: . Lm gim cng nng tim, gim nhp tim . Lm gim sc cn ngoi bin, nht l khi trng lc giao cm tng. . Lm gim sc cn mch thn, duy tr dng mu ti thn. . Nh methyl dopa, clonidin rt t khi gy tt huyt p th ng. - Cc tc dng khng lin qu an n h huyt p: . An thn (do hu giao cm trung ng?) khong 50% trng hp. . Kh ming do c ch trung ng: khong 50% trng hp. . Gim au do gim hot tnh nron sng sau tu sng. Nhng tc dng ny l do thuc gn vo receptor imidazolin c trong thn kinh trung ng. 4.1.2. Dc ng hc Thuc tan nhiu trong m, vo thn kinh trung ng nhanh. Ung hp thu tt, sinh kh dng t ging i 100%, t c pic huyt tng sau 1 -3gi, t/2 khong 12gi. Thi tr qua thn 50% di dng nguyn cht. 4.1.3. Ch nh - Tng huyt p - Tin m: do c tc dng an thn, gim au nn lm gim c lng thuc m v tng n nh huyt ng. - Cai nghin: ma tu{, ru, thuc l. 4.1.4. c tnh - Kh ming, an thn: l tc dng trung ng, lin quan n liu dng. - Ngng thuc sau dng lu v liu cao (>1mg/ngy) c th gp cn tng huyt p kch pht do tng trng lc giao cm: bun nn, tim nhp nhanh, nhc u,

v m hi. Cn gim liu dn v dng thuc thay th. iu tr nn tng huyt p ny bng dng li clonidin v dng cc thuc chn , chn giao cm. 4.1.5. Ch phm v liu lng Clonidin (Catapres) Vin nn: 0,1 - 0,2 - 0,3mg Ung 0,2 -1,2 mg/ngy, chia lm 2 ln Cao dn: Gii phng 0,1 - 0,2 - 0,3mg/24gi. C tc dng 7 ngy cho 1 ln dn. C th c phn ng ti ch dn. 4.2. Natri nitroprussid L thuc gin mch mnh dng theo ng tim iu tr cp cu cn tng huyt p v suy tim nng. Lm gin c ng mch v tnh mch. C ch: hot ho guanyl cyclase do tc dng kch thch trc tip hoc th ng qua gii phng NO, dn n lm tng GMPv, gy gin c trn. Nitroprussid l mt phc hp ca st, cc nhm cyanid v phn nitroso. c tnh nng nht lin quan n s tch lu cyanid; ngoi ra cn gp nhim acid, lon nhp, tt huyt p. Hydroxocobalamin (vitamin B 12) kthp vi cyanid to cyanocobalamin khng c, do c dng gii c nitroprussid. Natrinitroprussid c ch nh trong cn tng huyt p, suy tim sung huyt (do lm gim c tin gnh v hu gnh) v lm gim nhu cu oxy ca c tim sau nhi mu c tim. Trong ngoi khoa cn dng lm h huyt p c kim tra khi gy m lm gim chy mu do phu thut. Nitroprussid (Nipride): l 50mg. Khi dng pha trong dextrose 5% - 250 - 1000 ml, truyn tnh mch 0,5 g/kg/pht, c th tng ti 10 g/kg/pht. Chai thuc phi bc trong giy mu, trnh nh sng. Kim tra huyt p thng xuyn. 5. CHIN THUT IU TR TNG HUYT P V CN V THA v cn mang tnh cht rt a dng nn vic iu tr cng cn c th ha va c hiu qu, va c th dung np c. 5.1. Ai cn c iu tr - Mi ngi khi c HA 140 - 90 mmHg - Khi c tn thng c quan ch hoc c i tho ng, mc du HA cn gii hn trn (130-139/85-89 mmHg). Mc tiu iu tr l a HA v chun < 140/99mmHg, nhng khng n gin, M ch 27% bnh nhn THA t c ch t iu ny.

5.2. Cch iu tr 5.2.1. Phng php khng dng thuc - n gim mui, gim ru, gim cn (bo) - Th dc u, nh nhng 5.2.2. Thuc Cn c th ha, vi th cn iu tr th - Lc u dng li niu, chn , chn knh calci v thm ch c cc t huc khc (chn 1 c ch ECA). iu cn tuz thuc vo bnh km theo: thuc c ch ECA khi c i tho ng; chn khi c bnh mch vnh; chn knh Ca (loi dihydropyrindin) khi c THA tm thu ring bit ngi cao tui. Lc u nn chn mt loi thu c. - Khi mt thuc khng cho kt qu mong mun: Khng nn tng liu v s c t c dng ph: thuc li niu (ri lon chuyn ha), chn (tc dng trung ng, chm nhp tim), chn knh Ca (ph, nh trng ngc, nhc u, nng mt), chn 1 (h HA th ng ). Thay thuc khc Phi hp thuc c c ch khc nhau Mt thuc h HA c th gy phn ng b tr, lm gim tc dng ca chnh n. Dng thuc phi hp ngn chn phn ng b tr. Th d thuc li niu lm thi Na, gy tng renin (dng thm thuc c ch EC A); thuc chn knh Ca gy tng nhp tim phn x (dng chn ). Hin c vin thuc phi hp sn. Tin dng nhng khng hay v khng c th ha c. Trong nhng nm gn y, vic iu tr THA tr nn n gin hn trc rt nhiu nh c nhiu loi thu c hiu qu. Vn l phi c th ha trong iu tr mi bnh nhn c th tm c cho mnh mt thuc thch hp va c hiu qu, va dung np tt. 5.3. Tiu chun thuc h huyt p l{ tng - C tc dng h huyt p tt . H HA t t, m du, ko di . Gim c s ti a v s ti thiu . Gim c ngi tr v ngi cao tui . Lm mt nh tng huyt p trong ngy - Khng lm mch nhanh do khng lm tng cng c tim v tng nhu cu oxy. - Khng lm mch chm, trnh c nghn nh - tht

- Khng lm gim sc co bp ca c tim, nht l tht tri - Dng c cho nhiu i tng: suy thn, tiu ng, tng lipid mu - Khi ngng thuc, khng c nguy c phn hi. BI 32. THUC H GLUCOSE MU 1. I CNG c th bnh thng, glucose mu c duy tr nng hng nh nh s cn bng gia insulin v glucagon, hormon tng trng, cortisol, thyroxin v catecholamin. Khi c ri lon s cn bng ca h thng ny, c bit l gim s lng, cht lng cng nh s nhy cm ca cc t bo i vi insulin s gy ra bnh tng glucose mu. Da vo s lng insulin v mc nhy cm ca t bo vi insulin, b nh i tho ng c chia thnh hai nhm: - Nhm ph thuc insulin cn gi l tng glucose mu t{p I, thng gp ngi gy, tr, di 40 tui c gim s lng t bo tuyn tu v nng insulin mu rt thp. iu tr dng insulin. - Nhm khng ph thuc insulin cn gi l tng glucose mu t{p II, thng gp ngi ln tui, khng gim s lng nhng c gim chc nng gy nn s ri lon bi tit insulin ca t bo , nng insulin trong mu bnh thng hoc cao v c hin tng khng insulin cc m ngoi vi. Ngoi ra, cn c tng glucagon v gim p ng ca t bo vi GLP1(glucagon like peptid 1)v vi GIP(glucose dependent insulin tropic peptid ). Theo cc thng k, 80 -90% bnh nhn c tng glucose mu thuc typ II. Thuc iu tr ch yu l cc thuc chng i tho ng tng hp dng ng ung. 2. CC THUC H GLUCOSE MU Hin nay c 2 cch phn loi thuc h glucose mu: * Theo c ch tc dng, thuc h glucose mu c chia thnh 5 nhm chnh: - Insulin - Thuc kch thch bi tit ins ulin: sulfonylure, nateglinid. - Cc thuc lm tng nhy cm ca t bo vi insulin: dn xut biguanid, nhm thiazolindindion. - Thuc c ch - gl?ucosidase. - Cc thuc bt chc incretin (GLP1, GIP) v thuc c ch DPP4(dipeptidyl

peptidase 4). * Theo ng dng v ngun gc, cc thuc h glucose mu c chia thnh 2 nhm chnh: - Insulin - Thuc h glucose mu dng ng ung. 2.1. Insulin Insulin l mt hormon gy h ng huyt do tuyn tu tit ra. Ngy nay, da vo cu trc, insulin c th c b n tng hp t insulin ln hoc nh k thut ti t hp gen thng qua vi khun hoc nm. nh gi tc dng v tinh khit, insulin c quy thnh n v chun quc t. Mt n v insulin (1 IU) l lng insulin cn lm gim glucose mu th nng 2,5kg nhn i xung cn 45mg/100ml v gy co git sau khi tim 5 gi v bng 40 g insulin. 2.1.1. Tc dng v c ch tc dng Tt c t bo ca ngi v ng vt u cha receptor c hiu cho insulin. Receptor ca insulin l mt glycoprotein gm 2 n v di nm mt ngoi t bo v hai n v di nm mt trong t bo. Bn n v ny gn i xng nhau bng cu disulfid. Thng qua receptor ny, insulin gn vo di n v gy kch thch tyrosinkinase ca n v di lm hot ha h thng vn chuy n glucose mng t bo ( glucose transporters = GLUT), lm cho glucose i vo trong t bo mt cch d dng, c bit l t bo c, gan v t bo m. Hin nay ngi ta pht hin ra 5 cht vn chuyn glucose phn b nhng t bo khc nhau. Tc dng l m h glucose mu ca insulin xut hin nhanh ch trong vng vi pht sau khi tim tnh mch v b mt tc dng bi insulinase. C ch tc dng xin c thm bi Hormon. 2.1.2. Tc dng khng mong mun Nhn chung, insulin rt t c, nhng cng c th gp : - D ng: C th xut hin sau khi tim ln u hoc sau nhiu ln tim insulin, t l d ng ni chung thp. - H glucose mu: Thng gp khi tim insulin qu liu, gy chy m hi, h thn nhit, co git, thm ch c th hn m. - Phn ng ti ch tim : Nga, au, cng (teo m di da) hoc u m vng tim. trnh tc dng ph ny, nn thay i v tr tim thng xuyn.

- Tng ng huyt hi ng (rebound): Gp nhng bnh nhn dng insulin liu cao sau khi ngng thuc. 2.1.3. Ch phm Da vo dc ng hc v nhu cu iu tr insulin c xp thnh 3 nhm ch phm khc nhau: 2.1.3.1. Insulin tc dng nhanh: + Insulin hydroclorid: Thi gian xut hin tc dng sau khi tim 1 gi v t ti a sau 3 gi v ko di tc dng khong 6 gi. Thuc c s dng trong hn m do i tho ng, 1ml cha 20 -40 n v, c th tim bp, di da, tnh mch. + Nh dch Insulin - km: Ch tim di da; sau khi tim 1 gi bt u xut hin tc dng v ko di khong 14 gi. 2.1.3.2. Insulin tc dng trung bnh: - Insophan insulin: (NPH - Neutral Protamin Hagedorninsulin) dng nh dch, l s phi hp insulin, protamin v km trong mi trng m phosphat. C 100 n v insulin, c thm 0,4mg protamin. Tim di da, tc dng xut hin sau 2 gi v ko di khong 24 gi. - Lente insulin: Dng nh dch, tim di da xut hin tc dng sau 2 gi v ko di khong 24 gi. 2.1.3.3. Insulin tc dng chm: Insulin protamin km: Ch phm dng nh dch, c 100 n v insul?in c km theo 0,2mg protamin. Thi gian xut hin tc dn g sau khi tim di da 4 -6 gi v ko di ti 37 gi. Insulin km tc dng chm (Ultralente insulin) tim di da, thi gian xut hin tc dng v ko di tc dng gn ging insulin protamin - km. 2.1.4. p dng iu tr - Tt c cc bnh nhn tng glucose mu thuc t{p I u c ch nh dng insulin. Ngoi ra, insulin cn c ch nh cho bnh nhn tng glucose mu tp II, sau khi thay i ch n v dng cc thuc chng tng glucose mu tng hp khng c tc dng. - Tng glucose mu sau ct b ty tng, ph n c thai. - Tng glucose mu c ceton mu v niu cao. Trn c s nh lng insulin trong mu ca ngi bnh thng, ta thy lng insulin bi

tit trung bnh vo khong 18 - 40 n v/24 gi, mt na s c gi l insulin c s, lng insulin cn li c bi tit theo ba n. V vy, duy tr lng glucose mu n nh, insulin nn dng khong 0,2 - 0,5 n v cho 1 kilogam th trng/24 gi. Cho n nay, duy nht c insulin l dng ng tim, cn cc thuc h glucose mu khc c c ch tc dng khc nhau nhng ng dng duy nht l ung iu tr tng glucose mu typ II sau t nht 3 thng thay i ch n, tng cng tp luyn th lc khng c kt qu. Cc thuc ny khng thay th ch n gim glucid, gim nng lng v tng cng hot ng th lc trong qu trnh iu tr. Da vo c ch, cc thuc chng tng glucose mu ng ung c chia thnh: - Thuc kch thch bi tit insulin - Thuc lm tng nhy cm ca t bo ch vi insulin - Thuc lm gim hp thu glucose rut. - Cc thuc bt chc incretin(incretin mimetic) v thuc c ch DPP4(dipeptidyl peptidase 4 inhibitor). 2.2. Thuc kch thch bi tit insulin 2.2.1. Dn xut Sulfonylure T nhng nm 1942, Janbon v cng s pht hin c tc dng h glucose m u ca mt s sulfonamid sc vt th nghim v bnh nhn iu tr thng hn. Nh pht hin ny, carbutamid, mt sulfonamid c tng hp c tc dng h glucose mu, s dng trn lm sng. Nhng do c tc dng c ch tu xng, thuc b lng qun. Son g nhu cu iu tr bnh i tho ng ngy cng cao, khong 20 thuc c tng hp v da vo cng tc dng v dc ng hc cc thuc xp thnh hai th h I v II. - Th h I gm: tolbutamid, acetohexamid, tolazamid, clopropamid. - Th h II: tc dng mnh gp khong 100 ln v c thi gian tc dng di hn th h I nn ch cn dng 1 ln trong mt ngy, gm: glibenclamid, glipizid, gliclazid. Bng 32.1: Tm tt mt s thng s dc ng hc v liu dng mt s thuc nhm sulfonylure

2.2.1.1. C ch tc dng: Da vo nhng nghin cu thc nghim trn tuyn ty c lp, o ty c lp v

nui cy t bo , Pfeifer v cng s (1981) chng minh rng, tc dng h glucose mu ca cc dn xut sulfonylure l do tc dng trn receptor b mt K +ATPase ca t bo o Langerhans lm chn knh K + nhy cm vi ATP, gy gim K + i vo trong t bo to ra s kh cc mng dn n m knh calci lm tng lng calci t ngoi bo i vo trong t bo, kch thch gii phng insul?in. Mt s nghin cu gn y chng minh cc thuc ny cn lm tng s lng v tng tnh nhy cm receptor ca insulin bch cu n nhn to, t bo m, hng cu, do lm tng tc dng ca insulin. Theo Krall (1985), cc dn xut sulfonylure c tc dng kch thch gii phng ra somatostatin, chnh somatostatin c ch gii phng glucagon, cho nn cng gy h glucose mu. Ngoi ra, ngi ta cn thy thuc c tc dng c ch insulinase, c ch s kt hp insulin vi khng th khng insulin v s kt gn vi prot ein huyt tng. 2.2.1.2. Dc ng hc Thuc c hp thu nhanh qua ng tiu ha. Nng ti a trong mu t c sau khi ung khong 2 -4 gi, gn vo protein huyt tng 92 -99% ch yu l albumin. Gn mnh nht l glibenclamid, gn km nht l clopro pamid. Thuc c chuyn ha ch yu gan. Tolbutamid chuyn ha nh phn ng oxy ha thng qua h enzym chuyn ha microsom gan thnh mt s cht chuyn ha vn cn tc dng nh hydroxymethyl -tolbutamid, 4-hydroxymethyl-tolazamid. Clopropamid khng b chuyn ha s thi tr qua thn. Thn l ng thi tr ch yu ca cc thuc h glucose mu dng ng ung. Ring glibenclamid thi ch yu qua gan, v vy c ch nh cho nhng bnh nhn tng glucose mu c chc nng thn suy yu. 2.2.1.3. Ch nh: - Tt c bnh nhn tng glucose mu typ II, khng ph thuc insulin. - Ngi bo bu trn 40 tui c insulin mu di 40 n v mt ngy. 2.2.1.4. Chng ch nh: - Tng glucose mu typ I, ph thuc insulin - Ngi c thai, cho con b, suy chc nng gan, th n - Tng glucose mu nng trong tnh trng tin hn m hoc hn m. 2.2.1.5. Tc dng khng mong mun: - H glucose mu, d ng, ri lon tiu ha, bun nn, nn, vng da tc mt. - Tan mu, thoi ha bch cu ht.

- Phn ng ging disulfuram khi dng clo propamid cng ru (gp khong 1 15% bnh nhn). - H natri mu hay gp vi clopropamid, do c tc dng ging ADH ( 50% bnh nhn). 2.2.1.6. Tng tc thuc: Thuc th h I gn mnh vo protein huyt gy nn cnh tranh v tr gn vi mt s thuc: dicoumarol, diphenylhydantoin, salicylat, phenylbutazon, sulfonamid. Th h II khng c tng tc kiu ny. Cloramphenicol, IMAO, probenecid lm tng tc dng h glucose mu ca c hai th h I v II, nhng corticoid, thuc trnh thai, diphenylhydantoin, rifamp icin, INH, cc phenothiazin li gy gim tc dng h glucose mu ca thuc. Thuc c ch -adrenergic dng cng vi cc dn xut sulfonylure gy nhp tim nhanh, thay i huyt ng hc v tng tc dng h glucose mu v vy trnh dng phi hp. 2.2.2 Loi khng phi sulfonylure 2.2.2.1. Nateglinid: L dn xut ca D -phenylalanin c tc dng kim sot s tng ng huyt sau ba n, do vy s ci thin tnh trng tng ng huyt sau khi n bnh nhn tng glucose mu typ II. Trong c th, nateglinid gn v o receptor c hiu (SUR 1) t bo ca ty lm chn knh K+ nhy cm vi ATP, gy kh cc mng t bo lm m knh calci. Calci kch thch gii phng insulin. Do thuc c c im gn nhanh v tch ra nhanh khi receptor c hiu nn kch thch bi ti t insulin nhanh, nn nhanh chng kim sot ng huyt sau khi n. Nhng cng do thuc tch ra khi receptor c ?hiu nhanh lm rt ngn giai on kch thch bi tit insulin, lm gim nguy c tng cao insulin trong mu nn trnh c tnh trng h glucose mu v s suy kit t bo ca ty. Thuc c hp thu tt qua ng tiu ha, thc n tng hp thu thuc. Sau ung liu duy nht 60mg, nng ti a trong mu t c sau 55 pht. Thuc gn vo protein huyt vi t l 99% v c thi gian bn thi 1,4 - 2 gi. Trong c th thuc b chuyn ha qua Cyt-P450 (CyP3A4, CYP2C9) gan v thi tr qua mt v qua nc tiu. Thuc c phm vi an ton rng, t c tnh. Nghin cu trn lm sng vi liu 60, 120,

180mg ung trc ba n 20 pht, c tc dng kim so t ng huyt sau n r rt. Thuc c th dng ring r hoc kt hp vi metformin kim sot s tng ng huyt sau n ngi tng glucose mu typ II. 2.2.2.2.Repaglinid Ging nh nateglinid, repaglinid cng c tc dng kim sot ng huyt nhanh sau khi n do vy cch dng ging nhau vi liu khi u 500 mcg sau iu chnh liu ph thuc vo p ng ca bnh nhn nhng khng vt qu 16 mg/ngy. 2.3.Thuc lm tng nhy cm ca t bo ch vi insulin 2.3.1. Dn xut ca biguanid Cc dn xut ca biguanid c cu trc hon ton khc vi dn xut sulfonylure gm: phenformin (phenethylbiguanid) do gy acid lactic mu, nn b nh ch lu hnh trn th trng, hin ch cn metformin (dimethylbiguanid) . Mc d cc thuc ny c tc dng h glucose mu r rt nhng ngi tng glucose mu, nhng c ch tc dng cn cha c r. Mt s tc gi cho rng, thuc tc dng thng qua s tng dung np glucose, c ch s tn to glucose v tng tng hp glycogen gan do tng hot tnh glycogensynthetase v lm tng tc dng ca insulin t bo ngoi vi. Ngoi ra, thuc cn hn ch hp thu glucose rut. Thuc khng tc dng trc tip trn t bo ca o Langerhans, v ch c tc dng khi c mt insulin ni sinh, nn thuc c ch nh bnh nhn ty c n kh nng bi tit insulin. - Metformin (Glucophage): Hp th k m qua ng tiu ha, khng gn vo protein huyt tng, khng b chuyn ha, thi tr ch yu qua thn. Thi gian bn thi khong 1,3 - 4,5 gi, thi gian tc dng khong 6 -8 gi, liu trun g bnh 0,5-2,5g/24 gi, ti a 3g/24 gi v c chia lm 3 ln sau cc ba n hng ngy. + Ging nh dn xut sulfonylure, metfomin c ch nh dng ring r hoc kt hp vi cc thuc khc cho bnh nhn tng glucose mu typ II sau khi iu chnh ch n v tp luyn th lc khng c hiu qu. Metformin c th kt hp vi mt s thuc khc kch thch bung trng trong iu tr v sinh. Khng dng thuc ngi tng glucose mu c ceton mu cao v c ceton niu, ph n c thai, cho con b. + Thuc c th gy ri lon tiu ha, acid ha mu do tng acid lactic c bit

bnh nhn c km theo gim chc nng gan, thn. 2.3.2.Cc thuc thuc nhm thiazolidindion L nhng thuc c cu trc v c ch tc dng hon ton khc vi dn xut sulfonylure v biguanid. Cc thuc nhm ny l nhng cht ch vn v c i lc cao vi PPAR (peroxisome proliferator activated receptor ). Receptor ny trong nhn t bo chu trch nhim iu ha mt s gen lin quan ?n s chuyn ha lipid v glucose. Khi thuc gn vo receptor gy nn s tng tc vi ADN c hiu lm hot ha gii m gen, lm tng nhy cm ca t bo vi insulin gip tng chuyn ho glucid v lipid. Trn thc nghim, ngi ta thy cc thuc lm tng chuyn ha glucose v tng s lng insulin receptor mng t bo, tng tng hp glycogen thng qua tng hot tnh glycogensynthetase v tng s dng glucose ngoi vi. Cc thuc thuc dn xut thiazolidindion c th dng ring r hoc phi hp vi metformin hoc cc thuc trong nhm sulfonylure nhng khng phi hp vi insulin iu tr tng glucose mu typ II. Thuc khng c dng cho ngi b suy gan, suy tim, ph n c thai, cho con b.Trong qu trnh iu tr cn thng xuyn theo di chc nng gan. Hai thuc trong nhm s dng nhiu hin nay l : - Pioglitazon (Actos) vin 15,30,45 mg, ung 15 -45 mg/ngy. - Rosiglitazon (Avandia) vin 4;8 mg, ung 4 -8 mg/ngy. 2.4. Thuc lm gim hp thu glucose rut: acarbose (Glucobay ): Thuc c ch nh bnh nhn tng glucose mu typ II km theo b o bu. C ch tc dng ca thuc khng lin quan n s bi tit insulin t bo ca ty m thng qua s c ch - glucosidase b bn chi nim mc rut non. Ngoi ra, thuc cn c ch, glucoamylase, maltase rut. Cui cng, lm gim hp thu glucose gy h glucose mu. Thuc c th gy ri lon tiu ha nh trng bng, tiu chy v au bng. Khi iu tr, cn iu chnh liu cho ph hp vi tng bnh nhn, nhng nhn chung liu trung bnh cho ngi ln 300mg trong 24 gi. Cc thuc khng acid, cholestyrami n, mt s cht hp ph mnh v ch phm cha enzym tiu ha lm gim tc dng ca acarbose. Khng dng thuc nhng ngi c ri lon chc nng hp thu, ph n c thai, cho con b v tr em di 18 tui.

2.5. Cc thuc bt chc incretin (incretin mimeti c) v thuc c ch DPP4(dipeptidyl peptidase 4 inhibitor) . Gn y ngi ta tm ra 2 peptid hormon GLP1, GIP gi chung l incretin c ngun gcti nim mc rut, c tc dng iu ho glucose mu sau khi n thng qua s kch thchbi tit insulin v l m chm s tho rng d dy. Trn c s pht hin ny liraglutid vexenatid hai cht ging incretin (incretin mimetic) ang c th nghim lm sng pha IIv III trn bnh nhn tng glucose mu typ II. GLP1 kch thch bi tit insulin sau khi n rt mn h, ngoi ra cn c ch bi tit glucagon, lm chm s tho rng d dy, kch thch s sao chp gen glucokinase v GLUT2 nhng li mt tc dng nhanh do b enzym dipeptidylpeptidase ph hu nn c thi gian bn thi di 2 pht. Vildagliptin, sitagliptin, s axagliptin l cc cht c ch DPP4 lm ko di tc dng ca GLP1 ang c th nghim lm sng pha II trn bnh nhn tng glucose mu typ II. BI 33. THUC IU TR CN AU THT NGC Nguyn nhn ca cn au tht ngc l do c tim b thiu oxy t ngt v mt thng bng gia s tng nhu cu oxy ca c tim v s cung cp khng oxy ca mch vnh. C tim ch chim 0,5% trng lng c th, nhng khi ngh ngi cng lu gi 5% lu lng tim. C tim ly 80- 90% oxy ca dng mu qua c tim. Khi c gng, khi xc ng hoc dng catecholamin, tim phi lm vic tng, nhu cu oxy ch c tho mn bng tng ln ng mu cung cp cho tim. T lu, chng cn au tht ngc, vn dng thuc lm gin m ch vnh. Tuy nhin, nhiu thuc ngoi tc dng lm gin mch vnh, li ng thi lm gin mch ton thn, v vy mt khi lng mu ng l cn cung cp cho tim th li chy ra cc vng khc. Mt khc, p lc tnh mch gim, i hi tim phi lm vic nhi u hn, v v vy li cng tng s dng oxy ca tim. Khi mt phn mch vnh b tc, vng di ch tc b thiu mu, chuyn ho lm vo tnh trng k kh, lm tng to thnh acid lactic, adenosin, kali l nhng cht gy gin mch mnh ti ch. Nu cho thuc gin mch, s cung cp mu s tng ln vng lnh, khng c li g cho vng b thiu mu, tri li, s ti mu cho vng b thiu mu li cn b gim i. Hin tng ny c gi l ly trm ca mch vnh (vol coronarien). Trong cn au tht ngc m n guyn nhn l do thiu mu t ngt ca c tim th vic cn trc ht l lm gim nhu cu oxy ca c tim, v hn na l loi tr tt c nhng tc ng i hi tim phi lm vic nhiu ln v chuyn ho tng ln. V vy, cc thuc chng cn au tht

ngc tt cn t c nhng yu cu sau: - Tng cung cp oxy, ti mu cho c tim. - Gim s dng oxy bng cch gim cng nng tim (tnh trng co bp ca c tim, nhp tim). - Lm gim cn au. Tuy nhin cn thy rng v tr ca vng thiu mu c tim khng hon ton c lin quan n s c mt hoc mc ca cm gic au, ngha l c th thiu mu c tim m khng c au. Cc thuc iu tr c chia thnh hai loi: - Loi chng cn: cc nitrat v nitrit - Loi iu tr cng c lm gim cng nng tim v gim s d ng oxy: thuc phong to recptor adrenergic, thuc chn knh calci (c c tc dng gin mch) 1. LOI CHNG CN: NITRAT V NITRIT Cc nitrat hu c l cc este polyol ca acid nitric, cn cc nitrit hu c l cc este ca acid nit. Este nitrat (C ONO2) v este nitrit (C ONO) c c trng bi chui C ON, trong khi cc hp cht nitro l C NO2. Nh vy, nitroglycerin l tn gi khng ng ca glyceryl trinitrat v khng phi l hp cht nitro, nhng do dng quen v qu ph bin nn khng sa c! Cc thuc nhm ny hoc l dung dch bay hi (amylnitrit), hoc l dung dch bay hi nh (nitroglycerin), hoc l th rn (isosorbid dinitrat). Tt c cc hot cht trong nhm ny u gii phng nitric oxid (NO) ti m ch c trn thnh mch Cc loi thng dng lm sng l:

1.1. Tc dng dc l{ v c ch Nitrat lm gin mi loi c trn do bt kz nguyn nhn gy tng trng lc no. Khng tc dng trc tip trn c ti m v c vn. Trn mch, nitrat lm gin mch da v mt (gy mt) lm gin mch ton thn. Tnh mch gim, lm gim dng mu chy v tim (gim tin gnh). ng mch gin, lm gim sc cn ngoi bin (gim hu gnh). Mc d nhp tim c th nhanh mt cht do phn x gin mch, nhng th tch tm thu gim, cng nng tim gim nn vn gim s dng oxy ca c tim. Mt khc, s phn b mu cho c tim cng thay i, c li cho vng di ni tm mc. Trn c trn khc, nitrat lm gin ph qun, ng tiu ho, ng mt, ng tit niu sinh d h c. C ch lm gin c trn: Cc nitrit, nitrat v hp cht nitroso gii phng nitric

oxyd (NO) trong t bo c trn di tc dng ca h enzim cha hon ton bit r. NO c gii phng ra s hot ha guanylyl cyclase v lm t ng tng hp GMPv, dn n kh phos phoryl chui nh ca myosin, gy gin c trn (hnh 23.1). Myosin chui nh (myosin light chain) phosphoryl ha (Myosin LC PO4) th gy co c.

Hnh 23.1: c ch gy gin c trn ca nitrat Tc dng gin c ca nitrat ging tc dng ca yu t gin c ca t bo ni m (EDRF: Endothelium- derived relaxing factor). T bo ni m mch mu tit EDRF, chnh n l NO hoc l tin cht ca NO (nitrosothiol). EDRF thm t ni m mch vo t bo c trn thnh mch v hot ha guanylyl cyclase ti . Cc cht ni sinh gy gin mch c th cng do thng qua c ch gii phng EDRF (hnh 23.2) nh con ng chung cui cng.

Hnh 23.2. Tc dng gin c thng qua EDRF Vng gin mch ph thuc vo sinh kh dng v chuyn ho khc nhau ca thuc. Nitroglycerin cn c cystein mi chuyn thnh n itrosothiol. V vy, dng lu tc dng s gim (quen thuc), cn dng ngt qung hi phc cystein. Nitroprussiat trong qu trnh chuyn ha khng cn cystein nn khng c hin tng quen thuc. 1.2. Dc ng hc Cc nitrat hu c chu nh hng rt mn h ca enzim gan glutathion - organic nitrat reductase, thuc b kh nitrat tng bc v mt hot tnh. Nitroglycerin t di li, t nng ti a sau 4 pht, t/2 = 1 -3 pht. Cht chuyn ho dinitrat c hot tnh gin mch km 10 ln v t/2 khong 40 p ht. Isosorbid dinitrat t di li c pic huyt tng sau 6 pht v t/2 = 45 pht. Cc cht chuyn ho ban u l isosorbid - 2 - mononitrat v isosorbid - 5 mononitrat vn cn tc dng v c t/2 l t 2 5 gi. 1.3. c tnh c tnh cp tnh lin q uan n tc dng gin mch: tt huyt p th ng, nhp tim nhanh, au nhi u. Cc ch phm nitrat vn c th dng cho ngi c tng nhn p, tuy nhin khng dng c cho ngi c tng p lc ni s. 1.4. Cc ch phm v liu lng

Bng di y ghi c c ch phm ca nitrat v nitrit dng trong iu tr cn au tht ngc.

2. LOI IU TR CNG C 2.1. Thuc phong to adrenergic Lm gim cng nng tim do lm chm nhp tim. i khng vi tng nhp tim do gng sc. Lm tng th tch tm tht v ko di thi kz tm thu. Tuy vy, tc dng chnh vn l tit kim s dng oxy cho c tim. Mt khc, thuc lm h huyt p trn ngi tng huyt p. Khng dng cho ngi c suy tht tri, v c th gy try tim mch t ngt. Khng nn ngng thuc t ngt v c th gy hin tng bt li lm nhi mu c tim, t t. - Ch phm: cc thuc thng dng l timolol, me toprolol atenolol v propranolol. Xin xem mc ny trong bi thuc tc dng trn h thn kinh thc vt. 2.2. Thuc chn knh calci Trong hiu th hot ng ca tim, Ca 2+ c vai tr trong giai on 2 (giai on cao nguyn) v c bit l trong kh cc ca nt dn nhp (pacemaker), nt xoang v nt nh tht. Calci vo t bo theo knh chm. Trong c tim, Ca 2+ gn vo troponin, lm mt hiu qu c ch ca troponi?n trn b co tht, do actin v myosin c th tng tc vi nhau gy ra co c tim. V th, c c thuc chn knh calci lm gim lc co bp ca c tim (xim xem thm mc ny trong bi Thuc cha tng huyt p), lm chm nhp tim v gim dn truyn nh tht. 2.2.1. C ch tc dng chng cn au tht ngc - Cc thuc chn knh calci do lm gim lc co bp ca c tim nn lm gim nhu cu oxy ca c tim (c ch chnh). - Trn thnh mch, cc thuc lm gin mao ng mch, lm gim sc cn ngoi bin, gim huyt p v gim p lc trong tm tht, gim nhu cu oxy. - i khng vi co tht mch vnh. Tc dng tt trong iu tr cc cn au tht ngc cha n nh. Tc dng phn phi li mu trong c tim, c li cho vng di ni mc, l vng rt nhy cm vi thiu mu. 2.2.2. Ch nh - D phng cc cn co tht mch vnh - Cn au tht ngc do co tht mch vnh (Prinzmetal) l ch nh tt nht.

- Cn au tht ngc do co tht ngc khng n nh: tc dng tng t vi thuc chn . C th dng phi hp vi cc dn xut nitro 2.2.3. Tc dng khng mong mun Cc tc dng khng mong mun thng lin quan n tc dn g gin mch nh nhc u, cn bc ho, tt huyt p th ng, thu. Nng hn l cc du hiu c ch trn tim: tim nhp chm, nh tht phn ly, suy tim sung huyt, ngng tim. 2.2.4. Cc thuc Bng 23.1: So snh tc dng trn tim ca mt s thuc

Ghi ch: Thang im cho t 0 (khng tc dng) n 5 (tc dng mnh n ht). Qua bng trn cho thy nifedipin v cc thuc cng nhm (xem Thuc cha tng huyt p) lm gin mch vnh mnh, t nh hng n hot ng ca c tim. Verapamil c ch hot ng ca c tim mnh nht, dng tt cho iu tr lon nhp tim. Bng 23.2: Dc ng hc v liu lng mt s thuc thng dng

3. THUC KHC Cc hng nghin cu thuc mi ang pht trin v c n ang trong bc th nghim: - Yu t pht trin ni mc mch (VEGF: vascular endothelial growth factor) nhm pht trin cc mch bng h cho vng thiu mu. - Tremetazidin (Vastarel): duy tr chuyn ho nng lng cc t bo b thiu oxy hoc thiu mu do trimetazidin ngn nga s gim st mc ATP trong t bo, v vy m bo c chc phn ca cc bm ion qua mng t bo, duy tr c tnh hng nh ni mi. Dng iu tr di ngy. Vastarel vin nn 20mg. Mi ln ung 1 vin vo ba n, mi ngy ung 2 -3 ln. BI 34. THUC NG MU V TIU FIBRIN 1. THUC TC DNG LN QU TRNH NG MU 1.1. C ch ng mu ng mu l mt qu trnh mu chuyn t th lng thnh th c do chuyn fibrinogen thnh fibrin khng ha tan v cc si fibrin ny b trng hp to

thnh mng li giam gi cc thnh phn ca mu lm mu ng li. Bnh thng, trong mu v trong cc m c cc cht gy ng v cht chng ng, nhng cc cht gy ng dng tin cht, khng c hot tnh. Khi mch mu b tn thng s hot ha cc yu t ng mu theo kiu dy truyn lm cho mu ng li. Qu trnh ng mu xy ra qua 3 giai on : - Giai on to thnh phc hp prothrombinase (1) - Giai on to thnh thrombin (2) - Giai on to thnh fibrin (3)

1.1.1.Giai on to thnh phc hp prothrombinase L qu trnh phc tp v ko di nht th ng qua hai c ch ni sinh v ngoi sinh to ra phc hp prothrombinase. * C ch ngoi sinh: Khi mch mu tn thng, mu tip xc vi v tr tn thng. M v tr tn thng gii phng ra yu t III (thromboplastin m) v phospholipid. Yu t III, IV (calci) cng yu t VII, v phosphlipid m hot ha yu t X. Yu t X hot ha cng vi yu V, phospholipid m v ion calci to thnh phc hp prothrombinase. * C ch ni sinh : ng thi khi mu tip xc vi v tr tn thng s lm hot ha yu t XII v tiu cu lm gii phng phospho lipid. Yu t XII hot ha yu t XI v yu t XI hot ha yu t IX. Yu t IX cng vi yu t VIII hot ha, phospho lipid tiu cu v Ca +2 hot ha yu t X. Yu t X, yu t V, cng vi phospho lipid tiu cu v Ca +2 to nn phc hp prothrombinase. 1.1.2. Giai on to thnh thrombin Prothrombinase to ra theo c ch ngoi sinh v ni sinh cng vi ion calci xc tc cho phn ng chuyn prothrombin thnh thrombin 1.1.3. Giai on to thnh fibrin v cc mu ng Di tc dng ca throm bin, fibrinogen dng ha tan chuyn thnh fibrin khng ha tan. Cc si fibrin ni li vi nhau v di tc dng ca yu t XIII hot ha to ra mng li fibrin bn vng giam gi cc thnh phn ca mu lm mu ng li.

1.2. Thuc lm ng mu 1.2.1. Thuc lm ng mu ton thn 1.2.1.1. VitaminK (K: Koagulation - ng mu) + C 3 ngun cung cp vitamin K : - Vitamin K1 (phytonadion, phulloquinon) c ngun gc thc vt. - Vitamin K2 (menaquinon) do vi khun gram m ng rut tng hp. - Vitamin K3 (menadion) c ngun gc tng hp. + Vitamin K tan trong lipid, nhng ring vitamin K 3 dng mui natribisulfit hoc mui tetra natri tan trong nc vo c th b chuyn ha thnh vitamin K 3. * Vai tr sinh l : + Vitamin K gip cho gan tng hp cc yu t ng mu nh prothrombin (II), VII, IX v X. - C ch : Bnh thng, cc yu t II, VII, IX v X dng tin cht. Khi c mt vitamin K vi vai tr cofactor cn thit cho enzym microsom gan xc tc chuyn cc tin cht thnh cc cht c ho t tnh bi s chuyn acid glutamic gn acid amin cui cng ca cc tin cht thnh - carboxyglutamyl. Cht ny cng c mt trong protein c bi tit t ct bo v c vai tr trong s to xng. * Du hiu ca s thiu ht : Nhu cu hng ngy khong 1 g/kg. Khi thiu ht s xut hin bm mu di da, chy mu ng tiu ha, rng ming, i ra mu, chy mu trong s. * Dc ng hc : Vitamin K tan trong du, khi hp thu cn c mt ca acid mt. Loi tan trong du thng qua h bch huyt vo mu, cn d ng tan trong nc hp thu i trc tip vo mu.Vitamin K1 c hp thu nh vn chuyn tch cc cn K 2, K3 c hp thu nh khuych tn th ng. Sau hp thu vitamin K 1 tp trung nhiu gan v b chuyn ha nhanh thnh cht c cc thi ra ngoi theo phn v nc tiu. * c tnh : Mc d c phm vi iu tr rng, nhng c th gp thiu mu tan mu v cht do vng da tan mu tr di 30 thng tui dng vitamin K 3. Vitamin K3 c n K n gy kch ng da, ng h hp, gy i albumin, gy nn v c th gy tan mu ngi thiu G 6PD. * Ch nh v liu dng :

Vitamin K c th ung hoc tim bp, di da hoc tim tnh mch (dng tan trong nc) vi liu 100 - 200mg/ngy cho nhng bnh nhn : - Thiu vitamin K do nguyn nhn khc nhau. - Chun b phu thut ( ph ng chy mu trong v sau phu thut ). Nhng trng hp ny phi dng thuc trc 2 -3 ngy. - Gim prothrombin mu - Ng c dn xut coumarin. 1.2.1.2. Calci clorid: Ca+2 cn hot ha cc yu t VIII, IX v X chuyn prothrombin sang thrombin . Liu trung bnh: ung 2 - 4g mi ngy, dng cch qung tng thi kz 3 - 4 ngy, ri ngh. Tim tnh mch cho nhng trng hp chy mu: 20ml dung dch 5%. Thuc tim ra ngoi tnh mch s gy lot. Tuyt i cm tim bp tht. 1.2.1.3. Coagulen L tinh cht mu ton phn, c bit c tinh cht ca tiu cu. Dng trong ngoi khoa ngi bnh a chy mu v trong nhng trng thi chy mu (ban chy mu, i ngoi ra mu v.v). Ung 1-5 ng mi ngy (ng 20ml). Hemocoagulen: ng tim 5ml. Trng hp nng, c th tim ti 4 ng mi ngy. 1.2.1.4. Carbazochrom (Adrenoxyl): Lm tng sc khng mao mch, gim tnh thm thnh mch, nn lm gim thi gian chy mu. Tc dng sau khi tim 6 -24 gi (tim bp 1,5 - 4,5 mg mi ngy hoc ung 10 -30 mg mi ngy). Cha chy mu do gin mao mch hoc phng chy mu sau phu thut to hnh, tai mi hng, ct b tuyn tin lit. 1.2.1.5. Ethamsylat v dobesilat calci: Lm tng sc khng mao mch, gim tnh thm thnh mch. Dng phng chy mu cp trong phu thut to hnh, tai mi h ng, ct b tuyn tin lit, rong kinh. Mi ngy tim bp 250 -500mg hoc ung 750 -1500mg. 1.2.1.6. Vitamin P (flavonoid, rutosid rutin v dn xut): Rutosid v dn xut ngun gc thc vt c hot tnh vitamin P u gim tnh thm thnh mch v lm tng sc khng mao mch do c ch s t oxy ha ca adrenalin, v c ch COMT gan, do k o di tc dng ca hormon ny.. Hot tnh vitamin P biu hin r trn s tng hp mucopolysacharid v glyco-

protein ca m lin kt. Ung 20 -40mg mi ngy, cha gin mao m ch v tng tnh n hi mch mu, c tc dng sau khi ung 6 gi. 1.2.2. Thuc lm ng mu ti ch 1.2.2.1. Enzym lm ng mu * Thrombokinase (prothrombinase): l tinh cht ca ph tng ngi v ng vt, thng ly no v phi. Tinh cht ny cha th rombokinase v c nhng yu t ng mu khc. Tc dng khng chc chn bng thrombin. Dng khi chy mu t, ti ch, thng xuyn (chy mu cam, rng ming) v c trong trng hp chy mu nhiu (phi hp vi bng cht). * Thrombin: Chuyn fibrinogen thnh fibrin n phn, ri thnh fibrin polymer khng tan trong huyt tng. Ch dng ti ch, tuyt i khng tim tnh mch (v mu ang chy s gy ng mu nguy him). Ung cha chy mu d dy. 1.2.2.2. Nhng loi khc - Cc keo cao phn t gip tng nhanh ng mu : Pectin, albumin v.v - Gelatin, fibrin dng xp tng din tip xc, qua hy tiu cu nhiu hn, mu ng nhanh hn. - Mui kim loi nng: Lm bin cht albumin, lm kt ta fibrinogen v cc protein khc ca mu. Hay dng dung dch ?F eCl3 10% bi ti ch hoc tm bng FeCl 3 p ln vt thng. - Thuc lm sn: Lm co mao mch nh, nn chng ng. Thng dng tanin, mui Al, Pb, Zn hoc KMnO 4 pha long. 1.3. Thuc chng ng mu 1.3.1. Thuc dng phng th nghim v ngoi c th - gim v tiu cu, ng nghim phi trng parafin, colodion, phim silicon. ng nghim bng pyrex lm mu ng chm hn l khi dng loi bnh thng. - Dng natri oxalat, natri fluorid ngn tc ng ca Ca +2. - Natri citrat to phc hp vi Ca +2; kt hp vi fibrinogen v cc yu t II, VII, IX, X nn lm chm ng mu. Mu d tr truyn cho ngi bnh thng c natri citrat (3 -4,0 gam/0,5l mu), vo c th, nng b pha long, khng c tai bin chy mu in vivo. Nu truyn nhiu, cn ch { n c tnh ca natri citrat.

- Cht cng cua (chelating agents) nh dinatri tetracemat (mui natri ca acid etylen diamin tetracetic, EDTA, Complexon III, Sequestren) c tc dng gp Ca +2. 1.3.2. Thuc dng lm sng Trong thc t hay dng ba loi : - c ch s tng hp ca cc yu t ng mu gan (yu t II, VII, IX, X): Loi ny ch tc dng in vivo: dn xut coumarin v indandion. - c ch tc dng ca cc yu t ng mu : Loi ny tc dng c in vivo v in vitro: heparin. - Chng kt dnh tiu cu: aspi rin, dipyridamol, ticlopidin, clopidogel. 1.3.2.1. Thuc chng ng ng ung : Dn xut ca coumarin v indandion: L thuc tng hp, c bng B. - Dn xut 4 -hydroxycoumarin c: warfarin, phenprocoumon, acenocoumarol, dicoumarol, coumetarol, tromexan. - Dn xut indadion c : phenylindadion, clophenindion. * C ch tc dng : Do dn xut coumarin v indandion c cu trc gn ging vitamin K, nn c ch cnh tranh enzym epoxid -reductase lm cn tr s kh vitamin K -epoxid thnh vitamin K cn thit cho s carboxyl ha cc tin yu t ng mu di s xc ca carboxylase thnh cc yu t ng mu II, VII, IX v X.V th cc thuc nhm ny cn c gi l thuc khng vitamin K. * Dc ng hc : Hp thu nhanh qua ng tiu ha, nhng xut hin tc dng sau khi ung 2436 gi. Cc thuc gn vo protein t l rt cao, tromexan 90%, warfarin 97%, phenprocoumon 99%. Nhiu dn xut ca coumarin chuyn ha qua h enzym oxy ha microsom gan nh : dicoumarol, warfarin, tromexan Cht chuyn ha thi tr qua nc tiu v mt - nhiu thuc c chu kz gan rut. Thuc c th i qua rau thai, qua sa. Nng thuc trong rau thai v tr em b m cao c th gy xut huyt cho thai nhi v tr b m. Nu ung thuc vo 3 thng u thai kz c th gy cho tr s sinh mt s d thng mi, mt, xng. * c tnh : - Dng liu cao, ko di gy ri lon thm phn mao mch, xut huyt, rt nguy him bnh nhn lot d dy t trng, chn thng, cao huyt p. - D ng, rng tc, vim gan, thn, tng bch cu a acid, nhng li gim hoc

mt bch cu ht. - Nc tiu mu da cam. * Khi phi hp dn xut coumarin v indandion vi mt s thuc c th xy ra tng tc dn n thay i dc ng hc hoc tc dng . - Thuc lm thay i dc ng hc ca coumarin v indandion : + Gim hp thu coumarin qua ng tiu ha: Thuc lm tng pH d dy, thuc nhun trng, thuc khng cholinergic, du p?arafin, than hot, cholestyramin (to phc vi couramin). + Thuc y coumarin ra khi protein - huyt tng : Clofibrat, phenylbutazon, sulfa mid, tolbutamid, salicylat, acid ethacrynic + Thuc c ch chuyn ha coumarin microsom gan: Allopurinol, chloramphenicol, cimetidin, diazepam, metronidazol, phenylbutazon, sulfinpyrazon, thuc chng trm cm loi ba vng. + Thuc cm ng enzym micros om gan lm tng chuyn ha coumarin: barbiturat, rifampicin * p dng iu tr : - Ch nh : + Phng hoc cha bnh tc nghn mch nh: vim tnh mch, tc mch phi, nhi mu c tim. + Dit chut : warfarin. - Chng ch nh: Ph n c thai, cho con b; cao huyt p, vim ty cp; lot d dy - t trng tin trin; tai bin mch mu no v tng chy mu. - Liu lng - cch dng : + Tc dng chng ng ph thuc vo tng c th. + Trong qu trnh iu tr bng dn xut coumarin hoc indandion phi gim l iu dn v cn theo di thi gian Quick, thi gian Howell chnh liu nhm duy tr t l prothrombin khong 20% so vi bnh thng. Sau khi dng 36 -48 gi lm xt nghim nh gi tc dng, chn liu duy tr ph hp. Giai on iu tr duy tr c sau 2 tun cho xt nghim 1 ln. + Tc dng chng ng ca thuc l gin tip, lin quan n s tng hp cc yu t ng mu gan nn xut hin tc dng chm v ch tc dng trong c th, khng c tc dng trong ng nghim. Mun t hiu qu chng ng cn ph i c thi gian. + Cn theo di nhng triu chng chy mu nh chng t qu liu : Chy mu cam, chy mu li, chy mu tr, nc tiu c vt mu, t mu da v.v + Khi

qu liu hoc ng c dn xut coumarin hoc indandion dng vitamin K iu tr. + Da vo thi gian xut hin tc dng, cng tc dng cc thuc chn thi gian dng thuc ph hp. Hin nay c 3 nhm chnh : Liu duy tr cc thuc i khng vitamin K c tp hp trong bng 30.1. Bng 30.1: Liu duy tr ca cc d n xut coumari n v indandion

1.3.2.2. Heparin Thuc c bng B, va c tc dng trong c th v ngoi c th. * Ngun gc: Heparin lc u tm thy nm 1916 bi McLean v c nhiu gan nn t tn heparin. Ngoi gan ra, heparin cn c tm thy thn, phi, hch bch huyt, nim mc rut. Hin nay heparin c chit xut t nim mc rut ln hoc phi tru, b hoc bn tng hp. * Cu trc : Heparin khng phi n cht. L mt anion mucopolysacharid hoc glycosaminoglycan. Trong cu trc c nhm sulfat v carboxylic. Nhm sulfat cn thit cho s gn antithrombin vi thrombin. T l lu huznh trong phn t heparin chim 13,6%. * Tnh cht : + L acid ni sinh mnh nht, c ion ha mnh, rt tan trong nc v tch in m pH sinh l. + Vng bn pH trn 6,5. un si trong 20 pht nhit 120oC vn cn tc dng. Nhng ung b phn hy ng tiu ha mt hot tnh. + Trng lng phn t khc nhau dao ng t 2 -20 kDa nhng tc dng sinh hc ging nhau. Khi heparin c trng lng phn t t 2 -7 kDa gi l heparin trng lng ph n t thp. * Tc dng : - Chng ng mu. - Chng ng vn tiu cu do kch thch tng hp v bi tit yu t hot ho plasmin t chc (t-?PA). - H lipoprotein mu c bit l triglycerid do gii phng lipase gip thu phn

triglycerid thnh acid bo v g lycerol. Tc dng ny xut hin nhng liu thp hn liu c tc dng chng ng mu. C hin tng tng lipoprotein hi ng (rebound) khi ngng heparin. - Tng tc dng ca cc yu t pht trin nguyn bo si c tnh acid hoc base (aFGF v bFGF) lm tng s phn bo t bo ni m mao mch, t bo c trn, t bo trung m gy ra s tn to mch. * C ch chng ng mu : - Bnh thng antithrombin III trong huyt tng phn ng chm chp vi thrombin v cc yu t ng mu IX, X, XI, XII hot ha lm mt tc dng ca cc yu t ny. Khi c mt heparin, heparin to phc vi antithrombin III. Phc hp heparin antithrombin III thc y nhanh phn ng gia antithrombin v thrombin; antithrombin vi cc yu t IX, X, XI v XII. Hu qu cc yu t chng n g t hot ha mt hiu lc nhanh, mt kh nng chuyn fibrinogen thnh fibrin. - Nh tch in m do c cha cc gc sulfat nn heparin lm bin dng thrombin v prothrombin lm chng d dng to phc vi antithrombin. * Dc ng hc Ung khng hp thu v b phn hu ng tiu ha. Do vy, phi tim di da, tim tnh mch, khng tim bp. Heparin b heparinase ph hu v thi tr nhanh. Sau khi tim 1 gi, 30-50% c thi qua nc tiu. Khng i qua rau thai. Thi gian bn thi ph thuc vo l iu lng. Liu cao v ngi suy gan, thn th thi gian bn thi ca thuc di. * Tc dng khng mong mun. - Chy mu, gim tiu cu, triu chng ny thng xut hin sau khi tim heparin 7 -14 ngy v hi phc sau khi ngng thuc. - D ng, nhc u , nn, gy nt au, hoi t gn nu tim di da di ngy. Dng ko di vi liu trn 15000 n v/ngy gy long xng. - Tng AST, ALT. * p dng iu tr : - Ch nh: phng, chng huyt khi. Tc dng tng khi dng kt hp vi cc thuc chng ng vn tiu cu nh: aspirin, cc thuc chng vim phi steroid

khc, dipyridamol, ticlopidin v.vv s mt tc dng khi trn ln vi gentamicin, colistin, cefaloridin do b kt ta. - Chng ch nh: + Tng a chy mu; lot d dy - t trng tin trin; vt t hng. + Gim chc nng gan, thn; c th suy nhc, vim ni tm mc, nhim trng, lao tin trin. - Ch phm v liu dng : + L 5000 - 25000 n v/ml Mt n v heparin l lng heparin ngn cn c s ng c 1ml huyt tng c lm mt calci b i citrat. + Liu dng tuz thuc vo tng bnh nhn. Thng thng truyn tnh mch 6000 n v/trong 6 gi vi tc 1000 n v/gi. Hoc truyn tnh mch khi u 5000 - 10000 n v, sau cch 4 -6 gi truyn 5000 - 10000 n v. Liu tip theo ph t huc vo thi gian ng mu v thi gian Howell. - Khi qu liu phi ngng haparin ngay v tim tnh mch chm protamin sulfat trung ha vi tc 50 n v/pht. Protamin sulfat l protein kim trng lng phn t thp, thi tr nhanh hn heparin nhng c kh nng phn ly phc hp antithrombin III -heaprin v kt hp vi heparin lm mt tc dng chng ng. Mt mg protamin sulfat trung ha c 100 n v heparin. * Hin c heparin trng lng ?phn t thp, nhng c tc dng sinh hc ch nh, chng ch nh v tai bin gn ging heparin ngun gc t nhin. Tuy nhin, c tc dng i khng yu t X hot ha mnh v thi gian tc dng di hn heparin thng thng. Do vy, ch cn tim di da mt ln/ngy. Mt s heparin trng lng phn t thp ang c s dng tm tt trong bng 30.2. Bng 30.2: Ch phm v liu lng mt s heparin trng lng phn t thp

1.3.2.3. Heparinoid tng hp: L polysacharid b ester ha bi acid sulfuric, c cng th c ha hc gn ging heparin, c ch tc dng ging heparin nhng tc dng chng ng yu hn. - Partiol tc dng km heparin 7 ln.

- Trebuton tc dng yu hn heparin 3 -4 ln. 1.3.2.4. Hirudin L a peptid c 65 acid amin, trng lng phn t 7000 - 9000 c cha trong tuyn n bo trong thc qun ca a, vt, c tc dng chng ng mu do ngn cn tc dng ca thrombin thng qua s to phc vi thrombin lm cho fibrinogen khng chuyn thnh fibrin. Dng Hirudin trong chn on xc nh hot tnh ca cc yu t ng mu nh thrombin (Hirudin-toleranz-test; Hirudin test). Hin cha c dng iu tr v s lng tch chit cn hn ch.

Trong tng lai nh k thut gen c th sn xut c hirudin s dng trong iu tr, chng huyt khi. 1.4. Thuc chng kt dnh tiu cu Tiu cu l nhng t bo khng nhn, hnh a, tch in m mnh. Trn b mt mng tiu cu c cha cc yu t ng mu I, V, VII. C cc fibrinogen receptor (Gp IIb/IIIa) v c tnh kt dnh v kt t nn khi thnh mch b tn thng cc tiu cu dnh vo ni b tn thng v dnh vo nhau thnh tng lp to ra nt trng tiu cu cn gi l inh cm mu Hayem. Trong qu trnh kt dnh, tiu cu cn gii phng ra phos pholip id gip thc y qu trnh to ra phc hp prothrombinase. S kt dnh tiu cu l yu t to ra mng x va ng mnh v gy nn tc mch. Hin c mt s thuc chng kt dnh tiu cu c s dng trong lm sng phng v iu tr huyt khi nh: thuc chng vim phi steroid (aspirin), dipyridamol, ticlopidin, clopidogrel v thuc c ch glycoprotein IIb/IIIa. 1.4.1. Aspirin (acid acetylsalicylic) Ngoi tc dng h st, gim au, chng vim, aspirin cn c tc dng chng ng vn tiu cu. - C ch : xin xem bi Thuc h st, gim au, chng vim. - Dng liu thp duy nht 10mg/kg cn nng, cch qung 48 gi, aspirin c ch 90% cyclooxygenase ca tiu cu, rt t nh hng n cyclooxygenase ca ni m mao mch nn nh hng khng ng k s tng hp c a prostacyclin I 2. Do vy, tc dng chng kt dnh tiu cu v ko di thi gian chy mu liu ny l ti a. Dng liu cao aspirin khng ch c ch COX tiu cu m cn c

ch COX ni m mao mch nn hiu qu chng kt dnh tiu cu khng cao. - Ngoi c ch COX tiu cu, aspirin cn lm n nh mng tiu cu, hn ch s gii phng ADP v phospholipid nn gim s kt dnh tiu cu v tng thi gian chy mu. - Ch nh: dng aspirin trong phng v iu tr huyt khi ng - tnh mch vi liu duy tr 75 mg/ngy.. - Chng ch nh v tc dng kh?ng mong mun (xin xem bi thuc h st, gim au v chng vim). - Ht sc thn trng khi phi hp aspirin vi thuc chng kt dnh tiu cu khc v thuc chng ng mu nh heparin, dn xut coumarin. 1.4.2. Dipyridamol (Persantone, Peridamol) Va c tc dng gin mch vnh, va c tc dng chng ng vn tiu cu do : + c ch s nhp adenosin vo tiu cu v c ch adenosin desaminase lm tng adenosin trong mu. Adenosin tc ng ln A 2-receptor lm gim s ng vn tiu cu. + c ch phosphodiesterase lm tng AMP v trong tiu cu. - Ch nh: thuc c phi hp vi warfarin trong phng huyt khi bnh nhn thay van tim nhn to. 1.4.3. Ticlopidin (Ticlid) - Do ticlopidin tng tc vi glycoprtein IIb/III a receptor ca fibrinogen lm c ch s gn fibrinogen vo tiu cu hot ha, ngn cn s kt dnh tiu cu. Ngoi ra, thuc cn lm tng prostaglandin D 2 v E2 gp phn chng ng vn tiu cu v tng thi gian chy mu. - Thuc c dng phng huyt k hi bnh nhn b bnh tn thng mch no hoc mch vnh vi liu 500mg/ngy. Khng dng thuc cho tr em. Khi dng c th gp mt s tc dng khng mong mun: chy mu, bun nn, a chy, gim bch cu trung tnh. 1.4.4. Clopidogrel (Plavix) - Thuc c tc dng chng ng vn tiu cu do: + c ch chn lc th th ADP ca tiu cu. + Ngn cn s hot ha glycoprotein IIb/IIIa ca fibrinogen trn tiu cu, lm gim s gn fibrinogen vo tiu cu. - Ung liu duy nht 75mg/ngy phng ng vn tiu cu. 1.4.5. Cc cht c ch glycoprotein IIb/IIIa receptor: Glycoprotein IIb/IIIa c vai tr lm tng s gn ca fibrinogen vo receptor trn

tiu cu. Mt s thuc gn vo glycoprotein IIb/IIIa receptor ngn cn s gn ca fibrinogen vo tiu cu c tc dn g chng ng vn tiu cu. + Abcimab (Reopro): l mt khng th n dng, khi u tim chm tnh mch 250 mcg/kg, sau truyn tnh mch 125 nanogam/kg/pht (ti a 10mcg/pht). + Eptifibatid (Integrilin): l peptid tng hp, khi u tim tnh mc h 180 mcg/kg, sau truyn tnh mch 2 mcg/kg/pht lin tc trong 72 -96 gi. + Tirofiban (Aggrastat): khi u tim chm tnh mch 400 nanogam/kg/pht trong 30 pht, sau truyn tnh mch 100 mcg/kg/pht trong t nht 48 gi. 2. THUC TIU FIBRIN Cc mu ng c th tan tr li nh qu trnh tiu fibrin. l qu trnh ngc vi ng mu. Bnh thng, enzym plasmin xc tc cho s tiu fibrin trong mu th khng hot tnh gi l plasminogen. Trong iu kin nht nh, cc cht hot ha (kinase, act ivator) c gii phng ra khi t chc, hot ha plasminogen to thnh plasmin. Plasmin va to thnh gip fibrin tr thnh cht phn hu tan c. 2.1. Urokinase ( Abbokinase) L endopeptidase, gm 2 chui a peptid cha 411 acid amin, trng lng phn t 53000, c phn lp t nc tiu ngi (URO = urine = nc tiu) hoc t nui cy t bo phi thn ngi. Urokinase xc tc cho phn ng ct lin kt peptid ca plasminogen (plasminogen c 791 acid amin) to thnh lys -plasminogen v chuyn thnh plasmi n. Lysin cui cng ca plasmin l v tr gn c i lc cao vi fibrin gip cho s thu phn fibrin. UK b chuyn ha gan v c thi gian bn thi 15 -20 pht. Thuc ch c t?im tnh mch, khi u 1.000 - 4.500 n v/kg th trng, sau duy tr 4.400 n v/gi. Thuc hu nh khng c tnh khng nguyn, khng b trung ha bi khng th, nhng c th gy st. 2.2. Streptokinase ( SK, Streptase) Gm mt chui apeptid, phn t lng 48000, c phn lp t lin cu tan mu nhm A. Streptokinase kt hp v i plasminogen theo t l ng phn t (equimolar) to thnh phc hp SK-plasminogen. Phc hp ny ct lin kt arginin -valin v tr 560 ca plasminogen chuyn thnh SK -plasmin c hot tnh tiu fibrin. Ngoi tiu fibrin, streptokinase cn xc tc cho ph n ng thu phn nucleoprotein thnh cc base purin t do v pyrimidin nucleotid, do vy lm long cc dch ng c nh m. Sau khi tim tnh mch vi liu thp thi gian bn thi khong 18 pht, nhng

khi tim liu cao hoc liu thp ko di th thi gia n bn thi t 83 pht v ht hin tng kt hp khng th khng streptokinase do bo ha. Thuc b chuyn ha v thi tr qua thn. - Trong qu trnh dng thuc c th gp mt s tc dng khng mong mun: chy mu, d ng hay gp vo ngy th 8, nn s au khi dng thuc 8 ngy, cn phi chuyn sang dng thuc khc. - Liu dng : + Khi u tim tnh mch 500.000 n v trong 30 pht, sau mi gi tim 100.000 150.000 n v v dng trong 24 - 48 gi lin. Trong nhi mu c tim c th truyn tnh mch1500000 n v trong 60 pht. + C th ha tan 20.000 - 100.000 n v vo 5 -20ml nc mui sinh l{ tim thng vo ti m sau 6 - 24 gi ht ra. 2.3. Anitreplase (Aminase) L phc hp ca plasminogen ngi tinh khit v streptokinase ca vi khun c acetyl ho bo v v tr hot ng ca enzym. Khi s dng, nhm acetyl c thu phn, gii phng phc hp streptokinase - cht tin hot ho thnh phc hp, hot ho plas minogen thnh plasmin. Thuc c tc dng trn plasminogen ca cc mu ng mn h hn plasminogen t do nn lm tan cc huyt khi nhanh. Ngoi c ch trn thuc cn lm gim yu t V,VIII v cht c ch tiu fibrin -2-antiplasmin. 2.4. Cht hot ho plasminogen m(t -PA, Alteplase) L mt protease sn phm ca ca k thut ti to ge n cha 527 acid amin c tc dng trn plasminogen gn vi fibrin mnh gp vi trm ln plasminogen t do. Khi lng fibrin thp tc dng chuyn plasminogen thnh plasmin thp. Thuc c thi gian bn thi ngn 5-10 pht. Trong nhi mu c tim cp tim tnh mch 15 mg sau truyn tnh mch 50 mg trong 30 pht v trong 60 pht tip theo truyn 35 mg (tng liu truyn trong 90 pht khng vt qu 100 mg). 2.5.Reteplase (r -PA, Retavase, Rapilysin) L cht hot ho plasminogen ti t hp thuc th h th 3, t c dng ging Alteplase nhng cng v thi gian xut hin tc dng nhanh hn. Thuc c dng trong nhi mu c tim cp khi u tim chm tnh mch 10 n v trong 2 pht sau c 30 pht tim thm 10 n v. 2.6. Tenecteplase (Metalyse) Thuc mi c tc dng tiu fibrin v ch nh nh r eteplase, tim tnh mch

ton b liu 500-600 mcg/kg nhng khng vt qu 50mg. 2.7. Ch nh v chng ch nh ca cc thuc tiu fibrin * Ch nh: - Tc nghn ng, tnh mch - Nhi mu c tim - Vim m, ng mu mng phi hoc cc khp ?xng hay cc hch dng streptokinase ti ch. - Bm vo ng dn lu m trnh tc (streptokinase). * Chng ch nh: Sau khi phu thut cha qu 8 ngy; mi hoc sy thai cha qu 4 ngy; cao huyt p nghim trng, qu trn h cm mu bt thng; c a d ng; mi dng streptokinase cha qu 6 thng; mi b bnh do lin cu; c thai (thuc khng qua rau thai, nhng phng bong rau sm); chy mu ng tiu ha nng trong vng 3 thng; tin s tai bin mch mu no; vim mn g ngoi tim cp; phu thut ng mch ch; vim ty cp; bnh gan nng. 2.8. Cht hot ha plasminogen L nhng cht gip gii phng cht hot ha (kinase, activator) hot ha plasminogen hoc tng tng hp plasminogen v cui cng lm cho fibrin tr th nh cht phn hy tan c. Thng dng ethylestrenol, phenformin, nicotinamid. Dng khi c th khng t gii phng c cht hot ha, v d khi mu tnh mch do tai bin huyt khi tnh mch, hoc phng ti pht vim tnh mch (dng ethylestrenol cng phenformin). 3. THUC CHNG TIU FIBRIN C trng thi bnh lm tiu nhanh fibrin, gy chy mu trm trng, v d khi ngi b bnh tng plasmin trong mu. Plasmin khng nhng lm tiu fibrin, m cn kt hp vi mt s yu t ng mu v hy hoi chng, lm c ch ng mu cng ri lon. Nhng phn t mi sinh do fibrin b hy cng kt hp li vi fibrin cho phc hp khng ng c na. Nhng cht phn hu ny cn lm cho tiu cu khng ngng kt thnh cc c. Kt qu lm chy mu trm trng. Thuc lm gim s tiu fibrin s c tc dng cm mu. Hin c mt s thuc chng tiu fibrin ang c s dng trn lm sng cm mu. 3.1. Aprotinin (Trasylol) L thuc c ch protease gm 58 acid amin, c 3 cu ni disulfur, phn t lng 6500, ly t tuyn man g tai, phi, gan. iu ch t tin, thi gian bn thi ngn:150 pht; ch tim tnh mch hoc truyn tnh mch vi liu lng tuz

thuc vo ch nh. Phng chy mu khi phu thut tim m liu 2000000 n v, chy mu do tng plasmin mu khi u 500000-1000000 n v. Thuc to phc vi plasmin cho phc hp mi aprotinin -plasmin khng c hot tnh plasmin. Aprotinin cn c ch c cc enzym hu protein khc na, nh trypsin, chymotrypsin, kalikrein. Aprotinin thi qua nc tiu di dng mt hot tn h, nn khng dng chng tiu fibrin ng tit niu. Dng nhiu ln c th gy nhng phn ng qu mn ngi c c a d ng. 3.2. Thuc tng hp 3.2.1. Acid w- aminocaproic C cu trc ging lysine c tc dng chng tiu fibrin nh hai nhm amin v carboxyl cch nhau 0,7nm, c ch s hot ha ca plasminogen, km hm khng cho plasmin tc ng ln fibrin, lm cho fibrin khng b ging ha bi plasmin na. Thuc khng c ch c cc cht hot ha plasminogen (kinase, activator). Thuc c th ung 24 gam chia lm 4 ln trong ngy hoc tim chm tnh mch 5 7,5g d phng hoc iu tr chy mu. 3.2.2. Acid tranexamic (Cyclokapron ) L ng ng v c tnh cht, tc dng ging acid w- aminocaproic, c th tim tnh mch hoc ung phng ch y mu sau m tuyn tin lit, nh rng ngi b hemophilia hoc qu liu thuc tiu cc mu ng? hoc ph n b a kinh vi liu 2 - 4g/24 gi, chia lm 3 ln . 3.3. p dng iu tr ca thuc chng tiu fibrin - Ch nh: Dng trong trng thi tiu fibri n nguyn pht, tiu fibrin cp, d phng chy mu sau phu thut to hnh, tai mi hng, ct b tuyn tin lit v.v - Chng ch nh: c tnh ca Acid w- aminocaproic v acid tranexamic rt t, tuy nhin cn dng thn trng khi suy thn nng (c th g y tch lu thuc), khi c tin s hoc c biu hin huyt khi tc tnh mch hoc ng mch. BI 35. THUC TR TIM Thuc tr tim l nhng thuc c tc dng lm tng lc co bp ca c tim, dng trong cc trng hp suy tim. Cc thuc c chia lm 2 nhm: - Thuc loi glycosid c ch nh trong suy tim mn. - Thuc khng phi glycosid dng trong suy tim cp tnh. 1. THUC LOI GLYCOSID ( GLYCOSID TR TIM): DIGITALIS

Cc thuc loi ny u c 3 c im chung: - Tt c u c ng un gc t thc vt: cc loi Digitalis, Strophantus - Cu trc ho hc gn ging nhau: u c nhn steroid ni vi vng lacton khng bo ha C17, gi l aglycon hoc genin, c tc dng chng suy tim. V tr C 3 ni vi mt hoc nhiu phn t ng( ose), khng c tc dng dc l{ nhng nh hng n dc ng hc ca thuc. - Hin ch cn digoxin v digitoxin c dng lm sng. Digitoxin khc digoxin l khng c OH C 12 v th t tan trong nc hn. - Cc thuc tc dng trn tim theo cng mt c ch. 1.1. Dc ng hc 1.1.1. Hp thu Digoxin Glycosid khng ion ho, c khuch tn th ng qua ng tiu ha (d dy, t trng, rut non): thuc cng tan trong lipid, cng d khuch tn. Cc nhm OH ca genin l nhng cc a nc, lm hn ch tan trong lipid ca thuc: - Digitoxin ch c mt nhm OH t do C14, nn d tan trong lipid, c hp thu hon ton khi ung. - Uabain c 5 nhm OH t do, khng hp thu qua ng tiu ho, nn phi tim tnh mch. Hin khng cn c dng na. - Digoxin c 2 nhm OH t do, hp thu qua ng tiu ha tt hn uabain, nhng khng hon ton nh digitoxin. 1.1.2. Phn phi Thuc cng d tan trong lipid, cng d gn vo protein huyt tng, song khng vng bn v d dng c gii phng ra dng t do. Glycosid gn vo nhiu t chc, c bit l tim, gan, phi, thn, v nhng c quan ny c ti mu nhiu; vi c tim, thuc gn vng bn theo kiu lin kt cng ho tr. Kali - mu cao, glycosid t gn vo tim v ngc li khi kalimu gim, glycosid gn nhiu vo tim, d gy c. Digitalis c th qua c hng ro rau thai. 1.1.3. Chuyn ho Digitoxin chuyn ho hon ton gan, digoxin 5%, cn uabain khng chuyn ho. Nhng phn ng chuyn ho quan trng ca digitoxin v digoxin l: - Thu phn, mt dn phn ng, cui cng cho gennin - Hydroxyl ho genin v tr 5 -6 bi micrsm gan - Epime ho: chuyn -OH v tr 3 t bta sang alpha - Lin hp vi cc acid glucuronic v sulfuric.

1.1.4. Thi tr Digitoxin v digoxin thi tr qua thn v qua gan, nhng ni , mt phn thuc c ti hp thu, nn lm tng tch ly trong c th. Uabain khng b chuyn ho, thi tr qua thn di dng cn ho?t tnh. 1.2. Tc dng ca digitalis 1.2.1. Tc dng trn tim y l tc dng ch yu: digitalis lm tm thu ngn v mnh, tm trng di ra, nhp tim chm li. Nh , tim c ngh nhiu hn, mu t nh vo tht thi kz tm trng c nhiu hn, cung lng tim tng v nhu cu oxy gim. Do bnh nhn kh th v nhp h hp tr li bnh thng. Digitalis cn lm gim dn truyn ni ti v tng tnh tr ca c tim nn nu tim b lon nhp, thuc c th lm u nhp tr li. C ch tc dng: Cc glycosid tr tim u c ch cc ATPase mng, l enzym cung cp nng lng cho bm Na+ K+ ca mi t bo. Bm ny c vai tr quan trng trong kh cc mng t bo, do y 3 ion Na + ra trao i vi 2 ion K + vo trong t bo. Tc dng ca glycosid ph thuc vo tnh nhy cm ca ATPase ca tng m. Trn ngi, c tim nhy cm nht, v vy: vi liu iu tr, glycosid c tc dng trc ht l trn tim. Khi ATPase b c ch, nng Na + trong t bo tng s nh hng n mt h thng khc, h thng trao i Na + - Ca++. Bnh thng, h thng ny sau mi hiu th hot ng s y 1 ion Ca++ v nhp 4 ion Na + vo t bo. Di tc dng ca glycosid, nng Na + trong t bo s tng cn tr s trao i ny v lm nng Ca ++ trong t bo tng cao, gy tng lc co bp ca c tim, v ion Ca ++ c vai tr hot ha myosin ATPase cung cp nng lng cho s co c (cc si actin trt trn si myosin). (Hnh 22.1)

Hnh 22.1. Tc dng ca digitalis trn cc lung ion (-) c ch Sau c tim ATPase ca cc t bo nhn cm p lc ca cung ng mch ch v xoang ng mch cnh cng rt nhy cm vi glycosid. Khi ATPase b c ch, tn s phng xung tc gim p hng tm t ng, kch thch trung tm ph giao cm v lm gim trng lc giao cm s lm tim p chm li v lm gim dn truyn nh - tht.

1.2.2. Cc tc dng khc - Trn thn: digitalis lm tng thi nc v mui nn lm gim ph do suy tim. C ch ca tc dng n y l: mt mt, digitalis lm tng cung lng tim, nn nc qua cu thn cng tng; mt khc, thuc c ch ATPase mng t bo ng thn lm gim ti hp thu natri v nc. - Trn c trn: vi liu c, ATPase ca bm Na + - K+ b c ch, nng Ca ++ trong t bo thnh rut tng lm tng co bp c trn d dy, rut (nn, i lng), co tht kh qun v t cung (c th gy xy thai). - Trn m thn kinh: digitalis kch thch trc tip trung tm nn sn no tht 4 v do phn x t xoang cnh, quai ng mch ch. 1.3. Nhim c Cc du hiu nhim c digitalis rt a dng. Khi iu tr, cn ch pht hin cc du hiu, triu chng sau: - Tm thn: m sng, kh chu, mt mi, l ln, chong vng. - Th gic: nhn m, c qung sng. - Tiu ha: chn n, bun n n, nn, au bng. - H hp: th nhanh. - Tim mch: nhp xoang chm, lon nhp ngoi tm thu nh, tht; ri lon dn truyn nh - tht; nghn nh - tht cc loi; rung tht. Digitalis l thuc b tch lu trong c th, phm vi nng huyt tng c tc dng iu tr li hp, v vy trong lm sng, tuy dng liu iu tr vn c th g?p nhim c do nhiu yu t tng tc nh: ri lon in gii (h K + mu, h Mg++ mu, tng Ca++ mu); nhim kim chuyn ha; suy gan, suy thn lm gim chuyn ha v thi tr th uc. Trong gim st iu tr, cn o nng ca thuc trong huyt tng hiu chnh liu. 1.4. p dng lm sng - Ch nh: + Gin tm tht. + Nhp nhanh v lon. + Suy tim do tn thng van. - Chng ch nh: + Nhp chm. + Nhp nhanh tm tht, rung th t. + Vim c tim cp (bch hu, thng hn) + Nghn nh tht.

+ Khng dng cng vi cc thuc sau, c th gy cht t ngt hoc tng c ca digitalis: calci (nht l khi tim tnh mch), quinidin, thuc kch thch adrenergic, reserpin. 1.5. Ch phm v liu lng - Digitoxin: Nng iu tr trong huyt tng l 10 - 25 ng/ mL, nng c l > 35 ng/ mL Liu iu tr: 0,05 - 0,2 mg/ ngy. Ch phm: vin nn 0,05 v 0,1 mg - Digoxin: Nng iu tr trong huyt tng l 0,5 - 1,5 ng/ mL, nng c l 0,2ng/ mL. Liu iu tr: 0,125 - 0,5 mg/ ngy Ch phm: vin nn 0,125 - 0,25- 0,5 mg ng tim 0,1 - 0,25 mg/ mL 1.6. iu tr ng c Ng c do tch lu thuc hoc ung qu liu, v digitalis gn rt cht vo c tim, cho nn khi ng c phi dng thuc c ch gn tip tc digitalis vo tim (kali), thi tr calci l cht hip ng tc dng vi digitalis trn c tim (EDTA) v cc thuc cha triu chng lon nhp tim (diphenylhydantoin, thuc phong to bta vv) - KCl ung 20-80mEq/L/ngy; hoc 40 -60mEq/L chuyn tnh mch trong 2 3gi u. Truyn tnh mch th d kim tra v khi cn c th ngng ngay. Tuyt i khng dng khi suy thn. - Diphenylhydantoin: lm tng ngng kch thch ca tim, i khng vi tc dng in tim ca digital. Tim tnh mch 125-250mg trong 1-3pht. Tc dng nhanh v gi c 4-6 gi. C th truyn lidocain 2mg/ pht. Nu c nhp chm, thm atropin 0,5 -1,0mg tim tnh mch. - EDTA (acid etylen diamino tetraacetic) c tc dng gp calci ra khi c th. Dng khi kali v diphenylhydantoin khng c ch nh. Truyn tnh mch 3,0g pha trong 200ml glucose 5%. - Min dch tr liu khng digoxin (antidigoxin immuno therapy). Hin c thuc gii c c hiu cho digoxin v digitoxin di dng khng th, l cc phn on Fab tinh khi t t khng huyt thanh khng digoxin (antidigoxin antisera) ca cu (DIGIBIND). Pha trong dung dch nc mui, truyn tnh mch trong 30 - 60 pht. Liu lng tnh theo nng hoc tng lng digoxin c trong c th. Ch phm: Digibind l bt ng kh cha 38 mg Fab v 75 mg sorbitol. Mi l gn c khong 0,5 mg digoxin hoc digitalin. 1.7. Strophanthus Ht cy Strophanthus c glycosid l strophantin (genin l strophantidin). Trong

lm sng, c dng nhiu l G. strophantin (tc uabain) ly Strophanthus gratus, v K. strophantin ly Strophanthus kombe . Tc dng ca strophantin xut hin nhanh, 5 - 10 pht sau khi tim tnh mch, tc dng ti a sau khong 1 gi v thi tr nhanh. Thuc t tc dng trn dn truyn ni ti c tim, c th dng khi nhp ch m. Ch nh trong suy tim l khi digitalin t ra khng hiu lc, v trong cp cu (v tc dng nhanh). Nhc im l tim bp khng c tc dng v ung th b thu phn nhanh. Mi ngy tim tnh mch? 0,25 mg - 1 mg. v thuc thi nhanh, nn c th tim hn g ngy nu dng liu 0,25 mg. Strophantin cng c th gy nn, a chy v rung tm tht (c bng A). Hin ang c thay th bng cc thuc cng 1 giao cm. 2. THUC TR TIM KHNG PHI DIGITALIS: Thuc lm tng AMPv Thuc loi ny c dng cho suy tim cp tnh v t cp tnh ca suy tim mn, biu hin bng cn kh th nng, ph ngoi bin hoc ph phi. Vic iu tr trc tin l phi lm gim gnh nng cho tim bng thuc gin mch, thuc li niu (xin xem phn tng ng); sau l dng thuc lm tn g sc co bp ca c tim. Cc thuc loi ny u l thuc tim v bnh nhn thng phi nm vin. Thuc tng co bp tim loi digitalis, khng c dng trong shock v c nhiu tc dng ph, cng d xy ra khi c tng catecholamin ni sinh (stress), thiu ox y, acid huyt. Thng xy ra lon nhp. Hin a dng loi lm tng AMPv mng t bo c tim, tc dng lm m knh calci nn lm tng co bp tim: Thuc kch thch adenylcyclase, enzym tng hp AMPv, v c ch phosphodiesterase, enzym ging ho AMPv, u c tc dng lm tng AMPv (s ). Cc thuc ny lm tng bin co bp ca c tim, tc co bp nhanh v thi gian co ngn li, c tc dng tt trong iu tr suy tim cp, sc. Cc glycosid tim cng lm tng bin co bp ca c tim, nhng tc co bp ch tng va phi v thi g ian co bp li ko di (hnh 22.2), c tc dng ci thin c tnh trng suy tim mn

Tc dng qua trung gian AMPc Tc dng ca glycosid tim Hnh 22.2. Chu kz co bp ca tim b suy () v di nh hng ca thuc ( -) 2.1. Cc thuc cng adrenergic (Xin xem thm mc ny bi Thuc tc dng trn h adrenergic) 2.1.1. Isoprenalin - Tc dng dc l: + Cng 1: tc dng ln c 4 tnh cht ca tim, lm tim p mnh, p nhanh, tng tnh dn truyn v tnh chu kch thch. Do lm tim p nhanh, lm tng nhu cu oxy ca c tim. Lu lng tim tng, huyt p ti a tng. + Cng 2: lm gin kh qun, gin mch (gim sc cn ngoi bin, gim hu gnh). Huyt p ti thiu gim. Lu lng tim tng v gin mch l 2 tc dng quan trng lm ci thin c s ti mu, c bit l cho vng tng ni chu nh hng nhiu ca shock. Ngoi tc dng tim mch, isoprenalin cn lm tng ng huyt, tng hu lipid v do sinh nng lng. - Tc dng khng mong mun v c tnh: + H huyt p, lo n nhp, au vng trc tim, nhi mu c tim. Cn theo di bng in tim. Khng dng cng thuc m nh cyclopropan, fluothan, lm tng c tnh vi tim. - Ch nh chnh: + Shock c h huyt p, cn tr mu ti cc mch do co mch ngoi bin v thiu nng tim, th hin bng tng p lc tnh mch trung tm. + Ngng tim, kt hp vi xoa bp tim ngoi lng ngc. - Ch phm: + Isoprenalin clohydrat (Isuprel) + Isoprenalin sulfat (Aleudrine) ng 1ml = 0,2mg. Truyn tnh mch 2 -6 ng trong 250 - 500ml huyt thanh ngt ng trng, khng c base. Khi ngng tim tim 2 ng vo tim. 2.1.2. Dobutamin Tc dng chn lc ch trn 1 receptor. - c im tc dng trn h tim - mch:

+ Trn tim: lm tng co bp c tim, c bit l vi ?liu lm tng bin nh isoprenalin th dobutamin ch lm tng nhp tim rt t, do ch lm tng t nhu cu s dng oxy ca c tim, tuy lm tng c lu lng ca tim. + Lm gim nh sc cn ngoi vi v p lc mao mch phi. - Ch nh: + Shock - tim, nht l sau m tim vi tun hon ng oi c th. + Cc suy tim nng, khng b tr, khng p ng vi cc cch iu tr khc. - Ch phm: + Dobutrex l 20ml = 250mg Pha trong dung dch glucose hoc mui ng trng, khng c base, truyn tnh mch vi tc 2- 15 mg/ kg/ pht, tuz tnh trn g bnh v t/2 = 2 - 3pht. Khi xut hin nhp tim nhanh v lon nhp, cn gim liu. 2.2. Dopamin Dopamin l cht tin thn ca noradrenalin v l cht dn truyn thn kinh ca h dopaminergic. Trn tim mch, tc dng ph thuc vo liu (xin xem Thuc cn g h adrenergic). Tuy nhin, ngay c vi liu trung bnh (2 - 5 g/ kg/ pht- liu kch thch 1), dopamin lm nhp tim nhanh nn d gy thiu mu c tim, nht l trn bnh nhn c bnh mch vnh. Cn cn nhc khi ch nh. 2.3. Cc thuc phong ta p hosphodiesterase Nhm thuc mi phong ta phosphodiesterase c u im hn nhm thuc c in (nhm xantin) l: - Tc dng ch yu trn isoenzym F typ III ca phosphodiesterase c nhiu mng t bo c tim. - Khng kch thch thn kinh trung ng. 2.3.1. Dn xut bipyridin: amrinon (Inocor) v milrinon (Primacor) - Lm tng co bp c tim, tng lu lng tim - Lm gin mch nn lm gim tin gnh v hu gnh - Tc dng ph: t. C th gp st, nhc u, ri lon tiu ho, gim v gic v khu gic. Gim tiu cu, ngng thuc s khi, him gp vi milrinon - Ch dng thuc cho bnh nhn nm vin - Cch dng: + Amrinon (Inocor) ng 20mL c 100mg amrinon lactat pha trong dung dch mui ng trng dng ngay trong ngy. Tim tnh mch liu tn cng 0,5 g/kg, sau truyn vi tc 2-20 g/kg/pht; t/2 = 2 -3gi.

+ Milrinon (Primacor) 5mg/mL. ng tim tnh mch. Khong 10 ln mnh hn amrinon. Liu tn cng 50 g/kg tim tnh mch, sau truyn vi tc 0,25 1,0g /kg/ pht; t/2 = 30-60pht. ang l thuc c la chn v c ch c hiu PDE III. 2.3.2. Dn xut benzimidazol L cc dn xut c ch PDE III ang c nghin cu: - Pimobendan: ngoi c ch c ch PDE III cn c c ch lm mn cm cc yu t co tht ca c tim vi Ca ++ ni bo. 2.3.3. Vesnarinon : l quinolinon tc dng theo ng ung lm tng lc co bp tim mch v gin mch theo nhiu c ch: c ch PDE III, tng nhp Ca ++, ko di in th hot ng, lm chm nhp tim. Tuy nhin phm vi an ton hp, nhiu nc khng dng na. 2.4. Cc thuc khc 2.4.1. Spartein Alcaloid chit xut t hoa cy Kim tc (Spartium junceum L.), thng dng spartein sulfat. Lm tim p mnh u, v chm li. Ch nh: - e da try tim mch do chn thng nhim c. - nh trng ngc, nhi vng tim (khng phi hi chng ng mch vnh). - Tr tim gia hai t dng digitalis hay strophanthus. - C th phi hp vi morphin, scopolamin trong tin m; spartein cn c ch bi tit catecholamin. Nn dng, nu gy m bng cloroform. - Thc : lm t cung co bp mnh v u. Liu lng: u nh ng hay tim di da 0,05g/ ln, 1 -3 ln/ ngy. 2.4.2. Long no Lm nhp tim p mnh, u, kch thch h hp, gy tit m hi v h nhit (rt t). Ch nh: - Try tim mch. - Nhim khun, nhim c. Liu lng: - Dung dch du 10%: tim di da 2- 5 mL. - Long no tan trong nc (natri camphosulfonat): dung dch 10%. Tim di da 1 10 mL. Hai thuc trn ngy cng t dng v tc dng khng mnh. 2.4.3. Amino- 2- methyl- 6 heptaminol- 6 Lm tng cung lng ng mch vnh, cung lng tim, li niu, tng huyt p.

t c. Thng dng cng digitalis cha suy tim. c ch nh trong try tim mch, bin chng tim trong phu thut, vim c tim cp, nhim khun, nhi mu c tim. Ung mi ngy 0,3 - 0,5g. Tim bp, tnh mch: 0,05 - 0,1g (dung dch 5%). BI 36. THUC IU TR TRU TIM MCH V CHONG 1.i cng. 1.1 So snh 1.2. Lin quan gia tru tim mch v shock (chong) Try tim mch ko di dn n chong, chong th chc chn s l try tim mch( suy tun hon) Chong l ni n ri lon vi tun hon Huyt p ph thuc: - Tim - Sc cn ngoi vi - Khi lng mu - nht C th mt 30 % khi lng mu s dn ti tru tim mch tt huyt p, mch nhanh. V vy phi iu tr giai on shock cn b * Nguyn nhn: mt mu, chn thng, (dp nt cc t chc).Shock phn v, nhi mu c tim, nhim c, nhim khun huyt 1.3.C ch bnh sinh chnh. * Tng sc khng ngoi bin, mao mch co li * Gim sc khng ngoi bin, gp trong shock phn v (do tng tit his tamin) * Suy tim cp, gp trong mi loi shock * Ri lon ng mu: ng mu ri rc trong lng mch 1.4.Khuynh hng hin nay trong iu tr - Khng dng thuc co mch thun tu , nht l trong trng hp shock co mch - Ch yu phi tng khi lng mu lu hnh bng lm y lng mch theo kh nng lm vic ca tim. - iu chnh lm tng khi lng tun hon ca tim bng tng lu lng tim. 2.iu chnh gim th tch ca tun hon

2.1.Truyn mu: Khi mt mu nhiu > 30% th khng g thay th c mu (nhc im: ngun , ly bnh) 2.2.Truyn huyt tng: Ch nh trong mi loi shock Nhc: - Phn ng qu mn - Nhim siu vi trng - Khng dng khi Protid mu cao 2.3.Cc cht thay th mu: L nhng cht c trng lng phn t tng ng vi albumin huyt tng (> 40.000). Dng khi shock khng phi do mt mu * Gelatin lng: c sn xut t colagen ca xng, thu phn n khi protein c trng lng phn t gim n khong 35.000 (dng plas mion, plasmagel) u: - D bo qun - Khng cn xc nh nhm mu Nhc: - Khng gi c lu, (thi tr 75 % sau 24 h) - Cn phn ng khng nguyn - C th gy ri lon ng mu: gim tiu cu, gim protrombin -Phi hm nng trc khi truyn v gelatin b ng khi gp lnh Polyvinyl-Pyrrolidone (PVP): l cht tng hp, trng lng phn t khong 40.000. * Dextran: l plyme t nhin c hnh thnh t glucose di nh hng ca men vi khun to thnh dextran u: -?D bo qun - Duy tr nng huyt p lu - Lm d dng tun hon ca hng cu trong lng mch Nhc: -t c nhng qu mn - C th gy ri lon ng mu (to phc fibrrinogen, dextran, d gn vo hng cu, tiu cu, lm tng qu tnh ng mu. * Theo quan nim mi: trong sc khng dng dung dch glucose v ri lon vi

tun hon dn ti thiu oxy, glucose tng chuyn ho theo vng ym kh, tng axit lactic, gy nhim toan chuyn ho. 3.iu chnh suy tim. 3.1.Tng lu lng tim bng tng cng co bp ca chnh c tim Tt c cc glycogid tim (digoxin,ouabain) khng c dng trong sc, v n tng tc vi cc catecholamin ni sinh (stress), thiu oxy, toan hyt, ri lon ion (Ca++ tng, K+ gim), tng tc vi thuc cng b l nhng vn thng i km vi sc. Dng thuc tng AMP vng mng t bo c tim, tc dng lm m knh calci nn lm tng co bp tim. C ch chung : 3.1.1.Cc thuc cng b adrenergic: Isoprenalin *Tc dng iu tr: + Cng b1: tc dng ln c 4 tnh c bn ca tim: tim p mnh, p nhanh lu lng tim tng, tng huyt p, tng s dng oxy + Cng b2 gin KQ gin mch (gim sc cn ngoi vi, gim hu gnh) Kt qu: Lu lng tim tng v gin mch l 2 tc dng quan trng ci thin c s ti mu n cc t chc c bit l vng tng ni chu nh hng nhiu ca shock * Tng ng huyt , tng hu lipid v do sinh nng lng Tc dng khng mong mun v c tnh:Gim huyt p, lon nhp, au tht ngc, nhi mu c tim Tng tc: Thuc m (nhm halogen) Ch nh : - Cc trng hp shock c co mch ngoi vi - Gim huyt p trong shock - Ngng tim Ch phm: - Isoprenalin, clohydrat (Isuprel) - Isoprenalin sulfat (Aleudrrine) - ng 1 ml = 0,2 mg 3.1.2. Dobutamin Tc dng ch yu ln b1 + Lm tng co bp c tim, rt t tng nhp, tng lu lng tim trong khi t tng nhu cu x dng oxy

+ Lm gim sc cn ngoi vi v p lc mao mch phi Ch nh: - Cc trng hp suy tim cp: + Sc tim, sau m tim + Suy tim nng khng b tr, khng p ng vi cc thuc. Ch phm: Dobutrex (l 20 ml 250 mg) pha trong dung dch mui ng trng 3.2. Cc thuc phong to phos phodiesterase - Dn xut biperidin: am rinon (Inocor) Dn xut imidazon: perfane, enoximon * Tc dng: C nhiu u im hn nhm xanthin c in l - Tc dng ch yu ln isoenzym F ca phosphodiesterase ch c mng t bo c tim, nn rt c hiu - Khng kch thch thn kinh trung ng - Lm tng co bp c tim, tng lu lng tim khng thng qua knh ion -Lm gin mch, khng thng qua h thn kinh thc vt nn lm gim tin gnh v hu gnh. Ch dng trong bnh vin - t tc dng khng mong mun, c th gp ngoi tm thu, lon nhp, st, nhc u, ri lon tiu ho, gim v gic, dng lu gim tiu cu 3.3.1. Adrenalin: liu thng dng, tc dng b >a *Tc dng trn tim mch - Lm gim sc cn ngoi vi (do gin mch c, c bit l mao ng mch). Liu cao mi tc dng trn a receptor. - Lm tng bin , tn s, lu lng ( do co tnh mch) v cng nng tim? - Lm tng nh huyt p tm thu (khng gy phn x dy X) v lm gim nh huyt p tm trng. *Ch nh: -Ngng tim -Phn ng phn v nng (c bit tt vi phn v do c t nh: ong t, b cp, c ph thanh qun) *Chng ch nh: - Nhi mu c tim - Suy mch vnh -Tng huyt p phi

*c tnh: nh chng ngc, lon nhp tim, au vng trc tim, tng huyt p, nhc u, nng hn gy ph phi cp *Liu lng: Tim di da: 0,25 mg - 0,5 mg, nhc li khi cn 3.3.2. Noradrenalin: Tc dng a > > b *Tc dng trn tim mch : - Lm tng sc cn ngoi vi do gy co mch mnh - Lm co tht cc c vng sau mao qun gy mu vng mao mch, nht l vng mch tng, gy thot huyt tng (chnh noradrenalin c th gy chongsc) - Lm tng mnh huyt p ti thiu v huyt p trung bnh. Gy chm nhp tim do phn x ph giao cm *Ch nh: - Sc do gin mch lan to (gim trng lc giao cm) - C th dng trong mt s trng hp suy tim cp khi cc thuc khc khng c tc dng hoc chng ch nh (c bit l sc do nhi mu c tim cha c lon nhp) *Chng ch nh: Shock c co mch, shock do tc mch phi, ph n c mang *c tnh: Lo lng, bn chn, tng huyt p qu mc, hoi t t chc nu tim ra ngoi tnh mch *Liu lng: 1- 4 mg noradrenalin pha trong dung dch ngt hoc mnh ng trng, 250 ml n 500 ml, truyn nh git tnh mch 3.3.3.Dopamin Tc dng tu theo liu dng *Liu thp ( < 5mg/kg/pht), tc dng cng h dopamin: - Lm tng bin co bp tim, tng lu lng tim, nhp tim khng tng - Gin mch thn, tng thi Na+, tng li niu 3-5 ln - Gin mch mc treo v mch vnh (tng cung cp oxy cho c tim) *Liu trung bnh (5-20 mg/kg/pht), tc dng cng b - Tng bin co bp tim, tng lu lng tim, tng nh nhp tim - Gim sc cn ngoi bin do gin mao mch *Liu cao trn 20 mg/kg/pht, tc dng cng a: - Co mch, tng huyt p - Gim li niu Tng bin v tn s tim, lm tng s dng oxy ca c tim m khng b tr c do mch vnh khng gin

Ch nh: Cc loi sc do tim, do nhim trng, do chn thng c gim lu lng tim Chng ch nh: U tu thng thn, nhp tht nhanh Nu c gim th tch tun hon, phi truyn dch trc c tnh: Thng ch xut hin khi qu liu: bun nn, nn, co mch ngoi bin, lon nhp tim, au vng trc tim. C th c phn ng qu mn do ch phm c cha sulfit (SO2). Thn trng khi gy m bng cc thuc m c nhm halogen. BI 37. THUC CHNG LON NHP TIM 1. Mt s khi nim c bn Ri lon to xung (tnh t ng) nt xoang v cc cu trc b ni C th do: ri lon dn truyn (nghn mt chiu hay hai chiu, c mt s vng c dn nhp bt thng, phng ra cc xung tc khc nhau). Cc thuc cha ri lon nhp tim (RLNT) l cc thuc c tc dng iu chnh hoc y li mt cch c hiu lc cc RLNT ngoi v cn c tc dng chng rung nh. 2 - Cc thuc CLNT Ch ?l cc thuc cha triu chng, ngn nga hay ct cn lon nhp do bt kz nguyn nhn no. Theo cc cch :- Lm chm kh cc tm trng.- Lm gim tc dn truyn cc xung ngoi lai. Chng hin tng ti nhp . c ch trc tip trn c tim. 5 nhm chnh Nhm 1. Cc thuc chn knh Na+ (v c knh K+). Phn nhm 1/A: Quinidin, Procain amid, Disopiramid. Phn nhm 1/B: Lidocain, Mexiletin, Phenytoin. Phn nhm 1/C: Eucainid, Flecainid, Propafenon. Nhm 2: Thuc phong to thu th Beta -adrenergic. Propranolol, Acebulol, Esmolol. Nhm 3: Thuc ko di ti cc, tng thi gian tr Amiodaron, Bretylium, Sotalol. Nhm 4: Thuc chn knh Ca ++. Verapamil, Diltiazem. Nhm 5: Glycosid tr tim v cc thuc khc cha lon nhp chm (Atropin,

Adenosin, Isoporeternol). B. Cc thuc Nhm 1 Phn nhm 1/A: Thuc tc dng lm bn vng mng (hay n nh mng) t bo. Quinidin, Procainamid, Disopyramid *c im tc dng: - c ch ion Na+ vo trong t bo c tim, gim kh cc pha 0 (tc l c ch Vmax). - Tng thi gian ti cc, tng thi gian tr - Gim tc dn truyn, tng thi gian dn truyn - Gim tnh t ng - do c ch knh Na+ - Tc dng trc tip v mnh trn hu ht t bo c tim. - Tc dng gin tip lm thay i iu ho tnh t ng tim, tng phn x giao cm, c ch ph giao cm lm tng tn s tim (nhc im). - Trong lon nhp do ti nhp: thuc lm tng tnh tr v gim dn tryn, bin nghn (dn truyn) mt nhnh thnh nghn 2 nhnh. - Trn thn knh thc vt: ring Quinidin, c tc dng ging artopin, phong to a v tng hot tnh ( b- aderenergic). Ch nh: Quinidin (Serecor, LonGacor) Khi s dng nht thit phi th test quinidin trong iu kin ni tr. Theo di ECG v lm sng (V d gy t t). Quinidin l thuc hng u dng : + iu tr v d phng cn nhp nhanh kch pht ngun gc tm tht. + iu tr duy tr nhp xoang sau khi kh rung nh thnh cng bng Shook in. V mt ny, y l thuc duy nht c th chng c rung nh. Ch phm - lin : Vin 0,15 g; (0,30 g). - Vi vin 0,15: Ngy u 2 vin sau tng dn 4 vin - 5 vin dng lin tc trong ngy di s gim st in tim v lm sng nghim ngt. - Liu duy tr: Dng ko di, 1-2 vin/24h. Procainamid. (Pronestyl, vin 0,25, ng 10ml, 100mg). - Dng tim tnh mch iu tr nhp nhanh tht khi khng li thuc Lidocain.

- iu tr ngoi tm thu tht (ES). - L thuc tt nht dng iu tr nhp nhanh trong hi chng Wolf - Parkinson White (WPW). - Dng d phng rung nh sau Shock in. Liu: - Truyn tnh mch 100 mg/pht, tng liu < 10g trong trng hp cp cu. - Trng hp iu tr: Tnh mch 0,2 - 1,0g. Tim bp: 0,5 - 1,0gtric 4-6h mt ln. Ung 50 mg/kg th trng. Disopyramid (RHythmodan) - Lon nhp tht, lon nhp do nhim c Difitalis. - D phng lon nhp do nhi mu c tim, sau iu tr bng Shock in. * Ch phm - liu : vin 100 mg, ung cch 6 h 1 vin. Tim tnh mch 1,5 mg/kg th trng. * Chng ch nh - Quinidin: Ri lon dn truyn; nghn nh tht, nh tht phn ly. - Procain amid: Nghn nh tht lon n?hp km ph phi cp, suy tim nng. - Disopyramid: Khng c tc dng trong iu tr nhp nhanh trn tht. Nhm 1/B: Phenytoin (DPH, Sodanton, Dihydan), Lidocain (Lignocain, Xylocain) v Tocainid. * c im tc dng: + Lm bn vng mng t bo, khng c tc dng trn hot tnh ni ti ca c tim. + Gim tnh t ng, ko di thi gian kh cc ti pht th tm trng, rt ngn thi gian tr, ti cc. + t tc dng n sc co bp t bo c tim. + Khng tc dng trong cung ng nh, rung nh. Ngoi ra Lidocain c tc dng gin mch, thi gian tc dng ngn. * Ch nh: Phenytoin: . Lon nhp do nhim c digitalis. . Lon nhip tht (do thuc m, huyt khi c tim). . Ngoi tm thu tht. - Ch phm - liu : Dihydan, sodanton, DPH.

Vin 0,10g; ung 1 - 2 vin/ cch 6 gi mt ln, ng 250mg + 5ml nc mui sinh l{: tim tnh mch, liu 10mg/kg th trng. Lignocain, Xylocain: Ch dng tim: tnh mch 1 - 2 mg/kg, truyn nh git 2mg/pht, tng liu 1,0 2,0g/24h. TOCAINID * Ch nh: . Dng iu tr cc ngoi lai (atopic) gy lon nhp giai on sm v giai on sau ca nhi mu c tim cp. . Nhp nhanh tht dai dng, nguy c rung tht, lon nhp tht e da tnh mng bnh nhn. Nhm 1/c: eucainid, flecainid, tocainid * c im tc dng: C i lc cao vi knh Na+ c tng. L thuc chng lon nhp mnh nht nhm 1. - Khc nhm 1/A: Khng thay i mt cch c { ngha tnh t ng v thi gian in th hot ng. - Khc nhm 1/B: Khng c ch Vmax ( knh K+). Nhm 2: Cc thuc phong ta th th b- adrenergic :Propranolol, Acebutolol, Esmolol, Practolol (Timolol) c ch chn lc b1. * c im tc dng: + Lm gim tnh t ng: + Gim tnh chu kch thch + Gim tc dn truyn xung, tng thi gian tr (y l tc dng chnh ca thuc ny). + Gim lc co bp t bo c tim. + Liu cao: Ging Quinidin, c ch dn truyn. * Ch nh: Nhp nhanh trn tht, rung nh, cung ng nh. Cn nhp nhanh kch pht trn tht. D phng cn nhp nhanh sau nhi mu c tim cp. * Ch phm liu : Inderal, Avlocardin vin 40mg, ung 2 - 4 vin/24h; ng 1mg/1ml, tim tnh mch 1 ng. Nhm 3: Bretylium (Bretylol) l thuc tc dng trn giao cm, lc u lm gii phng Noradreralin (NA) sau lm cn kit NA. Amiodaron (Cordaron): phong b a-, b, Sotalol (khng b - adrenergic). Bretyli-

um: * c im tc dng: ko di thi gian in th hot ng, tng thi gian tr, tng tnh t ng ca cc si Purkinje, i lp vi hin tng ti nhp (re entry) khng c ch co bp c tim. * Ch nh: Lon nhp tht trong nhi mu c tim,rung tht e da tnh mng bnh nhn khi khng thuc khc. Cordaron: * c im tc dng: Gim tnh chu kch thch, gim dn truyn trong nh v cc nt t ng. Tng thi gian tr, phong b c a-, b- giao cm, gin mch vnh. * Ch nh: Nhp nh nhanh, rung nh, cung ng nh. Ngoi tm thu tht, LN trong nhi mu c tim. - Suy mch vnh, cn au tht ngc (Angina pectoris). Nhm 4: Thuc chn knh calci Verapamil (Isoptin) D?iltiazem (Tildiem) * c im tc dng: . Lm chm xung tc ca nt dn nhp (pacemaker). . Gim dn truyn nh - tht. . Tng thi gian tr. . Khng hoc rt t nh hng n thn kinh thc vt. * Ch nh: . Lon nhp trn tht: y l thuc hng u iu tr cn nhp nhanh kch pht trn tht. . Cung ng nh, rung nh. *Chng ch nh: - Giai on cp ca nhi mu c tim. -Suy tim. -Nghn nh tht. * Ch phm - liu : Vim 120 mg, ung 1-3 vin/24h. ng 5mg, tim tnh mch 1 - 2 ng/24h. Cch la chn thuc iu tr lon nhp tim

BI 38. THUC CHNG TNG HUYT P 1. I CNG : 1.1. Khi nim chung : + Bnh tng HA l tnh trng tng HA tm thu v/hoc tng HA tm trng c hoc khng c nguyn nhn. + Thng chia lm 2 loi : - Tng HA th pht : khi tng HA ch l triu chng ca nhng tn thng mt c quan nh thn, ni tit, tim mch, noiu tr nguyn nhn, HA s tr li bnh thng. - Tng HA nguyn pht : khi nguyn nhn cha r, lc c gi l bnh tng HA. 1.2. C ch bnh sinh bnh THA : Huyt p= cung lng tim x sc cn ngoi vi. + Hai yu t ny li ph thuc vo hng lot cc yu t khc nhau nh : - Hot ng ca h TKT. - Hot ng ca h TKTV. - Hot ng ca v, tu tuyn thng thn. - Hormon ADH ?. - H renin - angiotensin - aldosteron. ADH = anti diuretic hormone - Tnh trng c tim. - Tnh trng thnh mao mch. - Khi lng mu. - Cn bng th dch. Mt yu t rt quan trng trong tng HA l lng cc ng mch nh v mao mch thu hp li, phn ln khng tm c nguyn nhn tin pht ca tng HA. Chnh v vy phi dng thuc tc ng ln cc khu ca c ch iu ho HA lm gin mch, gim lu lng tim dn n h HA. Tt c u l nhng thuc iu tr triu chng. 1.3. Phn loi thuc cha tng huyt p : Sau y l bng phn loi thuc iu tr tng HA theo v tr tc dng hoc c ch tc dng. 1.3.1. Thuc li niu : + Thuc li niu lm gim K+/mu : thiazid, li niu quai. + Thuc li niu gi K+/mu : spironolacton. 1.3.2. Thuc hy giao cm :

+ Tc dng trung ng : a-methyl dopa, clonidin + Thuc lit hch : trimethaphan. + Thuc phong ta neuron : guanethidin, reserpin. + Thuc chn beta : propranolol, metoprolol + Thuc hy a: prazosin, phenoxybenzamin 1.3.3. Thuc gin mch trc tip : + Gin ng mch : hydralazin, minoxidil, diazoxid + Gin cng mch v tnh mch : nitroprussid 1.3.4. Thuc chn knh Ca2+ : Nifedipin, felodipin, nicardipin, amlodipin 1.3.5. Thuc c ch enzym chuyn angiotensin : + Captopril, enalapril, ramipril + Thuc i khng ti receptor AT2 : losartan, ibesartan 1.4. Nguyn tc s dng : + Bnh tng HA ch yu l cha r nguyn nhn ( 95 % ), do cc thuc chng tng HA ch l thuc iu tr triu chng, v vy phi dng lin tc, lu di, khng c ngng thuc. + Vn phi hp thuc : - Khng phi hp cc thuc cng nhm. - Phi ?hp cc thuc khc c ch : tc dng trn cc receptor khc nhau. - Phi hp gim TDKMM ca thuc chng tng HA. 2. MT S NHM THUC : 2.1. Nhm thuc c ch enzym chuyn angiotensin ( ECA ) : Mi c dng t thp k 80 vi nhiu trin vng. 2.1.1. c im tc dng : Cc thuc c ch ACE khc nhau 3 im chnh : hiu lc, tc dng do bn thn cht m hoc do cht chuyn ho, dc ng hc; ging nhau : ch nh, chng ch nh, TDKMM. 2.1.2. Tc dng dc l : Lin quan n gim angiotensin II : + Lm gim sc cn ngoi bin, nhng khng lm tng nhp tim do c ch trng lc giao cm v tng trng lc ph giao cm. + Tc dng h HA t t, m du v ko di. + Lm gim c HA tm thu v tm trng. + Lm gim tnh trng thiu mu c tim do lm tng cung cp mu cho mch vnh.

+ Lm chm dy tht tri, gim hu qu ca tng HA. + Khng gy tt HA th ng, dng c cho mi la tui. + Trn TKT : khng gy trm cm, ri lon gic ng v suy gim tnh dc V vy thuc c ch nh tt trong tng HA v suy tim ( gim tin gnh, gim hu gnh ). 2.1.3. C ch tc dng Enzym chuyn angiotensin ( ECA ) hay bradykinase II l mt peptidase c tc dng : + Chuyn angiotensin I ( decapeptid khng c hat tnh ) thnh angiotensin II ( octapeptid c hat tnh ) l cht c tc dng co mch v chng thi tr Na+ qua thn. + Lm mt hat tnh ca bradykinin ( l cht gy gin mch v thi tr Na+ qua thn ). Sau khi c hnh thnh, angiotensin II s tc ng trn cc receptor ring, hin bit cc receptor AT1, AT2, AT3, AT4, trong ch c AT1 l c bit r nht. Cc receptor AT1 c nhiu mch mu, no, tim, thn, tuyn thng thn.Vai tr sinh l : co mch, tng gi Na+, c ch tit renin, tng gii phng aldosteron, kch thch giao cm, tng co bp c tim v phi tht tri. Cc receptor AT2 c nhiu tuyn thng thn, tim, no, c t cung, m bo thai.Vai tr sinh l : c ch s tng trng t bo, bit ha t bo, sa cha m, kch hat prostaglandin, bradykinin v NO ( nitric oxyd ) thn. Cc thuc ny c ch ECA nn lm cho angiotensin I khng chuyn c thnh angiotensin II ( c hat tnh gy co mch ) v cng ngn cn ging ha bradykinin, lm tng tng hp cc prostaglandin v NO. Ngoi ra n cn c ch gii phng aldosteron ( mt cht khng li niu ), do lm gim th tch dch, ng thi gin mch ngoi vi. Kt qu l lm gin mch, tng thi tr Na+ v h HA. 2.1.4. Ch nh : + Cc th tng HA. + Suy tim sung huyt sau phu thut v nhi mu c tim. 2.1.5. Chng ch nh : + Ph n c thai ( gy qui thai, thai cht ) + Suy thn nng, hp ng mch thn. + Mn cm vi thuc 2.1.6. TDKMM : + Gy h HA ( thng gp liu u tin ), c th tt HA th ng. + Suy thn

cp, nht l trn bnh nhn c hp ng mch thn. + Tng K+/mu khi c suy thn hoc i tho ng, c bit r khi dng km vi thuc li niu gi K+/mu v thuc phong ta beta. + Gy ho khan ( khng ph thuc liu , ht sau khi ngng thuc ) v ph mch th?n kinh ( vng mi, hng, thanh qun, mi, li ) : do bradykinin khng b ging ha, prostaglandin tch ly phi gy ho. + c tnh : d ng, st, gim bch cu ( hay gp vi nhng cht c nhm sulhydril nh captopril ), thay i v gic. 2.1.7. Phn loi v dc ng hc : a- Thuc c ch ECA : Bng : c im dc ng hc ca mt s thuc c ch ECA Enalapril, perindopril, benazepril u l cc tin thuc, vo c th phi c gan chuyn ha mi c tc dng. b- Thuc c ch ti receptor ca angiotensin II : Do vic chuyn angiotensin I thnh angiotensin II cn c s tham gia ca cc enzym khc ( nh chymase ) khng chu s tc ng ca cc thuc c ch ECA nn s to thnh angiotensin II vn cn. Mt khc, do thuc c ch ECA ngn cn s ging ha ca bradykinin nn bradykinin phi tng, kch ng nim mc kh ph qun, gy cn ho khan rt kh iu tr. V th thi gian gn y, ngi ta bt u dng loi thuc c ch receptor AT1 ca angiotensin II. Ch nh v chng ch nh tng t cc thuc c ch enzym chuyn angiotensin nhng c u im khng gy ho, ph mch v khng lm bt hot bradykinin. BI 39. THUC IU TR RI LON LIPOPROTEIN MU 1. I CNG Tng lipoprotein mu l mt yu t gy nn va x ng mch v bnh mch vnh. iu tr ri lon lipoprotein mu, ngoi thay i ch n, c bit l n t lipid, tng cng hot ng th lc l nhng bin php rt quan trng, th khng th thiu c cc thuc h lipopro tein mu. 1.1. Cu trc v phn loi lipoprotein trong mu, cc lipid khng tan c, v vy phi kt hp vi protein nh lin kt Van

der-Walls to thnh lipoprotein. Nh to thnh lipoprotein, tan c trong nc vn chuyn n cc m. Lipoprotei n c dng hnh cu vi ng knh 100 -500 A gm 2 thnh phn chnh: - Phn a nc (phn v ) cha apoprotein, cholesterol t do v phospholipid . - Phn k nc (trung tm) cha cholesterol este ho, triglycerid. Protein gn vo cc lipid c ngun gc t i nim mc rut hoc ti gan gi l apolipoprotein. Da vo cu trc cc acid amin, phn t lng v cc chc nng, apolipoprotein c xp thnh cc nhm khc nhau theo th t ch ci A, B, C, D, E. Trong mi nhm, li c xp thnh di nhm, v d nhm A gm A1, A2, A4; nhm B gm B48, B100; C gm C1, C2, C4 v nhm E gm E1, E2, E4. Do t l protein v lipid khc nhau nn t trng dao ng t 0,9 n trn 1,2. Da vo t trng, lipoprotein c xp thnh 5 loi c chc nng khc nhau. - Ht vi th dng chp (chylomicron) - Lipoprotein t trng rt thp (VLDL: very low density lipoprotein) - Lipoprotein t trng thp (LDL: low density lipoprotein) - Lipoprotein t trng trung bnh (IDL: intermediate density lipoprotein) - Lipoprotein t trng cao ( HDL: high density lipoprotein) Trong mi t bo, c bit l t bo gan, t bo ni m mao mch c cha b phn nhn cm c hiu LDL gi l LDL -receptor. Receptor ny c chc nng nhp LDL vo trong t bo v gii phng lipid thng qua enzym trong lysosom . Khi lng cholesterol trong t bo tng cao so vi nhu cu, s tng hp LDL receptor mng t bo gi i m xung. Ngc li, khi lng cholesterol trong ni bo gim, th s tng hp LDL -receptor mng t bo tng ln. Cho n nay, c ch vn chuyn choles terol ca HDL vn cn cha c bit r. Theo mt s tc gi, th di tc dng ca lecithin cholesterol acyltransferase (LCAT), cng vi s hot ha apolipoprotein AI, cholesterol t do ca VLDL v LDL b ester ha i vo phn trung tm khng phn cc ca HDL; HDL s vn chuyn cholesterol ny n gan v b chuyn ha. HDL c vai tr rt quan trng trong bnh va x ng mch, khi HDL trong mu < 0,3g/l, th t l va x ng mch cao v ngc li khi nng HDL > 0,76 g/l th t l va x ng mch rt t hp. Mt thuc h lipoprotein tt l thuc

lm gim mnh LDL v gy tng HDL r rt. Mi t bo cng t tng hp cholesterol t acetyl CoA nh hydroxymethyl glutaryl - CoA - reductase (HMG - CoA - reductase). Hot tnh ca enzym ny b gim khi lng cholesterol trong t bo tng cao v ngc li, hot tnh tng khi lng cholesterol trong ni bo gim xung. 1.2. Tng lipoprotein mu v phn loi s tng lipoprotein mu c th bnh thng, nng cc lipoprotein trong mu tn ti trong trng thi cn b ng ng. Khi c ri lon trng thi cn bng ng ny s gy nn ri lon chuyn ha lipoprotein mu. S ri lon c th do: - Tng cng cholesterol, triglycerid ngoi sinh. - Ri lon chc nng xc tc chuyn ha lipoprotein ca lipoproteinase. - Yu t ton thn lm tng chuyn ha glucid, protid tng hp lipid v tng hot ng ca s hormon lm gim thu phn lipid trong c, gan v m nh bnh i tho ng, hi chng thn h, tng ure mu, suy gip, nghin ru, dng thuc trnh thai, corticoid , c ch - giao cm - Yu t di truyn: mt s ngi c ri lon chuyn ha lipoprotein, mang tnh cht di truyn. nhng ngi ny, thy c s gim s lng LDL -receptor hoc gim cht lng receptor ny. Da vo tng cc loi lipoprotein s tng l ipoprotein mu c chia thnh 6 typ khc nhau: I, IIa, IIb, III, IV v V. n nay, 99% hi chng tng lipoprotein mu thuc typ IIa, IIb v IV. Nhiu thuc h lipoprotein c nghin cu v c dng trn lm sng vi nhiu c ch khc nhau, nhng cha c thuc no c tc dng tt trn tt c cc typ ca ri lon lipoprotein mu. 2.THUC IU TR RI LON LIPOPROTEIN MU Da vo c ch tc dng trn lipoprotein, thuc c chia thnh 2 nhm chnh: - Lm gim hp thu v tng thi tr lipid - Lm gim tng hp lipid. 2.1. Thuc lm gim hp thu v tng thi tr lipid L nhng thuc c tnh hp th mnh, to phc vi acid mt, lm gim qu trnh nh ha cc lipid rut, dn n gim hp thu v tng thi lipid qua phn. Ngoi ra, cc thuc nhm ny gin tip lm tng chuyn ha cholesterol

to thnh acid mt thng qua s thot c ch hydroxylase microsom gan (hydroxylase l enzym iu ha tng hp acid mt t cholesterol b c ch bi acid mt), v lm tng s lng v hot tnh LDL receptor mng t bo. 2.1.1. Cholestyramin L cht nha trao i ion, c tnh base mnh, khng tan trong nc, ung hu nh khng hp thu qua ng tiu ha, nhng khng nh hng n cc enzy?m cc ng tiu ha. Do c s trao i ion clo vi acid mt mang in m to nn phc hp nha gn acid mt khng hp thu lm tng thi acid mt qua phn; c ch chu kz gan rut ca acid mt lm tng s tng hp acid mt t cholesterol bi s thot c ch hydroxylase. Do gim acid mt nn thuc cng lm gim s hp thu sterol ngun tng hp cholesterol.. Thuc bt u c tc dng h LDL trong mu sau khi dng 4 -7 ngy v tc dng ti a trong vng 2 tun. Trn hu ht bnh nhn, thuc lm tng triglycerid t 5 20% so vi trc khi iu tr, nhng dn dn s tr v gi tr ba n u trong vng 4 tun. Cholestyramin lm tng HDL -cholesterol khong 5% v gim LDL cholesterol khong 10 - 35% tuz theo liu lng, v c ch nh tt bnh nhn tng lipoprotein mu typ IIa. Do to c phc vi acid mt, nn thuc c th gy ri lon ng tiu ha nh: bun nn, y bng, to bn, h prothrombin. Ngoi ra do tnh hp thu mnh, nn thuc cn lm gim hp thu mt s thuc khi dng cng ng ung nh: digitoxin, pheylbutazon, phenobarbital, clorothiazid, thuc chng ng dn xut c oumarin, thyroxin. trnh tng tc thuc, nhng thuc trn nn ung mt gi trc hoc 4 gi sau khi dng cholestyramin. + Ch phm v liu dng: - Cholestyramin (Questran) gi bt 4g, ung 16 -32 gam trong 24 gi chia lm 2 - 4 ln. 2.1.2. Colestipol L polyme ca diethylpentamin v epiclohydrin, tan trong nc, ht m rt mnh. Tc dng, c ch tc dng v tc dng khng mong mun ging nh cholestyramin. Ch phm: Colestipol (Colestid) gi 5 gam hoc vin 1 gam, ung 10 -30 gam/24 gi, chia 2 -4 ln. Thuc c ch nh trong tng lipoprotein mu typ II. 2.1.3. Neomycin

L khng sinh nhm aminoglycosid, ung lm h lipoprotein mu, c bit l h LDL - cholesterol (khng ph thuc vo tc dng khng khun) v c ch nh trong tng lipoprotein mu typ IIa . - Ung liu 0,5 - 2g/24 gi. - Tc dng khng mong mun (xin c bi Khng sinh). 2.1.4 .Ezetimib L thuc c ch s hp thu cholesterol rut c dng ring r hoc phi hp vi dn xut statin trong trng hp tng cholesterol mu do ch n hoc do di truyn vi liu 10 mg /ngy. Khi dng thuc c th gp mt s tc dng khng mong mun nh: a chy, au bng, au u, ph mch v pht ban. Khng dng thuc cho tr em di 10 tui v ngi gim chc nng gan . 2.2. Thuc lm gim tng hp lipid Gm nhng dn xut ca acid fibric ( bezafibrat, ciprofibrat, fenofibrat v gemfibrozil); dn xut statin (pravas tatin, simvastatin, lovastatin, rosuvastatin); acid nicotinic; probucol. Cc dn xut acid fibric tng hot tnh lipoproteinlipase, cc dn xu t statin c cu trc gn ging vi HMG -CoA nn c ch cnh tranh HMG -CoA-reductase (hydroxymethylglutaryl - CoA- reductase) lm gim tng hp cholesterol, ng thi cng lm tng sinh LDL -receptor mng t bo. Acid nicotinic l mt vitamin dng iu t r bnh Pellagra, nhng cng lm h lipoprotein mu. Tc dng ny c thng qua bi s tng sinh LDL -receptor v c ch s tch t AMP trong m, tng hot tnh triglyceridlipase lm gim LDL cholesterol. Probucol c cu trc ha hc hon ton khc vi nh m thuc trn, c ch tc dng ca thuc vn cn cha c gii thch y . Nh?iu nghin cu chng minh thuc lm tng chuyn ha LDL -cholesterol khng thng qua LDL -receptor v ngi tng lipoprotein mu c thiu ht LDL -receptor do di truyn, thu c vn cn tc dng. C tc gi cho rng probucol ngn cn oxy ha ca acid bo v lm gim kh nng tip nhp LDL ca t bo ni m. 2.2.1. Acid nicotinic (Vitamin PP, Vitamin B3, Niacin) L vitamin tan trong nc, c nhiu trong gan, tht, c, rau, qu v ng cc. Vi

khun rut c th tng hp mt lng nh vitamin PP. Ngoi vai tr NAD, NADP tham gia vo chuyn ha protid, glucid v oxy ha trong chui h hp t bo cc m, acid nicotinic cn lm h lipoprotein mu r rt. Sau 1 - 4 ngy iu tr, vi tamin PP lm gim triglycerid 20 - 80%. i vi LDL cholesterol, thuc c tc dng r sau 5 - 7 ngy. Sau 3 - 5 tun iu tr thuc c tc dng ti a. C ch tc dng ca thuc c th do gim sn xut v tng thi VLDL, c ch phn hu lipid, gim cung cp acid bo cho gan, gim tng hp triglycerid, gim vn chuyn triglycerid, VLDL v gim sn xut LDL. Thuc gy tng HDL -cholesterol nhng c ch cha r rng. Khi thiu ht vitamin PP nng s gy bnh pellagra c biu hin vim da, a chy v ri lon tr nh. - gim tc dng khng mong mun c bit l nng bong ,nga na ngi trn ca thuc, nn ung thuc vo ba n vi liu tng dn, khi u 300 -600 mg chia lm 3 ln trong ngy sau 3 - 4 tun s dng liu duy tr 2 -6 g/ngy. Mt s tc gi kh uyn nn ung aspirin 160 - 325 mg/24 gi cng c th lm gim tc dng khng mong mun ca acid nicotinic. Thuc c ch nh trong tng lipoprotein mu typ II, III, IV v V. Nn phi hp vi cholestyramin v colestipol trong iu tr s gim c liu l ng v gim tc dng khng mong mun ca thuc. Ngoi ra, vitamin PP cn c ch nh trong trng hp thiu mu v ph n dng thuc trnh thai. 2.2.2. Dn xut ca acid fibric Cc thuc nhm ny hp thu tt qua ng tiu ha, gn mnh vo protein huy t v c tc dng rt khc nhau trn lipoprotein mu, nhng c cng mt c ch chung l tng hot tnh lipoprotein lipase trong t bo c bit l t bo c, dn n lm tng thu phn triglycerid v tng thoi ha VLDL. S tng HDL cholesterol vi c ch cha r rng. Cc ch phm fenofibrat (Lypanthyl), bezafibrat (Bezalip), gemfibrozil (Lopid) v ciprofibrat ( Lipanor) ang c u tin la chn s dng trong tng triglyceride nhng do cn c tc dng trn LDL nn cn c dng trong tng lipoprotein t yp II, III, IV v V vi liu lng t 200 mg -1200 mg tuz tng ch phm.Thuc c rt t tc dng khng mong mun, tuy nhin c th gp ri lon tiu ha, au u, chng mt, mt mi v au c, tiu c vn( c bit ngi gim chc nng thn), thiu mu, t ng nh transaminase, gim phosphatase kim. - Chng ch nh ging nhau vi tt c cc thuc cng nhm:

+ Gim chc nng gan, thn v si mt. + Ngi c thai, cho con b, tr em di 10 tui. 2.2.3. Dn xut statin Cc thuc nhm ny c ch HMG -CoA nn lm gim LDL-cholesterol t 25 45% tuz theo tng thuc v liu lng. Tc dng h triglycerid k m hn dn xut acid fibric nn c la chn u tin trong nhng trng hp tng cholesterol mu c bit typ II, III, IV v V. Do i qua c d c rau thai v sa n n thuc khng dng cho ngi c chc nng gan, thn gim nng, ph n c thai v cho con b, tr em di 18 tui v thuc c th gy bt thng xng ca sc vt th nghim . Dng lu di thuc gy tng transaminase gp 3- 4 ln bnh thng, ngng thu c enzym li tr v bnh thng. Khi iu tr cn theo di chc nng gan v creatinin phosphokinase. + Thuc c tc dng khng mong mun ging nhau: - au c, tiu c vn, sn nga, au u, chng mt, ri lon tiu ha v tng cao transaminase trong mu. - Cc thuc trong nhm c tm tt trong bng 30.1. Bng 30.1: Ch phm v liu lng mt s thuc trong nhm statin

2.2.4. Probucol (Lorelco, Lurselle) C cu trc hon ton khc vi cc thuc nu t rn. Rt tan trong lipid nhng hp thu km. Thc n lm tng s hp thu thuc. Do tan trong lipid, nn thuc ng li lu trong c th. Sau khi ngng thuc 6 thng, nng thuc ch gim 80% so vi nng ti a trong mu. Thuc lm h LDL -C tht thng, khng lm h triglycerid. Thuc gy h HDL-cholesterol mnh v ko di nn n ch c la chn trong iu tr sau cc thuc khc. Probucol l cht chng oxy ha mnh nn c tc dng chng x va mnh sc vt th nghim. Khi dng thuc c th gp mt s tc dng khng mong mun: a chy, y bng, au bng, bun nn. Khng dng thuc nhng bnh nhn mi b nhi mu c tim, c khong QT C ko di, ph n c thai, cho con b, tr em di 18 tui, ang dng cc thuc chng lon nhp tim nhm I, III, chng trm cm loi 3 vng, dn xut phenothiazin. - Vin 250 mg, ngy ung 500mg chia 2 ln. 2.2.5. D-Thyroxin

D-Thyroxin l ng phn quay phi ca L -Thyroxin mt mt s tc dng ca hormon tuyn gip, nhng li c tc dng h lipoprotein mu mnh do tng chuy n cholesterol thnh acid mt v tng thi sterol qua phn. c ch nh cho tr em c lipoprotein mu cao. Khng dng cho ngi c bnh tim v d c cn nhi mu c tim v cn au vng trc tim. Liu khi u 1mg, sau tng dn, ti a 4-8 mg/24 gi. Vi liu ny, khng thy c phn ng c hi. 2.2.6. Cc acid b o khng no a tr h omega 3 Trong du mt s loi c c bit l c hi, c ng, c trch, c thu c cha mt s acid b o khng no a tr h Omega 3 c tc dng lm gim triglycerid v VLDL nh ng t nh hng n LDL v HDL -cholesterol trong mu. C 2 acid bo khng no h Omega 3 hay dng l: -Omega-3-acid ethylesters: 1 gam bit dc Omacor 90% omega -3-acid ethylesters cha 46% acid eicosapentaenolic(EPA) , 38 % acid docosahexaenoic (DHA) v 4 mg - tocopherol. -Omega-3-marin triglyceride: 1 gam bit dc Maxepa cha170 mg acid eicosapentaenolic(EPA), 115 mg acid docosahexaenoic (DHA) v di 100 n v vitamin A v 10 n v vitamin D. Liu lng cc ch phm xin xem t hng dn s dng thuc. hn ch s tng v gip h triglycerid v cc lipoprotein mu, nn tng cng n c, c bit l c hi, c thu, c ng, c trch trung bnh 30g/ngy hoc 3 ln/tun. 2.2.7.Mt s thuc iu tr ri lon lipoprotein mi - Hai thuc mi ang c th nghim trn lm sng pha II v III ngi c ri lon lipoprotein mu: + BMS-201038 l cht c ch microsomal triglycerid transfer protein lm gim s vn chuy n triglycerid v cc lipid khng phn cc n apolipoprotein v gim s bi tit triglycerid t rut dn n gim triglycerid v VLDL -cholesterol. + Avasimibe : thuc c ch ACAT1 v ACAT2(cholesterol acyltransferase) lm gim s ester ho cholesterol gan, rut, i thc bo v gim tng hp acid mt thng qua s cm ng hydroxy lase gy nn gim chylomicron, VLDL, LDL cholesterol v triglycerid. 3. NGUYN TC IU TR RI LON LIPOPROTEIN MU hn ch nguy c gy bnh tim mch cn phi h LDL v tng HDL trong

mu. Theo mt s nghin cu cho thy mun ngn chn c bnh mch v nh nguyn pht hoc th pht cn phi gim cholesterol ton phn trong mu 20 25 % hoc LDL khong 30 %. Nhm t hiu qu iu tr cn phi p dng mt s nguyn tc sau: - Trc tin phi c ch n thch hp duy tr trng lng bnh thng v gi m lipoprotein mu. nhng ngi c ch s khi c th (BMI body mass index ) cao hn bnh thng, cn c ch n cha < 300 mg cholesterol, acid bo bo ho chim 10%, acid bo khng bo ha 10 -15%, glucid 50 - 60% v protein chim 10 - 20% tng s calo/ngy. - iu tr nguyn nhn gy tng lipoprotein mu nh: i tho ng, suy gip, hi chng thn h, tng ure mu. - Gim hoc chm dt cc nguy c gy tng lipoprotein mu nh: ht thuc l, ung ru, dng cc thuc corticoid, thuc trnh thai, t huc c ch adrenergic. - Tng cng hot ng th lc. - Sau 3 - 6 thng thay i ch n, tng cng hot ng th lc v iu tr cc nguyn nhn v loi b cc nguy c m lipoprotein mu vn cao th phi dng thuc h lipoprotein mu. - Tuz theo c ch tc dng, cc thuc c th c dng ring r hoc phi hp 2 hoc 3 thuc c c ch khc nhau t c tc dng hip ng trong iu tr nh : + Cholestyramin vi dn xut statin; + Cholestyramin phi hp vi acid nicotinic hoc cho lestyramin phi hp vi dn xut statin v acid nicotinic. + Cc thuc thuc dn xut statin c la chn trc tin cho tng cholesterol cn dn xut acid fibric u tin cho trng hp tng triglycerid. Hai dn xut ny c th dng ring r hoc k t hp trong nhng trng hp tng lipoprotein hn hp. Nhng phi thn trng v theo di tc dng khng mong mun, c bit l du hiu tiu c vn. Do c tng nguy c tiu c vn nn gemfibrozil v dn xut statin khng dng phi hp trong iu tr. - Trong qu trnh iu tr, ngoi vic thng xuyn theo di lng lipoprotein mu nh gi hiu qu iu tr, bnh nhn cn c theo di tc dng khng mong mun do thuc gy ra nh vim c, tiu c vn, tng transaminase, ri lon in tim v.v

BI 40. THUC IU TR THIU MU 1. I CNG 1.1. nh ngha thiu mu Thiu mu l tnh trng gim s lng hng cu hoc huyt sc t hoc hematocrit di mc bnh thng so vi ngi cng tui, cng gii kho mnh. - i vi nam gii c coi l th iu mu khi: s lng hng cu di 4 triu hoc hemoglobin di 12 g/ 100 mL hoc hematocrit di 36%. - i vi n gii c coi l thiu mu khi: s lng hng cu di 3,5 triu hoc hemoglobin di 10 g/ 100 mL hoc hematocrit di 30%. 1.2. Nguyn nh u n th iu mu Thiu mu do rt nhiu nguyn nhn c th : do chn thng, sau phu thut, do giun mc, tc, rong kinh, tr, lo t d dy - t trng, do tan mu ngi c bt thng v hemoglobin, thiu G 6PD, bnh t min, do thuc hoc ha cht, st rt hoc do tu xng k m hot ng hoc khng hot ng hoc do thiu ht cc thnh phn tng hp hemoglobin, sn xut hng cu. Da vo ch s nhim sc v kch thc hng cu thiu mu c xp thnh 3 loi: . Thiu mu nhc sc: hng cu nh v ch s nhim sc < 1 . Thiu mu ng sc: hng cu bnh thng v ch s nhim sc = 1 . Thiu mu u sc: hng cu to v ch s nhim sc > 1 2. NGUYN TC IU TR THIU MU Trong qu trnh iu tr thiu mu phi kt hp iu tr nguyn nhn vi dng thuc hoc vi iu tr triu chng v bi dng c th. - Trng hp mt mu cp vi khi lng ln: cn phi truyn mu ngay. Trong khi ch i mu phi truyn nc mui sinh l hoc Ringer lactat v tm nguyn nhn, v tr chy mu iu tr. - Mt mu mn tnh do giun tc , mc, rong kinh, tr, st rt dng cc thuc iu tr nguyn nhn kt hp vi b sung st v bi dng c th. - Thiu mu do gim sn xut hng cu: c th da vo th tch trung bnh hng cu dng cc thuc. Hng cu nh khi th tch trung bnh di 70 fl. Ngc li hng cu gi l to khi th tch trung bnh > 110 fl. . Trng hp thiu mu hng cu nh: dng st kt hp vi vitamin B 6 v tng lng protid, lipid trong khu phn n v iu tr nguyn nhn. . Thiu mu hng cu to phi tm nguyn nhn iu tr kt hp dng B 12 hoc

acid folic. . Thiu mu do tan mu: dng cc phng php hn ch nguyn nhn gy tan mu kt hp vi dng acid folic. 3. CC THUC CHA THIU MU 3.1. St 3.1.1. Vai tr v nhu cu st ca c th C th ngi ln cha khong 3 - 5 gam st, trong 1,5 - 3 gam tn ti trong hng cu, phn cn li 0,5 gam cha trong sc t c (myoglobulin), mt s enzym xanthinoxidase, - glycerophosphatoxidase. ngi bnh thng, nhu cu st hng ngy khong 0,5 - 1 mg . Ph n giai on ngi bnh thng, nhu cu st hng ngy khong 0,5 - 1 mg . Ph n giai on 6 mg trong 24 gi. Khi thiu ht st, c th khng ch c thay i s to mu, m cn thay i chc nng ca nhiu enzym quan trng. Do vy, b sung st l bin php rt quan trng iu tr thiu mu nhc sc. 3.1.2. ng hc ca st trong c th Ngun cung cp st hng ngy cho c th ch yu t cc thc n c ngun gc ng vt v thc vt. Thc n cha lng st trn 5 mg trong 100 gam: gan, tim, trng, tht nc, gi u, hoa qu. * d dy: st t ngun thc n c th dng ion Fe 2+ hoc Fe3+. Fe2+ c hp thu d dng qua nim mc d dy, rut; cn Fe 3+ s kt hp vi albumin nim mc ng tiu ha, nn khng hp thu c, gy kch thch nim mc ng tiu ha. Mun hp thu c, Fe3+ phi c chuyn thnh Fe 2+ nh tc dng ca acid hydrocloric d dy. * Ti rut: Fe2+ c gn vi mt albumin t bo nim mc rut l apoferritin to thnh ferritin i vo mu.? Apoferritin l cht mang st, c nhim v a st vo mu xong quay tr li nim mc rut vn chuyn tip st. Khi c th thiu st th s lng apoferritin tng ln lm tng hp thu st v ngc li. Mt s cht nh vitamin C, protein c cha nhm - SH lm Fe3+ chuyn thnh Fe 2+ d hp thu. Nhng c mt s cht cn tr hp thu nh: phosphat, acid nucleic, acid phytic, tanin, tetracyclin. * Trong mu: st tch ra t ferritin v c gn vi - globulin, cht vn chuyn st c hiu to thnh transferritin. Dng phc hp st c chuyn

n cc m nh tu xng, c mt phn dng d tr cn mt phn to ra hng cu v cc enzym (Hnh 28.1). * m: st i vo trong t bo c phi thng qua transferritin receptor mng t bo. Nh qu trnh nhp bo, phc hp transferritin receptor i vo trong t bo gii phng ra ion st. Sau khi gii phng st trong ni bo, transferritin quay li mng t bo lm nhim v vn chuyn st tip. Khi thiu ht st th s lng transferritin receptor tng v gim ferritin (gim d tr st) v ngc li, khi lng st trong c th tng cao th s lng transferritin receptor gim xung v tng dng d tr st ln (ferritin) v tng thi tr st qua phn, m hi v nc tiu.

Hnh 28.1. S vn chuyn st trong c th 3.1.3. S thiu ht st S thiu ht st c th do: - Cung cp khng y , gp nhng ngi c mc sng thp. - Mt cn bng gia cung v cu: ph n c thai, cho con b, tr em ang ln. - Gim s hp thu st ng tiu ha: gp nhng ngi ct mt phn d dy, vim rut, thiu apoferritin, dng mt s thuc hoc thc n cha mt s cht ngn cn s hp thu st. - Chy mu: ng tiu ha (giun tc, giun mc, tr), t cung cp hoc mn tnh (rong kinh) 3.1.4. Ch nh - Thiu mu thiu st do cc nguyn nhn khc nhau. - Ph n c thai, cho con b, chng xanh lt ca ph n. 3.1.5. Ch phm v liu lng Trong iu tr st c th dng ring r hoc phi hp vi mt s ion hoc v cc vitamin. Trn lm sng s t c th dng ng ung hoc tim tnh mch chm. Tim tnh mch khi bnh nhn khng dung np hoc ri lon hp thu st theo ng ung hoc ngi suy

thn mn tnh km theo phi lc mu. Hin c 2 ch phm st dextran v st sucrose dng tim chm tnh mch hoc truyn tnh mch. Khi dng cn phi th vi liu thp trc phng phn ng phn v. Cc ch phm st thng dng ng ung trn lm sng u dng mui sulfat, clorid, fumarat, gluconat, aminoat v ascorbat. - Ngi ln liu trung bnh 2 -3 mg/ kg cn nng tng ng 200 mg/ ngy. - Tr nh liu trung bnh 5 mg/ kg cn nng/ ngy. - Ph n c thai hoc cho con b liu trung bnh 4 - 6 mg/ kg cn nng/ ngy. Trong qu trnh iu tr cn theo di lng hemoglobin. Khi hemoglobulin mu tr v gi tr bnh thng cn tip tc ung thuc trong 3 -4 thng to s bo ho d tr st. 3.1.6. Tc dng khng mong mun - Khi dng ng ung: lm ging, bun nn, nn, to bn, a chy, kch ng ng tiu ha. - Khi dng ng tim: au ti ch tim , a?u u, bun nn, nn, st, shock kiu phn v khi tim tnh mch do vy khi dng cn phi tim tnh mch chm. 3.1.7. S qu liu lng Ng c st do qu liu t gp ngi ln, nhng hay gp tr em. tr em liu 1- 2 g c th gy t vong. Triu c hng ng c c th xut hin sau khi ung nhm 30 pht n vi gi. - Khi gp ng c, ngoi bin php iu tr tch cc v iu tr triu chng, cc bin php loi tr cht c nh gy nn, ra rut bng dung dch natribicarbonat hoc phosphat cng c s dng. Khi st trong mu cao trn 3,5 mg/ L phi dng deferoxamin tim tnh mch hoc tim bp hoc c th dng deferipron ng ung. Hai thuc ny c tc dng to chelat vi ion st. 3.2. Vitamin B12 3.2.1. Ngun gc Vitamin B12 l tn chung ch 5 cobalami d: cyanocobalamin, hydroxycobalamin, methyl cobalamin v 5 - deoxyadenosylcobalamin.Vitamin B 12v cyanocobalamin c dng ch tt c cc cobalamid c hot tnh ngi. Nhng trn thc t ch c 2 cobalamid: cyanocobalamin v hydroxycobalamin c dng trong iu tr v cc cobalamid ny ng vai tr coenzym ca nhiu phn ng chuyn ha, c bit

l s tng hp ADN. Hn th na, cc cobalamid ny n nh hn cc cobalamid khc. T bo c th khng t tng hp c vitamin B 12. Ngun cung cp vitamin B 12 nhiu nht l gan, tht, c, trng. Trong thc vt khng c vitamin B 12. 3.2.2. Dc ng hc ca vitamin B 12 Trong thc n vitamin B 12 (yu t ngoi lai) c dch v v protease gii phng ra khi cc lin kt vi protein v c gn ngay vi glycopro tein d dy (yu t ni). Phc hp vitamin B12- yu t ni xung rut tc ng ln receptor c hiu trn nim mc hng trng v c chuyn vo mu. Trong mu vitamin B 12 gn vo - globulin c ngun gc gan gi l transcobalamin II. Phc hp vitamin B12- transcobalamin nhanh chng c phn phi vo cc m c bit l nhu m gan. Ngoi transcobalamin II, vitamin B 12 cn c gn vo transcobalamin I v III. Phc hp transcobalamin I - B12 l dng d c gn vo transcobalamin I v III. Phc hp transcobalamin I - B12 l dng d 10 mg). Vitamin B12 c thi tr qua phn, nc tiu. V c chu kz gan rut, cho nn c trng hp sau ct d dy 3- 4 nm mi c biu hin thiu vitamin B 12. 3.2.3. Vai tr ca vitamin B 12 Vitamin B12 l cht cho methyl nn r t cn cho s chuyn ha acid folic tng hp acid nhn gip cho t bo nhn ln pht trin. - Chuyn homocystein thnh methionin v 5 -methyltetrahydrofolic thnh acid tetrahydrofolic. - Chuyn L- methylmalonyl - CoA thnh succinyl - CoA trong chui cc ph n ng chuyn ha glucid, lipid thng qua chu trnh Krebs. - Duy tr nng myelin bnh thng trong cc neuron ca h thng thn kinh. 3.2.4. Thiu ht vitamin B 12 Nhu cu hng ngy ca vitamin B 12 ph thuc vo tui, gii, tnh trng bnh l v nm trong khong t 0,3- 2,6 g. Thiu vitamin B 12 c th do: Cung cp khng y , gim hp thu do gim yu t ni, vim rut, ct hng trng, bnh ty tng gy thiu protease, t sinh khng th chng yu t ni, ri lon chu kz gan rut hoc do gim s lng, cht lng transcobalamin II do di truyn. Khi thiu vitamin B 12 gy nn thiu mu u sc hng cu to (thiu mu c tnh Biermer), t?n thng neuron h thn kinh: ph n, mt myelin. C th gy cht neuron thn kinh tu sng, v no, gy ri lon cm gi c, vn ng

 chi, ri lon tr nh, ri lon tm thn. ngi cao tui c th gp tn thng thn kinh do thiu vitamin B 12 nhng khng c du hiu thiu mu. 3.2.5. Ch nh- chng ch nh - Thiu mu u sc hng cu to Biermer. - Vim au dy thn kin h, ri lon tm thn. - Suy nhc c th, chm pht trin, gi yu. - Nhim c, nhim khun. - Khng dng thuc cho ngi d ng vi thuc v ung th cc th khc nhau. 3.2.6. Ch phm v cch dng Vitamin B12 c th dng di dng n cht hoc kt hp v i cc vitamin v cc mui kim loi ung hoc tim bp hay tim di da. Hin nay c 2 ch phm c dng vi hm lng khc nhau l cyanocobalamin v hydroxycobalamin nhng hydroxycobalamin c s dng nhiu hn v tn ti trong c th lu hn cyanoco balamin. Ch nh dng dng thuc v liu lng da vo nguyn nhn v tn thng do thiu vitamin B12 gy ra. - Thiu ht vitamin B 12 do yu t ni phi dng dng tim. - Trong iu tr thiu mu, suy nhc c th ch cn dng liu trung bnh 100 g/ ngy, nhng trong trng hp vim dy thn kinh, ri lon tr nh, ri lon tm thn phi dng dng tim liu 500, 1000, 5000 g/ ngy. 3.3. Acid folic (vitamin L 1, vitamin B9) L s kt hp ca pteridin, acid paraaminobenzoic v acid glutamic. Acid folic khng ch c nhiu trong tht, c, trng, gan, men bia m cn c trong rau xanh, hoa qu. Khi nu chn thc n, c bit l rau xanh 90% acid folic b phn hy. 3.3.1. Dc ng hc v vai tr ca acid folic Acid folic trong thc n tn ti di d ng folatpolyglutamat. Dng ny cng l kho d tr folat trong cc t bo ngi. * ng tiu ha, folatpolyglutamat b thu phn to thnh folat monoglutamat v b kh to thnh methyltetrahydrofolat (MTHF). Nh hot tnh ca enzym pteroyl - - glutamyl- carboxypeptidase nim mc rut, MTHF c hp thu v i vo mu. * Trong mu, methyltetrahydrofolat c vn chuyn n m v thng qua nhp bo, MTHF vo trong t bo.

* Trong t bo ca m, methyltetrahydrofolat ng vai tr cht cho methyl ch uyn vitamin B12 thnh methylcobalamin. Methylcobalamin gip chuyn homocystein thnh methionin. Sau khi mt methyl, methyltetrahydrofolat s thnh tetrahydrofolat, tham gia vo mt s qu trnh chuyn ha quan trng nh: - Chuyn serin thnh glycin vi s tham gia ca vitamin B 6. - Chuyn deoxyuridylat thnh thymidylat to ADN - thymin. Ngoi ra, tetrahydrofolat cn tham gia vo qu trnh chuyn ha histidin v tng hp base purin. * gan, methyltetrahydrofolat mt phn tham gia chuyn ha, phn khc c a vo mt thi xung t trng. t trng, MTHF c ti hp thu tr li. Ru lm gii phng MTHF t t bo gan vo mt lm gim nng folat trong mu (hnh 29.2)

Hnh 29.2. Vai tr ca acid folic v vitamin B 12 trong chuyn ha 3.3.2. S thiu ht acid folic - Hng ngy, ngi ln cn 25 - 50 g, ph n c thai, cho con b v tr em cn 100 200 g. Khi cung cp khng y hoc do mt cn bng gia cung v cu hoc do mt s bnh lm gim hp thu hoc do mt s thuc khng chuyn? ha trong iu tr ung th, primaquin, trimethoprim, sulfonamid hoc do tan mu gy nn thiu ht acid folic. Khi thiu ht acid folic s gy nn thiu mu hng cu to khng km tn thng thn kinh 3.3.3. Ch nh - Thiu mu hng cu to khng c du hiu tn thng thn kinh. - Thiu mu tan mu. - Gim bch cu ht, mt bch cu ht. - D phng thiu ht acid folic khi dng mt s thuc, ph n c thai, cho con b. 3.3.4. Ch phm v liu lng Acid folic c bo ch di dng ung hoc tim bp hoc tnh mch c dng n cht hoc phi hp vi cc vitamin khc v cc mui kim loi. Liu trung bnh t 2 - 5 - 15 mg/ 24 gi. 3.4. Cc thuc chng thiu mu khc Ngoi st, acid folic v vitamin B 12, vitamin B2 , vitamin B6, ng v Cobalt

cng c tc dng chng thiu mu. 3.5. Erythropoietin L yu t iu ha s nhn ln ca t bo gc trong tu xng, kch thch s trng thnh ca hng cu non v gii phng hng cu khi tu xng i vo tun hon. Yu t ny c cu trc protein gm 165 acid amin, phn t lng 3040 0, c sn xut ch yu t bo cnh cu thn, th yu t bo gan. Trong mu ngi khng thiu mu c nng erythropoietin di 20 UI/L v c gn vo glucose khng c tc dng dc l{. Khi c th thiu mu, thiu oxy s tng hp v bi tit ca y u t ny tng ln gp 100 ln so vi bnh thng. Khi cu thn b vim cp hoc mn tnh hay tn thng tu xng hoc thiu st, s bi tit erythropoietin gim xung r rt, gy nn thiu mu. Chnh v l{ do , erythropoietin c ch nh ch yu trong cc trng hp thiu mu do vim thn. Ngoi ra, erythropoietin cn c dng trong thiu mu do bnh AIDS, iu tr thuc chng ung th, thiu mu do mt mu sau phu thut v phng thiu mu tr non trng lng thp. - Ch phm v liu dng: + Epoetin alpha (Epogen; Eprex) ng tim cha 2000, 3000, 4000, 5000,6000,8000, 10000 v l cha 40000 n v, l erythropoietin ngi ti t hp nh k thut ti t hp ADN. Tim tnh mch hoc di da 50 - 100 n v/ kg th trng,3 ln trong mt tun. ngi c suy thn mn tnh thuc c t/2 t 4 -12 gi. + Epoetin beta ( NeoRecormon ) ng tim cha 500,1000, 2000, 4000 5000, 6000, 10000v l cha 50000,100000 n v. Thuc c th tim di da hoc tim tnh mch liu khi u 40-60 n v /tun trong 4 tun l in, sau tuz theo p ng ca c th m iu chnh liu ph hp. Khi dng thuc iu tr, nn cung cp thm st nhm gip tu xng sinh sn nhanh hng cu. Do thuc c th gy tng th tch mu v hematocrit v tng sc cn ngoi vi, nn phi chnh liu cho ph hp vi bnh nhn b bnh thn c cao huyt p BI 41. THUC IU CHNH RI LON H HP 1. THUC LM THAY I BI TIT DCH KH - PH QUN Dch kh- ph qun c bi tit : - T cc t bo nim mc: cc t bo hnh i tit dch nhy (do c nhiu mucoprotein v

mucopolysaccharid) v cc t bo thanh dch tit dch lng, qunh thp. - T cc tuyn tit di nim mc: l tuyn hn hp tit nc hoc dch nhy. Acetylcholin v cc thuc cng ph giao cm lm tng bi tit d?ch kh - ph qun. Dch kh- ph qun l cht lm du t nhin ca nim mc ng h hp. Dch nhy c tc dng bm dnh cc ht bi, vi khun, sau nh h thng lng mao y chng ra ngoi. 1.1. Thuc lm gim tit dch Thuc hu ph giao cm hoc thuc khng histamin H 1. Thc t t dng v c th lm cht tit c qunh, kh tng ra ngoi, d gy xp ph nang. 1.2. Thuc lm long m 1.2.1. Thuc lm tng dch tit L thuc lm tng bi tit dch ng h hp, bo v nim mc chng li cc tc nhn kch thch v khi lm tan c nhng tc nhn s cho php loi tr chng d dng. C 2 c ch tc dng: 1.2.1.1. Kch thch cc receptor t nim mc d dy gy phn x ph giao cm lm tng bi tit dch ng h hp, nhng liu c tc dng thng lm au d dy v c th gy nn. Mt s thuc thng dng l: - Natri iodid v kali iodid: ung 1 - 2g/ ngy. Dng ko di lm tch lu iod. Khng dng cho ph n c thai, tr em, ngi b bu gip. - Natri benzoat: ung 1 - 4 g/ ngy. Dng ko di lm tch lu Na +. - Amoni acetat: 0,5 - 1g/ ngy. Khng dng ngi suy gan hoc suy thn - Ipeca hoc ipecacuanha, hot cht l emetin. Dng liu thp (ti a 1,4 mg alcaloid) trong trng hp ho c m. Liu c ao gy nn. 1.2.1.2. Kch thch trc tip cc t bo xut tit Thng dng cc tinh du bay hi nh terpin, gaicol, eucallyptol. Nhng tinh du ny cn c tc dng st khun. Khng dng gaicol cho tr em di 30 thng tui. 1.2.2. Thuc lm tiu cht nhy Cc thuc ny lm thay i cu trc, dn n gim nht ca cht nhy, v vy cc nt nhy c th d dng di chuyn ra khi ng h hp nh h thng lng chuyn hoc s khc m. Nhng thuc c nhm thiol t do (nh

acetylcystein) c tc dng ct t cc cu ni disulfit S S ca cc si mucopolysaccharid nn lm lng dch tit ca nim mc ph qun. Cc thuc lm tiu cht nhy c th lm ph v hng ro cht nhy bo v d dy, phi thn trng nhng ngi c tin s lot d dy - t trng. 1.2.2.1. Nacetylcystein Dng lm thuc tiu cht nhy trong bnh nhy nht, cc bnh l h hp c m nhy qunh nh trong vim ph qun cp hoc mn. Cn dng lm thuc gii c khi dng qu liu paracetamol. Khng dng ngi c tin s hen (nguy c p hn ng co tht ph qun) Tc dng khng mong mun: bun nn, nn, bun ng, nhc u, phn ng d ng. Khng dng ng thi vi cc thuc chng ho hoc cc thuc lm gim bi tit dch ph qun. Liu dng: Ung mi ln 200 mg, ngy 3 ln. Kh dung 3- 5 mL dng dch 20%, 3 - 4 ln/ ngy. Nh trc tip vo kh qun 1 - 2 mL dung dch 10 - 20%, mi gi 1 ln. Do tc dng nhanh, i khi c th lm trn dch trong kh qun nu ngi bnh khng c kh nng ho tng ra ngoi kp thi. C th ht m long b ng my ht. 1.2.2.2. Bromhexin (Bisolvon) Dng iu tr nhng ri lon h hp i km vi ho c m. Khi iu tr nhim khun ng h hp, bromhexin lm tng s xm nhp ca mt s khng sinh vo dch bi tit ph qun, tng p ng vi khng sinh. Thn trng ngi c tin s lot d dy -? t trng, bnh hen, suy gan hoc suy thn nng. Tc dng khng mong mun: ri lon tiu ha, tng nh enzym gan, chng mt, nhc u, pht ban da. Kh dung bromhexin i khi gy ho hoc co tht ph qun nhng ngi nhy cm. Liu dng: ung mi ln 8 - 16 mg, ngy 3 ln. C th dng ng kh dung, tim bp su hoc tim tnh mch chm. 1.2.2.3. Cc thuc khc : Carbocistein, mucothiol, mecystein 2. THUC CHA HO Ho l c ch t v sinh l quan trng tng ra ngoi cc d vt phn trn ca ng h hp c th gy tc ng th. Ho cng c th l triu chng ca mt s ri lon trong c th (hen, tro ngc d dy - thc qun ), m khi iu tr nhng bnh ny s gim ho, nhng nhiu khi cng cn iu tr triu chng .

Ch dng thuc gim ho trong trng hp ho khng c m (ho khi cm cm, ho do kch ng, d ng), ho nhiu lm ngi bnh mt mi, mt ng. Khng dng thuc lm gim ho trong trng hp ho c m (trong bnh vim ph qun mn, gin ph qun ) v ho c coi nh c ch bo v c li, lm sch ng th. Cc thuc gim ho c chia lm 2 loi: 2.1. Thuc gim ho ngoi bin Lm gim nhy cm ca cc receptor gy phn x ho ng h hp - Thuc lm du ho do c tc dng bo v, bao ph cc receptor cm gi c hng, hu: glycerol, mt ong, cc siro ng ma - Thuc gy t cc ngn dy thn kinh gy phn x ho: benzonatat, bc h (menthol), lidocain, bupivacain. 2.2. Thuc gim ho trung ng Cc thuc ny c ch trc tip, lm nng cao ngng kch thch c a trung tm ho hnh tu, ng thi c tc dng an thn, c ch nh trung tm h hp. 2.2.1. Alcaloid ca thuc phin v cc dn xut 2.2.1.1. Codein Codein (methylmorphin) l alcaloid ca thuc phin. Trong c th, khong 10% codein b kh methyl thnh m orphin. So vi morphin, codein c hp thu tt hn khi ung, t gy to bn hoc co tht ng mt, t gy c ch h hp v t gy nghin hn nhng tc dng gim au cng k m hn. Codein c tc dng gim ho do c ch trc tip trung tm ho, nhng lm kh v tng qunh ca dch tit ph qun. Dng codein trong trng hp ho khan gy kh chu, mt ng v trong cc chng au nh v va. Chng ch nh: mn cm vi thuc, tr em di 1 tui, bnh gan, suy h hp, ph n c thai. Liu dng iu tr ho khan: ung mi ln 10 - 20 mg, ngy 3 4 ln. 2.2.1.2. Pholcodin Tc dng gim ho mnh hn codein 1,6 ln, t gy tc dng khng mong mun hn. Liu dng: 5- 15 mg/ ngy 2.2.1.3. Thuc gim ho khng gy nghin * Dextromethorphan: L cht tng hp, ng phn D ca morphin nhng khng tc dng ln cc receptor ca morphin nn khng gy nghin, khng c tc dng gim au v rt t

tc dng an thn. Do c ch trung tm ho, dextromethorphan c tc dng chng ho tng t codein, nhng t gy tc dng ph hn. Dextromethorphan ch nh tt trong trng hp ho khan, mn tnh. Chng ch nh: qu mn vi thuc, tr em di 2 tui, ang iu tr bng thuc c ch monoaminoxydase (MAO). Thn trng: ngi c nguy c hoc ang suy gim h hp, tin s b hen, d ng. Liu dng: ung mi ln 10 - 20 mg, 4 gi/ ln hoc m cc d i ln 30 mg, 6 - 8 gi/ ln, ti a 120 mg/ ngy. * Noscapin: Tc dng, cch dng, tc dng khng mong mun v thn trng tng t nh dextromethorphan. Khng dng cho ph n c kh nng mang thai (v nguy c gy t bin) Liu dng: mi ln 15 - 30 mg, ngy 3 ln. 2.2.2. Thuc gim ho khng his tamin Mt s thuc c tc dng khng histamin H 1 trung ng v ngoi bin (khng H 1 th h 1) ng thi c tc dng chng ho, khng cholinergic, khng serotonin v an t hn. Ch nh: cc chng ho khan do d ng, do kch thch, nht l v ban m. Tc dng an thn ca thuc l iu bt li khi dng thuc ban ngy, nhng c th thun li khi ho ban m. Cc thuc: - Alimemazin: ngi ln ung 5 - 40mg/ ngy, chia nhiu l n. Tr em: 0,5- 1 mg/ kg/ ngy, chia nhiu ln. - Diphenhydramin: mi ln ung 25 mg, 4 - 6 gi/ ln. 3. THUC CHA HEN PH QUN 3.1. i cng Hen ph qun l hi chng vim mn tnh ng h hp, c gia tng tnh phn ng ca ph qun vi cc tc nhn gy kch thch, gy nn tnh trng co tht, ph n, tng xut tit ph qun, lm tc nghn ng th. Hen ph qun c th do d ng (bi, phn hoa, lng v, thc phm ) hoc khng do d ng (nhim khun, ri lon ni tit, gng sc, dng thuc chng vi m khng steroid ) ngi hen do d ng, khi tip xc vi d nguyn, rt nhiu cht trung gian ha hc c gii phng t dng bo (t bo mastocyt), gy nhiu tc dng ph

qun v cc ni khc trong c th. Nu pht hin c d nguyn gy bnh, c th iu tr bng phng php gim mn cm c hiu. iu tr khng c hiu bnh hen, theo c ch bnh sinh, c hai nhm thuc c dng: - Cc thuc lm gin ph qun: thuc cng 2 adrenergic, thuc hu ph giao cm, theophylin. - Cc thuc chng vim: corticoid, cromolyn natri. Thuc khng leucotrien (montelukast, zafirlukast) lm gim tc dng co tht ph q un v gy vim ca LTD 4. 3.2. Thuc lm gin ph qun 3.2.1. Thuc cng 2 adrenergic 3.2.1.1. C ch tc dng C trn ng h hp c nhiu receptor 2, khi b kch thch s gy gin c trn kh ph qun do lm tng AMPv trong t bo. Khi dng di dng kh dung, cc thuc cng 2 c ch gii phng histamin v leucotrien khi dng bo phi, lm tng chc phn ca h thng lng mao, gim tnh thm ca mao mch phi v c ch phospholipase A 2, tng kh nng chng vim ca corticoid kh dung. 3.2.1.2. Phn loi Cc thuc cng 2 adrenergic c chia lm 2 loi: - Loi c tc dng ngn (short acting 2 agonist: SABA): salbutamol, terbutalin, fenoterol ch yu dng ct cn hen; Dng di dng ht, tc dng sau 2 3 pht, ko di 3- 5 gi. - Loi c tc dng di (long acting 2 agonist: LABA): salmeterol, formoterol gn vo receptor 2 mnh hn salbutamol, tc dng ko di khong 12 gi, dng phi hp vi corticoid d phng di hn v kim sot hen. 3.2.1.3. Tc dng khng mong mun v thn trng - Tc dng khng mong mun thng gp: nh trng ngc, nhp tim nhanh, run nh (c bit u ngn tay). Him gp: nhc u, mt ng, gin mch ngoi bin, lon nhp tim, h kali mu, tng glucose v acid bo t do trong mu, phn ng qu mn. Dng ng kh dung c th gy co tht ph qun. Dng nhiu ln s c hin tng quen thuc nhanh do s lng receptor 2 ca ph qun gim dn (c ch iu ha gim), bnh nhn c xu hng phi tng liu.

- Thn trng: cng tuyn gip, bnh tim mch, tng huyt p, lon nhp tim, i tho ng, ang iu tr bng MAOI. 3.2.1.4. Cc thuc - Salbutamol Ch nh: hen, tc nghn ng h hp hi phc c, chng non. Liu dng: . Cn hen cp: ht nh liu mi ln 100 - 200 g (1- 2 xt), ti a 3 - 4 ln/ ngy. Hoc: tim bp hoc tim di da mi ln 500 g, nhc li sau mi 4 gi nu cn. . Cn hen cp nghim trng: du ng dch kh dung 2,5 5 mg, ti a 4 ln/ ngy hoc tim tnh mch chm 250 g, dng nhc li nu cn. . phng cn hen do gng sc: ht 100 - 200 g (1- 2 xt) truc khi vn ng 15 30 pht, hoc ung 2 - 4 mg trc khi vn ng 2 gi. Dng ng kh du ng, nng thuc trong mu ch bng 1/10 - 1/50 so vi liu ung. - Terbutalin Ch nh: ging nh salbutamol Liu dng: cn hen cp: ht 250 - 500 g (1- 2 ln xt), ti a 3 - 4 ln/ ngy, hoc tim di da, tim bp hoc tnh mch chm 250 - 500 g, ti a 4 ln/ ngy. Bambuterol l tin thuc ca terbutalin, mi ngy ung mt ln 10 - 20 mg trc khi i ng - Salmeterol Ch nh: iu tr d phng di hn bnh hen, tc nghn ng h hp phc hi c (k c hen ban m v phng co tht ph qun do gng sc) ngi phi iu tr bng thuc gin ph qun thng xuyn, bnh phi tc nghn mn tnh. Liu dng: . Bnh hen: mi ln ht 50 - 100 g (2- 4 xt), 2 ln/ ngy. Tr em trn 4 tui: mi ln ht 50 g (2 xt), 2 ln/ ngy. . Bnh phi tc nghn mn tnh: mi ln ht 50 g (2 xt), 2 ln/ ngy. 3.2.2. Thuc hu ph giao cm Ipratropium bromid (Atrovent) l dn xut amin bc 4, dng ng ht. Khi kh dung, ch khong 1% thuc c hp thu, 90% b nut vo ng tiu ha, khng c hp thu, thi theo phn nn t gy tc dng khng mong mun ton thn. Tc dng gin ph qun ca ipratropium trn ngi bnh hen thng chm v khng mnh bng thuc cng 2 tc dng ngn (SABA), nn thng ch c phi hp s dng khi cc thuc SABA khng mnh hoc c tc dng ph nng. Phi hp ipratropium vi SABA lm gin ph qun mnh hn,

cho ph p gim liu SABA nn hn ch c tc dng ph ca SABA. Kh dung ipratropium c tc dng ti a sau 30 - 60 pht, thi gian tc dng ko di 3 - 6 gi. Ipratropium cng c tc dng tt trong iu tr bnh phi tc nghn mn tnh. Thn trng: tng nhn p, ph i tuyn tin lit v tc nghn dng chy ra t bng quang, c thai v cho con b. Tc dng khng mong mun: kh ming, bun nn, to bn, au u. Liu dng: ht n h liu: mi ln 20 - 40 g (1- 2 xt), 3-4 ln/ ngy. Berodual (ipratropium bromid + fenoterol): mi ln xt c 20 g ipratropium v 50 g fenoterol. Liu thng thng 1 - 2 xt/ ln, ngy 3 ln. Oxitropium c tc dng tng t nh ipratropium. 3.2.3. Theophylin v dn xut Theophylin l base xanthin (cng vi cafein v theobromin) c nhiu trong ch, c ph, ca cao. 3.2.3.1. C ch tc dng v tc dng dc l Do c ch ph?osphodiesterase - enzym ging ha AMPv, theophylin lm tng AMPv trong t bo nn tc d ng tng t thuc cng adrenergic. - Trn h hp: lm gin ph qun, ng thi kch thch trung tm h hp hnh no, lm tng bin v tn s h hp. - Trn tim mch: lm tng bin , tn s v lu lng tim, tng s dng oxy ca c tim v tng lu lng mch vnh. - Trn thn kinh trung ng: tc dng kch thch thn kinh trung ng k m cafein, lm d dng cho cc hot ng ca v no, gy mt ng c th do tc dng ln h thng li kch thch. - Lm gin c trn ng mt v niu qun. - Tc dng li niu km theobromin. Theophylin c chuyn ha qua gan. Nng trong huyt tng, thi gian bn thi ca theophylin thay i ng k trong mt s tnh trng sinh l v bnh l (tng trong suy tim, x gan, nhim virus, ngi cao tui) hoc do tng t c thuc, trong khi gii hn an ton gia liu iu tr v liu c ca theophylin kh hp. Tc dng gin ph qun ca theophylin khng mnh bng cc thuc kch thch 2, trong khi nguy c xut hin cc tc dng khng mong mun kh cao, v vy theophylin khng c la chn u tin trong ct cn hen. Hin nay, theophylin ung gii phng nhanh t c dng trong iu tr hen, ch yu dng theophylin gii phng chm, duy tr nng thuc trong mu trong 12 gi

iu tr d phng v kim sot hen v m. Trong cn hen nng, theophylin c dng phi hp vi cc thuc cng 2 hoc corticoid lm tng tc dng gin ph qun, nhng li c th lm tng tc dng khng mong mun ca thuc cng 2 (h kali mu). Theophylin c th dng ng tim l aminophylin, hn hp ca theophylin v ethylendiamin, tan trong nc gp 20 ln so vi theophylin n c. Trong iu tr cn hen nng, tim tnh mch aminophylin rt chm (t nht trong 20 pht). 3.2.3.2. Chng ch nh v thn trng Chng ch nh: qu mn vi thuc, lot d dy - t trng tin trin, ri lon chuyn ha porphyrin, ng kinh khng kim sot c. Thn trng: bnh tim, tng huyt p, cng gip, tin s lot d dy- t trng, suy gan, ng kinh, c thai v cho con b, ngi cao tui, ang b st, dng cng cc thuc c ch enzym chuyn ha thuc gan. 3.2.3.3. Tc dng khng mong mun: thng gp nhp tim nhanh, tnh trng kch thch, bn chn, bun nn, nn. t gp: kch ng ng tiu ha, au u, chng mt, mt ng, run, co git, lon nhp tim, h huyt p, phn ng d ng. 3.2.3.4. Liu dng: Vin theophylin gii phng chm (Theostat, Nuelin SA): mi ln ung 200 - 400 mg, cch 12 gi ung 1 ln. Hen ban m: ung mt ln duy nht vo bui ti vi liu bng tng liu dng trong mt ngy. . Aminophylin: ung mi ln 100 - 300 mg, ngy 3 - 4 ln, sau ba n. Tim tnh mch chm t nht trong 20 pht liu 5 mg/ kg. 3.3. Thuc chng vim 3.3.1. Glucocorticoid (GC) Glucocorticoid c hiu qu rt tt trong iu tr hen, do thuc c tc dng chng vim, lm gim ph n, gim bi tit dch nhy vo lng ph qun v lm gim cc phn ng d ng. Glucocorticoid phc hi p ng ca cc receptor 2 vi cc thuc cng 2 adrenergic (xin xem thm bi Hormon v thng thn). - Dng di? dng ht c tc dng tt, iu tr d phng hen khi ngi bnh phi dng thuc cng 2 nhiu hn 3 ln/ tun, t gy tc dng khng mong

mun ton thn. Bt buc phi dng thuc u n t li ch ti a v lm gim nguy c tng nng ca hen. Tc dng khng mong mun ti ch thng gp khi dng GC ht l nhim nm Candida ming hng, khn ting v ho. Dng liu cao ko di c th gy c ch thng thn, gim mt khong xng, tng nhn p. Cc GC dng ng ht: beclometason dipropionat, budesonid v fluticason propionat. (ba thuc ny c tc dng tng ng nhau), ciclesonid, mometason furoat. * Beclometason dipropionat (Becotide): kh dung nh liu mi ln 100 - 400 g, 2 ln/ ngy, sau iu chnh theo p ng ca ngi bnh. * Budesonid (Pulmicort): ht mi ln 200 g, 2 ln/ ngy. Ch phm phi hp: Sym bicort cha formoterol v budesonid vi cc hm lng formoterol/ budesonid mi ln xt l 4,5 g/ 80 g; 4,5g/ 160 g; 9g/ 320g. Ngi ln v tr em trn 12 tui: mi ln 1 - 2 xt, ngy 2 ln. iu tr duy tr: 1 ln xt/ ngy. * Fluticason propionat: ht nh liu mi ln 100 - 250 g, 2 ln/ ngy. tr em 416 tui: mi ln 50 - 100 g, 2 ln/ ngy Ch phm phi hp: Seretide cha salmeterol v fluticason propionat vi cc hm lng salmeterol / fluticason propionat mi ln xt l 25 g/ 50 g; 25 g/ 125 g; 25 g/ 250 g Ngi ln v tr em trn 12 tui: mi ln 2 xt, ngy 2 ln. Dng ch phm c hm lng thuc ph hp vi mc nng ca bnh hen. * Ciclesonid: ngi ln xt mi ngy mt ln 160 g. * Mometason furoat: ngi ln ht 200 - 400 g vo bui ti hoc chia lm 2 ln trong ngy. - Dng ton thn: iu tr cn hen cp nn g hoc kim sot hen mn tnh nng. . Hen nng cp tnh: ngi ln ung prednisolon 40 - 50 mg/ ngy, t nht trong 5 ngy (tr em 1- 2 mg/ kg/ ngy, trong 3 ngy), sau iu chnh liu theo p ng ca ngi bnh, hoc tim tnh mch hydrocortison 400 mg/ ngy, chia lm 4 ln. . Hen mn tnh nng khng p ng y vi cc thuc chng hen khc, ht GC liu cao phi hp vi ung GC mi ngy mt ln vo bui sng. Tm liu thp nht kim sot

c triu chng 3.3.2. Cromolyn natri - Tc dng: c ch dng bo ca phi gii phng cc cht trung gian ha hc do p ng vi cc kch thch hoc do tng tc khng nguyn - khng th IgE. c ch tc dng hot ha ca cc peptid ha hng ng trn bch cu trung tnh, a acid hoc n nhn. Cromolyn natri ch c tc dng phng cn, ngn nga p ng hen vi cc kch thch do d ng hoc khng do d ng, c dng iu tr di hn sm trong hen, khng c tc dng iu tr cn hen cp. Tr em p ng vi thuc tt hn ngi ln. Nhn chung tc dng d phng hen ca cromolyn natri km hiu qu hn so vi GC ng ht. - Cromolyn natri dng theo ng ht, t c hp thu nn t gy c tnh ton thn. - Tc dng khng mong mun: ho, co tht nh ph qun, nhc u, bun ng, ri lon tiu ha, phn ng qu mn. - Liu dng: ht mi ln 10 mg (2 xt, ngy 4 ln cch u nhau). Phng cn hen do gng sc, kh lnh, tc nhn mi trng: ht 10 mg (2 xt) ngay trc khi tip xc? vi cc yu t gy cn. 3.3.3. Thuc khng leucotrien Thuc khng leucotrien ngn cn tc dng ca cc cysteinyl leucotrien ng h hp. Chng c tc dng khi dng ring hoc khi phi hp vi GC ht (tc dng hip ng cng) - Ch nh: iu tr d phng hen Phi hp vi thuc cng 2 v GC ng ht iu tr hen mn tnh nng - Tc dng khng mong mun: ri lon tiu ha, kh ming, kht, au u, chng mt, ri lon gic ng, au khp, au c, ph, phn ng nhy cm. C th gp hi chng Churg- Strauss (c tin s hen, thng vim mi, vim xoang, vim mch v tng bch cu a eosin). - Cc thuc: . Montelukast: Ngi ln: nhai hoc ung 10 mg trc khi i ng. Tr em 6 thng 5 tui: 4 mg/ ngy, 6 - 14 tui: 5 mg/ ngy Thn trng khi dng ngi mang thai v cho con b . Zafirlukast: ung mi ln 20 mg, ngy 2 ln.

Khng dng cho tr em di 12 tui, suy gan, cho con b. Thn trng khi dng ngi cao tui, ngi mang thai, suy then. 3.4. S dng thuc trong iu tr hen 3.4.1. ng dng thuc Cc thuc iu tr hen c th dng bng cc ng khc nhau: + ng ht: thuc c a trc tip vo ng h hp nn t nng cao ti , liu ht thng thp hn liu ung, gim c tc dng khng mong mun ton thn . . Ht nh liu l phng php thun tin v c hiu qu khi s dng thuc iu tr hen mc nh v trung b nh. iu rt quan trng l phi hng dn ngi bnh tht cn thn v cch s dng ng dng c ht nh liu t kt qu ti u. . Bung ht (spacing devices) to ra mt khoang gia dng c ht v ming, dng tt hn ngi gi, tr em, nhng ngi k h s dng dng c ht nh liu ng cch, hoc dng khi ht corticoid liu cao gim lng ng thuc ming v hng, d gy nhim nm Candida. Dn ngi bnh phi sc ming sau khi ht thuc. . Dung dch kh dung thng dng trong cn hen nng cp tn h, dng cng vi oxygen trong bnh vin. - ng ung: khi khng th dng bng ng ht hoc ng ht km hiu qu. Dng ng ung gy nhiu tc dng khng mong mun ton thn hn ng ht. - ng tim: cc thuc cng 2, corticoid hoc aminophylin ch dng ng tim trong cp cu cn hen nng, cp tnh, khi ng kh dung khng hoc khng ph hp. 3.4.2. X tr hen - Ct cn hen: ht thuc cng 2 tc dng ngn (SABA) c hiu qu nht. - iu tr duy tr, kim so t di hn hen: phi hp corticoid ht v thuc cng 2 tc dng di (LABA) ht c hiu qu nht. Nu hen vn cha kim sot c, cn nhc phi hp thm vi ung mt trong cc thuc sau: theophylin gii phng chm, thuc cng 2 gii phng chm, thuc kh ng leucotrien hoc corticoid. Xem xt li iu tr sau mi 3 thng iu chnh ch iu tr cho ph hp. - Cn hen nng cp tnh: th oxy, kh dung dung dch SABA, corticoid (ung, tim tnh mch).

- D phng cn co tht ph qun khi gng sc, do kh lnh hoc do tc nhn mi trng: ht cromolyn natri hoc SABA (ht, ung). 4.THUC IU TR BNH PHI TC NGHN MN TNH Bnh phi tc nghn mn t?nh l tnh trng bnh c trng bi ri lon thng kh tc nghn khng c kh nng phc hi hon ton. S h n ch thng kh thng tin trin t t v lin quan n phn ng vim bt thng ca phi do cc phn t hoc kh c hi. Cc yu t nguy c ca bnh phi tc nghn mn tnh: ht thuc l, khi bi do nhim mi trng, nhim khun ng h hp v yu t di truyn (thiu 1 antitrypsin). c im ca bnh phi tc nghn mn tnh l tnh trng vim nhim thng xuyn ton b ng dn kh v nhu m phi, dn n x ha ng th v ph hu ph nang. V vy, iu tr bnh phi tc nghn mn tnh, tr c ht phi loi b cc yu t nguy c. Cc thuc iu tr bnh bao gm: 4.1. Thuc gin ph qun: iu tr triu chng ca bnh - Ht thuc cng 2 tc dng ngn (salbutamol, terbutalin, fenoterol) hoc thuc khng cholinergic tc dng ngn (ipratrop ium) khi cn thit. - Nu bnh tin trin nng: phi hp thuc cng 2, thuc khng cholinergic v/ hoc theophylin. - Tiotropium l thuc khng cholinergic tc dng k o di dng iu tr duy tr trong bnh phi tc nghn mn tnh, khng dng trong co tht ph qun cp. - Ht mi ngy mt ln 18 g. Khng dng cho ngi di 18 tui. 4.2. Glucocorticoid : Phi hp LABA v GC dng ht iu tr bnh phi tc nghn mn tnh mc trung bnh v nng. Ngng phi hp nu khng thy ch li sau 4 tun. Nu bnh tin trin nng hn: dng thuc gin ph qun (dung dch kh dung) v th oxy, ung GC trong thi gian ngn. 4.3. Cc thuc khc - Tim vaccin cm mi nm mt ln, vaccin phng ph cu. - Dng khng sinh khi c nhim khun. - Thuc lm long m (a cetyl cystein, carbocistein ) trong t cp c ho khc m dnh qunh. - iu tr tng cng 1 antitrypsin.

5. THUC KCH THCH H HP Ngoi cafein l thuc tc dng u tin trn v no, cc thuc khc u c tc dng ch yu trn hnh no. Vi liu iu tr, trn ngi bnh thng khng c tc dng r rng. Vi liu cao, cc thuc u gy co git, lc u l co git cng, ri ngay sau chuyn sang co git rung. C ch ca tc dng co git cha c hon ton bit r, nhng ni chung l lm gim ngng k ch thch ca thn kinh trung ng. Trn trung tm h hp, cc thuc u c tc dng kch thch, i lp vi tc dng ca barbiturat. 5.1. Cafein v cc alcaloid dn xut ca xanthin Ly l ch, ht c ph, ht cla, cacao, hoc c th tng hp t acid u ric. C 3 cht c dng trong iu tr l cafein, theophylin v theobromin, trong cng thc u c nhn purin. 5.1.1. Tc dng - Trn v no, cafein c tc dng r rt lm mt cm gic mt nhc, bun ng, lm tng qu trnh hng phn, tng cng nhn cm ca cc gic quan, lm kin n nhanh, tr tu minh mn. Nu dng thuc lin tc v k o di th sau giai on hng phn thng tip theo giai on c ch, mt mi. - Trn h thng tim mch: theophylin tc dng mnh hn cafein. Kch thch trc tip trn c tim lm tim p nhanh, mnh, tng lu lng tim v lu lng mch vnh. Trn c th nguyn vn, do cn c tc dng kch thch t?rung tm dy thn kinh X nn c tc dng ngc li. V vy, tc dng ca cafein trn tim l phc tp, tuz theo liu: liu nh l m tim p chm, liu cao lm tim p nhanh. Liu iu tr t lm thay i huyt p. - Trn h hp: kch thch trung tm h hp hnh no, lm gin ph qun v gin mch phi do tc dng trc tip trn c trn. Tc dng cng r khi trung tm h hp b c ch bi thuc m, thuc ng hay morphin. - Trn c quan: lm gin mch thn v li niu. Lm tng tit dch v c s, tng tnh acid ca dch v do trc tip kch thch nim mc d dy v kch thch qua trung tm ph giao cm. 5.1.2. C ch tc dng - Gii phng catecholamin - Huy ng calci v c ch s thu hi calci vo ti li ni bo. - c ch phosphodiesterase, lm vng bn v tng AMPc. Catecholamin cng lm tng AMPc nhng l do kch thch adenylcyclase, tng tng hp AMPv t ATP. V vy, gi i thch c nhiu tc dng ging nhau gia catecholamin

v cafein trn tim mch, ph qun, mt s chuyn ha nh tng ng huyt, tng hu lipid (xin xem trong bi Thuc tc dng trn h thn kinh thc vt).

5.1.3. p dng iu tr Qu trnh hng phn ca thn kinh trung ng b gim, hen, suy tim (khng dng trong trng hp vim c tim), phi hp vi thuc h st ( i khng vi tc dng c ch tim ca cc thuc ny). Liu lng: - ng tim cafein natri benzoat 0,07g/ mL, tim di da hoc tim bp 1 - 2 ng/ ngy. - Theophylin mi ln ung 200 mg, ngy 2 ln. 5.2. Nikethamid L thuc tng hp, lm nhp th nhanh v su do kch thch qua phn x xoang cnh, nhng tc dng chnh l kch thch trc tip cc trung tm hnh no. Khng c tc dng trc tip trn tim v mch mu. Ch nh trong cc trng hp suy ti m mch v h hp. Tim di da, bp tht hoc tnh mch chm, mi ln 1 ng 1mL (dung dch 25%), mi ngy 3 ng. Ung dung dch 25% mi ln X - XX git, ngy 2 - 3 ln. 5.3. Bemegrid Cng thc ha hc gn ging bar biturat, nhng c tc dng i khng vi ba rbiturat. Bemegrid kch thch trc tip cc trung tm h hp v tun hon hnh no, lm tng nhp tim, tng huyt p, tng bin h hp. Liu cao cng gy cc cn co git, nhng phm vi an ton rng hn, d s dng hn, nn c xu hng c s dng tro ng iu tr mt s bnh tm thn bng cc cn co git. Ngoi tc dng trn thn kinh trung ng, bemegrid cn kch thch cc si thn kinh vn ng, lm d dng s vn chuyn xung tc thn kinh qua cc nron, nn cn c dngiu tr mt s chng vim d y thn kinh, au tht lng hng Liu lng: nhim c barbiturat c th tim hng gam vo tnh mch lm nhiu ln tuz theo tnh trng nhim c. Tim bp 25- 50 mg iu tr vim dy thn kinh. 5.4. Doxapran hydroclorid - Ch nh: dng trong trng h p suy h hp cp, suy gim h hp sau m - Chng ch nh: tng huyt p nng, tnh trng hen, bnh mch vnh, nhim

c do tuyn gip, ng kinh, tc nghn c hc ng h hp. - Tc dng khng mong mun: chng mt, tot m hi, tng huyt p v nhp t im. Tc dng khng mong mun trong giai on sau m bao gm: co cng c cc b, tng ho?tng, ln ln, o gic, ho, kh th, co tht thanh qun, co tht ph qun, nhp nhanh xoang, nhp tim chm, ngoi tm thu, bun nn, nn, tit nc bt. - Liu dng: . Suy gim h hp sau m: tim tnh mch (t nht trong 30 giy) 1 - 1,5 mg/ kg, nhc li nu cn thit sau 1 gi hoc truyn tnh mch 2 - 3 mg/ pht. iu chnh liu theo p ngca ngi bnh. . Suy h hp cp: truyn tnh mch 1,5 - 4 mg/ pht, iu ch nh theo p ng ca ngi bnh. Dng cng vi oxygen v phi theo di thng xuyn p sut kh trong mu v pH mu. Khng dng cho tr em. BI 42. THUC IU CHNH RI LON TIU HO 1. THUC IU TR VIM LOT D DY - T TRNG 1.1 i cng Lot d dy- t trng l bnh l{ ng tiu ha ph bin, hu qu ca s mt cn bng gia cc yu t gy lot (acid clohydric, pepsin, xon khun Helicobacter pylori ) v cc yu t bo v ti ch nim mc d dy (cht nhy, bicarbonat, prostaglandin). Xon khun H.pylori ng vai tr quan trng trong nguy c gy lot: khong 95% ngi lot t trng v 70 - 80% ngi lot d dy c vi khun ny. Chng gy vim d dy mn v lm tng bi tit acid. Dit tr c H.pylori s lm lot lin nhanh v gim r rt t l ti pht. Mc tiu ca iu tr lot d dy - t trng l: - Chng cc yu t gy lot: . Cc thuc khng acid: trung ha acid trong lng d dy (magnesi hydroxyd, nhm hydroxyd) . Cc thuc lm gim bi tit acid v pepsin: thuc khng histamin H 2 v thuc c ch bm proton. . Thuc dit H.pylori: cc khng sinh, bismuth. - Tng cng yu t bo v: sucralfat, bismuth, misoprostol. Vic iu ha bi tit HCl ca t bo thnh d dy l do histamin, acetylcholin v gastrin thng qua H +/ K+- ATPase (bm proton) . Prostaglandin c vai tr quan trng trong c ch iu ha ngc: PGE 2 c ch

adenylcyclase lm gim AMPv, i khng vi tc dng ca his tamin v c ch gii phng gastrin. PGI2 kch thch t bo biu m ca nim mc d dy, lm tng tit cht nhy, bicarbonat bo v nim mc. Cc thuc chng vim khng steroid c ch tng hp prostaglandin, c th gy lot v chy mu ng tiu ha.

Hnh 27.1. C ch iu ha sinh l{ v dc l ca bi tit dch v v cc v tr tc dng ca thuc

Hnh 27.2. Vai tr trung ha acid ca NaHCO 3 ti lp nhy nim mc d dy 1.2. Thuc khng acid 1.2.1. Tnh cht chung Cc thuc khng acid l nhng thuc c tc dng trung ho acid trong dch v, nng pH ca d dy ln gn 4, to iu kin thun li cho ti to nim mc. Khi pH d dy tng, hot tnh ca pepsin s gim (pepsin b bt hot trong dung dch pH ln hn 4). Cc thuc khng acid c tc dng nhanh nhng ngn, ch l thuc iu tr triu chng, ct cn au. Khi d dy rng, cc thuc khng acid thot khi d dy sau 30 pht, khi c thc n th khong 2 gi. Thuc khng acid thng dng nht l cc ch phm cha nhm v magnesi, c tc dng khng acid ti ch, hu nh khng hp thu vo mu nn t gy tc dng ton thn. Thuc khng acid cha magnesi c tc d ng nhun trng, ngc li thuc cha nhm c th gy to bn. V vy, cc ch phm khng acid ch 80/ a c hai mui magnesi v nhm c th lm gim tc dng khng mong mun trn rut ca hai thuc ny. Nu chc nng thn bnh thng, rt t nguy c tch lu ma gnesi v nhm. Natribicarbonat c tc dng trung ha acid dch v mnh, nhng hin nay hu nh khng dng lm thuc khng acid na v hp thu c vo mu, gy nhiu tc dng khng mong mun ton thn v c hin tng tit acid hi ng (tng tit acid sau khi ngng thuc). Dng thuc khng acid tt nht l sau ba n 1 - 3 gi v trc khi i ng, 3 - 4 ln (hoc nhiu hn) trong mt ngy. Cc ch phm dng lng c hiu qu hn

dng rn nhng thi gian tc dng ngn hn. Do lm tng pH d dy, cc thuc khn g acid lm nh hng n s hp thu ca nhiu thuc khc, phi dng cc thuc ny cch xa thuc khng acid t nht 2 gi. Mt s ch phm phi hp thuc khng acid vi simeticon (cht chng si bt) lm gim s y hI hoc lm nh triu chng nc. 1.2.2. Magnesi hydroxyd - Mg(OH)2 1.2.2.1. Tc dng v c ch d dy, magnesi hydroxyd phn ng nhanh vi acid clohydric: Mg(OH)2 + 2HCl MgCl2 + 2H2O Xung rut non, Mg 2+ tc ng vi cc ion phos phat (PO 43-) v carbonat (CO 32-) to thnh mui rt t tan hoc khng tan, do trnh c s hp thu base, trnh c base mu ngay c khi dng lu. C th dng cc mui khc ca magnesi nh magnesi carbonat, magnesi trisilicat. 1.2.2.2 Ch nh - Tng tit acid (au, y bng, kh tiu, nng, chua) ngi c lot hoc khng c lot d dy- t trng. - Tro ngc d dy - thc qun. 1.2.2.3. Chng ch nh Mn cm vi thuc, suy thn nng, tr nh (c bit tr mt nc v suy thn). 1.2.2.4. Tc dng khng mong mun Ming ng cht, bun nn, nn , cng bng, a chy, tng magnesi mu (gp ngi suy thn hoc dng liu cao, ko di). 1.2.2.5. Tng tc thuc - Cc thuc gim hp thu khi dng cng thuc khng acid: tetracyclin, digoxin, indomethacin, cc mui st, isoniazid, benzodiazepin, ranitid in - Cc thuc tng tc dng do gim thi tr khi dng cng thuc khng acid: amphetamin, quinidin. 1.2.2.6. Liu lng, cch dng Ngi ln: mi ln ung 300 - 600 mg, ti a ti 1g, ngy 3 - 4 ln. Nhai k vin thuc trc khi nut. 1.2.3. Nhm hydroxyd - Al(OH)3 1.2.3.1. Tc dng v c ch d dy, nhm hydroxyd phn ng vi acid clohydric: chm Al(OH)3 + 3HCl AlCl3 + 3H2O Nhm hydroxyd c tc dng trung ha acid yu nn khng gy phn ng tng

tit acid hi ng. rut, nhm kt hp vi phosphat t thc n, to phosphat nhm khng tan, hu nh khng hp thu, thi tr theo phn, khng gy base mu. V phosphat b thi tr, c th phi huy ng phosphat t xng ra, d gy chng nhuyn xng. V vy, cn n ch nhiu phosphat v protein. 1.2.3.2. Ch nh : nh magnesi hydroxyd (mc 1.2.2.2) Tng phos phat mu (t dng) 1.2.3.3. Chng ch nh : nh magnesi hydroxyd. (mc 1.2.2.3) Gim phosphat mu. Ri lon chuyn ha porphyrin. 1.2.3.4. Tc dng khng mong mun Cht ming, bun n n, cng bng, to bn, phn trng, gim phosphat mu. Nguy c nhuyn xng khi ch n t phosphat hoc iu tr lu di. Tng nhm trong mu gy bnh no, sa st tr tu, thiu mu hng cu nh. 1.2.3.5. Tng tc ?thuc : ging nh magnesi hydroxyd (mc 1.2.2.5) 1.2.3.6. Liu lng, cch dng Ngi ln: dng vin nhai mi ln 0,5 - 1,0g, dng hn dch ung mi ln 320 640 mg, ngy 4 ln. Tr em: 6- 12 tui: dng hn dch ung mi ln 320 mg, ngy 3 ln. * Ch phm phi hp magnesi hydroxyd v nhm hydrox yd - Dng hn dch cha magnesi hydroxyd 195 mg v nhm hydroxyd 220mg trong 5mL. Ngi ln ung mi ln 10 - 20 mL - Dng vin: cha magnesi hydroxyd 400 mg v nhm hydroxyd 400 mg. Ngi ln mi ln nhai 1- 2 vin, ti a 6 ln mt ngy. * Ch phm phi h p thuc khng acid v simeticon: dng vin hoc dng hn dch (cha magnesi hydroxyd 195 mg, nhm hydroxyd 220 mg v simeticon 25 mg trong 5 ml. Ngi ln ung mi ln 5 - 10 mL, ngy 4 ln). 1.3. Thuc lm gim bi tit acid clohydric v pepsin ca d dy 1.3.1. Thuc khng histamin H 2 1.3.1.1. c im chung C ch tc dng Do cng thc gn ging vi histamin, cc thuc khng histamin H 2 tranh chp vi histamin ti receptor H 2 v khng c tc dng trn receptor H 1. Tuy receptor H 2 c nhiu m nh thnh mch, kh qun, tim, nhng thuc khng histamin H 2 tc dng ch yu ti cc receptor H 2 d dy. Thuc khng histamin H 2 ngn cn bi tit dch v do bt kz nguyn nhn no lm tng tit his-

tamin ti d dy (cng ph giao cm, thc n, gastrin, bi tit c s). Tc dng ca thuc khng histamin H 2 ph thuc vo liu lng, thuc lm gim tit c s lng v nng HCl trong dch v Ch nh - Lot d dy- t trng lnh tnh, k c lot do dng thuc chng vim khng steroid. - Bnh tro ngc d dy - thc qun. - Hi chng tng tit acid dch v (Hi chng Zollinger - Ellison) - Lm gim tit acid dch v trong mt s trng hp lo t ng tiu ha khc c lin quan n tng tit dch v nh lo t ming ni d dy - rut - Lm gim cc triu chng ri lo n tiu ha (nng rt, kh tiu, chua) do tha acid dch v. - Lm gim nguy c ht phi acid dch v khi gy m hoc khi sinh (Hi chng Mendelson). Chng ch nh v thn trng - Chng ch nh: qu mn vi thuc - Thn trng: trc khi dng thuc khng histamin H 2, phi loi tr kh nng ung th d dy, c bit ngi t trung nin tr ln v thuc c th che lp cc triu chng, lm chm chn on ung th. C nhy cm cho gia cc thuc trong nhm khng his tamin H 2. Dng thn trng, gim liu v / hoc ko di khong cch gia cc ln dng thuc ngi suy thn. Thn trng ngi suy gan, ph n c thai v cho con b (ngng thuc hoc ngng cho con b). Tc dng khng mong mun a chy v cc ri lon tiu ha khc, tng enzym gan, au u, ch ng mt, pht ban. Him gp vim ty cp, chm nhp tim, nghn nh tht, ln ln, trm cm, o gic (c bit ngi gi), ri lon v mu, phn ng qu mn. Chng v to n ng v thiu nng tnh dc gp ngi dng cimetidin nhiu hn cc thuc khng histamin H2 khc. Tng tc thuc - Do pH d dy tng khi dng thuc khng histamin H 2 nn lm gim hp thu ca mt s thuc nh penicilin V, ketoconazol, itraconazol - Cimetidin c ch cytochrom P 450 gan nn lm tng tc dng v c tnh ca nhiu thuc nh warfari?n, phenytoin, theophylin, propranolol, benzodiazepin Ranitidin c tng tc ny nhng mc thp hn nhiu (km 2 - 4

ln). Famotidin v nizatidin khng gy tng tc kiu ny. Mt s thng s dc ng hc ca thuc khng his tamin H 2

1.3.1.2. Cc thuc Cimetidin Hp thu nhanh khi ung. Ung 200 mg cimetidin c tc dng nng pH v gim au trong 1,5 gi. Liu 400 mg trc khi i ng gi c pH ca d dy > 3,5 sut c m. Vi liu 1,0g/ 24 gi, t l ln so l 60% sau 4 tun v 80% sau 8 tun. Liu dng iu tr lot d dy - t trng ngi ln: ung mi ln 400 mg, ngy 2 ln (vo ba n sng v trc khi i ng) hoc 800 mg trc khi i ng. Thi gian dng t nht 4 tun i vi lot t trng v 6 tun i vi lot d dy. Liu duy tr: 400 mg trc khi i ng Khi lot nng hoc ngi bnh nn nhiu, tim bp hoc tnh mch chm (t nht trong 5 pht) mi ln 200 mg, cch 4 - 6 gi mt ln. Gim liu ngi suy thn. Liu dng tr em: tr trn 1 tui mi ngy ung 25 - 30 mg/ kg, chia lm nhi u ln. Tr di 1 tui mi ngy ung 20 mg/ kg, chia lm nhiu ln. Cimetidin gy nhiu tc dng khng mong mun, c nhiu tng tc thuc hn cc thuc khng histamin H 2 khc. V vy, trong trng hp cn phi hp nhiu thuc, khng nn chn cimetidin. Ranitidin Tc dng mnh hn cimetidin 4 - 10 ln, nhng t gy tc dng khng mong mun v t tng tc thuc hn cimetidin. Liu dng: ung mi ln 150 mg, ngy 2 ln (vo bui sng v bui ti) hoc 300 mg vo bui ti trong 4 - 8 tun. Liu duy tr: 150 m g vo bui ti. Tim bp hoc tnh mch chm (t nht trong 2 pht, phi pha long 50 mg trong 20 mL): mi ln 50 mg, cch 6 - 8 gi/ ln. Famotidin Tc dng mnh hn cimetidin 30 ln. Liu dng: ung mi ngy 40 mg trc khi i ng trong 4 - 8 tun. Liu duy tr: 20 mg trc khi i ng. Tim tnh mch chm hoc truyn tnh mch (pha trong natri clorid 0,9%) mi ln 20 mg, cch 12 gi mt ln cho n khi dng c ng ung. Nizatidin Tc dng v liu lng tng t ranitidin, nhng t tc dng khng mong mun

hn cc thuc khng histamin H 2 khc. 1.3.2. Thuc c ch H +/ K+- ATPase (bm proton) 1.3.2.1. c im chung C ch tc dng Cc thuc c ch bm proton l nhng tin thuc, khng c hot tnh pH trung tnh. t bo thnh d dy (p H acid), chng c chuyn thnh cc cht c hot tnh, gn vo bm proton, c ch c hiu v khng hi phc bm ny. Do , cc thuc c ch bm proton lm gim bi tit acid do bt kz nguyn nhn g v l con ng chung cui cng ca s bi tit aci d. Thuc rt t nh hng n khi lng dch v, s bi tit pepsin v yu t ni ti ca d dy. Dng mt liu, bi tit acid d dy b c ch trong khong 24 gi (so snh vi thuc khng histamin H 2 ti a ch 12 gi). Bi tit acid ch tr li sau khi enzym mi c tng hp.. T l lin so c th t 95% sau 8 tun. Ch nh - Lot d dy- t trng lnh tnh. Phng v iu tr cc trng hp lot do dng thuc chng vim khng steroid. - Bnh tro ngc d dy - thc qun khi c triu chng nng hoc bin chng. - Hi chng Zollinger - E?llison (k c trng hp khng vi cc thuc khc). - D phng ht phi acid khi gy m. Chng ch nh v thn trng - Chng ch nh: qu mn vi thuc - Thn trng: suy gan, ph n c thai hoc cho con b. Phi loi tr kh nng ung th d dy trc khi dng thuc c ch bm proton. Tc dng khng mong mun Ni chung thuc dung np tt. C th gp kh ming, ri lon tiu ha, tng enzym gan, au u, chng mt, ri lon th gic, thay i v mu, vim thn, lit d ng, phn ng d ng. Do lm gim acid trong d dy, nn lm tng nguy c nhim khun ng tiu ha, c th gy ung th d dy. Tng tc thuc - Do pH d dy tng nn lm gim hp thu mt s thuc nh ketoconazol, itraconazol

- Omeprazol c ch cyto chrom P450 gan nn lm tng tc dng v c tnh ca diazepam, phenytoin, warfarin, nifedipin Lansoprazol t nh hng n cytochrom P 450, trong khi pantoprazol khng nh hng n enzym ny. - Clarithromycin c ch chuyn ha ca omeprazol, lm tng n ng omeprazol trong mu ln gp hai ln. 1.3.2.2. Cc thuc Omeprazol Lot d dy- t trng: ung mi ngy mt ln 20 mg trong 4 tun nu lot t trng, trong 8 tun nu lot d dy. Trng hp bnh nng hoc ti pht c th tng liu ti 40 mg mt ngy (ung hoc tim tnh mch). D phng ti pht: 10 - 20 mg/ ngy - Hi chng Zollinger - Ellison: liu khi u 60 mg/ ngy. Sau iu chnh liu trong khong 20- 120 mg/ ngy tuz p ng lm sng. Esomeprazol L ng phn ca omeprazol. Mi ngy ung 20 - 40 mg trong 4- 8 tun Pantoprazol Ung mi ngy mt ln 40 mg vo bui sng trong 2 - 4 tun nu lot t trng hoc 4 - 8 tun nu lot d dy. Trng hp bnh nng c th tim tnh mch chm hoc truyn tnh mch mi ngy mt ln 40 mg n khi ngi bnh c th ung li c. Lansoprazol - Lot d dy: mi ngy ung 30 mg vo bui sng trong 8 tun. - Lot t trng: mi ngy ung 30 mg vo bui sng trong 4 tun. - Liu duy tr: 15 mg/ ngy. Rabeprazol Mi ngy ung 20 mg vo bui sng trong 4 - 8 tun nu lot t trng hoc 6 12 tun nu lot d dy. Lu {: cc thuc c ch bm proton b ph hu trong mi trng acid nn phi dng di dng vin bao tan trong rut. Khi ung phi nut nguyn c vin vi nc (khng nhai, nghin) v ung cch xa ba n (tr c khi n sng, trc khi i ng ti). 1.4. Cc thuc khc 1.4.1. Cc mui bismuth c dng di dng keo subcitrat (trikalium dicitrato), subsalicylat Cc mui bismuth c tc dng:

- Bo v t bo nim mc d dy do lm tng tit dch nhy v bicarbon at, c ch hot tnh ca pepsin. - Bao ph chn lc ln y lot, to chelat vi protein, lm thnh hng ro bo v lot chng li s tn cng ca acid v pepsin. - Dit Helicobacter pylori . Khi dng ring, cc mui bismuth ch dit c H.pylori khong 20% ngi bnh, nhng khi phi hp vi khng sinh v thuc c ch bm proton, c th ti 95% ngi bnh tit tr c H.pylori. V th bismuth c coi l thnh phn quan trng trong cng thc phi hp thuc. Bismuth dng keo t hp thu qua ng ung (ch khong 1%) nn t gy c vi liu thng thng. Nu dng liu c?ao hoc dng ko di c th gy bnh no. Chng ch nh: qu mn vi thuc, suy thn nng, ph n c thai. Tc dng khng mong mun: bun nn, nn, en ming, en li, en phn (thn tr ng ngi c tin s chy mu ng tiu ha, v d nhm vi i tin phn en). Ch phm: Bismuth subcitrat vin nn 120 mg Ung mi ln 1 vin, ngy 4 ln vo 30 pht trc cc ba n v 2 gi sau ba n ti, hoc mi ln ung 2 vin, ngy 2 ln vo 30 pht trc ba n sng v ti. iu tr trong 4- 8 tun. Khng dng iu tr duy tr, nhng c th iu tr nhc li sau 1 thng. * Ch phm phi hp ranitidin v mui bismuth: ranitidin bismuth citrat d dy ranitidin bismuth citrat c phn ly t hnh ranitidin v bismuth, do c c hai tc dng ca hp cht bismuth v ca ranitidin. Ung mi ln 400 mg, ngy 2 ln trong 4 - 8 tun nu lot t trng hoc 8 tun nu lot d dy lnh tnh. Khng dng iu tr duy tr. 1.4.2. Sucralfat Sucralfat l phc hp ca nhm hydroxyd v sulfat sucrose. Ging nh bismuth, sucralfat t hp thu, ch yu c tc dng ti ch. Thuc gn vi protein xut tit ti lot, bao ph vt lot, bo v lot khi b tn cng bi acid dch v, pepsin v acid mt. Ngoi ra , sucralfat cn kch thch sn xut prostaglandin (E 2, I1,) ti ch, nng pH dch v, hp ph cc mui mt. Thn trng khi dng ngi suy thn (trnh dng khi suy thn nng) do nguy c tng nng nhm trong mu, ph n c thai v cho con b. t gy tc dng khng mong mun, ch yu l cc ri lon tiu ha. Ung mi ngy 4,0g, chia lm 2 - 4 ln vo 1 gi trc cc ba n v trc khi i ng, trong 4- 8 tun.

Sucralfat lm gim hp thu ca nhiu thuc, v vy phi ung cc thuc ny trc sucralfat 2 gi. 1.4.3. Misoprostol L prostaglandin E 1 tng hp, c tc dng kch thch c ch bo v nim mc d dy v gim bi tit acid, lm tng lin vt lot d dy - t trng hoc d phng lot d dy do dng thuc chng vim khng steroid. Do hp thu c v o mu nn gy nhiu tc dng khng mong mun: bun nn, y bng, kh tiu, au qun bng, tiu chy, chy mu m o bt thng, gy sy thai, pht ban, chng mt, h huyt p. Chng ch nh dng misoprostol ph n c thai (hoc d nh c thai) v cho con b. Thn trng: bnh mch no, bnh tim mch v nguy c h huyt p. Liu dng: - Lot d dy- t trng: mi ngy 800 g chia lm 2- 4 ln vo ba n v trc khi i ng, trong 4- 8 tun. - D phng lot d dy - t trng do dng thuc chng vim khng steroid: mi ln ung 200 g, ngy 2- 4 ln cng vi thuc chng vim khng steroid. 1.5. Khng sinh dit Helicobacter pylori Nu xc nh c s c mt ca H- pylori trong lot d dy t trng (bng test pht hin), phi dng cc phc dit H.pylori vt lot lin nhanh v trnh ti pht. Phc ph bin nht, t hiu qu cao, n gin, sn c v chi ph hp l l phc dng 3 thuc trong 1 tun (one - week triple- therapy) gm mt thuc c ch bm proton v 2 khng sinh: amoxicilin vi clari thromycin hoc metronidazol. Phc ny dit tr c H.pylori trong hn 90% trng hp. Gii thiu mt s phc dng 3 thuc trong ?1 tun dit tr H.pylori:

Nu lot ti pht nhiu ln, lot to, c nhiu lot hoc cc trng hp lot khng p ng vi phc 3 thuc, dng phc 4 thuc trong 2 tun gm thuc c ch bm proton, mui bismuth v 2 khng sinh. Cng c th phi hp tinidazol hoc tetracyclin vi cc khng sinh khc v thuc c ch bi tit acid dit tr H. pylori.

2. THUC IU CHNH CHC NNG VN NG V BI TIT CA NG TIU HA ng tiu ha c chc nng vn ng hp thu cc cht dinh dng, in gii, nc v bi tit cc cht cn b. Khi ri lon cc chc nng ny s sinh ra cc triu chng bun nn, nn, chng bng, kh tiu, to bn, tiu chy Ngoi vic cha triu chng, thy thuc cn tm nguyn nhn iu tr. 2.1. Thuc kch thch v i u chnh vn ng ng tiu ha 2.1.1. Thuc gy nn Nn l mt phn x phc hp, bao gm co tht hang - mn v, m tm v, co tht c honh v c bng, kt qu l cc cht cha trong d dy b tng ra ngoi qua ng ming. Trung tm nn nm hnh no, c hu s chi phi ca cc trung tm cao hn l m o v vng nhn cm ha hc sn no tht 4 (area postrema) hay trigger zone (Hnh 27.3)

Hnh 27.3: V tr, c ch tc dng ca nn v thuc chng nn C 3 loi thuc gy nn: 2.1.1.1. Thuc gy nn trung ng: L thuc kch thch vng nhn cm ha hc trigger: apomorphin, ng 5 mg tim di da. Tr em dng liu 1/20 - 1/10 mg/ kg. 2.1.1.2. Thuc gy nn ngoi bin L thuc c tc dng kch thch cc ngn dy thn kinh li, hu v dy ph v ti nim mc d dy. - ng sulfat 0,3 g/ 100mL nc, c th ung thm sau 10 - 20 pht. - Km sulfat 0,6 - 2 g/ 200 mL nc. 2.1.1.3. Thuc gy nn c c ch hn hp Ipeca hoc ipecacuanha: bt vng sm ng trong nang 1 - 2g, hoc ru thuc 5 - 20 mL, hoc siro 15 mL, c th dng nhc li tng 15 pht cho n khi nn. Thuc gy nn c ch nh tro ng cc ng c cp tnh qua ng tiu ha, nhng trong thc hnh thng ra d dy s tt hn. Khng dng thuc gy nn cho ngi hn m hoc nhim c cht n da. 2.1.2. Thuc lm tng nhu ng rut 2.1.2.1. Thuc nhun trng

L thuc lm tng nhu ng ch yu rut gi, y nhanh cc cht cha trong rut gi ra ngoi. Ch dng thuc nhun trng khi chc chn b to bn, trnh lm dng thuc v c th gy hu qu h kali mu v mt trng lc i trng. Him khi cn iu tr to bn ko di, tr m t s ngi cao tui. C th phng to bn bng ch n cn bng, nc v cht x, vn ng hp l. Theo c ch tc dng, thuc nhun trng c chia thnh 5 nhm chnh. Mt s thuc nhun trng c c ch tc dng hn hp. - Thuc nhun trng lm tng khi lng phn: methylcellulose. - Thuc nhun trng kch thch: kch thch trc tip c trn thnh rut lm tng nhu ng rut, c th gy co cng bng: bisacodyl, glycerin, nhm anthraquinon, cc thuc cng ph giao cm, docusat natri - Cht lm mm p hn: paraphin lng, du arachis. - Thuc nhun trng thm thu, c tc dng gi li dch trong lng ?rut: mui magnesi, lactulose, sorbitol, macrogol, glycerin - Dung dch lm sch rut dng trc khi phu thut i trng, soi i trng hoc chun b chiu chp X - quang i trng, khng dng iu tr to bn. Bisacodyl - Bisacodyl lm tng nhu ng rut do kch thch m ri thn kinh trong thnh rut, ng thi lm tng tch ly ion v dch trong lng i trng. - Ch nh: . To bn do cc nguyn nhn khc nhau. . Lm sch rut trc khi phu thut. . Chun b chp X - quang i trng. - Chng ch nh: Tc rut, vim rut tha, chy mu trc trng, vim d dy - rut. - Tc dng khng mong mun: Thng gp au bng, bun nn. t gp kch ng trc tr ng khi t thuc. Dng di ngy lm gim trng lc i trng v h kali mu. - Liu dng: . To bn: ung 5 - 10 mg vo bui ti hoc t trc trng vin n 10 mg vo bui sng . Tr em di 10 tui ung 5 mg vo bui ti hoc t trc trng vin n 5 mg vo bui sng. . Chun b chp X - quang i trng hoc phu thut: ngi ln ung mi ln

10 mg lc i ng, trong 2 ngy lin trc khi chp chiu hoc phu thut. Tr em dng na liu ngi ln. Lu {: dng vin bao bisacodyl phn r rut, do kh ng c nhai hoc nghin vin thuc. Khng dng thuc qu 7 ngy, tr khi c hng dn ca thy thuc. Magnesi sulfat L thuc nhun trng thm thu. Do t c hp thu, magnesi sulfat lm tng p lc thm thu trong lng rut, gi nc, lm tng th tch lng rut, gy kch thch tng nhu ng rut. Ung magnesi sulfat liu thp (5g) c tc dng thng mt v nhun trng, liu cao (15 - 30g) c tc dng ty. Tim tnh mch magnesi sulfat c tc dng chng co git trong sn khoa. Chng ch nh: cc bnh c p ng tiu ha. Thn trng: suy thn, suy gan, ngi cao tui, suy nhc. Liu dng nhun trng: ngi ln v tr em trn 12 tui: 10g; 6 - 11 tui: 5g; 2 - 5 tui: 2,5g. Pha thuc trong cc nc y (t nht trong 240 ml) ung trc ba n sng. Thuc tc dng trong 2 - 4 gi. 2.1.2.2. Thuc ty L thuc tc dng c rut non v rut gi, dng tng mi cht cha trong rut ra ngoi (cht c, giun sn) nn thng ch dng 1 ln. Thuc ty mui L cc mui t c hp thu, lm tng p lc t hm thu, gi nc, lm tng th tch lng rut. Thng dng megnesi sulfat, natri sulfat ung 15 - 30g vi nhiu nc. Thuc ty du Thng dng du thu du (ricin) c cha triglycerid ca acid ricinoleic. Di tc dng ca lipase ty tng, triglycerid b thu phn, gii phng acid ricinoleic. Acid ny c tc dng kch thch nim mc rut non lm tng nhu ng rut v tng xut tit. Mt khc, khi acid ricinoleic chuyn thnh natri ricinoleat, th cht ny khng b hp thu, c tc dng nh thuc ty mui. Liu lng ung 15 - 30g. Du ricin c th lm d dng hp thu mt s thuc qua rut, gy ng c: v d khi dng cng vi mt s thuc chng giun sn. Khi iu tr ng c thuc cp tnh, thng dng thuc ty mui, khng dng thuc ty du. 2.1.3. Thuc iu ho chc nng vn ng ng tiu ha Cc thuc loi ny c tc dng phc hi li nhu ng ng tiu ha nh b

z, dng iu tr chng y bng, kh tiu khng do lot. 2.1.3.1. Thuc khng dopamin ngoi bin Domperidon Domperidon l thuc i kh ng vi dopamin ch ngoi bin v khng qua c hng ro mu no. V vy c tc dng: - Chng nn trung ng: c ch cc receptor dopamin vng nhn cm ha hc sn no tht IV (nm ngoi hng ro mu - no). - Lm tng tc y cc cht cha tron g d dy xung rut do lm gin vng y d dy, tng co hang v, lm gin rng mn v sau ba n. - Tng trng lc c tht thc qun, chng tro ngc d dy - thc qun. - Tng bin v tn s ca nhu ng t trng, iu ho nhu ng ng tiu ha. Ch nh: iu tr triu chng bun nn v nn cp, c bit ngi bnh ang iu tr bng thuc c t bo; chng bng, kh tiu sau ba n do thc n chm xung rut. Chng ch nh: chy mu ng tiu ha, tc rut c hc, nn sau khi m, tr em di 1 tui. Tc dng khng mong mun: nhc u, tng prolactin mu (chy sa, ri lon kinh nguyt, au tc v) Liu dng: ung 10 - 60 mg/ ngy, trc ba n 15 - 30 pht. Khng dng thng xuyn hoc di ngy. Metoclopramid Khc vi domperidon, metoclopramid p hong b receptor ca dopamin, i khng vi tc dng ca dopamin c trung ng v ngoi bin do thuc d dng qua c hng ro mu no. ngoi bin, metoclopramid c tc dng tng t nh domperidon. Do c tc dng c trn trung ng, metoclopramid c tc dng an thn v c th gy phn ng lon trng lc c cp tnh (co tht c xng v c mt, cc cn vn nhn), thng xy ra ngi bnh l n tr hoc ngi rt gi. Ch nh: chng nn, chng tro ngc d dy - thc qun, y bng kh tiu, chun b chp X- quang d dy hoc t ng thng vo rut non. Chng ch nh: ng kinh, chy mu ng tiu ha, tc rut c hc hoc thng rut. Tc dng khng mong mun: a chy, bun ng, phn ng ngoi thp (lon trng lc c cp), mt mi, yu c.

Liu dng: ung 5- 10mg/ ln, ngy 3 ln. C th dng ng tim (bp, tnh mch) hoc truyn tnh mch nu bnh nng. 2.1.3.2. Thuc cng ph giao cm ng tiu ha: Cisaprid. Cisaprid kch thch gii phng ACh u tn cng ca m ri thn kinh tng, khn g kch thch trc tip receptor M hoc phong to ChE nn tc dng ch khu tr rut, tng. Khc vi metoclopramid, cisaprid kch thch vn ng tt c cc phn ca ng tiu ha, k c thc qun v rut gi. Tc dng: tng nhu ng thc qun, tng p lc qua tm v. Tng nhu ng d dy t trng nn lm nhanh rng d dy. Tng chuyn vn ca d dy - rut nonrut gi. Ch nh: Tro ngc d dy - thc qun. Chm tiu. To bn mn tnh. Liu dng: ung mi ln 5 - 20mg, ngy 2- 4 ln, trc ba n 30 ph t. 2.1.3.3. Thuc tc dng trn h enkephalinergic ti rut Cc receptor ca h enkephalinergic ti rut c tc dng iu ha nhu ng: tc dng kch thch trn c gim vn ng v tc dng chng co tht trn c tng vn ng Trimebutin Kch thch recepto r enkephalinergic rut khi c ri lon. Ch nh: hi chng kch thch ru ng n? t/ lit rut sau m. Ri lon chc nng tiu ha: au bng, chm tiu, tiu chy/ to bn. Liu dng: ung mi ln 100 - 200 mg, ngy 3 ln. Racecadotril Cht c ch enkephalinase c hi phc ti rut, lm gim tit dch rut v in gii ca nim mc rut khi b vim hoc c t vi khun kch thch. Khng c tc dng trn rut bnh thng v khng nh hng n nhu ng rut nn dng trong tiu chy cp. Liu dng: ung mi ln 10 0 mg, ngy 3 ln trc cc ba n. Khng dng cho tr em di 15 tui 2.2. Thuc chng co tht v lm gim nhu ng ng tiu ha 2.2.1. Thuc chng nn Cc thuc chng nn c ch nh trong cc chng nn do c thai, sau m, nhim khun, nhim c (do nhim acid, do ur mu cao), say tu xe v do tc dng ph ca thuc, nht l cc thuc chng ung th. 2.2.1.1. Gy t ngn dy cm gic d dy : kh CO2, natri citrat, procain 2.2.1.2. Thuc c ch ph giao cm : atropin, scopolamin, ben zatropin 2.2.1.3. Thuc khng histamin H 1: diphenhydramin, hydroxyzin, cinnarizin, cyclizin,

promethazin. Ngoi khng H1, cc thuc ny cn c tc dng khng M cholinergic v an thn kinh (xin xem bi Histamin v thuc khng histamin H 1) 2.2.1.4. Thuc k hng receptor D 2 (h dopaminergic) Thuc c tc dng c ch receptor dopamin vng nhn cm ha hc sn no tht IV. Ngoi ra, thuc cn c ch cc receptor D 2 ngoi bin ng tiu ha. - Loi phenothiazin: clopromazin, perphenazin. - Loi butyrophen on: haloperidol, droperidol - Domperidon, metoclopramid. 2.2.1.5. Thuc khng serotonin Phng v iu tr bun nn, nn do ha tr liu ung th, do chiu x hoc sau phu thut. Cc thuc: - Ondansetron: ung hoc tim tnh mch 8 - 32 mg/ ngy. - Granisetron: ung hoc tim tnh mch 1 - 3 mg/ ngy. - Dolasetron mesilat: ung hoc tim tnh mch 12,5 - 200 mg/ ngy. 2.2.1.6. Cc thuc khc - Benzodiazepin: lorazepam, alprazolam - Corticoid: dexamethason, metylprednisolon. C ch cha hon ton bit r, c mt phn tc dng c ch trung tm nn. 2.2.2. Thuc chng co tht c trn ng tiu ha Do c tc dng chng co tht c trn theo cc c ch khc nhau, cc thuc ny c dng iu tr triu chng cc cn au do co tht ng tiu ha, ng mt v c ng sinh dc, tit niu. 2.2.2.1. Thuc hu ph giao cm Atropin sulfat: Hu ph giao cm c trung ng v ngoi bin (xin xem bi Thuc tc dng trn h thn kinh thc vt) Hyoscin N- butylbromid V mang amin bc 4 nn khng vo c thn kinh trung ng, ch c tc dng hu ph giao cm ngoi bin. Tc dng khng mong mun: kh ming, mch nhanh, b i, to bn, ri lon iu tit mt. Chng ch nh: glcm gc ng, ph i tuyn tin lit, nhc c, tc lit rut, hp mn v, ri lon chuyn ha porph yrin. Liu dng: mi ln ung 10 - 20 mg, ngy 3- 4 ln.

2.2.2.2. Thuc chng co tht c trn trc tip Papaverin hydroclorid Papaverin l mt alcaloid trong nha kh ca qu cy thuc phin, khng c tc dng gim au, gy ng ging morphin. Tc dng ch yu ca papaverin l lm gin c trn ng tiu ha, ng mt v ng tit niu. Chng ch nh: qu mn vi thuc, bloc nh - tht hon ton, mang thai (c th gy c cho thai). Tc dng khng mong mun: bng mt, nhp tim nhanh, chng mt, nhc u , ng g, ri lon tiu ha, vim gan. Liu dng: ung hoc tim (bp, tnh mch) mi ln 30 - 100mg, ngy 2- 3 ln. Alverin citrat L thuc chng co tht, tc dng trc tip ln c trn ng tiu ha v t cung. So vi papaverin, tc dng mnh hn 3 ln n hng c tnh km 3 ln. Chng ch nh: tc nghn rut hoc lit rut, mt trng lc rut kt. Tc dng khng mong mun: bun nn, au u, chng mt, phn ng d ng. Liu dng: mi ln ung 60 - 120 mg, ngy 1 -3 ln. Cc thuc khc : mebeverin, dicyclov erin, phloroglucinol, drotaverin. 2.3. Thuc chng tiu chy Trong iu tr tiu chy, ngoi vic iu tr nguyn nhn, vn u tin trong mi trng hp l nh gi v x l{ ng nhng ri lon nc v in gii. Cc thuc lm gim triu chng (hp ph, bao ph nim mc, gim tit dch, gim nhu ng rut) c th dng trong mt s trng hp tiu chy ngi ln, nhng khng nn dng tr em v chng khng lm gim c s mt dch v in gii, m cn c th gy ra nhiu tc dng c hi. 2.3.1. Thuc ung b nc v in gii (ORS, Oresol) 2.3.1.1. Thnh phn v c ch tc dng - Thnh phn mt gi bt (ORS ca Unicef) Natri clorid: 3,5g; Kali clorid: 1,5g; Natribicarbonat: 2,5g; Glucose: 20,0g. Nc ha tan: 1gi/ 1 lt. - C ch tc dng: s hp thu ca natri v nc rut c tng cng bi glucose (hoc carbohydrat khc). Glucose hp thu tch cc rut ko theo hp thu natri (h thng ng vn chuyn glucose - natri rut non).

B kali trong tiu chy cp c bit quan trng tr em, v tr mt kali trong phn cao hn ngi ln. Bicarbonat (hoc citrat) c tc dng khc phc tnh trng nhim toan chuyn ha trong tiu chy. 2.3.1.2. Ch nh : phng v iu tr mt nc v in gii mc nh v va. 2.3.1.3. Chng ch nh : Gim niu hoc v niu do gim chc nng thn. Mt nc nng (phi truyn tnh mch dung dch Ringer lactat). Nn nhiu v ko di, tc rut, lit rut. 2.3.1.4. Tc dng khng mong mun: Nn nh, tng natri mu, suy tim do b nc qu mc. 2.3.1.5. Liu dng: - Mt nc nh: ung 50 ml/ kg trong 4 - 6 gi u. - Mt ncva: ung 100 ml/ kg trong 4 - 6 gi u. Sau iu chnh theo mc kht v p ng vi iu tr. Cn tip tc cho tr b m hoc n ung bnh thng. C th cho ung nc trng gia cc ln ung ORS trnh tng natri mu. 2.3.2. Cc cht hp ph, bao ph nim mc rut Do c trng lng phn t cao, cu trc phin mng, tnh cht do dai nn cc cht ny c kh nng gn vi protein ca nim mc ng tiu ha, to thnh mt lp mng bao ph, bo v nim mc. - Atapulgit: ngoi tc dng to mng bo v nim mc rut, thuc cn hp ph cc c t ca vi khun, cc kh trong rut, c tc dng cm mu ti ch . Liu dng: gi bt 3g atapulgit hot ha, ung 2 - 3 gi/ ngy. Khng dng trong iu tr tiu chy cp tr em. - Smecta: gi bt 3g, 2- 3 gi/ ngy, ung xa ba n. 2.3.3. Cc cht lm gim tit dch, gim nhu ng rut ?Loperamid Tc dng: loperamid l opiat tng hp nhng c rt t tc dng trn thn kinh trung ng. Loperamid lm gim nhu ng rut, ko di thi gian vn chuyn qua rut, gim tit dch ng tiu ha, tng vn chuyn nc v cht in gii t lng rut vo mu, tng trng lc c tht hu mn. Ch nh: iu tr triu chng tiu chy cp khng c bin chng hoc ti u chy mn ngi ln. Chng ch nh: mn cm vi thuc, khi cn trnh c ch nhu ng rut, vim i trng nng, tn thng gan, hi chng l, trng bng.

Tc dng khng mong mun: bun nn, to bn, au bng, trng bng, chng mt, nhc u, d ng. Liu dng: - Ngi ln: lc u ung 4 mg, sau mi ln i lng ung 2 mg cho ti khi ngng tiu chy. Liu ti a: 16 mg/ ngy. Khng dng qu 5 ngy trong tiu chy cp. - Tr em: khng dng thng qui trong tiu chy cp. Ch dng cho tr em trn 6 tui khi tht cn thit. Mi ln ung 2 mg, ngy 2 - 3 ln tuz theo tui. Ngng thuc nu thy khng c kt qu sau 48 gi. 2.3.4. Vi khun v nm 2.3.4.1. Lactobacillus acidophilus Vi khun sn xut acid lactic v 2 cht dit khun: lactocidin v acidophil lin. C kh nng tng hp vitamin nhm B. Bnh thng, cc vi khun cng sinh trong lng rut c s cn bng gia vi khun hu saccharose v cc vi khun hu protein. Mt s cht tn cng vo vi khun hu saccharose nh ru, stress, nhim khun, khng sin h gy ra s mt cn bng, lm tng vi khun hu protein, dn n ri lon tiu ha (tiu chy, to bn, trng bng) Lactobacillus acidophilus c tc dng lp li thng bng vi khun cng sinh trong rut, kch thch vi khun hu saccharose pht trin, k ch thch min dch khng c hiu ca nim mc rut (tng tng hp IgA) v dit khun. Ch nh: cc tiu chy do lon khun rut Ch phm: Antibio: gi bt 1g cha 100 triu vi khun sng. Ngi ln ung mi ln 1gi, ngy 3 ln. Tr em ung mi ngy 1- 2 gi. 2.3.4.2. Saccharomyces boulardii L nm men c tc dng tng hp vitamin nhm B, km khun, dit Candida albicans , kch thch min dch khng c hiu. Ch nh: d phng v iu tr tiu chy do dng khng sinh, tiu chy cp. V nm men l cc t bo sng nn khng c trn vo nc hay thc n nng (trn 500C), qu lnh hoc c ru. Khng dng cng vi cc thuc chng nm. Ch phm: Ultra - levure, vin nang cha Saccharomyces boulardii ng kh 56,5mg. Mi ln ung 1 vin, ngy 4 ln. 2.4. Thuc li mt v thuc thng mt 2.4.1. Thuc li mt Phn bit hai loi: - Thuc li mt nc (secretin, thuc cng ph giao cm) lm tng bi tit

nc v in gii ca t bo biu m ng mt, gy tng tit mt long. - Thuc li mt thc th kch thch t bo gan tng bi tit mt ging nh mt sinh l. Tuz theo ngun gc, c: 2.4.1.1. Thuc li mt c ngun gc ng vt l mui mt, cc acid mt, hoc mt ton phn loi b sc t v cholesterol Ch phm: Bilifluine, vin nang 0,1g, ung 2 vin trc mi ba n tra v ti. 2.4.1.2. Thuc li mt c ngun gc thc vt : ngh, actiso, boldo. Thng dng ch phm phi hp nhiu cy thuc 2.4.1.3. Thuc li m?t tng hp - Cyclovalon: vin bao ng 50 mg, ung 6 - 12 vin/ ngy - Anthol trithion: d ng thuc ht c 0,0125g/ ht. Mi ngy ung 3 - 6 ht. Ch nh chung ca cc thuc li mt - iu tr triu chng cc ri lon tiu ha: trng bng, y hi, hi, bun nn - iu tr ph tr chng to bn Chng ch nh : tc mt v suy gan nng 2.4.2. Thuc thng mt L nhng thuc gy co tht ti mt, ng thi lm gin c trn Oddi. Mt hon ton thot khi ti mt. V mt sinh l, tc dng ny ph thuc vo cholecystokinin pancreatozinin (CCK PZ) do t trng tit ra khi lipid v peptid t d dy tr n xung. Hu nh cc thuc c tc dng thng mt l do lm bi tit CCK - PZ. Ch nh: cc ri lon tiu ha nh y bng, chm tiu, hi, bun nn Chng ch nh: si ng mt, c tin s amip. Cc thuc: Sorbitol gi bt 5g. Mi ln pha 1 gi trong n c, ung trc ba n. Magnesi sulfat: ung 2 - 5g BI 43. THUC LI NIU 1. I CNG Tt c cc cht lm tng khi lng nc tiu u c coi l c tc dng li niu (ung nc nhiu lm i nhiu). Song nu ch nh vy th khng gii quyt c ph, l tnh trng ng Na + dch ngoi t bo. Cho nn thuc li niu phi l thuc lm tng thi tr Na+, km theo l thi tr nc ly t dch ngoi t bo. Trn ngi khng c ph, thuc li niu vn c tc dng. l c s s dng n trong iu tr cao huyt p: lm gim Na + ca thnh

mch s lm tng tc dng ca thuc h p v gim tc dng ca cc hormon gy co mch (nh vasopressin). Ngoi tc dng c ch chn lc ti hp thu Na +, cc thuc li niu cn c nh hng trc tip hoc gin tip n s bi xut ca mt s in gii hoc cc cht khc: K +, Cl-, HCO3- , acid uric v gy ra cc ri lon khi dng ko di. hiu r c ch v cc tc d ng khng mong mun ca thuc li niu, cn nhc li qu trnh vn chuyn ca mt s ion khi qua thn. 1.1. Vn chuyn ca Na + - ng ln gn, khong 70 - 80% Na+ c ti hp thu cng vi cc cht hu c ha tan (ng, acid amin), vi cc anion (acetat, phosphat, citrat, Cl -), vi bicarbonat di nh hng ca carbonic anhydrase. - on ln ca quai Henle, Na + tip tc c ti hp thu khong 15 - 20%, theo c ch cng vn chuyn 1 Na +, 1 K+ v 2 Cl-. - ng ln xa, ti hp thu Na + (0- 10%) ph thuc vo bi xut K+ v H+: . Trao i Na+ v K+ di nh hng ca aldosteron, hormon lm tng ti hp thu Na + v tng thi K+ . Trao i gia Na + v H+ ph thuc vo trng thi thng bng acid - base. Trong nhim acid, c s tng thi tr H + nn lm tng ti h p thu Na+: c 1 ion H+ thi tr vo lng ng thn th 1 ion Na + c ti hp thu. Trong nhim base c hin tng ngc li. Kt qu cui cng l sau khi lc qua cu thn (25.000 mEq/ 24h), Na + c ti hp thu ti 98- 99%, ch thi tr 20 - 400 mEq/ 24h. 1.2. Vn chuyn K + K+ qua cu thn c ti hp thu hon ton ng ln gn. S c mt ca K + trong nc tiu l do c bi xut ng ln xa bng cc qu trnh sau: - nh hng ca aldosteron: thi K + ?v ti hp thu Na + - nh hng ca trng thi thng bng acid- base: H+ v K+ l 2 ion c thi tr tranh chp ng ln xa. Trong nhim acid, khi tng thi tr H + trao i vi ti hp thu Na + th s gim bi xut K +. Trong nhim base th ngc li, ion H + c to ra phn ln l do enzym carbonic anhy drase (CA). ng ln xa, CA ng vai tr ch yu trong acid ha nc tiu. 1.3. Bicarbonat ng ln gn, 4/5 bicarbonat lc qua cu thn c ti hp thu do nh hng ca enzym CA (hnh 25.1). Phn cn li hu nh s b ti hp thu nt ng ln xa (p H ca nc tiu l acid nn khng cha bicarbonat).

1.4. Vn chuyn nc - ng ln gn, nc c ti hp thu th ng theo cc cht in gii. Nc tiu trong lng ng ng trng. - nhnh xung ca quai Henle, nc c ti hp thu n thun, khng km theo in gii, nc tiu ngy cng u trng.

Hnh 25.1. Ti hp thu bicarbonat ng ln gn - nhnh ln ca quai Henle, nc khng thm qua c, trong khi Na + li c ti hp thu, nn nc tiu dn dn tr thnh nhc trng. V vy, phn cui ca nhnh ln v phn u ca ng ln xa c gi l on pha long.

Hnh 25.2. Vn chuyn nc v in gii n v thn = : Nc tiu ng trng + : u trng - : Nhc trng - Trong ng gp, tnh thm vi nc c thay i ph thuc v o ADH, hormon chng bi niu ca thuz sau tuyn yn. Vi s c mt ca ADH, ng gp thm nc mnh, nc c ti hp thu khng km theo ion, nc tiu c c c dn v tr thnh u trng. Khi khng c ADH th ng gp khng thm nc, nc tiu t ng ln xa n vn gi trng thi nhc trng trong ng gp (H.29). Nh vy, cu thn lc 130 ml/ pht v bi xut nc tiu l 1 ml/ pht (1440 ml/ 24h). Ngha l trn 99% nc tiu lc qua cu thn c ti hp thu. R rng l mun c tc dng li niu n hanh khng phi l lm tng sc lc ca cu thn m l cn c ch qu trnh ti hp thu ca ng thn. 2. CC THUC LI NIU Mi thuc li niu thng tc dng mt v tr nht nh ca ng thn, lm thay i thnh phn ion ca nc tiu trong lng ng th n. S thay i s gin tip hoc trc tip gy ra cc phn ng trong s vn chuyn cc ion v nc cc phn khc, v s l nguyn nhn ca cc ri lon in gii, thng bng acid - base ca thuc. tin theo di lm sng khi dng thuc li niu ko d i, ta chia thnh 2 nhm ln:

- Thuc li niu lm gim K + mu (tng thi tr K +) - Thuc li niu gi K + mu (gim thi tr K +) - Ngoi ra, c loi thuc li niu thm thu, khng gy ri lon ion. 2.1. Thuc li niu lm gim K + mu Cc thuc ny do tc dng lm tng thi Na + on trn ca ng ln nn on cui ca ng ln c phn ng tng thi K + gi Na+, gy cc ri lon gim K + mu v lm tng c tnh ca thuc dng cng (nh loi digitalis). 2.1.1. Thuc phong to car bonic anhydrase (CA) Cn gi l sulfamid li niu. Tt c u c nhm sulfonamid ( -SO2NH2) trong cng thc, nhng khn?g c tc dng km vi khun. 2.1.1.1. Tc dng v c ch ng ln gn, trong t bo ng thn, CA c tc dng lm gii phng ion H + vo lng ng thn theo phn n g sau: CA H2O + CO2 H2CO3 HCO3- + H+ H+ c gii phng vo lng ng thn s trao i vi Na + c ti hp thu (hnh 1). Khi enzym CA b phong ta, lng ion H + bi xut b gim nn Na + khng c ti hp thu, thi tr ra nc tiu di dng bicarbonat, k o theo nc nn li niu. Mt khc, do s bi xut tranh chp gia H + v K+, khi thiu H+, K+ s b tng thi tr. Tm li, thuc lm tng thi tr Na +, K+ v bicarbonat (c th lm thi tr ti 45% lng HCO 3- qua thn), do lm gim K+ mu v gy nhim acid chuyn ha. Tnh trng nhim acid ny ch b tr sau 3- 7 ngy v sau l nguyn nhn t gii hn hiu qu ca thuc: dng thuc lin tc, tc dng b gim nhanh. Do qu trnh b tr, nng Cl - huyt tng tng (do t ng ti hp thu NaCl) Ngoi ra mt (cun m) v thn kinh trung ng cng c enzym CA. Thuc c ch enzym lm gim tit thu dch ca mt, gim sn xut dch no ty v gy toan chuyn ha trn thn kinh trung ng. 2.1.1.2. Ch nh - V c nhiu thuc li niu tt hn nn thuc ny khng cn c dng vi mc ch li niu. Ch nh ca thuc lin quan n tc dng thi tr bicarbonat v tc dng ngoi thn. - iu tr tng nhn p (glcm gc m) do thuc lm gim tit dch nhn cu. - iu tr chng ng kinh: ngoi tc dng lm gim to thnh dch no tu,

thuc cn c tc dng chng co git. Trong no, cc qu trnh oxy ha xy ra rt nhanh cho nn CO 2 cng c sinh ra nhanh. Thuc phong to enzym CA bo tng, lm tch lu H 2CO3 gy nhim acid t bo nn lm thay i chc phn t bo thn kinh. 2.1.1.3. Chng ch nh - Bnh tim phi mn tnh, hoc cc bnh phi mn tnh c suy h hp v tng CO2 mu, v cc thuc phong to CA ngn cn ti hp thu bicarbonat cn thit nh l cht m trung ha trng thi qu tha CO 2 trong m. - X gan v suy gan, v thuc gy acid mu, d lm xut hin hn m gan. 2.1.1.4. Tai bin - Gy acid huyt do lm gim d tr base, khi tc dng ca thuc cng b gim i nu dng thuc nhiu liu lin nhau, cho nn cn d ng ngt qung. - Gim K+ mu, gy mt mi, hoc d xy ra nhim c khi ang iu tr bng digitalis. 2.1.1.5. Ch phm

Vin 0,25 g. Mi ngy ung 1 vin. Trong bnh tng nhn p, c th ung 4 6 vin mt ngy. Hp thu nhanh qua ng tiu ha, gn v i protein huyt tng 92%. Thi gian bn hy ngn, khng b chuyn ha. Thi tr hon ton qua nc tiu trong 24 gi. 2.1.2. Nhm thiazid (benzothiadiazid) Trong phn t c 2 nhm sulfonamid ( -SO2NH2), 1 t do v 1 nm trong d vng. 2.1.2.1. Tc dng v c ch Tc dng c ch CA k m acetazolamid (Diamox), nhng tc dng li niu li nhanh hn v vy cn c nhng tc dng khc m c ch cn cha hon ton bit r. L thuc tc dng trc tip trn thn, tim vo 1 thn th gy li niu ch cho thn (tuy nhin cha tm thy receptor hay enzym c hiu). Thiazid c ch ti hp thu Na + v km theo l c Cl - (v tr ng vn chuyn) on pha long (phn cui ?ca nhnh ln quai Henle v phn u ca ng ln xa), thi tr Na + v Cl- vi s lng gn ngang nh au nn cn gi l thuc li niu thi tr mui (saluretics). Khong 5- 10% Na+ lc qua cu thn b thi tr nn thuc loi thuc c tc dng li niu trung bnh. Thuc c tc dng c mi trng acid v base.

- Lm tng thi tr K +, theo 2 c ch: mt ph n do thuc c ch enzym CA, lm gim bi tit ion H+ nn tng thi K + (c ch thi tr tranh chp ng ln xa); mt phn do c ch ti hp thu Na+ lm m Na+ tng cao ng ln xa, gy phn ng b tr bi xut K + ko Na+ li. - Khng lm tng th i tr bicarbonat nn khng gy acid mu. - Lm gim bi tit acid uric qua ng thn nn c th lm nng thm bnh gut. Cc thiazid c thi tr qua h thi tr acid hu c ca ng thn nn tranh chp mt phn vi thi tr acid uric qua h ny. - Dng lu, lm gim calci niu do lm tng ti hp thu Ca ++ ng ln gn v c xa nn c th dng d phng si thn. Tuy nhin, him khi gp tng calci mu do thiazid v c th c cc c ch b tr khc. - Lm h huyt p trn nhng bnh nhn b tng huyt p v ngoi tc dng lm tng thi tr mui, cc thuc cn c ch ti ch tc dng ca thuc co mch trn thnh mch, nh vasopressin, noradrenalin. Mt khc, do lng Na + ca m thnh mch gim nn dch gian bo ca thnh mch cng gim, lm lng mch rng ra , do sc cn ngoi vi gim xung (huyt p ti thiu h). 2.1.2.2. Ch nh - Ph cc loi: tim, gan, thn, c th gy thiu mu thai v teo thai, khng dng cho ph v tng huyt p khi c thai. C th dng cho ph tim, gan, thn ngi c thai. - Tng huyt p: dng ring hoc dng cng vi cc thuc h p khc, v c tc dng hip ng. - Tng calci niu khng r nguyn nhn d dn n si niu. 2.1.2.3. Chng ch nh hoc dng thn trng - Trng thi gim kali - mu trn bnh nhn b x gan (v d l m xut hin hn m gan), trn bnh nhn ang iu tr bng digital (s lm tng c tnh ca digital). Khc phc bng ung KCl 1 - 3 g mt ngy. - Bnh gut: do thiazid lm tng acid uric mu - Suy thn, suy gan, khng dung np sulfamid (gy bnh no do gan ). 2.1.2.4. Tai bin Khi dng lu, thuc c th gy cc tai bin sau: - Ri lon in gii: h Na + v K+ mu (theo c ch trnh by trn), gy mt mi, chn n, nhc u, bun nn, chut rt. - Tng acid uric mu gy ra cc cn au ca bnh gut. iu tr bng probenecid.

- Lm nng thm i ng ty. C ch cha r. Mt s tc gi thy thiazid c ch gii phng insulin v lm tng bi tit catecholamin u dn ti tng ng huyt. - Lm tng cholesterol v LDL mu khong 5 - 15%. Tuy nhin khi dng k o di th c 2 mc li tr v bnh thng. - Mt s biu hin d ng hoc khng chu thuc. 2.1.2.5. Tng tc thuc - Cc thiazid lm gim tc dng ca cc thuc chng ng mu, thuc lm tng thi tr uric iu tr gut, cc sulfonylure v insulin. - Cc thiazid lm tng tc dng ca thuc t, diazoxid, glycosid tr tim, lithi, thuc li niu quai v vitamin D. - Tc dng li niu ca thiazid b gim khi dng cng vi thuc chng vi u< m phi steroid. Amphotericin B v corticoid lm tng nguy c h kali mu ca thiazid. 2.1.2.6. Ch phm: mt s thuc thng dng Chc halogen C 6 v nhm sulfamid C 7 rt cn cho tc dng li niu ca c nhm. Thay nhm -SO2 NH2 C7 bng Cl, c diazoxid c tc dng ngc vi chlorothiazid, gi Na +, nhng c tc dng gin mch, h huyt p. Hydrochlorothiazid do bo ha ng ni 3 - 4, c tc dng thi tr Na + mnh gp 10 chlorothiazid.

Bng 25.1: Mt s ch phm Hin nay c thm mt s ch phm mi: - Chronexan (Xipamid) . Vin 20 mg D hp thu qua tiu ha. nh huyt tng 45 pht - 2 gi sau khi ung liu duy nht. T1/2: 6- 8h. Gn vo protein huyt tng 95%. Thi 90% qua thn, ch yu l dng khng i. Ung liu duy nht bui sng 10 - 40 mg - Hygroton (Chlorthalidone) . Vin 25 mg Hp thu chm. T 1/2 l 50 gi.Thi 1/2 qua thn di dng khng i. Qua c sa. Ung 1 ln vo bui sng, 1 - 2 vin - Fludex (Indapamid) vin 2,5 mg, Natrilix vin 1,5 mg. c im: . Gin mch (thay i dng ion, c bit l Ca) . Kch thch tng hp PGE 2 v PGI2 (gin mch v chng vn tiu cu) . Khng nh hng n chuyn ha ng v lipid

ng hc: t c nh huyt tng sau 1 - 2h. Gn 75% vo protein huyt tng, T 1/2 = 14- 24h 2.1.3. Thuc li niu tc dng mnh hay thuc li niu quai (loop diuretics) l nhm thuc c tc dng rt mnh so vi cc thuc li niu bit v v tr tc dng l on phnh to ca nhnh ln quai Henl e. on ny c qu trnh ti hp thu ti 35% lng Na+ v Cl- ca nc tiu ban u. Thuc tiu biu l furosemid v acid ethacrynic. 2. 1.3.1. Tc dng v c ch - c ch c ch cng vn chuyn (cotransport mechanism) ca 1Na +, 1K+ v 2 Cl on phnh to ca nhnh ln quai Henle. V vy lm tng thi tr Na +, Cl(gn ngang nhau) v K+ (t hn thiazid). - Furosemid v bumetanid cn c c tc dng c ch carbonic anhydrase do trong cng thc cng c gc sulfonamid. Nhng tc dng ny ch rt yu. - Tuy c lm tng thi tr ion H +, nhng pH nc tiu t thay i v tc dng c ch carbonic anhydrase b tr li. - Cc thuc nhm ny lm tng thi tr Ca ++ v c Mg++, tri vi tc dng ca thiazid, v vy c th dng iu tr tng calci mu triu chng. V Ca++ cn c ti hp thu ng ln nn thng ch thy h Mg ++ mu khi dng lu. Kt qu l cc thuc li niu quai c th lm thi tr ti 30% s lng nc tiu lc qua cu thn, vt qu s lng nc ti hp thu ca quai Henle, cho nn c th cn c mt s c ch ph c ch ti hp thu ng ln gn. Hin l thuc c tc dng li niu mnh nht. 2.1.3.2. Ch nh - Nh nhm thiazid - V c tc dng nhanh nn cn c dng trong cp cu: cn ph nng, ph phi cp, cn tng huyt p, tng calci huy t cp tnh. 2.1.3.3. Tai bin - Do thi tr qu nhanh nc v in gii nn c th gy mt mi, chut rt, tin hn m gan, h huyt p. - Ging nhm thiazid, c th gp tng acid uric mu, tng ng mu. - Dng lu, do tng thi tr Cl -, K+ v H+ nn c th gy nhim base gim Cl -, hoc nhim base gim K+. - Do lm tng thi tr Mg ++ v Ca++ nn c th gy h c Mg ++ mu (d gy lon nhp tim) v h Ca++ mu (him khi dn n ttani) - Nhng biu hin khc c th gp: ri lon tiu ha (c khi l chy mu), gim s lng hng bch cu, ri lon chc phn gan thn, sn da, t b.

- Duy nht vi nhm ny l c tnh vi dy VIII, c th gy ic tai do ri lon ion trong ni dch hoc do c ng. V vy khng nn dng cng vi khng sinh nhm aminosid. 2.1.3.4. Ch phm v liu lng * Ethacrynic acid (Edecrin): trong cng thc c cha ceton khng bo ha cho nn d phn ng vi nhm sulfydril ca cc enzym vn chuyn ion ca ng thn. - Vin 25 hoc 50 mg. Ung 50 - 200 mg/ ngy - ng bt Edecrin natri 50 mg. T im tnh mch 50 mg hoc 0,5mg/kg cn nng. Khng tim bp hoc di da v thuc kch thch ti ch gy au. Hp thu nhanh qua ng tiu ha. Gn nhiu vi protein huyt tng, t/2 di 1 gi. Thi tr qua thn 40% di dng khng chuyn ha. * Furosemid (Lasix, Lasilix, Trofurit) L dn xut ca acid anthranilic, c cha gc sulfonamid trong cng thc. - Vin 20, 40 v 80 mg. Ung 20 - 80 mg/ ngy - ng 2 ml = 20 mg. Tim bp hoc tnh mch: 1 - 2 ng Trong ph phi cp, sau liu u 60 - 90 pht c th tim nhc li. Tc dng li niu xut hin nhanh, 3 - 5 pht sau khi tim tnh mch, 20 pht sau khi ung. Ht tc dng sau 4 - 6h. Thuc d hp thu qua tiu ha, mt phn gn vi protein huyt tng. Ch yu nm ngoi t bo v t tan trong m. Thi tr phn l n di dng khng chuyn ha. * Bumetanid (Bumex): L dn xut ca acid 3 - aminobenzoic, trong cng thc cng cha nhm sulfonamid. Mnh hn furosemid 40 ln. - Vin 0,5- 1,0 v 2,0 mg. Ung 0,5 - 2,0 mg - ng 0,5- 1,0 mg. Tim bp hoc tnh mch 0,5 - 1,0 mg. 2.2. Thuc li niu gi kali - mu (gim thi tr K +) Cc thuc li niu thuc cc nhm trn khi dng lu u gy gim kali - huyt. Cc thuc thuc nhm ny tc dng phn cui ng ln xa, do c ch ti hp thu Na + bng c ch trao i vi bi xut K +, v th lm gim bi xut K +. ng thi thuc lm tng thi tr bicarbonat, gim bi xut H + cho nn nc tiu nhim base. Cc thuc ny hu nh khng dng mt mnh v tc dng thi Na + yu v tai bin tng kali- mu thng bt li. Dng phi hp vi cc t huc li niu lm gim kali

- mu s gi c tc dng thi tr Na + v khc phc c ri lon h K + mu. C nhiu bit dc phi hp. 2.2.1. Thuc i lp vi aldosteron Spironolacton (Aldacton) : cng thc gn ging vi aldosteron, tranh chp vi aldostero n ti receptor ng ln xa, nn cn gi l thuc khng aldosteron. Tc dng thi tr Na + ca thuc ph thuc vo s lng aldosteron bi tit v b c ch. Tc dng xut hin chm sau 12- 24 gi. - Vin 25 mg. Ung mi ngy 2 - 4 vin - Dng lu c th g y tc dng ph ging hormon: nam gy chng v to, n gy chng rm lng v lon kinh nguyt. 2.2.2. Thuc khng i lp vi aldosteron Triamteren (Teriam) . Cn gi l khng aldosteron gi (pseudo - anti- aldosterone). Cng thc hon ton khng ging vi aldosteron nn khng c tc dng tranh chp vi aldosteron. Lm tng thi Na +, Cl- do lm gim tnh thm ca ng ln xa vi Na +. Lm gim bi xu kali t K+ v H+. Tc dng c khi c mt cng nh khi khng c mt aldosteron (ng vt ct b thng thn). Spiron olacton lm tng tc dng ca triamteren cho nn 2 thuc tc dng trn 2 receptor khc nhau. Tc dng ti a t c sau khi ung 2 gi v ch gi c tc dng trong 10 gi. - Nang 100 mg. Ung 1 - 2 nang/ ngy - C th gy bun nn, nn, chut rt, ng g . Amilorid (Modamid) : tc dng thi Na +, lu K+ mnh hn triamteren. Ngoi c ch tc dng theo kiu triamteren, amilorid cn tc dng trn c ng ln gn. Nng ti a trong mu t c 4 gi sau khi ung, thi gian bn hu khong 6 gi, tc dng ko di 24 gi. - Vin 5 mg. Ung mi ngy 1 vin. Khng vt qu 20 mg/ ngy 2.3. Thuc li niu thm thu Thuc li niu thm thu dng ch mt s cht ha tan c cc tnh cht sau: - c lc t do qua cu thn - c hp thu c gii hn khi qua ng thn - Hu nh khng c hot tnh dc l Nhng cht ny c dng vi s lng tng i ln lm thay i mt cch c { ngha nng osmol trong huyt tng hay trong nc lc cu thn, hoc dch ng thn. Hin ch c mannitol l c dng nhiu hn c.

2.3.1. Ch nh Do khng lm tng thi tr Na + nn khng dng c trong cc chng ph. Thng dng phng nga i t sau m, sau chn thng, tng p lc trong s, hoc lm tng li niu trong cc trng hp nhim c thi tr cht c. 2.3.2. Chng ch nh - Mt nc trong t bo - Suy tim 2.3.3. Ch phm Mannitol dung dch 10 - 20% ng trong l 250 - 500 v 1000 ml dng truyn nh git tnh mch. Mannitol thi tr qua cu thn v ch khong 10% c ti p thu ng ln, do lm tng p lc thm thu trong ng ln, c ch ti hp thu nc, gy li niu. BI 44. THUC CHA GOT Gt l mt bnh do tng acid uric -mu, trong dch bao khp c nhiu tinh th urat l sn phm chuyn ha cui cng ca purin. Bnh c th nguyn pht do ri lon chuyn ha acid uric di truyn, hoc th pht do bnh thn, do dng cc thuc phong ta thi tr urat hoc do sn xut qu nhiu urat (metabol ic overproduction). Acid uric-mu bnh thng l 2 -5mg/100ml, trong bnh gt c th tng ti 8,8mg/100ml. iu tr gt nhm gii quyt cn cp tnh v ngn nga s ti nhim, da trn sinh bnh hc ca bnh ny. Cc tinh th urat lc u b thc bo bi cc t bo mng hot dch (syno vioucytes). Trong qu trnh thc bo, cc t bo ny gii phng ra cc prostaglandin, cc enzym tiu th v interlenkin-1. Cc cht trung gian ha hc ny li gi cc bch cu ht ti khp v lm nng thm qu trnh vim: s lng bch cu ht, i th c bo tng, lng cht ha hc trung gian gy vim tng. Cc thuc iu tr cn gt cp tnh s c ch cc giai on hot ha bch cu. c hiu nht l colchicin. Ngoi ra cn dng thuc CVKS phenylbutazon, indometacin, loi c ch COX -2, hoc corticoid. iu tr gt mn tnh, dng thuc lm gim acid uric trong c th bng cc thuc lm i ra acid uric nh probenecid, sunfinpyrazol v allopurinol. 1. COLCHICIN Colchicin l alcaloid ca cy colchicum antumnal. Bt v nh hnh, ?vng

nht, khng mi. c dng t th k 18. Tc dng iu tr c hiu cn gt cp tnh, lm gim au v gim vim trong vng 12 - 24 gi u dng thuc, v th cn c dng lm test chn on. Colchicin khng c tc dng gim au v chng vim khp khc. 1.1. C ch tc dng Trong bnh gt, colchicin khng nh hng n bi xut acid uric thn v khng lm gim acid uric mu. Colchicin gn vo protein ca tiu qun (protein tubulin) trong t bo bnh cu v cc t bo di chuyn khc, v th, ngn cn s trng hp ca nhng pro tein ny trong vi tiu qun (microtubulin), dn n c ch s di chuyn ca bch cu v gim hot tnh thc bo ca bch cu ht, lm gim gii phng acid lactic v cc enzym gy vim trong qu trnh thc bo. Trong qu trnh tiu ha cc tinh th urat, bch cu ht sn xut glycoprotein, cht ny c th l nguyn nhn gy ra cn gt cp tnh. Colchicin ngn cn sn xut glycoprotein ca bch cu ht nn chng c cn gt. Colchicin cn ngn cn s phn bo ca cc t bo ng -thc vt giai on trung kz v do lm gim s hnh thnh cc thoi phn bo. 1.2. c tnh Phn ln lin quan n tc dng c ch s trng hp ca tubulin v c ch phn bo: bun nn, nn, tiu chy, au bng (tn thng t bo biu m nim mc tiu ha), c ch tu xng, rng tc, vim thn kinh, c vi thn 1.3. Dc ng hc Hp thu nhanh qua ng ung, t nng ti a trong huyt tng sau 0,5 2 gi. Chuyn ha gan, phn ln thi tr qua phn (c chu kz rut - gan), ch 10 20% thi qua thn. 1.4. Ch nh - iu tr cn gt cp tnh: tim tnh mch 2 mg ha trong 10 - 20 ml dung dch NaCl 0,9%. Tng liu khng vt qu 4mg. Khng tim nhc li trong vng 7 ngy. Nu khng chu c thuc, c th thay bng indometacin. - D phng: ung 0,5mg mi tun 2 - 4 ln. Vin 0,5 mg, 1 mg. ng tim 2ml = 1mg 2. PROBENECID (BENNEMID) Probenecid l dn xut ca acid benzoic, tan nhiu trong lipid. Bt tinh th

trng, khng mi. Acid uric c lc qua cu thn v bi xut qua ng thn, song phn ln li c ti hp thu on gia ca ng ln gn. Probenecid vi liu thp do cnh tranh vi qu trnh thi tr acid uric nn lm lu acid uric trong c th (Demartini v cng s, 1962), nhng vi liu cao li c ch ti hp thu acid uric ng thn nn lm tng thi tr acid q ua nc tiu. Probenecid cn c ch c tranh chp qu trnh thi tr ch ng ti ng ln gn ca mt s acid yu nh penicilin, para aminosalicylat, salicylat, clorothiazid, indometacin, sunfinpyrazon, v.v Probenecid khng c tc dng gim au. Khi c n gim au, c th dng cng vi paracetamol. Khng dng cng vi salicylat, v probenecid s mt tc dng. Dng thuc li niu loi thiazid ko di nh trong iu tr cao huyt p thng lm urat v nhng thuc ny c ch bi xut urat ng thn. Probe necid i khng c tc dng ny m khng nh hng n tc dng li niu ca thuc. Tuy nhin, li c ch tc dng i natri ca furosemid. Probenecid c hp thu nhanh qua rut, vo mu, hn 70% kt hp vi albumin huyt tng, thi tr qua thn phn l n di dng glucuro -hp. Thi? gian na thi tr khong 6 -12 gi. Tc dng ph rt t (2 -8%): bun nn, nn, mng da, st. Khi lm i nhiu acid uric, c th gy cn si urat vi cn qun thn (khi cn base ho nc tiu). Liu lng: vin 0,5g. T un u ung 250mg 2ln/ngy. Tng dn tng tun. Ti a 2g/ngy, ung 4 ln. Ung nhiu nc trnh si acid uric thn. Dng hng nm. C th dng vi allopurinol, sunfinpyrazon. 3. SUNFINPYRAZON (ANTURANT) Cng thc gn ging phenylbutazon. Gy i ra acid uric mnh do ngn cn ti hp thu ng thn, ging c ch ca probenecid. Hp thu nhanh v hon ton qua ng tiu ho. Gy tai bin mu nh phenylbutazon, ri lon tiu ho khong 10%. Salicylat lm mt tc dng ca sunfinpyrazon do tranh chp vi sunfinpyrazon khi vn chuyn qua ng thn v c khi gn vo protein huyt tng. Liu lng: vin 50mg 4ln/ngy, tng dn ti 400mg hoc 800mg mt ngy. Chia lm 2 -4 ln, ung vo ba n trnh kch ng d dy. Ung nhiu nc trong ngy. 4. ALLOPURINOL (ZYLOPRIM) Allopurinol l cht ng phn ca hypoxanthin.

4.1. C ch tc dng Acid uric l sn phm chuyn ho ca purin. Cc purin c chuyn thnh hypoxanthin v xanthin ri b oxyho nh xc tc ca xanthin oxydase thnh acid uric. Allopu rinol l cht c ch mnh xanthin oxydase nn lm gim sinh tng hp acid uric, gim nng acid uric mu v nc tiu, lm tng nng trong mu v nc tiu cc cht tin thn hypoxanthin v xanthin d tan hn. Nh vy, allopurinol cn ngn nga c s to si acid uric trong thn. Nh vy, allopurinol cn ngn nga c s to si acid uric trong thn. 4.2. c tnh t c. Phn ng qu mn khong 3% (mn da, st, gim bch cu, gan to, au c). Trong nhng thng u iu tr, c th c cc cn gt c p tnh do s huy ng acid uric t cc m d tr. Khi , cn phi hp iu tr bng colchicin. 4.3. Dc ng hc Hp thu qua ng ung khong 80%, t nng ti a trong mu sau 30 -60 pht. Allopurinol cng b chuyn ho bi xanthin oxydase thnh alox anthin, vn cn hot tnh, v th tc dng ko di, ch cn ung thuc mi ngy 1 ln. 4.4. Ch nh, liu lng - Gt mn tnh, si urat thn. - Tng acid uric mu th pht do ung th, do iu tr bng cc thuc chng ung th, thuc li tiu loi thiazid - Tng acid uric mu m khng th dng c probenecid hoc sunfinpyrazon do c phn ng khng chu thuc. Mc tiu ca iu tr l lm gim nng acid uric mu xung 6mg/dl (360 micro M). Liu lng: Allopurinol (Zyloprim) vin 100 - 300 mg. Liu u 100mg, tng dn ti300mg/ngy tuz theo nng acid uric mu. BI 45. THUC KHNG HISTAMIN H1 1. I CNG : 1.1. Khi nim chung : + Histamin : l mt amin hot mch, sn phm chuyn ha ca histidin ( di s xc tc ca histidin decarboxylase ). Histamin do cc dng bo ( mastocyte - t bo mast ) ( da, rut, gan, kh -

ph qun, khi u ), bch cu a base ( trong mu ) v mt vi loi t bo khc ( t bo thnh d dy, rut, t bo no ) sn xut ra. Histamin trong c th dng kt hp ( c d tr trong cc ht ca t bo ) kh?ng hot tnh. Mt s rt t dng t do ( dng c hot tnh ) lu thng trong mu. Histamin l cht trung gian ha hc c vai tr quan trng trong phn ng vim v d ng, trong s bi tit dch v v cng c chc nng nh mt cht dn truyn thn kinh v iu bin thn kinh. + Do histamin tch in dng nn d dng lin kt vi cc cht tch in m nh protease, chondroitin sulfat, proteoglycan hoc heparin to thnh phc hp khng c tc dng sinh hc. Phc hp ny c d tr trong cc ht ca dng bo, bch cu a base, t bo nim mc d dy, rut, t bo thn kinh Da, nim mc, rut, gan, cy kh ph qun l nhng m c nhiu dng bo nn d tr nhiu histamin. + Thuc khng histamin : l nhng thuc tng hp c tc dng ngn cn s gii phng ra histamin, lm trung ha hoc c ch tc dng ca histamin biu hin trong phn ng d ng. 1.2. S gii phng histamin: C nhiu yu t kch thch s gii phng histamin : + Tc nhn gy phn ng min dch : phn ng khng nguyn - khng th xy ra trn b mt dng bo v bch cu a base ( lm ) ( lm thay i tnh thm ca mng t bo vi Ca2+, lm tng lng Ca2+ i vo trong ni bo, ng thi lm tng gii phng Ca2+ t kho d tr ni bo; Ca2+ ni bo tng gy nn s p cc ht d tr histamin lm v cc ht ny, lm tng tit histamin ). y l yu t ch yu. + Tc nhn vt l : nh nng mt tri, tia cc tm, nhit ( nng, lnh ). + Tc nhn ho hc : nc rn, nc ong, nc cn trng, mt s thuc ( morphin, D-tubocurarin ). Cc yu t trn lm tng tit histamin t do cng nhiu cht trung gian ho hc khc nh serotonin, bradykinin, leucotrien, prostaglandin, yu t hot ha tiu cu ( PAF ) tham gia vo cc phn ng vim, phn ng d ng hoc phn ng qu mn. PAF = platelet activation factor 1.3. Chuyn ho ca histamin : Theo 2 con ng :

+ Oxy ho kh amin : di s xc tc ca histaminase ( diaminoxidase ), histamin b oxy ha kh amin to thnh acid imidazol acetic. + Phn ng methyl ho : nh imidazol N-methyl transferase, histamin b chuyn ha thnh methyl histamin v sau b oxy ha bi histaminase thnh acid imidazol acetic. Hai sn phm chuyn ho ca histamin khng c tc dng sinh hc. 1.4. Receptor ca histamin : Hin nay tm thy 3 loi receptor ca histamin : receptor H1, H2 , H3 . Cc receptor ca histamin c s phn b v chc nng khc nhau ( bng 1 ). + Receptor H1 + Receptor H2 + Receptor H3 1.6. Cc biu hin lm sng ch yu ca phn ng d ng : + Mn , ni m ay : do gin mch ngoi vi. + Kh th : do co tht c trn kh - ph qun, d gy ra cn hen. + H huyt p, nu nng c th try tim mch : do gin mch. + Cc du hiu khc : au bng, tng tit dch v, nc mt, nc bt Thuc khng histamin c tc dng trung ha nhng tc dng dc l k trn ca histamin. 1.7. Phn loi thuc khng histamin : 1.7.1. Thuc khng histamin H1 : i khng vi histamin ch yu c trn v mch mu. 1.7.2. Thuc khng histamin H2 : c ch bi tit dch v d dy do histamin. 1.7.3. Thuc khng histamin H3 : 2. Cc thuc khng histamin H1 : 2.1. Cu trc ?: Phn ln cc thuc khng histamin H1 u c cng thc chung nh sau : Ring astemizol v terfenadin c chui mch thng ni vi nhn thm trc khi gn vi X. 2.2. Phn loi : 2.2.1. Phn loi theo cu trc ha hc : a- Dn xut ethanolamin : - Dimedrol. - Clemastin

- Bromodiphenyldramin - Diphenhydramin. - Dimenhydrinat b- Dn xut etylendiamin : - Antazolin. - Clemizol. c- Dn xut piperazin : - Hydroxyzin. - Clocyclizin HCl. - Meclizin HCl d- Dn xut phenothiazin : - Promethazin. - Trimerprazin - Alimemazin e- Nhm alkylamin: - Brompheniramin - Dimethidin - Chlopheniramin. f- Nhm piperidin : - Terfenadin - Astemisol - Azatadin - Naphazolin - Loratadil 2.2.2. Phn loi theo dc ng hc v tc dng : chia 2 th h : a- Th h I : gm cc thuc c th i qua hng ro mu no d dng, c tc dng trn receptor H1 c trung ng v ngoi vi, c tc dng an thn mnh, chng nn v c tc dng khng cholinergic ging atropin. b- Th h II : gm cc thuc rt t i qua hng ro mu no, c t1/2 di, t tc dng trn receptor H1 trung ng, ch c tc dng trn receptor H1 ngoi vi, khng c tc dng khng cholinergic, khng an thn v khng c tc dng chng nn, chng say tu xe. 2.3. Tc dng dc l : 2.3.1. Tc dng khng histamin thc th : + Do c cng thc ha hc gn ging cng thc ca histamin nn thuc khng histamin H1 c ch c cnh tranh vi histamin ti receptor histamin H1. Khi d

tha cht ch vn ( histamin ) th histamin y cht i khng ( l cc thuc trn ) ra khi receptor, lm thuc gim hoc mt tc dng. c tc dng dc l ko di, cn phi tm cht i khng khng cnh tranh, khi thuc chm b histamin y ra khi receptor. + Mt s thuc nh clemastin, terfenadin, astemizol th c c 2 kiu c ch c cnh tranh v khng cnh tranh mnh tng ng nhau, nn thuc c tc dng mnh v ko di. + Thuc khng histamin H1 c tc dng d phng tt hn l iu tr, bi v mt khi c bi tit ra th histamin tip tc to ra hng lot phn ng v cc ht ( lysosom ) s gii phng tip nhng cht trung gian ha hc khc ( bradykinin, leucotrien, mt s prostaglandin, thromboxan ) m thuc khng histamin H1 khng i khng c. Tc dng ca thuc mnh nht c trn rut v yu nht ph qun ( t c tc dng iu tr hen ph qun v cc bnh phi - ph qun tc nghn khc ). Cn phi hp 2 loi thuc khng histamin H1 v histamin H2 c ch trit s gim huyt p do histamin gy ra. 2.3.2. Cc tc dng khc : a- Trn h TKTW : c ch TKTW, lm an thn, gim kh nng tp trung t tng, gy ng g, chng mt Tc dng c ch receptor H1 trung ng ny c th ko theo tc dng khng cholinergic, lm tng tc dng an du thn kinh, gim tr nh. Mt s thuc th h II ( nh terfenadin, astemizol, fexofenadin, mequitazin, loratadin ) hu nh khng c tc dng ny ( do thuc c tnh a nc v c i lc mnh vi receptor H1 ngoi bin nn thuc t qua hng ro mu - no ). b- c ch h M-cholin: v d promethazin, dimenhydrinat, diphenhydramin, ?mequitazin gy gin ng t, kh ming, to bn, mch nhanh, tng nhn p v trong mt s trng hp phi chng ch nh. c- Chng say sng( do khng cholinergic ) v d promethazin, dimenhydrinat, diphenhydramin nn c dng chng say tu xe. d- Chng ho( v d promethazin, oxomemazin, doxylamin, dexclopheniramin, mequitazin ) song hiu lc km cc thuc chng ho trung ng loi morphin. Thuc khng histamin H1 lm tng tim lc ca thuc gin ph qun khc ( nh cc amin cng giao cm loi ephedrin ) Tc dng chng ho ca thuc khng his tamin H1 l ngoi bin do c ch s co tht ph qun gy phn x ho. e- Chng nn : cc thuc loi cyclizin.

f- Trn h tim mch: + Lm thay i h giao cm : v d promethazin c ch receptor a-adrenergic, gy h HA. + Diphenhydramin, dexclopheniramin lm tng tim lc tc dng ca catecholamin ( do c ch thu hi catecholamin ), lm tng HA. + Mt s thuc c th gy ri lon nhp tim + Cc tc dng khc - Khng serotonin. - Kch thch tiu ha, lm n ngon : v d cyproheptadin, doxylamin. - Chng nga, gy t ( khng c lin h vi tc dng khng histamin ) : nh mepyramin, diphenhydramin. 2.4. TDKMM : 2.4.1. Do tc dng trung ng ( trn h TKTW ) : c ch thn kinh ( gy ng g, kh chu, mt mi, hin tng gii th nhn cch, gim phn x, gim s tp trung ch {), mt kt hp vn ng. Nhng biu hin trn s tng mnh nu dng thuc khng histamin H1 cng ru ethylic hoc cc thuc c ch TKTW. Do cm dng cho ngi ang li xe, vn hnh my mc chuyn ng hoc lm vic ni nguy him ( trn cao). i khi c th gy hng phn, nhc u, mt ng, kch ng, co git nu dng liu cao ( nht l tr em ang b ). Nu c cc triu chng trn, c th gim liu, dng thuc vo lc chiu ti, hoc dng loi thuc histamin H1 khng c tc dng trn h TKTW. 2.4.2. Do tc dng khng cholinergic : tng t TDKMM ca cc thuc khng Mcholin ( atropin ): - Tiu ha : kh ming, kh hu hng, gim tit nc bt, to bn. - Ph qun - phi : kh khc m ( do tit dch ph qun ). Tit niu - sinh dc : i tiu kh hoc b i, lit dng. - Mt : ri lon iu tit ( nhn m ), tng nhn p - Tim mch : ri lon nhp tim ( nhp tim nhanh ). - Thn kinh : phn ng ngoi b thp, ri lon vn ng mt. - V : gim tit sa. 2.4.3. Phn ng qu mn v c ng : c qu mn cho gia cc loi thuc khng histamin H1. C th ct ngha cc phn ng d ng ngoi da l do cc thuc ny lm tng gii phng histamin.

2.4.4. TDKMM khc : + Ri lon tiu ha : lm ging, bun nn v nn, tiu chy + Ri lon v mu : thiu mu tan mu, gim bch cu ht. + Cm quang ( phenothiazin ) + Tim mch : thay i huyt p. Ring terfenadin v astemizol c th gy ko di khong QT trn ECG c th dn n hin tng xon nh. Hin nay khng dng ter fenadin. 2.5. Ch nh : 2.5.1. Ch nh tt nht l: + Vim mi d ng ( s mi ma, lm chy nc mt, nga mt, chy nc mi ), vim mi hng nm. + Vim kt mc d ng. + Hen ph qun, vim ph qun th co tht. + Bnh da d ng ( nht l th sn , ph n ) : my ay cp, eczema ( chm ), cn trng t + Ph Quincke. + Bnh huyt thanh. + D ng thuc ( tr cc th nng nh da ton thn, shock phn v ) 2.5.2. Cc ch nh khc + Say tu xe : promethazin, dimenhydrinat, diphenhydramin + Mt ng : alimemazin, promethazin + Ho : alimemazin, promethazin, oxomemazin, doxylamin, mequitazin ( thng phi hp vi mt thuc gim ho khc ) + Kch thch tiu ha, lm ngon ming : doxylamin, cyproheptadin + Tin m ( d phng tai bin phn x dy X khi thm d bng ni soi, phu thut ): phi hp vi thuc khng M-cholin ( atropin ). 2.6. Chng ch nh chung + Do tc dng khng cholinergic : ph i tuyn tin lit, glaucoma gc ng, tc rut, tc nghn ng tit niu ( do si thn ), nhc c, ang iu tr bng IMAO + Tn thng ngoi da : khi dng thuc khng histamin H1 ngoi da. + Mn cm vi thuc. + Ph n c thai ( vi cc dn xut cyclizin ) v gy qui thai. + Ngi ang li xe, ng my chuyn ng, lm vic ni nguy him ( trn cao ).

BI 46. HORMON V THUC KHNG HORMON 1. HORMON TUYN GIP Tuyn gip sn xut 2 loi hor mon khc nhau: - Thyroxin v triiodothyronin c vai tr quan trng trong s pht trin bnh thng ca c th v chuyn ha nng lng. - Calcitonin (thyrocalcitonin) l hormon iu ha chuyn ha calci v phospho. 1.1.Thyroxin v triiodothy ronin (T4 v T3) 1.1.1. Tc dng sinh l - iu ha pht trin c th: kim tra hu ht cc qu trnh tng hp protein v s pht trin ca h thn kinh. Rt nhiu enzym chuyn ha lipid, protid v glucid chu nh hng ca thyroxin. Thiu thyroxin th enzym gi m hot ng. - Lm tng qu trnh chuyn ha ca c th, c bit l chuyn ha ca cc t chc tim, gan, thn. C vai tr quan trng trong to nhit v iu ho thn nhit ca ng vt ng nhit. Khi chc phn tuyn gip km th gy ph nim dch, chuyn ha c s gim, thn nhit h, rng tc, mch chm, rut gim nhu ng, k m n, sc kho v tr khn gim ( tr em, gi l chng n n). Ngoi cc triu chng trn, tr chm ln, tuyn gip to ra v tuyn yn vn bi tit thm cc cht kch thch tuyn gip. Trong tuyn y cht dng keo, nhng rt km v s lng hormon. vi vng ni, nc ung t iod cng gy bu c a phng. Bnh thng mi ngy ta cn 0,075 g iod. Khi cng tuyn th gy Basedow: bu c, mt li, tay run, mch nhanh, cholester ol- mu gim, chuyn ha c s tng (vt trn 20%). Thyroxin mu tng, nhng v c ri lon tin yn- gip, nn tuyn gip vn to ra (cng c trng hp khng to). T bo tuyn c thyreoglobulin, khi b thu phn s cho thyroxin (3,5 diiodothyrozin - T4) v 3, 5, 3 triiodotyronin (T 3). T l T4/ T3 trong thyreoglobulin l 5/1, ngha l phn ln hormon c gii phng l thyroxin, cn phn ln T 3 tun hon trong mu li l t chuyn ha ngoi bin ca T 4. Tc dng ca T 3 mnh hn T4 3- 4 ln. trong huyt t ng, T3 v T4 gn vo thyroxin - binding globulin (TBG), dng t do ca T 4 ch bng khong 0,04% tng lng v T 3 l khong 0,4%. S kh iod ca T 4 c th xy ra vng trong, to ra 3, 3, 5 triodotyronin, c gi l T 3 ngc (reverse T3 hoc r T3), khng c hot tnh. Thuc chn , corticoid, i lu ngy, c ch enzym chuyn T 4 thnh T3, lm gim lng T 3

v lm tng r T 3 trong huyt tng. Hormon TSH iu ha s thu phn thyreoglobulin v s nhp iod vo tuyn gip. Ngc li m thyroxyn v 3, 5, 3 triod tironin trong huy t tng iu ha s tit TSH. Trong huyt tng, c mt gama globulin tng hp trong lympho tc ng cng tng t nh TSH, nhng thi gian lu hn, l yu t L.A.T.S. (long - acting thyroid stimulator). 1.1.2. Ch nh v ch phm Hai ch nh chnh l suy tuyn gip (hay myxoedme) v bu c a phng. - Thyreoidin; bt tuyn gip kh ca ng vt (c 0,17 - 0,23% iod), ung 0,1 0,2g mi ln, mi ngy ung 2 - 3 ln. Liu ti a mt ln 0,3g, mt ngy 1,0g. - Thyroxin: vin 0,1 mg; dung dch ung 1 gi t = 5 g. Ung liu u 0,1 mg. Sau tng dn tng 0,025 mg. - Kali iodid: trn 1 mg vo 100 g mui n thng gi l mui iod d phng bu c a phng. - Levothyroxin (Levothyrox, Thyrax, Berithyrox) vin nn 25 - 50- 100- 150 g. L ch phm tng hp c nhiu u im nn l thuc c chn la trong iu tr: thuc c tnh n nh cao, thun nht, khng c protein ngoi lai nn khng gy d ng, d xc nh nng trong huyt tng, thi gian bn thi di (7 ngy), gi thnh h. Liu lng: i t li u thp, tng dn tng 25 g tuz theo tnh trng bnh v tui bnh nhn. 1.2. Calcitonin 1.2.1. Tc dng sinh l L hormon lm h calci mu, c tc dng ngc vi hormon cn gip trng, do t bo C ca tuyn gip bi tit. L mt chui a peptid hoc gm 32 acid amin c trng lng phn t l 3600. Tc dng chnh ba ni: - Xng: c ch tiu xng bng c ch hot tnh ca cc hu ct bo (ost oclaste), ng thi lm tng to xng do kch thch to ct bo (ostoblaste). - Thn: gy tng thi tr calci v phosphat qua nc tiu do tc dng trc tip. Tuy nhin, do c ch tiu xng nn calcitonin lm gim bi tit Ca 2+, Mg2+ v hydroxyprolin qua nc tiu. - ng tiu ha: lm tng hp thu calci Tm li, calcitonin nh mt hormon d tr, hormon tit kim calci v n lm ngng s hu xng v lm tng hp thu calci qua tiu ha.

1.2.2. Ch nh - Calcitonin c tc dng lm h calci - mu v phosphat - mu trong cc trng hp cng cn gip trng, tng calci mu khng r nguyn nhn tr em, nhim c vitamin D, di cn ung th gy tiu xng, bnh Paget (c ng ha v d ha ca xng u tng rt mnh). - Cc bnh long xng: sau mn kinh, tui cao, dng corticoid ko di. - Ngoi ra, calcitonin cn c tc dng gim au xng, c dng trong cc di cn ung th. 1.2.3. Tc dng khng mong mun - Triu chng tiu ha: bun nn, nn, tiu chy, au bng - Triu chng v mch mu: nng mt, mt, nng chi v c cm gic kin b. - Thn: i tiu nhiu ln, a niu 1.2.4. Ch phm - Calcitonin: 100 UI/ ngy u, sau gim xung 50 UI mi tun 3 ln. - Calcitonin ca c hi (salmon): Miacalcic ng 1 mL cha 50 UI - chai xt nh liu 50 v 200 UI. Tim di da hoc xt vo m?i 50 - 100 UI mi ngy hoc cch ngy. Calcitonin ca c hi mnh hn calcitonin ca ngi v ln t 10 - 40 ln v tc dng lu hn 10 ln. 1.3. Thuc khng gip trng tng hp Qu trnh tng hp thyroxin c 4 giai on: - Gn iodid v c vo tuyn (iodid l iod dng ion I -) - Oxy ha iodid thnh iod t do - To mono- v diiodotyrosin (MIT - DIT) - Ghp 2 iodotyrozin thnh L - thyroxin- tetraiodotyrosin T 4 (TIT) (xem hnh ) Thuc khng gip trng c dng cha cng gip (bnh Basedow). C th chia thnh 4 nhm:

Hnh 35.1.V tr tc dng ca thuc khng gip trng MIT: monoiodotyrosin, DIT: diiodo - tyrosin (1): Thiocyanat, perclorat (2): Nhm thiamid carbimazol, benzylthiouracil, propylthiouracil, methimazol (3): Lithium 1.3.1. Thuc c ch gn iodid vo tuyn

c ch qu trnh vn chuyn iod nh thiocyanat (SCN -), perclorat (ClO 4-), nitrat. c v thng gy mt bch cu ht, khng c dng trong lm sng. 1.3.2. Thuc c ch trc tip tng hp thyroxin: Thioamid 1.3.2.1. C ch Loi ny khng c ch gn iod vo tuyn gip, nhng c ch to thnh cc phc hp hu c ca iod do c ch mt s enzym nh iod per oxydase, cc enzym oxy ha iod. V vy tuyn khng tng hp c mono - v diiodotyrosin. 1.3.2.2. c tnh Dng thuc c ch tng hp thyroxin k o di, lng thyroxin gim, lm tuyn yn tng tit TSH. TSH tng, kch thch tuyn gip nhp iod, lm tng sinh, dn n chng ph nim (tuyn gip cha nhiu cht dng keo, nhng t hormon) Nhm thuc ny t gy tai bin. Tai bin nng nht l gim bch cu ht (0,3 0,6%) thng xy ra sau vi thng iu tr. V vy cn kim tra s lng bch cu c nh kz v nn dng thuc ngt qung. Cc tai bin khc: pht ban, st, au khp, nhc u, bun nn, vim gan, vim thn. Thng ngng thuc hoc i thuc khc s ht. 1.3.2.3. Ch phm Cc loi thuc ny thng c dng lm sng cha cng tuyn gip, gm: - Aminothiazol: mi ngy 0,6- 0,8g. Gim dn, ri dng liu duy tr 0,2g. Hin nay t dng v c. - Thio- uracil: mi ln 0,5g. Mi ngy 2- 3 ln, tai bin 5,8%. R = CH3 metyl thiouracil (MTU) R = C3H7 propyl thiouracil (PTU) R = CH2 - C6H5 benzyl thiouracil (Basden) - Thiamazol (Basolan): mi ngy ung 15 - 60 mg. Tai bin 3,4%. - Carbimazol (Neomecazol): mi ngy ung 15 - 60 mg. Vo c th chuyn thnh methiazol, cht ny mnh gp 10 ln PTU nn a dng hn. 1.3.2.4. Cch dng Ung thuc lm 3 giai on: - Tn cng: 3- 6 tun vi liu 150- 200 mg - Duy tr: 3- 6 thng vi liu 100 mg - Cng c: hng thng. Liu hng ngy bng 1/4 liu tn cng. 1.3.3. Iod

Nhu cu hng ngy l 150 g. Khi thc n khng cung cp iod, s gy bu c n thun. Tri li, khi lng iod trong mu qu cao s lm gim tc dng ca TSH trn AMPv. Lm gim gii phng thyroxin. - Ch nh: chun b bnh nhn trc khi m ct tuyn gip. - Dng cng vi thuc khng gip trng v thuc phong to adrenergic trong iu tr tng nng tuyn gip. - Ch phm: dung dc h Lugol (iod 1g, kali iodid 2g, nc va 20mL), ung XXX git mi ngy (XX git cha 10mg iod). - c tnh: thng t v hi phc khi ngng dng: trng c, sng tuyn nc bt, lot nim mc, chy mi? (tng t nh nhim c brom) 1.3.4. Ph hu t chc tu yn: iod phng x 1.3.5. Thuc phong to h adrenergic Nhiu triu chng ca cng gip l cng giao cm. V vy dng guanethidin, reserpin. Nhng tt hn c l thuc chn propranolol. Nhm thuc ny ch c tc dng cha triu chng, khng tc dng vo tuyn. 2. HORMON TUYN TY o Langerhans ca tuyn ty c 4 loi t bo bi tit: - T bo A () chim 20%, tit glucagon v proglucagon - T bo B () chim 75%, tit insu lin, proinsulin v C peptid - T bo C ( ) chim 3%, tit somatostatin - T bo F (PP) chim < 2%, tit pancreatic polypeptid (PP) Bi ny ch trnh by 2 hormon quan trng l insulin l glucagon. 2.1. Insulin Insulin l mt protein c trng lng phn t l 5800 Da, gm 2 chui peptid A (21 acid amin) v B (30 acid amin) ni vi nhau bng 2 cu disulfid. Ton b tuyn ty ca ngi c 8 mg insulin, tng ng 200 n v sinh hc. Khi i, tuyn ty tit khong 40 g (1 n v) insulin vo tnh mc h ca. Glucose l tc nhn ch yu gy tit insulin, thi gian bn thi trong huyt tng l 5 - 6 pht vi insulin v khong 17 pht vi proinsulin. Insulin b ging ha ch yu gan v thn do b ct ng ni disulfid gia chui A v B bi insulinase. 2.1.1. Tc dng v c ch Insulin iu ha ng huyt ti cc m ch ch yu l gan, c v m. Insulin l hormon ch yu kim tra s thu hi, s dng v d tr cc cht dinh dng cho t bo. Insulin kch thch cc qu trnh ng ha ca t bo (s dng v d tr glucose, acid amin, acid b o), ng thi c ch cc qu trnh d ha (phn

hu glycogen, m v protein). Tc dng chung l kch thch vn chuyn cc c cht v ion vo trong t bo, hot ha v bt hot cc enzym c hiu. Glucose nhp vo t bo bng s khuch tn thun li nh vo cc cht vn chuyn glucose (glucose transporters - GLUT): GLUT 1 c mi m, c bit l hng cu v no GLUT 2 c t bo ca ty, gan, thn, rut GLUT 3 c no, thn, rau thai GLUT 4 c c v m m GLUT 5 c rut v thn Glucose c s dng l nh vo h thng enzym hexokinase chuyn thnh glucose - 6- phosphat (GGP). Sau G6P s chuyn thnh glycogen d tr hoc b oxy ha cung cp nng lng cho m. Hexokinase IV l mt glucokinase c thy k t hp vi GLUT 2 trong gan v t bo ca ty; hexokinase II li c thy kt hp vi GLUT 4 trong t bo c vn, c tim v m m. C 2 hexokinase ny u c iu ha bi insulin ngay mc phin m di truyn. 2.1.1.1. Tc dng ca insulin ti gan - c ch hy glycogen (c ch phosphorylase) - c ch chuyn acid bo v acid amin thnh keto acid - c ch chuyn acid amin thnh glucose - Thc y d tr glucose di dng glycogen (gy cm ng glucokinase v glycogen synthetase) - Lm tng tng hp trigly cerid v VLDL. 2.1.1.2. Tc dng ca insulin ti c vn - Lm tng tng hp protein, tng nhp acid amin vo t bo - Lm tng tng hp glycogen, tng nhp glucose vo t bo 2.1.1.3. Tc dng ca insulin ti m m - Lm tng d tr triglycerid v lm gi m acid bo t do trong tun hon theo 3 c ch: . Gy cm ng lipoproteinlipase tun hon nn lm tng thu phn trigl?ycerid t lipoprotein tun hon. . Este ha cc acid bo t thu phn lipoprotein . c ch trc tip lipase trong t bo nn lm gim lipo lyse ca triglycerid d tr. 2.1.2. Receptor ca insulin Hu nh mi t bo ca ng vt c v u c receptor vi insulin, nhng s lng rt khc nhau: mng t bo hng cu ch c 40 receptor trong khi mng

t bo m, t bo gan c ti 300.000. Khi insul in gn vo receptor, n s hot ha cc tyrosin kinase trong t bo (ngi truyn tin th 2) v thc y cc qu trnh phosphoryl ha gy ra s chuyn v ca cc cht vn chuyn glucose (GLUT) v pha mng t bo nhp glucose vo trong t bo. Khi thiu insulin, t bo s khng s dng c glucose, glucose huyt s tng gi l bnh i tho ng. C 2 loi (typ) i tho ng. (Xin xem thm bi Thuc h glucose mu). - i tho ng typ I, do tn thng t bo ca ty, ty khng bi tit insul in nn phi iu tr b bng insulin ngoi lai, gi l bnh i tho ng ph thuc vo insulin. Bnh thng gp ngi tr, th gy. - i tho ng typ II, do tn thng ti receptor (gim s lng hoc gim tnh cm th ca receptor vi insulin), ins ulin mu vn bnh thng hoc c khi cn tng nn gi l bnh i tho ng khng ph thuc vo insulin. Bnh thng gp ngi trn 40 tui, bo bu. 2.1.3. p dng iu tr - Bnh i tho ng v cc bin chng ca n (xin xem thm bi Thuc h glu cose mu) - Nn, tr gy yu, k m n: dng insulin vi glucose 2.1.4. Cc ch phm chnh Cc ch phm thng c ngun gc t b, ln hoc bng k thut ti t hp DNA ca insulin ngi. Insulin b mang tnh khng nguyn nhiu hn ln. Cc loi ch phm: x in xem bi Thuc h glucose mu. 2.2. Glucagon Do t bo alpha ca o Langerhans tit ra, glucagon c tc dng tng glucose mu, tng acid lactic mu, tng acid pyruvic mu, tng acid b o t do huyt tng. Vi liu cao, glucagon kch thch thng thn bi tit catecholamin. Glucagon lm tng sc co bp ca c tim, nhp tim v cung lng tim, h huyt p, tng t nh isoprenalin (thuc c tc dng cng adrenergic). Liu cao lm gin c trn ca rut khng thng qua AMPv. 2.2.1. C ch tc dng Glucagon hot ha adenylcyclase, lm tng m 3, 5 AMP vng, 3, 5 AMP vng hot ha phosphorylase gan, chuyn glycogen thnh glucose. C vn khng c receptor vi glucagon. C ch ny cng ging nh c ch v tc dng ca catecholamin hot ha cc

recepto r adrenergic. 2.2.2. Ch nh - H glucose- mu do dng qu liu insulin (kt hp vi glucose tim tnh mch), hoc cn sc insulin ko di. - Sc (glucagon c dng thay isoprenalin). - nh gi d tr glycogen trong gan, phn loi cc th bnh v g lycogen. 2.2.3. Ch phm Glucagon: 1 mL = 1mg. Tim di da, tim bp hoc tnh mch. Tc dng xut hin nhanh. Cng tc dng ph thuc vo d tr glycogen ca gan. 3. HORMON V THNG THN: GLUCOCORTICOID V thng thn c 3 vng sn xut hormon: - Vng cun pha ngoi, sn xut hormon iu ha thng bng in gii (mineralocorticoid), i din l aldosteron, chu s kim tra chnh ca h renin angiotensin. - Vng b v vng li pha trong, sn xut ?hormon iu ha glucose (glucocorticoid - hydrocortison hay cortisol) v androgen, chu s kim tra chnh ca ACTH tuyn yn. Trong lm sng thng dng glucocorticoid nn y ch trnh by nhm thuc ny. Corticoid iu ha glucose: CORTISOL (hydrocortison ) 3.1. Tc dng sinh l v tai bin Mi tc dng sinh l ca corticoid u l ngun gc ca cc tai bin khi dng ko di. 3.1.1. Trn chuyn ha - Chuyn ha glucid: corticoid thc y to glucose t protid, tp trung thm glycogen gan, lm gim s dng glucose ca cc m, nn lm tng glucose mu . V th c khuynh hng gy ra hoc lm nng thm bnh i tho ng. - Chuyn ha protid: corticoid lm gim nhp acid amin vo trong t bo, tng acid amin tun hon, dn n teo c, thng bng nit ( -). Do tng d ha protid, nhiu m b nh hng: m lin kt km bn vng (gy nhng vch rn di da), m lympho b teo (tuyn hung, lch, hch lympho), xng b tha do lm teo cc thm m lin kt, ni lng ng cc cht v c to nn khung xng (do xng di d b gy, t sng b ln, hoi t v khun c xng i). - Chuyn ha lipid: corticoid va c tc dng hu lipid trong cc t bo m, lm tng acid b o t do; va c tc dng phn b li lipid trong c th, lm m ng nhiu mt (khun mt mt trng), c, na thn trn (nh dng Cushing) ,

trong khi cc chi v na thn di th teo li. C gi thit gii thch rng t bo m ca na thn trn p ng ch yu vi tng insulin do glucocorticoid gy tng ng huyt, trong khi cc t bo m khc li km nhy cm vi insulin v p ng vi t c dng hu lipid. - Chuyn ha nc v in gii: . Na+: lm tng ti hp thu Na + v nc ti ng thn, d gy ph v tng huyt p. . K+: lm tng thi K + (v c H+), d gy base mu gim K + (v c base mu gim Cl -). . Ca2+; lm tng thi Ca 2+ qua thn, gim hp thu Ca 2+ rut do i khng vi vitamin D. Khuynh hng lm gim Ca - mu ny dn ti cng cn gip trng phn ng ko Ca 2+ t xng ra, cng lm xng b tha, lm tr em chm ln. . Nc: nc thng i theo cc ion. Khi ph do aldosteron t ng th corticoid gy i nhiu (nh trong x gan) v n i khng vi aldosteron ti thn. 3.1.2. Trn cc c quan, m - Kch thch thn kinh trung ng, gy lc quan, c th l do ci thin nhanh c tnh trng bnh l. V sau lm bt rt, bn chn, lo u, kh ng (c th l do ri lon trao i ion Na+, K+ trong dch no tu). Gy thm n, do tc dng trn vng i. - Lm tng ng mu, tng s lng hng cu, bch cu, tiu cu, nhng lm gim s lng t bo lympho do hu cc c quan lympho. - Trn ng tiu ha: corticoid va c tc dng gin tip, va c tc dng trc tip lm tng tit dch v acid v pepsin, lm gim sn xut cht nhy, gim tng hp prostaglandin E 1, E2 c vai tr trong vic bo v nim mc d dy. V vy, corticoid c th gy vim lot d dy. Tai bin ny thng gp khi dng thuc ko di hoc dng liu cao. - Do c ch cu to nguyn bo si, c ch cc m ht, corticoid lm chm ln so cc vt thng. 3.2. Cc tc dng c dng trong iu tr Ba tc dng chnh c dng trong iu tr l chng vim, chng d i kh ng v c ch min dch. Tuy nhin, cc tc dng ny ch t c khi nng cortisol trong mu cao hn nng sinh l{, l nguyn nhn d dn n cc tai bin trong iu tr. V vy, trong trng hp c th, nn dng th uc ti ch trnh tc dng ton thn v nng cao hiu qu iu tr n ti a. C ch tc dng ca corticoid rt phc tp v c nhiu tc dng trn mt t bo ch, v li

c nhiu t bo ch. 3.2.1. Tc dng chng vim Glucocorticoid tc dng trn nh iu giai on khc nhau ca qu trnh vim, khng ph thuc vo nguyn nhn gy vim: - c ch mnh s di chuyn bch cu v vim. - Lm gim sn xut v gim hot tnh ca nhiu cht trung gian ha hc ca vim nh histamin, serotonin, bradykinin, cc d n xut ca acid arachidonic (s 1). Glucocorticoid c ch phospholipase A 2, lm gim tng hp v gii phng leucotrien, prostaglandin. Tc dng ny l gin tip v glucocorticoid lm tng sn xut lipocortin, l protein c mt trong t bo, c tc dng c ch phospholipase A 2. Khi phospholipase A 2 b c ch, phospholipid khng chuyn c thnh acid arachidonic. - c ch gii phng cc men tiu th, cc ion superoxyd (cc gc t do), lm gim hot tnh ca cc yu t ha hng ng, cc cht hot ha c a plasminogen, collagenase, elastase - Lm gim hot ng thc bo ca i thc bo, bch cu a nhn, gim sn xut cc cytokin.

Hnh 35.2. v tr tc dng ca glucocorticoid v thuc chng vim phi steroid trong tng hp cc prostaglandin 3.2.2. Tc dng chng d ng Cc phn ng d ng xy ra do s gn ca cc IgE hot ha trn cc receptor c hiu dng bo (mastocyte) v bch cu base tnh di tc dng ca d nguyn. S gn hot ha phos pholipase C, cht ny t ch phosphatidyl - inositol diphosphat mng t bo thnh diacyl- glycerol v inositoltriphosphat. Hai cht ny ng vai tr ngi truyn tin th hai, lm cc ht bo tng ca t bo gii phng cc cht trung gian ha hc ca phn ng d ng: histamin , serotonin (hnh 7.2).

Hnh 35.3. Tc dng chng d ng ca glucocorticod Bng cch c ch phospholipase C, glucocorticoid phong to gii phng trung gian ha hc ca phn ng d ng. Nh vy, IgE gn trn dng bo nhng khng hot ha c nhng t bo . Glucocorticoid l nhng cht

chng d ng mnh. 3.2.3. Tc dng c ch min dch Glucocorticoid tc dng ch yu trn min dch t bo, t nh hng n min dch th dch. Tc dng c ch min dch biu hin nhiu khu: - c ch tng sinh cc t b o lympho T do lm gim sn xut interleukin 1 (t i thc bo) v interleukin 2 (t T 4). - Gim hot tnh gy c t bo ca cc lympho T (T 8) v cc t bo NK (natural killer: t bo dit t nhin) do c ch sn xut interleukin 2 v interferon gamma. - Do c ch sn xut TNF (yu t hoi t u) v c interferon, glucocorticoid lm suy gim hot tnh dit khun, gy c t bo v nhn dng khng nguyn ca i thc bo. Mt s tc dng ny cng ng thi l tc dng chng vim. Do c ch tng sinh, glucoc orticoid c tc dng tt trong iu tr bnh bch cu lympho cp, bnh Hodgkin. 3.3. Ch n?h 3.3.1. Ch nh bt buc: thay th s thiu ht hormon 3.3.1.1. Suy thng thn cp - B th tch tun hon v mui: NaCl 0,9% 1lt (5% trng lng c th tro ng 24 gi). - Glucocorticoid liu cao: Hydrocortison 100 mg t/m. Sau 50 - 100 mg 8h/ ln trong ngy u. Sau 24 n 72 gi thay bng tim bp hoc ung 25 mg 8h/ ln. 3.3.1.2. Suy thng thn mn tnh (bnh Addison) Hydrocortison 20 mg un g vo bui sng v 10 mg vo bui tra. 3.3.2. Ch nh thng thng trong chng vim v c ch min dch 3.3.2.1. Vim khp, vim khp dng thp - Mt khi dng corticoid th phi dng hng nm ! V th rt d c tai bin. - Liu u tin thng l pred nison 10 mg (hoc tng ng) - Khi au qu: triamcinolon acetonid 5 - 20 mg tim khp (ch lm ti bnh vin, tht v khun) 3.3.2.2. Bnh thp tim - Ch dng corticoid khi salicylat khng c tc dng - Bnh nng, corticoid c hiu qu nhanh. Liu predn ison 40mg/ngy - Khi ngng corticoid, bnh c th tr li. Nn phi hp vi salicylat 3.3.2.3. Cc bnh thn

3.3.2.3. Cc bnh thn 4 tun. Liu duy tr 3 ngy/ tun, ko di ti hng nm . 3.3.2.4. Cc bnh dy h (collagenose) - Nm da cng (sclerodermia): khng chu thuc - Vim nhiu c, vim nt quanh mch, vim au nhiu c do thp: prednison 1mg/ kg/ ngy. Gim dn - Lupus ban ton thn bt pht: prednison 1 mg/ kg/ ngy. Sau 48 gi nu khn g gim bnh, tng mi ngy 20 mg cho n khi c p ng. Sau dng liu duy tr 5 mg/ tun. C th dng thm salicylat, azathioprin, cyclophosphamid. 3.3.2.5. Bnh d ng - Dng thuc chng d ng: khng his tamin, adrenalin trong cc biu hin c p tnh. - Corticoid c tc dng chm 3.3.2.6. Hen - Dng corticoid dng kh dung, cng vi cc thuc gin ph qun (thuc cng 2 adrenergic, theophylin). phng tai bin nm candida ng mi hng 3.3.2.7. Bnh ngoi da - Ngoi tc dng chung, khi bi ngoi, corticoid c ch ti ch s phn bo, v vy c tc dng tt trong iu tr bnh vy nn v cc bnh da c tng sinh t bo. - Trn da bnh thng, khong 1% liu hydrocortison c hp thu. Nu bng p, c th lm tng hp thu n 10 ln. S h p thu tuz thuc tng vng da bi thuc, tng cao vng da vim, nht l vng trc vy. * Tc dng khng mong mun - Bi thuc trn din rng, ko di, nht l cho tr em, thuc c th c hp thu, gy tai bin ton thn, tr chm ln. - Tc dng ti ch: teo da, xut hin cc im gin mao mch, chm xut huyt, ban , sn, mn m, trng c, mt sc t da, tng p lc nhn cu * Mt s ch phm Flucinolon acetonid (Synalar) 0,01% - 0,025%- 0,2% Triamcinolon acetonid (Aristocor, Kenalog) 0,025% - 0,1% Betametason dipropionat (Diproson) 0,05% 0,1% (tc dng mnh) Cc ch phm trn thng c bo ch di cc dng khc nhau nh thuc m (thch hp vi da kh), kem (da mm, tn thng c dch r, cc hc ca c th nh m o), dng gel (dng cho vng da u, nch, bn).

Khi bi thuc, cn xoa u thnh lp mng, 1 - 2 ln/ ngy, theo ng ch dn, nht l thuc c tc dng mnh. 3.4. Chng ch nh - Mi nhim khun hoc nm cha c iu tr c hiu. - Lot d dy- hnh t trng, long xng. - Vim gan si?u vi A v B, v khng A khng B. - Ch nh thn trng trong i tho ng, tng huyt p. 3.5. Nhng im cn ch khi dng thuc - Khi dng corticoid thin nhin (cortisol, hydrocortison) phi n nht. i vi thuc tng hp, n tng i nh t. - Lun cho mt liu duy nht vo 8 gi sng. Nu dng liu cao th 2/3 liu ung vo bui sng, 1/3 cn li ung vo bui chiu. - Tm liu ti thiu c tc dng. - Kim tra nh kz nc tiu, huyt p, in quang d dy ct sng, ng mu, kali mu, thm d chc phn trc h khu no - tuyn yn- thng thn. - Dng thuc phi hp: tng liu insulin i vi bnh nhn i tho ng, phi hp khng sinh nu c nhim khun. - Ch n: nhiu protein, calci v kali; t mui, ng v lipid. C th dng th m vitamin D nh Dedrogyl 5 git/ ngy (mi git cha 0,005mg 25 - OH vitamin D3) - Tuyt i v khun khi dng corticoid tim vo khp. - Sau mt t dng ko di (trn hai tun) vi liu cao khi ngng thuc t ngt bnh nhn c th cht do suy thng thn cp: cc triu chng tiu ha, mt nc, gim Na, gim K mu, suy nhc, ng lm, tt huyt p. V th khng ngng thuc t ngt. Hin c xu hng dng liu cch nht, gim dn, c v an ton cho tuyn thng thn hn. Mt s th d: . ang ung prednison 40 mg/ ngy: c th dng 80 mg/ ngy, cch nht; gim dn 5 mg mi tun (hoc gim 10% tng 10 ngy) . ang dng 5- 10 mg/ ngy: gim 1 mg/ tun . ang dng 5 mg/ ngy: gim 1 mg/ thng . Mt phc in hnh cho bnh nhn dng liu prednison duy tr 50 mg/ ngy c th thay nh sau: Ngy 1: 50 mg Ngy 2: 40 mg

Ngy 3: 60 mg Ngy 4: 30 mg Ngy 5: 70 mg Ngy 6: 10 mg Ngy 7: 75 mg Ngy 8: 5 mg Ngy 9: 70 mg Ngy 10: 5 mg Ngy 11: 65 mg Ngy 12: 5 mg v.v 3.6. Lin quan gia cu trc v tc dng Mi corticoid dng trong iu tr u l dn xut ca cortisol hay hydrocortison (hormon thin nhin c OH v tr 11). Bng cch thay i cu trc ca cortisol, ta c th lm tng rt nhiu tc dng chng vim v thi gian bn thi tr ca thuc, ng thi lm gim kh nng gi mui v nc. Cu trc steroid c 4 vng: - Vng A: khi c thm ng ni kp gia v tr 1 - 2, tc dng chng vim tng v gi mui gim (prednison, prednisolon). - Vng B: thm -CH3 v tr 6 (methylprednisolon), ho c F 9 , hoc c 2 v tr 9 6 (fludrocortison, flucinonid), tc dng chng vim cng mnh v ko di t 1/2. Nhng F v tr 9 li lm tng tc dng gi Na + - Vng D: thm -CH3 hay -OH v tr 16 , lm gim mnh kh nng gi mui ca hp cht 9 F (triamcinolon, dexametason betametason). V th hin nay c rt nhiu ch phm corticoid mnh v tc dng di. Liu lng v thi gian dng rt khc nhau. Thy thuc cn lu { trnh tai bin cho bnh nhn. 3.7. Dc ng hc Glucocorticoid hp thu d dng qua ng tiu ha, t 1/2 huyt tng khong t 90 - 300 pht. Trong huyt tng, cortisol gn vi transcortin (90%) v vi albumin (6%). Cortisol b chuyn ha ch yu gan bng kh ng ni 4 - 5 v kh ceton v tr 3. Thi tr qua thn di dng sulfo- v glycuro- hp. Tc dng sinh hc (t 1/2 sinh hc) ln hn r 70 mg Ng t nhiu so vi t1/2 huyt tng. Bng 35.1: Lit k mt s corticoid thng dng

Mt s ch phm dng tim c t dc l polyetylen glycol, glysorbat lm thuc thi tr rt chm, tuz theo bnh v liu lng, c th ch tim 1 tun, 2 tun ho c 1 thng 1 ln, nh Depomedrol (cha metylprednisolon acetat 40 mg trong 1 mL ), Rotexmedica, Kenacort (cha triamcinolon acetonid 40 - 80 mg/ mL). Tuy nhin, loi ny thng c nhiu tc dng ph nh teo da, teo c, xp xng v ri lon ni tit. 4. HORMON TUYN SINH DC 4.1. Androgen (testosteron) Ging nh bung trng, tinh hon va c chc nng sn xut tinh trng (t tinh nguyn bo v t bo Sertoli, di nh hng ca FSH tuyn yn), va c chc nng ni tit (t bo Leydig bi tit androgen di nh hng ca LH tuyn yn). ngi, androgen quan trng nht do tinh hon tit ra l testosteron. Cc androgen khc l androstenedion, dehydroepiandros teron u c tc dng yu. Mi ngy c th sn xut khong 8 mg testosteron. Trong , 95% l do t b o Leydig, cn 5% l do thng thn. Nng testosteron trong mu ca nam khong 0,6 g/ dL vo sau tui dy th; sau tui 55, nng gim dn. Huyt tng ph n c nng testosteron khong 0,03 g/ dL do ngun gc t bung trng v thng thn. Khong 65% testosteron trong mu gn vo sex hormonebinding globulin (TeBG), phn ln s cn li gn vo albumin, ch khong 2% dng t do c kh nng nhp vo t bo gn vo receptor ni bo. 4.1.1. Tc dng - Lm pht trin tuyn tin lit, ti tinh, c quan sinh dc nam v c tnh sinh dc th yu. - i khng vi oestrogen - Lm tng tng hp protein, pht trin xng, lm cho c th pht trin nhanh khi dy th (c bp n nang, xng di ra). Sau sn ni b ct ha. - Kch thch to hng cu, lm tng tng hp heme v globin. Testosteron khng phi l dng c hot tnh mnh. Ti t bo ch, di tc dng ca 5 - reductase, n chuyn thnh dihydrotestosteron c hot tnh. C 2 cng gn vo receptor trong bo tng pht huy tc dng. Trong bnh lng tnh gi, tuy c th vn tit testosteron bnh thng, nhng t bo ch thiu 5 reductase hoc thiu protein receptor vi testosteron v dihydrotestosteron (Griffin, 1982), nn testosteron khng pht huy c tc dng. Di tc dng ca aromatase mt s m (m, gan, h khu no), testosteron

c th chuyn thnh estradiol, c vai tr iu ha chc phn sinh dc. 4.1.2. Ch nh Testosteron v cc mui c sp xp vo bng B - Chm pht trin c quan sinh dc nam, dy th mun. - Ri lon kinh ng uyt (kinh nhiu, k o di, hnh kinh au, ung th v, tc dng i khng vi oestrogen. - Suy nhc c nng, gy yu,. - Long xng. Dng ring hoc cng vi estrogen. - Ngi cao tui, nh mt liu php thay th. 4.1.3. Ch phm v liu lng Testosteron tim l dung dch tan trong du, c hp thu, chuyn ha v thi tr nhanh nn km tc dng. Loi ung cng c hp thu nhanh, nhng cng km tc dng v b chuyn ha nhiu khi qua gan ln u. Cc este ca testosteron (testosteron propionat, cypionat v enantat) u t phn cc hn, c hp thu t t nn duy tr c tc dng di. Nhiu androgen tng hp b chuyn ha chm nn c thi gi an bn thi di. * Loi c tc dng hor mon: * Loi c tc dng hor mon: 3 ngy tim 1 ln 50 mg. Liu ti a mi ngy: 50 mg. - Metyl- 17 testosteron: 2 - 3 ln yu hn testosteron. C th ung. Tt hn l t di li thm qua nim mc. Liu 5 - 25 mg. Liu ti a 50 mg mt ln, 100 mg mt ngy. - Testosteron chm: Dung dch du testosteron onantat: 1 mL = 0,25g. Mi ln tim bp 1 mL. Hn dch tinh th testosteron isobutyrat: tim bp, di da 50 mg, 15 ngy 1 ln. Vin testosteron acetat: 0,1g testosteron acetat cy trong c, 1 - 2 thng 1 ln. * Loi c tc dng ng ha: Loi ny u l dn cht ca testosteron v methyl - 17- testosteron khng c tc dng hormon (khng lm nam tnh ha), nhng cn tc dng ng ha mnh: tng ng ha protid, gi nit v cc mui K +, Na+, phospho nn lm pht trin c xng, t ng cn (tt nhin l ch n phi gi c cn i v cc thnh phn, nht l v acid amin) V cu trc ha hc, cc androgen ng ha khc vi methyl testosteron l hoc V cu trc ha hc, cc androgen ng ha khc vi methyl testosteron l hoc C5. Th d (xem cng thc):

Ch nh: gy st, t ha xng, k m n, mi m dy, sau m v cc thuc trn vn cn rt t tc dng hormon, cho nn khng dng cho tr em di 15 tui. Thuc cn b lm dng dng cho cc vn ng vin th thao vi liu rt cao, thuc loi doping, b cm. 4.1.4. Tai bin ca androgen Liu cao v ko di : gy nam tnh, qu sn tuyn tin lit mt gan: ngng thuc th ht. 4.1.5. Chng ch nh - Tr di 15 tui - Ph n c thai - Ung th tuyn tin lit (phi dng estrogen) 4.1.6. Tthuc khng androgen Thuc khng andro gen do c ch tng hp hoc i khng tc dng ca androgen ti receptor. Thuc thng c dng iu tr qu sn hoc carcinom tuyn tin lit, trng c, hi u ca nam, chng nhiu lng ca n, dy th sm. 4.1.6.1. Thuc c ch 5 reductase: Finas terid mt s m (tuyn tin lit, nang lng), di tc dng ca 5 reductase, testosteron mi c chuyn thnh dng hot tnh l dihydrotestosteron. V vy, thuc c ch 5 reductase s c ch chn lc tc dng androgen trn nhng m ny, nhng khng lm gim nng testosteron v LH huyt tng. Finasterid c dng iu tr qu sn v u tin lit tuyn vi liu 5 mg/ ngy. Tc dng sau ung 8 ting v ko di 24 ting. Cn c ch nh cho hi u. 4.1.6.2. Thuc i khng ti receptor - Cyproteron v cyproteron acetat Tranh chp vi dihydrotestosteron gn vo receptor ca m ch. Dng acetat cn c tc dng progesteron, c ch tng tit LH v FSH theo c ch iu ha ngc nn tc dng khng androgen cng mnh. Ch nh trong chng rm lng n, trng c. Vi nam, dng iu tr hi, u tuyn tin lit, dy th sm. Thuc cn ang c theo di, nh gi.

- Flutamid: Flutamid l thuc khng androgen khng mang nhn steroid nn trnh c hot tnh hormon khc. Vo c th, c chuyn thnh 2 hyd roxyflutamid, gn tranh chp vi dihydrotestosteron ti receptor. Ch nh trong u tin lit tuyn. Vin nang, 750 mg/ ngy. 4.2. Estrogen ph n, cc estrogen c sn xut l estr?adiol (E 2- 17 estradiol), estron (E 1) v estriol (E3). Estradiol l sn phm ni tit chnh ca bung trng. Phn ln estron v estriol u l cht chuyn ha ca estradiol gan hoc m ngoi bin t androstenediol v cc androgen khc. ph n bnh thng, nng E 2 trong huyt tng thay i theo chu kz kinh nguyt: giai on u l 50 pg/ mL v thi kz tin phng non l 350 - 850 pg/ mL. Trong mu, E2 gn ch yu vo 2 globulin (SHBG - sex hormonebinding globulin) v mt phn vo albumin. Ti m ch, n c gii phng ra dng t do, vt qua mng t bo gn vo receptor ni bo. 4.2.1. Tc dng - L nguyn nhn chnh ca cc thay i xy ra trong tui dy th con gi v cc c tnh sinh dc ca ph n (vai tr th yu l androgen; pht trin xng, lng, trng c). - C tc dng trc tip lm pht trin v trng thnh m o, t cung, vi trng. Ngoi tc dng lm pht trin c t cung E 2 cn c vai tr quan trng lm pht trin ni mc t cung. - Trn chuyn ha: . E2 c vai tr c bit duy tr cu trc bnh thng ca da v thnh mch ph n. . Lm gim tc tiu xng do c tc dng i khng vi PTH ti xng, nhng khng kch thch to xng. . Trn chuyn ha lipid: lm tng HDL, lm gim nh LDL, gim cholesterol, nhng lm tng nh triglycerid. - Trn ng mu: estrogen lm tng ng mu , do lm tng yu t II, VII, IX v X, lm gim antithrombin III. Ngoi ra cn lm tng hm lng plasminogen v lm gim s kt dnh tiu cu. - Cc tc dng khc: estrogen lm d thot dch t lng mch ra khong gian bo, gy ph. Khi th tch mu gim, thn s gi Na + v nc, thc y tng hp receptor ca progesteron.

- Trn nam gii, estrogen liu cao lm teo tinh hon, lm ngng to tinh trng v lm ngng pht trin, lm teo c quan sinh dc ngoi. 4.2.2. Ch nh 4.2.2.1. L thnh phn ca thuc t rnh thai theo ng ung (xem bi Thuc trnh thai). 4.2.2.2. Thay th hormon sau thi kz mn kinh Bung trng gim bi tit estrogen dn dn, k o di vi nm sau khi mn kinh. Nhng khi ct b bung trng th s c ri lon t ngt, cn dng hormon thay th ngay. Trong iu tr ri lon sau mn kinh, estrogen c ch nh trong d phng cc biu hin sau: - Chng long xng: long xng l do mt hydroxyapatit (phc hp calci phosphat) v cht c bn protein hoc cht keo (to khung xng), lm x ng mng, yu, d gy t nhin (ct sng, c xng i, c tay). Estrogen lm gim tiu xng, c tc dng d phng nhiu hn iu tr chng long xng. Thng dng phi hp vi calci, vitamin D, biphosphonat. - Triu chng ri lon vn mch: cn nng b ng, bc ha vi cm gic n lnh, v m hi, d cm. Estrogen rt c hiu qu. - D phng bnh tim mch: khi thiu estrogen, d dn n tng choles terol mu, tng LDL, s lng receptor LDL ca t bo gim. Tuy nhin, nng HDL, VLDL v triglycerid t ch u nh hng. Nhiu thng k cho thy sau tui mn kinh, bnh tim mch v nhi mu c tim thng tng nhanh v l nguyn nhn gy t vong. Tuy nhin, dng estrogen iu tr thay th ch nn mc liu thp, thi gian ngn, trnh nguy c ung th v. 4.2.2.3. Cc ch nh khc - Chm pht tri?n, suy gim bung trng tui dy th - Tc dng i khng vi androgen: trng c, rm lng n, vim tinh hon do quai b, u tin lit tuyn. Hin c xu hng dng cc cht tng t GnRH (Leuprolid) c tc dng c ch tng hp andrrogen. 4.2.3. Tc dng khng mong mun Estrogen c hiu qu rt tt cho phn ln cc ch nh iu tr. Tuy nhin, mi khi quyt nh cn cn nhc gia li ch v nguy c cho tng bnh nhn. Nhng nguy c thng c coi l do estrogen gm ; ung th (v, ni mc t cung), vim tc mch, thay i chuyn ha ng v lipid, tng huyt p, bnh ti mt (do tng cholesterol trong mt), bun nn, thay i tnh tnh. 4.2.4. Chng ch nh - Tuyt i khng dng cho trc tui dy th, khi c thai

- Khi u ph thuc vo estrogen nh carcinom ni mc t cung, v. - Chy mu ng sinh dc, bnh gan ang trong giai on chn on, c tin s vim tc mch. 4.2.5. Ch phm v liu lng Cc estrogen ch khc nhau v cng tc dng v ng dng do b chuyn ha nhiu gan. Estradiol l estrogen thin nhin mnh nht sau l estron v estriol. Khi ung, b chuyn ho qua gan ln th nht nn mt tc dng nhanh. Mt khc, mt cht chuyn ha quan trng ca n l 2 - hydroxyestron (catechol estrogen) c tc dng nh mt cht dn truyn thn kinh no. V vy cc ch phm ca estradiol v estron c th gy tc dng ph trn thn kinh trung ng nhiu hn cc ch phm tng hp. C 2 nhm ch phm tng hp: nhm c nhn steroid ging estrogen t nhin nh ethinyl estradiol, mestranol, quinestrol; nhm khng c nhn steroid nh diethylstilbestrol (DES), mnh ngang estradiol nhng t/2 di), clorotrianisen, methallenestril. Trong mt s cy v nm, trong mt s thuc tr su tng hp (p p - DDT) cng c nhi u estrogen khng mang nhn steroid c hot tnh ging estrogen hoc ngc li, khng estrogen v c cha vng phenol ging vi vng A ca estrogen l v tr gn vo receptor ca estrogen. Cc ch phm tng hp c th dng di dng ung, tim, hp thu qua da, bi ti ch. C dng tc dng ngay, c dng tc dng ko di vi ngy hoc dng gii phng lin tc. - Estradiol (Estrace) Ung: vin nn 0,5 - 1- 2 mg Kem bi m o: 0,1 mg/ g - Estradiol valerat Dung dch du 10 - 20- 40 mg/ ml tim bp - Estradiol qua da (Estraderm) Cao dn gii phng hot cht chm thm qua da vi cc tc khc nhau 0,05 0,075- 0,1 mg/ ngy. - Ethinyl estradiol (Estinyl) Ung: vin nn 0,02 - 0,05- 0,5 mg 4.2.6. Cc thuc khng estrogen Cc thuc khng oestrogen l cc thuc c tc dng i khng vi tc dng sinh hc ca estrogen. C 2 thuc c dng lm sng: 4.2.6.1. Clomifen (Clomid) Clomifen citrat l mt cht khng mang nhn steroid.

C ch Clomifen tranh chp vi oestrogen ni sinh ti cc receptor vng di i v tuyn yn, i lp vi c ch c ch ngc chiu, v vy lm tng bi tit LHRH ca vng di i v tng bi tit FSH, LH ca tuyn yn. kt qu l lm tng gii phng oestrogen ca bung trng. Nu iu tr vo trc giai on phng non, s gy c p hng non. Ch nh - Dng chn on d tr gonadotrophin ca tuyn yn - Dng trong iu tr v sinh do khng phng non. C?ch dng Clomid vin 50 mg. Liu u tin ung 1 vin/ ngy, ung 5 ngy lin k t ngy th 5 ca chu kz kinh. Nu khng thnh c ng, phi i 30 ngy, trc khi bt u t iu tr th hai bng ung 1 hoc 2 vin/ ngy. 4.2.6.2. Tamoxifen (Nolvadex) Tamoxifen l dn xut ca triphenyl ethylen khng mang nhn steroid. C ch Cc thuc ny ngn cn phc hp oestrogen - receptor gn vo v tr tc dng trn ADN ca t bo ch. V vy, ngn cn s pht trin ca cc khi u ph thuc vo estrogen. Ch nh Ung th v ph thuc vo hormon trn ph n mn kinh Cch dng - Nolvadex, vin nn 10 v 20 mg - Liu trung bnh t 20 - 40 mg, ung lm 2 ln. 4.3. Progestin Cc progestin bao gm hormon thin nhin progesteron t c dng trong iu tr,v cc ch phm tng hp c hot tnh ging progesteron. Progesteron l progestin quan trng nht ngi. Ngoi tc dng hormon, n cn l cht tin thn tng hp estrogen, androgen v steroid v thng thn. Progesteron c tng hp t cholesterol ch yu l vt th vng ca bung trng, sau l tinh hon v v thng thn. Khi c thai, rau thai tng hp mt

s lng ln. na u ca c hu kz kinh, mi ngy ch vi mg progesteron c bi tit, sang na sau ca chu kz s lng bi tit tng ti 10 - 20 mg/ ngy v vo cui thi kz mang thai l vi trm mg. nam l khong 1- 5 mg/ ngy. 4.3.1. Tc dng - Trn t cung: progesteron c bi tit nhiu na sau ca chu kz kinh (giai on hong th) s lm chm giai on tng sinh ca ni mc t cung ca estrogen na u ca chu kz v lm pht trin ni mc xut tit, to iu kin cho trng lm t. Cui chu kz kinh, hong th t ngt gim gii phng progesteron l yu t chnh khi pht kinh nguyt. Khi c thai, progesteron c ch to vng kinh v c ch co bp t cung, c tc dng gi thai. - Trn tuyn v: na sau ca chu kz kinh v nht l khi c thai, cng vi estrogen, progesteron lm tng sinh chm nang tuyn v chun b cho vic tit sa. Tri vi tuyn v, s tng sinh ni mc t cung li xy ra mnh nht l di nh hng ca estrogen. Cn ghi nh s khc bit ny s dng trong iu tr v nhn nh v tc dng khng mong mun. - Trn thn nhit: gia chu kz kinh, khi phng non, thn nhit thng tng 0,56 0C v duy tr cho n ngy thy kinh. C ch chnh xc cn cha r, nhng c vai tr ca progesteron v h khu no. - Trn chuyn ha: progesteron kch thch hot t nh ca lipoproteinlipase v lm tng ng m, lm gim LDH v lm gim tc dng c li ca estrogen trn chuyn ha m. Tuy nhin, tc dng cn ph thuc vo ch phm, liu lng v ng dng. Progesteron cng c th lm gim tc dng ca aldosteron trn ng thn, lm gim ti hp thu natri, do d lm tng bi tit b aldosteron. 4.3.2. Ch nh Hai ch nh rt thng dng l: - Phi hp vi estrogen hoc dng ring trong vin trnh thai (xem bi thuc trnh thai) - Liu php thay th hormon sau th i kz mn kinh. Thng phi hp vi estrogen lm gim nguy c gy ung th v, t cung. Ngoi ra, cn dng trong mt s trng hp sau: - c ch bung trng trong cc triu chng au kinh, chy mu? t cung, rm lng, bnh lc mng trong t cung: dng li u cao theo ng tim (th d medroxyprogesteron acetat 150 mg tim bp cch 90 ngy/ ln) Trc y, cn dng chng da xy thai do tc dng c ch co bp t cung.

Hin khng dng v c nhiu thuc gin t cung khc tt hn (thuc cng 2, thuc c ch tng hp prostaglandin ) v prgesteron d c nguy c cho thai ( gy nam ha v d dng sinh dc) 4.3.3. Thn trng v chng ch nh - C thai - Tng lipid mu. Progestin trong thuc trnh thai hoc dng mt mnh c th gy tng huyt p trn mt s bnh nhn. 4.3.4. Cc ch phm Progesteron thin nhin t dng trong iu tr v b chuyn ha nhanh. Cc progestin tng hp c chia lm 2 nhm: - Nhm c 21 carbon c tc dng chn lc cao v ph hot tnh ging vi hormon ni sinh. Thng c dng phi hp vi estrogen trong iu tr thay th hormon ph n sau mn kinh. - Nhm dn xut t 19 - nortestosteron (th h 3), khng c C 19, C20 v C 21 do c hot tnh progestin mnh nhng cn cc tc dng estrogen, androgen v chuyn ha, tuy yu (lin quan n tc dng khng mong mun) v ung c.

Bng 35.2: Mt s ch phm thng dng

4.4. Thuc khng progestin Mifepriston c dng u tin Php vo nm 1988 Mifepriston l dn xut ca 19 - norprogestin, gn mnh vo receptor ca progesteron. Nu c mt progestin, mifepriston tc dng nh mt cht i khng tranh chp ti receptor, nu tc dng mt mnh th mifepriston li c tc dng nh progestin, nhng yu (ng vn mt phn - partial agonist) Dng vo giai on sm ca thai kz, mifepriston lm bong mng rng do phong ta cc receptor progesteron ca t cung, dn n bong ti mm (blastocyst), lm gim sn xut choriogonadotropin (CG). Chnh nhng tc dng ny s lm hong th gim tit progesteron, cng lm bong thm mng rng. Progesteron gim lm tng sn xut prostaglandin ti t cung, gy co bp t cung v sy thai. Mifepriston cng c dng trnh th thai sau giao hp do ngn cn trng lm t. Tc dng c th cn hn c thuc phi hp estrogen proge stin

liu cao. Ngoi ra mifepriston cn c dng y thai cht lu trong t cung, bnh lc mng trong t cung. Ung th v, u c trn (leiomyomas) Cc thuc loi ny c dng t khong 1998 - 2000 v cn cn theo di lm sng. Gy sy thai trong qu{ u bng cho ung ung 400 - 600 mg/ ngy 4 ngy; hoc 800 mg/ ngy 2 ngy. Kt qu ti 85%. Nu ung 1 liu 600 mg mifepriston, sau 48h cho ung hoc t m o misoprostol (tng t PGE 1), kt qu sy thai c th ti 95%. 5. THUC TRNH THAI 5.1.C s sinh l Trong na u chu kz kinh nguyt, di tc dng ca hormon gii phng FSH (FSH - RH) ca vng di i, tuyn yn bi tit FSH, lm cho nang trng trng thnh, tit foliculin (oestrogen). Sau , vng di i tit hormon gii phng LH (LH RH), lm tuyn yn bi tit LH, n ngy th 14, khi FSH/LH t c t l thch hp th bung trng s phng non. Nu gp tinh trng, trng s th tinh v lm t. 5.2. Cc loi thuc chnh 5.2.1. Thuc trnh thai phi hp Phi hp oestrogen v progesteron t ng hp. Cc loi thuc ny u dng estrogen l ethinylestradiol. Nhng thuc c cha 50 g et?hinyl estradiol u c gi l chun (standard) phn bit vi loi liu thp (minidosage) ch cha 30 - 40 g ethinyl estradiol. Hm lng v bn cht ca progesteron phi hp th thay i theo tng loi, phn ln l 19 nortestosteron. Ngoi ra cn phn bit loi 1 pha (monophasic pills) l loi c hm lng hormon khng i trong sut chu kz kinh, loi 2 v 3 pha (diphasic, triphasic pills) c hm lng progesteron tng dn trong khi hm lng estrogen khng thay i hoc hi tng vo gia chu kz kinh. Loi 2 hoc 3 pha c tng lng progesteron thp hn loi 1 pha. 5.2.1.1. C ch tc dng - Tc dng trung ng: theo c ch iu ha ngc chiu, estroge n c ch bi tit FSH - RH v LH- RH, tuyn yn s gim tit FSH v LH, do khng t c nng v t l thch hp cho s phng non, cc nang bo km pht trin. - Tc dng ngoi bin: lm thay i dch nhy ca c t cung, tinh trng kh hot ng,

ng thi lm nim mc ni mc t cung km pht trin, trng khng lm t c. + Tc dng ca estrogen vi nhng liu t 50 - 100 g cho t ngy th 5 ca chu lz kinh l c ch phng non. Trn bung trng, lm ngng pht trin nang trng: trn ni mc t cung, lm qu sn nim mc cho nn l nguyn nhn ca rong kinh: trn t cung, lm tng tit cc tuyn: trn m o, lm dy thnh v trc vy. Nhng thay i ny lm d nhim candida v trichomonas. + Tc dng ca progesteron: trn bung trng lm n gng pht trin, gim th tch: trn ni mc t cung, lm teo: t cung mm, c t cung t bi tit, lm dch tit nhy hn, tinh trng kh chuyn ng. Gy mc lng, tng cn. Do nhng bt li ca tng hormon, nn thng dng phi hp hai th cng mt lc, hoc ni tip nhau, c hai u c gim liu. S phi hp m bo cho t cung, m o t thay i so vi bnh thng. Sau ngng thuc, chu kz bnh thng tr li ti 98% trng hp. 5.2.1.2. Cc tc dng dc l Trn bung trng : c ch chc phn ca bu ng trng, nang trng khng pht trin v khi dng lu, bung trng nh dn. Sau khi ngng thuc, khong 75% s li phng non trong chu kz u v 97% trong chu kz th 3, khong 2% vn gi v kinh sau vi nm. Trn t cung: sau thi gian di dng thuc c t h c qu sn t cung v hnh thnh polyp. Cc thuc c cha 19 nor progestin v t estrogen s lm teo tuyn nhiu hn v thng t chy mu. Trn v: thuc cha estrogen thng gy kch thch, n v. Trn mu: xy ra huyt khi tc mch. C th l d o tng cc yu t ng mu II, VII, IX, X v lm gim antithrombin III. Nhiu ngi b thiu acid folic. Trn chuyn ha lipid : estrogen lm tng triglycerid, tng cholesterol este ha v cholesterol t do, tng phospholipid, tng HDL. Cn LDL li thng gim. Chuyn ha ng : ging nh ngi mang thai, gim hp thu ng qua tiu ha. Progesteron lm tng mc insulin c s.

Da: lm tng sc t da i khi tng b nhn, trng c (do progestin). Tuy nhin, v androgen ca bung trng gim nn nhiu ngi c gim b nhn, trng c v pht trin tc. 5.2.1.3. Tc dng khng mong mun Loi nh: - Bun nn, au v, kinh nhiu, ph do estrogen trong thuc. Thay thuc c t es?trogen hn hoc nhiu progesteron. - Nhc u nh, thong qua. i khi c migren. Thay th uc. - V kinh i khi xy ra, lm nhm vi c thai. Thay thuc. Loi trung bnh: Cn ngng thuc. - Kinh nhiu: thay bng loi 2 - 3 pha, lng hormon t hn. - Tng cn - Da sm mu: khong 5% sau mt nm v 40% sau 8 nm dng thuc. - Thiu vitamin B cn g lm tng mu da. Phc hi chm khi ngng thuc. - Trng c: vi ch phm cha nhiu androgen. - Rm lng: ch phm c 19 nortestosteron. - Nhim khun m o: thng gp v kh iu tr. - V kinh: t gp, 95% phc hi sau ngng thuc. Loi nng: - Huyt khi tc mch, vim tc tnh mch: khong 1/1000 - Nhi mu c tim: d gp ngi bo c tin s tin sn git tng huyt p, tng lipid mu, i tho ng, ht thuc. Tai bin thng gim i nhng ngi dng thuc khng lin tc. - Bnh mch no: d gp ngi trn 35 tui vi t l 37 ca/ 100.000 ngi/ nm. - Trm cm, i hi phi ngng thuc khong 6%. - Ung th: cha c mi lin quan vi dng thuc. 5.2.1.4. Chng ch nh Cao huyt p, cc bnh v mch mu (nh vim tc mch) vim gan, ung th vt cung, i tho ng, bo bu, ph n trn 40 tui (v d c tai bin v mch u). 5.2.1.5. Tng tc thuc Lm gim tc dng chng th thai - Cc thuc gy cm ng enzym chuyn ha thuc gan, lm tng ging ha oestrogen v progesteron: Rifampici n, phenytoin, phenobarbital.

- Cc thuc lm thay i vi khun ng rut, tng thi tr oestrogen progesteron qua phn: ampicilin, neomycin, tetracyclin, penicilin, cloramphenicol, nitrofuratoin. Lm tng c tnh i vi gan ca thuc chng th thai Cc thuc chng trm cm loi 3 vng, IMAO, troleandromycin 5.2.1.6. Ch phm C rt nhiu loi. Th d: - Marvelon 21: vin c Desogestrel 150 mcg + Ethinylestradiol 30 mcg. Mi v c 21 vin thuc + 7 vin khng thuc - Nordette: mi vin c Levonorgestrel 1 50 mcg + Ethinylestradiol 30 mcg. - Rigevidon 21 + 7 v Rigevidon 21 + 7 Fe (st: Fe fumarat 25 mg): mi vin c Levonnorgestrel 150 mcg + Ethinylestradiol 30 mcg. - Tri- regol:

T ngy th 5 sau kinh, vin vng ung trc, sau n vin mu m chn ri vin trng. Nu khong cch gia hai vin trn 36 gi th khng an ton. Thuc thng ng thnh v 21 vin c hot cht + 7 vin khng c hot cht ung theo th t, mi ngy ung 1 vin vo bui chiu sau ba n. Ngy bt u thy kinh, tnh l ngy th nht, nu vng kinh l 28 ngy. Nu hm trc qun, th hm sau ung b. Nu gin on qu 36 gi, tc dng khng m bo. 5.2.2. Thuc trnh thai c progesteron n thun 5.2.2.1 C ch Do ch c progesteron, nn tc dng ch yu l ngoi bin: thay i dch nhy c t cung v lm km pht trin nim mc ni mc t cung. Hiu qu trnh thai khng bng thuc phi hp. Hiu lc ch c sau 15 ngy dng thuc, v ch m bo nu ung u, khng qun. Thng dng cho ph n c bnh gan, tng huyt p, c vim tc mch. Chm kinh, bnh tm thn. 5.2.2.2. Tai bin - Do khng c oestrogen nn khng c tai bin tim mch - Ri lon kinh nguyt. Thng xy ra trong nm u, l nguyn nhn gy

b loi 3 v thuc. Dn dn kinh nguyt s tr v bnh thng sau 1 nm. - Nhc u, chng mt, ph, tng cn. 5.2.2.3. Chng ch nh Do thuc c tc dng lm kh nim mc dch m o, cho nn khng dng cho ph n di 40 tui. 5.2.2.4. Ch phm v cch dng Tt c u l loi norsteroid Loi liu cao: Dng khng lin tc, ung t ngy th 5 n ngy th 25 ca chu kz, c dng cho nhng ph n c tai bin mch, hoc ph n trn 50 tui, tai b in v mch thng cao. - Khng dng cho ngi c cao huyt p, i tho ng hoc c lipid mu cao. - Cc ch phm: Lynesterol, Orgametrin vin 5 mg, ung 2 vin/ ngy. Loi liu thp Dng lin tc hng ngy, ngay c khi thy kinh. Ch nh cho nhng ng i khng dng c oestrogen, hoc c chng ch nh vi thuc trnh thai loi phi hp. Cc ch phm . Norgesstrel (Microval) vin 0,03 mg. Ung 1 vin/ ngy . Lynestrenol (Exluton) vin 0,5 mg. Ngy u thy kinh bt u ung, ung lin tc 28 ngy. Cc thuc khc - Cc polyme tng hp, cc vi nang silastic c mang thuc chng th thai c cy, gh p vo c th, c th gii phng mt lng thuc n nh vo mu sut trong 6 thng. - Cc loi kem v thuc si bt c tc dng ti ch, dng bi vo cc mng ngn hoc bm vo m o trc khi giao hp dit tinh trng. - Ortho- crem; c acid ricinoleic, acid boric v lauryl natri sulfat. - Nonoxynol- 9: cha nonylphenoxy - polytoxyetanol. Thuc trnh thai dng cho nam gii Thuc c ch sn xut tinh trng: t uy c nhiu hng nghin cu, nhng cho ti nay cha c mt thuc no c hiu qu v an ton. 5.2.3. Thuc trnh thai sau giao hp. Cn gi l vin trnh thai khn cp Dng thuc phi hp hoc mt mnh estrogen trong vng 72 gi c hiu qu ti 99%. Ethinyl estradiol 2,5 mg 2 ln/ ngy 5 ngy; Diethylstilbestrol 50 mg/ ngy 5 ngy: Norgestrel 0,5 mg ethinyl estradiol 0,05 mg 2 vin 2 ln/ 2 gi. Thuc

c th tc dng theo nhiu c ch: c ch hoc lm chm phng non; lm ni mc t cung khng tip nhn c trng; sn xut dch nhy c t cung, lm gim s xm nhp ca tinh trng; cn tr s di chuyn ca tinh trng, trng trong vi t cung. Tc dng ph 40% bun nn v nn (dng km thuc chng nn) nhc u, chngmt, cng v, au bng, chut rt . V phi dng liu cao nn c nhiu tc dng ph, trnh s dng rng ri (FDA ca M khng cho dng). . Postinor (thuc c dng Vit nam). Mi vin cha Levononorgestrel (progesteron) 0,75 mg. Dng cho ph n giao hp khng c k hoch. Nu c giao h p thng xuyn, nn dng loi thuc phi hp. Liu dng: ung 1 vin trong vng 1 gi sau giao hp. Nu c giao hp li, ung thm 1 vin sau vin u 8 gi. Ni chung, hng thng ung khng qu 4 vin. Chng ch nh : ang c thai hoc nghi ng c thai, chy mu m o cha r nguyn nhn, bnh gan- thn, c tin s carxinom v, bung trng hoc t cung. Li ch khng lin quan n tc dng trnh thai Sau hng chc nm dng thuc trnh thai phi hp, ngoi hiu qu trnh thai cao (ti 98 - 99%), ngi ta c n nhn thy 1 s li ch sau ca thuc: - Lm gim nguy c u nang bung trng, ung th bung trng v ni mc t cung sau 6 thng dng thuc. Sau 2 nm dng thu c t l mi mc gim ti 50%. - Lm gim u lnh tnh tuyn v. - Lm gim cc bnh vim nhim vng h chu. - iu ha c kinh nguyt, lm gim mt mu khi thy kinh, do gim c t l thiu mu thiu st. - Gim c t l lot tiu ha, vim khp dng thp, ci thin c trng c, rm lng. BI 47. HISTAMIN V THUC KHNG HISTAMIN Histamin l cht trung gian ha hc quan trng c vai tr trong phn ng vim v d ng, trong s bi tit dch v v cng c chc nng nh cht dn truyn thn kinh v iu bin thn kinh, c to ra d o s kh carboxyl ca histidin di s xc tc ca decarboxylase 1. HISTAMIN 1.1. Sinh tng hp v phn b histamin Histamin l cht trung gian ha hc quan trng c vai tr trong phn ng vim

v d ng, trong s bi tit dch v v cng c chc nng nh cht dn truyn thn kinh v iu bin thn kinh, c to ra d o s kh carboxyl ca histidin di s xc tc ca decarboxylase. Do histamin tch in dng nn d dng lin kt vi cht tch in m nh protease, chondroitin sulfat, proteoglycan hoc heparin to thnh phc hp khng c tc dng sinh hc. Phc hp n y c d tr trong cc ht trong dng bo, bch cu a base, t bo nim mc d dy, rut, t bo thn kinh v.v Da, nim mc, cy kh ph qun l nhng m c nhiu dng bo nn d tr nhiu histamin. 1.2. S gii phng histamin Nhiu yu t kch t hch s gii phng histamin, nhng ch yu l do phn ng khng nguyn - khng th xy ra trn b mt dng bo . Khi c phn ng khng nguyn - khng th lm thay i tnh thm ca mng t bo vi ion calci lm tng calci i vo trong ni bo, ng thi t ng gii phng calci t kho d tr ni bo. Ca +2 ni bo tng lm v cc ht d tr gii phng histamin. nh sng mt tri, bng, nc c ca cn trng, morphin, D -tubocurarin lm tng gii phng histamin. Ngoi ra, mt s yu t khc cng c gii phng trong phn ng d ng nh: yu t hot ha tiu cu (PAF); cc prostaglandin, bradykinin, leucotrien. 1.3. Chuyn ha histamin Histamin c th chuyn ha qua 2 con ng khc nhau nh histaminase v N methyltransferase to thnh acid imidazol acetic v met hylhistamin khng c tc dng sinh hc. 1.4. Receptor ca histamin Hin nay tm thy 4 receptor khc nhau ca histamin l H 1, H2, H3 v H4. S phn b s lng receptor v chc nng ca tng loi receptor rt khc nhau. Khi histamin gn vo receptor H 1 s lm tng IP 3 (inositol 1,4,5 triphosphat) v diacylglycerol t phospholipid. IP 3 lm tng gii phng calci t li ni bo. Diacylglycerol (DAG) v calci lm hot ha protein lipase C, protein kinase ph thuc Ca+2/calmodulin v phospholipasse A 2 cc t bo ch khc nhau gy cc phn ng sinh hc khc nhau. Histamin gn vo receptor H 2 kch thch adenylcyclase lm hot ha protein kinase ph thuc AMPv cc t bo ch gy nn phn ng sinh hc. Receptor H 2 c nhiu nim mc d dy, khi kch thch gy tng tit dch v acid (xin xem bi Thuc cha vim lot d dy. Cimetidin, ranitidin, famotidin l nhng

thuc khng trn receptor H 2. Receptor H3 l receptor trc synap, c mt nt tn cng neuron h histaminergic thn ?kinh trung ng, c vai tr iu ha sinh tng hp v gii phng histamin. Cng ging receptor H1, H2, receptor H3 l receptor cp vi protein G v c phn b trong nhiu m. Hin nay tm c mt s cht ch vn v i khng trn receptor H 3:thioperamid, iodophenpropit, cl obenpropit, Imipromidin, Burimamid. Receptor H4 c mt t bo a acid, dng bo, t bo T v t bo hnh cy(dendritic cell).Thng qua receptor ny histamin lm thay i ho hng ng mt s t bo v s sn xut cytokin. Cc cht i khng trn recep tor H4 ang nghin cu c tc dng chng vim invivo v c tc dng chng hen v vim i trng trn m hnh ng vt thc nghim. 1.5. Tc dng sinh hc ca histamin 1.5.1. Trn h tim -mch - Histamin lm gin cc mch mu nh, tiu ng mch, mao mch v tiu tnh mch lm gim sc cn ngoi vi, gim huyt p v tng cng dng mu n m: thng qua receptor H1 s xut hin tc dng nhanh, cng mnh nhng khng k o di, cn i vi receptor H2 s xut hin tc dng gin mch chm, nhng k o di. - Thng qua receptor H 1 histamin lm co t bo ni m mao mch, tch s kt gn cc t bo ni m lm bc l mng c bn to thun li cho s thot dch v protein ra ngoi bo gy ph n, nng, , au. - Trn tim: Histamin c tc dng trc tip trn c tim v thn kinh ni ti lm tng co bp c tm nh, tm tht, chm kh cc nt xoang v chm dn truyn nh tht. 1.5.2. Trn kh-ph qun - phi: Thng qua receptor H 1 histamin lm co c trn kh ph qun, gy cn hen. Ngoi ra, histamin cn gy xut tit n im mc kh ph qun, gy vim ph n nim mc v tng tnh thm mao mch phi. 1.5.3. Trn h tiu ha Histamin lm tng tit dch acid thng qua receptor H 2, lm tng nhu ng v bi tit dch rut. 1.5.4. C trn mt s loi vt, histamin lm tng co bp c trn t cung, nhng t cung ngi, c trn bng quang, niu o, ti mt rt t b nh hng. 1.5.5. H bi tit

Histamin lm tng bi tit nc mt, nc mi, nc bt, dch ty. 1.5.6. Trn h thn kinh Kch thch u mt si thn kinh ngoi vi g y nga, au. Trn thn kinh trung ng histamin gy gim thn nhit, gy mt ng, c th chn n, tng tit ADH. Tc dng ny thng qua c 2 loi receptor H 1 v H2. 2. CC THUC KHNG HISTAMIN 2.1. Cu trc - phn loi C nhiu cht i khng chn lc tr n 3 receptor khc nhau ca histamin. Thuc i khng H2 receptor (xin c bi thuc cha vim lot lot d dy). Cc cht i khng H 3 ang trong giai on nghin cu. Trong phm vi bi ny, ch gii thiu thuc i khng chn lc trn receptor H 1. Da vo dc ng hc, tc dng, cc thuc khng H 1 c xp thnh 2 th h: * Th h I: gm cc thuc c th i qua hng ro mu no d dng, c tc dng trn receptor H1 c trung ng v ngoi vi, c tc dng an thn mnh, chng nn v c tc dng khng choline rgic ging atropin. * Th h II: gm cc thuc rt t i qua hng ro mu no, c thi gian bn thi di, t tc dng trn H1 trung ng, ch c tc dng trn H 1 ngoi vi, khng c tc dng khng cholinergic, khng an thn v khng c tc dng chng nn, c hng say tu xe. Bng 33.1: Liu lng mt s thuc khng histamin? H 1 2.2. Tc dng dc l 2.2.1. Tc dng khng histamin thc th Thuc khng histamin H 1 c ch c cnh tranh vi histamin ti receptor H 1 lm mt cc tc dng ca histamin trn recetor. Khi d tha histamin, th histamin y cht i khng ra khi re ceptor, t thuc gim hoc ht tc dng khng histamin. c tc dng dc l ko di, cn tm cht va i khng cnh tranh v khng cnh tranh, khi thuc chm b y khi receptor bi histamin. Terfenadin, astemizol c hai kiu c ch (c cnh tranh v khng cnh tranh) vi histamin ti receptor, nn t c dng di hn nhng do c nhiu tc dng khng mong mun trn tim nn hai thuc ny hin nay khng c s dng. Thuc khng H1 c tc dng d phng tt hn l cha, v khi histamin c gii phng

to hng lot phn ng v s gii phng ng thi cc cht trung gian khc m thuc khng H1 khng i khng c. Tc dng ca thuc mnh nht c trn ph qun, c trn rut. Thuc cho kt qu khng r rt trong cha hen hoc cha nhng bnh tc nghn ph qun. Cn phi hp hai loi khng H 1 v khng H2 c ch ton vn s h huyt p do histamin gy nn. 2.2.2. Tc dng khc - Trn thn kinh trung ng: Cc thuc khng histamin th h I c tc dng c ch thn kinh trung ng, lm du, gim kh nng tp trung t tng, ng g, chng mt. Tc dng c ch receptor H1 trung ng ny c th ko theo tc dng khng cholinergic, lm tng tc dng lm du, gim kh nng nh. Mt s thuc khng H 1 th h II, do tnh a nc v c i lc vi receptor H 1 ngoi bin, nn t qua hng ro mu - no, v rt t c tc d ng trung ng, v d fexofenadin, loratidin - Trn thn kinh thc vt: + Khng cholinergic (c ch h M). Nhiu thuc khng H 1 th h I nh promethazin, dimenhydrinat, diphenhydramin) c tc dng khng cholinergic ngay vi liu iu tr v trong m t s trng hp phi chng ch nh. + Thay i h giao cm: Promethazin c ch receptor -adrenergic, lm h huyt p. Diphenhydramin, dexclopheniramin c ch thu hi catecholamin, lm tng tim lc tc dng ca catecholamin. - Chng say tu xe chng nn: Do khng cholinergic, an thn, chng nn; tt nht l promethazin (c hiu lc ngang scopolamin). Hin nay diphenhydramin (Nautamin) v dimenhydrin hay c dng chng nn trn lm sng. - Chng ho: Nhiu thuc khng H 1 chng c ho theo c ch ngoi bin do c ch s co ph qun gy phn x ho (promethazin, oxomemazin, doxylamin, dexclopheniramin) nhng hiu lc km thuc chng ho trung ng. Thuc khng H 1 lm tng tim lc ca thuc gin ph qun khc (nh cc amin cng giao cm loi ephedrin). - Tc dng khc: + Khng serotonin receptor ti vng di i gy kch thch n ngon (cyproheptadin, doxylamin).

+ Chng nga, gy t (khng c lin h vi tc dng khng histamin), nh mepyramin, diphenhydramin. 2.3. Tng tc thuc

Tc 2.4 tc dng khng mong mun 2.4.1. Do tc dng trung ng Thay i tuz theo tng c th, thng biu hin c ch thn kinh (ng g, kh chu, gim phn x, mt), mt kt hp vn ng, chng mt. Nhng biu hin trn tng mnh nu dng thuc khng H 1 cng ru ethylic ho rami c thuc c ch thn kinh trung ng. Cm dng khi li xe, ang vn hnh my mc hoc lm vic ni nguy him (trn cao). mt s ngi, t c dng biu hin dng kch thch (nht l tr cn b): Mt ng, d kch ng, nhc u, c khi co git nu liu cao. hn ch tc dng khng mong mun trn thn kinh trung ng c th gim liu hng ngy hoc dng lc chiu ti, hoc dng loi khng H1 th h II. 2.4.2. Do tc dng khng cholinergic Kh ming, hu hng; khc m kh; kh tiu tin, b i, lit dng; ri lon iu tit th gic, tng p lc trong mt c bit ngi c glcm gc ng, nh trng ngc; gim tit sa. 2.4.3. Phn ng qu mn v c ng C th gp qu mn nghim trng sau khi dng thuc khng H 1 bi ngoi, nht l khi c xc da. C qu mn cho gia cc loi khng H 1. Biu hin ngoi da (ban , chm) ngay c khi ung hoc tim, mt phn c ct ngha bi vai tr l m gii phng histamin ca thuc khng H 1. 2.4.4. Tc dng khng mong mun khc - Trn tim mch: terfenadin, astemizol ko di khong QT c th a n hin tng xon nh, hin nay khng dng . - Khng dung np, thay i huyt p, ri lon mu (thiu mu tan mu, gim bch cu, thoi ha bch cu ht) tng nhy cm vi nh sng. 2.5. Ch nh v chng ch nh

2.5.1.Ch nh - Thuc khng H 1 ch thun tu cha triu chng m khng cha c nguyn nhn gy ra d ng. Thuc khng lm thay i phn ng khn g nguyn - khng th; khng i khng vi nhng cht trung gian khc c vai tr rt quan trng trong d ng, shock phn v, hen ph qun (nh leucotrien). Nh vy, thuc khng H 1 hn ch trong cha hen, mt s thuc phng c cn hen (promethazin, clophen iramin, thiazinamin, diphenhydramin, clemasin) c l do khng cholinergic. Khng H 1 th h II khng khng cholinergic nh mepyramin dng d phng co tht ph qun khi tp luyn. - Thuc khng H 1 t hiu qu khi cn tc dng nhanh v mnh (ph thanh m n, phn v c h thng). * Ch nh tt nht l: - D ng: s mi ma, bnh da d ng (my ay cp tnh, ph n ban ; nga do d ng (nh trong chm); ph Quincke; nga do cn trng t; d ng thuc. - Bnh huyt thanh. - Ch nh khc: Cha say tu x e (promethazin, diphenhydramin, diphenhydrinat); gy ng (promethazin); phi hp vi thuc ho lm tng tc dng chng ho; kch thch n ngon (doxylamin, cyproheptadin) hin nay khng dng; dng cng thuc khng cholinergic phng tai bin do phn x khi thm d bng ni soi hoc khi phu thut (nh khi chc mng phi). 2.5.2. Chng ch nh + Lin quan ti tc dng khng cholinergic: Ph i tuyn tin lit, glcm gc hp, nghn ng tiu ha v ng niu, nhc c, khi dng IMAO. + Do tc dng gy d ng ca thuc khng histamin: Qu mn vi thuc; khng dng thuc khng H1 ngoi da khi tn thng da. + ngi c thai, khng dng cyclizin v dn xut (c th gy qui thai). + Khng dng cc thuc th h II nh terfenadin, astemizol vi erythromyci n, ketoconazol, itraconazol. BI 48. CC CHT IN GII CHNH V CC DCH TRUYN 1. CC CHT IN GII CHNH 1.1. Natri? 1.1.1. Vai tr sinh l

- Gi vai tr sng cn: duy tr nng v th tch dch ngoi t bo. Na+ l ion ch yu ngoi t bo, v vy ri lon Na + bao gi cng km theo ri lon nc. - Gi tnh kch thch v dn truyn thn kinh - c do duy tr hiu th hot ng gia trong v ngoi t bo. - Duy tr thng bng base acid iu ha Na trong c th d o hormon v thng thn aldosteron (ti hp thu Na + v thi K+, H+ qua ng thn) v hormon vasopressin (hay ADH, hormon chng bi niu) ca tuyn hu yn. Natri mu bnh thng l 137 - 147 mEq/L 1.1.2. Thiu Na (gim natri - mu; hyponatremia) Khi Na- mu < 137 mEq/L 1.1.2.1. Nguyn nhn - Nhp nhiu nc, tng tit ADH - Mt nhiu Na +: do m hi, do dng thuc li niu thi Na (nh loi thiazid), do thiu aldosteron. 1.1.2.2. Lm sng - Na+ gim, lm gim p lc thm thu ca huyt tng, nc t ngoi t bo s i vo trong t bo. c bit l khi t bo thn kinh b trng, s gy cc triu chng thn kinh nh: kch thch, mi mt, lo s, run tay, tng phn x co tht cc c, hn m. Khi Na+ mu t 120- 125 mEq/L: cha c du hiu thn kinh 115- 120 mEq/L: bun nn, u oi, nhc u < 115 mEq/L : co git, hn m - Mt Na+ c th i km theo mt dch, lm gim th tch dch ngoi t bo + Nguyn nhn: . Tiu ha: tiu chy, nn, c ng thng ht dch . Thn: dng li niu, suy thng thn . Da: bng, dn lu vt thng + Lm sng: gim th tch mu, gim p lc tnh mch trung tm, gim p lc ng mch phi v huyt p trung bnh - Na+ mu gim , nhng th tch dch ngoi t bo vn bnh thng hoc tng. + Nguyn nhn . Hi chng tng ADH, gi nc . Ph do suy tim, s gan, thn h . Truyn tnh mch qu nhiu dung dch nhc trng

+ Lm sng: ngc vi cc du hiu trn: th tch mu tng, tng p lc tnh mch trung tm, tng p lc ng mch phi v huyt p trung bnh. 1.1.2.3. iu tr -Bo v bnh nhn khi nguy c trc tip: nng ngay Na + ln trn 120 mEq/L, sau dn dn a v bnh thng v cho thng bng vi dch ngoi t bo (xem 1.3.4.) - Ch { iu chnh in gii khc: K +, HCO3- (khi tiu chy nhiu). - Ch dng dung dch mui u trng (3 -5%) khi Na+ di 115 mEq/L v rt thn trng v c th lm tng th tch trong mch. - Nu Na+ mu gim m dch ngoi t bo tng th dng li niu quai nh furosemid (Lasix 0,2 - 0,3g/ ngy), v lm mt nc nhiu hn mt mui. Khng dng loi thiazid v lm mt mui nhiu hn mt nc. 1.1.3. Tha natri (tng natri - mu, hypernatremia) Khi Na+ mu > 147 mEq/L do mt nc hoc do nhp nhiu Na + 1.1.3.1. Nguyn nhn - Mt nc qua da, qua phi, bnh i nht, dng li niu thm thu, tng ng huyt. - Nhp nhiu mui: tru yn dung dch mui u trng, NaHCO 3, tng aldosteron, n nhiu mui. 1.1.3.2. Lm sng Tng p lc thm thu, tng trng lc ca dch ngoi t bo, nc trong t bo ra ngoi t bo, gy kht, mt mi, nhc c, hn m, gim p ng vi ADH. nh gi tnh trng t ng hoc gim khi lng dch ngoi t bo bng o p lc tnh mch trung ng v p lc ng mch phi. 1.1.3.3. iu tr Ph thuc vo ?nguyn nhn - Nu do mt nc: cho ung v truyn nc vo tnh mch - iu chnh tng natri mu cn t t, khong 2 ngy tr nh mt lng nc ln vo no, gy ph no. Cn theo di cc du hiu ph no: tng huyt p, gim nhp tim, lon cm gic. 1.1.3.4. Tnh lng nc v mui iu chnh * Thiu nc (trong Na+ mu cao): Th d Na+ mu hin c l 160 mEq/L ([Na] 1), mun lm gim xung 150 mEq/L ([Na] 2) bng pha long, cn bao nhiu nc (TNC 2)?

Gi s ngi bnh nng 50 kg, tng lng nc ca c th (TNC) chim 60%, l 30 lt. Cng thc tnh l: TNC1 *Na+1 = TNC2 [Na]2 30 160 = x 150 30 160 x = = 32 L 150 S nc cn thm l 32L - 30 = 2 L * Thiu Na+ Th d: Na+ mu l 120 mEq/L, cn bao nhiu Na + nng ln 130 mEq/L? Nh vy, mi lt cn 130 mEq - 120 mEq = 10 mEq. Vi th d trn, tng lng nc trong c th (TNC) cho c dch trong v ngoi t bo l 30 lt, cn 10 30 = 300 mEq Na+. Pmg ha tr mEq phn t lng Ta bit: mEq = Pmg = Phn t lng Ha tr Nh vy, lng Na + tng ng vi 300 mEq l: 300 23 Pmg = = 6900 mg 1 T tnh ra lng dung dch cn truyn tuz theo vic ch nh dng nc mui ng trng (0,9%) hoc u trng. C th tnh ring cho dung dch ngoi t bo. Nc chim 60% trong lng c th. Nc trong t bo chim 2/3 v ngoi t bo l 1/3. 1.2. Kali 1.2.1. Vai tr sinh l K+ l ion ch yu trong t bo, c vai tr: - m bo hiu th mng, tnh chu kch thch ca thn kinh - c - Trn c tim, K + lm gim lc co bp, gim tnh chu kch thch v gim dn tru yn. Tc dng i khng vi Ca ++ v glycosid, tim. - Tham gia vo iu ha acid - base y l qu trnh phc tp v K + tham gia vo: + C ch trao i ion qua mng t bo

+ Chc phn thi tr qua thn; lin quan vi thi tr H + * Thng bng ion qua mng t bo: Nng trong t bo ca K + v H+ ln hn ngoi t bo - Khi H+ thay i l nguyn pht: . Nu nng H + ngoi t bo tng (acid mu) th H + s i vo t bo, v gi thng bng ion, K+ s ra khi t bo, gy tng K + mu: acid huyt tng kali (hyperkaliemic acidosis). . Ngc li, nu H + dch ngoi t bo gim (base mu) th H + trong t bo s i ra. V gi thng bng ion, K + s i t ngoi vo trong t bo, gy gim kali mu: base mu gim kali (hypokaliemic alkalosis). pH huyt tng th ay i 0,1 th K+ thay i 0,6 mEq/L - Khi K+ thay i l nguyn pht th lm H+ thay i theo: nu K + i t trong ra ngoi t bo th H+ v Na+ s i vo gi thng bng ion, kt qu l ngoi t bo th base v trong t bo th acid (trng hp mt nhi u K+). * Chc phn iu ha ca thn: Khi K+ tng cp tnh trong mu, thn tng thi K +, gim thi H+, nc tiu base v mu cng acid. Kali mu bnh thng l 3,5 - 5,0 mEq/L 1.2.2. Thiu kali (gim kali - mu- hypokaliemia) Khi K+ mu < 3,5 mEq/L 1.2.2.1. Nguyn nhn - Gim kali ton b c th: hi chng cng aldosteron, dng thuc li niu thi K + (loi thiazid), mt K +qua ng tiu ha (nn nhiu, tiu chy, dn lu), mt K + qua? thm phn. - K+ nhp t ngoi t bo vo trong t bo: do dng insulin hoc tng insulin n i sinh, base mu, thi kz phc hi t chc sau bng, sau chn thng. Trong t bo tp trung mt s lng ln cc cht hu c khng khuch tn qua mng (cc protein). mi trng pH ca dch th, cc nhm chc ca cc hp cht hu c ny u tch in m nn gi l anion c nh ca t bo. m bo trung ha in, t bo phi gi li mt s lng tng ng cation, l K + (chnh) v cc cation khc. T , h qu l: . Khi anion c nh tng (tng ng ha, sau n, tng insulin) th K + s i vo t bo . . Khi anion c nh gim (d ha, i, sc, tng cortisol) th K + s ra khi t bo.

- Stress: do c tng tit aldosteron v adrenalin t thng thn. Adrenalin lm tng nhp K+ vo t bo. 1.2.2.2.Lm sng - Lit gc chi, sau l u chi. S thy c chc, g im phn x gn xng, cm gic cn bnh thng, sau l chut rt v d cm (thm c ri lon Na v Ca) - Chng bng, lit rut, to, b i - Tim: mch rng, nhy, tng nh. in tim: ST h dn, T c bin gim dn, ng in ri m, QT di. 1.2.2.3. iu tr - Cc ch phm: . Dung dch KCl: cha 20 mEq/ 15 mL (hoc 1 tha canh) . Vin bao cha 4 - 8 mEq. . ng tim: 1 mL cha 1 mEq (dung dch 7,5%) hoc 1 mL cha 2 mEq (dung dch 15%); ng ng 10 - 20 mL- 30mL. Khi dng pha long trong huyt thanh ngt ng tr ng. - Liu lng: . D phng gim K - mu (khi dng li niu lu): 50 mEq/ ngy (tng ng 4,0g KCl), chia liu nhiu ln. . Liu truyn ti a 10 - 20 mEq/ h ; 50 - 100 mEq/ ngy Dung dch truyn tnh mch cha 30 - 40 mEq/L. Dung dch m c qu gy huy t khi v hoi t nu tim chch tnh mch. - Tai bin khi dng qu liu: . Du hiu in tm : T rng v nhn, P dt, PR di, phc hp QRS rng. . X tr: truyn dung dch NaHCO 3, hoc dung dch huyt thanh ngt c thm 10 n v insulin cho 100 g gluco se (xem phn iu tr tng kali mu) 1.2.3. Tha kali (tng kali mu; hyperkaliemia) Khi kali mu > 5 mEq/L 1.2.3.1. Nguyn nhn - Ung hoc truyn qu tha kali - Tn thng nng m (t bo v, kali c gii phng) - Acid huyt cp tnh (i khi acid huyt mn tnh) - Bnh Addison - Kch thch cp tnh receptor giao cm

- Dng li niu lu kali khng ng liu lng - ng huyt tng 1.2.3.2. Lm sng - n v cm. D cm u chi, li, mi. - Lon vn mch: da lnh, m, ti. Nhc c, t b nht l chi di - Trn in tim: nu kali tng va phi (5 - 7 mEq/L huyt tng), dn truyn trong c tim b gim nh: sng T tng cao hoc ko di, PR di, P mt. - Nu kali tng cao hn (8 -9 mEq/L huyt tng) s c ch mnh hn trn nt dn nhp v s dn truyn trong ton b c tim: QRS di, c th mt tm thu (asystole), i khi trc l nhp tht nhanh hoc rung tht. 1.2.3.3. iu tr - Nha trao i cation: natri polystyren sulfonat (Kayexalate) l nha trao i Na +- K+, c i lc vi K+ mnh hn nhiu so vi Na +. rut, c bit l rut gi, n gii phng Na + v gn K+ ri b thi tr theo phn. Kayexalat khng c hp thu khi ung v khn?g b tc dng ca dch tiu ha. Ngoi K+, n cn gn c c ion ha tr 2 l Mg ++ v Ca++, nn c th gy gim Mg v Ca - mu. Thng gy to, n n dng cng vi sorbitol (vin 5 mg, 1 - 2 vin/ ngy, c tc dng nhun trng). . Ung 15 g 1- 4 ln/ ngy . Cn kim tra K+, Mg++, Ca++, mu. . Khng dng khi K + < 5 mEq/L v cn nh rng 1g nha gii phng 1 mEq Na +. - Glucose v insulin: insulin lm K + nhp vo t bo, v glucose chng h ng huyt do insulin gy ra. Insulin 10- 15 n v Huyt thanh ngt u trng 5 -%- 250- 500 mL Tc dng h K+ trong 6h. - Natri bicarbonat: lm K + nhp vo t bo, tc dng tm thi trong 1 - 2h. Tim truyn tnh mch dung dch 1,4% (c 166,6 mEq HCO 3- v 166,6 mEq Na + trong 1000 mL), hoc dung dch 4,2% (c 500 mEq HCO 3-, 500 mEq Na/ lt). - Calci gluconat: khng c tc dng trn nng K + nhng chng li tc dng c ca K + trn tim. ng 10 mL cha 4,5 mEq Ca ++. Tim tnh mch (trong khi CaCl 2 cha 13,6 mEq). - Thm phn: dng nha trao i ion c th thi qu nhiu K +. Thm phn an

ton hn, c th dng cho c ngi suy thn. 1.3. Calci 1.3.1. Vai tr sinh l - To xng, rng di dng calci phosphat - Co c, dn truyn thn kinh, bi xut ca cc tuyn tit - ng mu - Tnh thm ca mng t bo dch ngoi t bo c 1 - 2% tng lng Ca. Trong mu, Ca di 3 dng: 50% di dng ion Ca++, gn 50% kt hp vi protein huyt tng, ch yu l albumin v ch cn rt t di dng phc hp vi phos phat, citrat, carbonat. Ch calci di dng ion mi c vai tr sinh l quan trng. iu ho calci do hormon cn gip trng (PTH) v calcitonin. Calci- mu bnhthng l 4,3 - 5,3 mEq/L 1.3.2. Thiu calci (gim calci - mu; hypocalcemia ) Khi calci- mu < 4,3 mEq/L 1.3.2.1. Nguyn nhn - Gim dng ion ha; base mu, dng nhiu citrat hoc mu long - Mt Ca qua dch th: dng li niu quai loi furosemid - Gim hp thu qua rut: ch n thiu Ca, thiu vitamin D, tiu chy mn, ct d dy. - Suy cn gip trng. - Tng phospho mu (hyperphosphatemia), gim magnesi mu . P v Ca c tc dng qua li: P - mu tng khi Ca - mu gim v ngc li. l c ch bo v sinh l quan trng v nu c 2 cng tng s dn ti kt ta calci phosphat vo cc m. Khi P tng th Ca gim v lm gim sn xut dng hot ng ca vitamin D v lm gim huy ng calci phosphat t xng. . Mg gim, th Ca mu cng gim v lm gim tit v gim tc dng ca PTH. - Vim ty cp cng lm gim calci mu v c th l lm lng ng Ca vo m m hoi t, gim tit PTH, gim albumin - huyt v tng sn xut calcitonin ca tuyn gip. 1.3.2.2. Lm sng T, nga cc ngn, tng phn x, chut rt, tetani vi cc du hiu Trousseau (+), Chvostek (+), co git do ngng kch thch ca thn kinh b gim. Nu mn tnh, gy xp xng, gy xng, du hiu gim calci nng: co tht thanh qun, kh th, ting th rt (stridor)

1.3.2.3. iu tr - Tim tnh mch: . Calci gluconat: ng 10 mL dung dch 10% cha 4,5 mEq Ca . Calci clorid: ng 10 mL, dung dch 10% ch a 13,6 mEq Ca Tim chm 1mL/ pht phng ngt tim v tt huyt p do gin mch nhanh. - Ung: . Calci lactat, calci carbonat, calci gluconat: di dng gi ?bt . Vitamin D: Ergocalciferol (D 2): calcitriol 1,25 (OH) 2 D3 Khng dng cng vi fluor v phosph at v to phc khng tan, khng hp thu c. 1.3.3. Tha calci (tng calci -mu, hypercalcemia) Khi calci- mu > 5,3 mEq/L 1.3.3.1. Nguyn nhn - Ch n nhiu Ca - Hp thu nhiu Ca: tha vitamin D, cng ph gip trng. - Tng gii phng ca t xng: ung th cn gip t rng, bnh Paget (tng tit PTH) - Gim thi tr Ca qua thn; thn suy, dng li niu loi thiazid lu. - Tng Ca++ dng ion v acid huyt. 1.3.3.2. Triu chng Suy nhc, chn nn, bun nn, nn, i nhiu, m mng, l ln, t b, thay i nhn cch, hn m. in tim: ST v QT ngn, PR di. 1.3.3.3. iu tr iu tr nguyn nhn: cn gip trng, ch n Khi calci mu > 7 mEq/L phi iu tr tch cc: - Ung hoc tim tnh mch thanh huyt mn 0,45% hoc 0,9%, c th ti hng lt/ ngy vi iu kin chc phn thn bnh th ng: th tch mu tng, pha long c Ca, thn tng thi Na+ (gim ti hp thu), ng thi tng thi Ca. C th cho ung thm 2 - 3 lt/ ngy. Li niu quai furosemid lm tng thi Ca v d phng c tha nc do dng huyt thanh mn: 40- 60 mg cch 6 h ung 1 ln. Khng dng li niu loi thiazid v gim thi Ca. Phosphat tim tnh mch dng cha cc cn cp tnh. Tim tnh mch Na phosphat hoc K phosphat lm gim nhanh ion Ca ++ v to Ca phosphat. Nhng khi Ca phosphat > 75 mg/ dl th gy lng ng C a vo cc m.

Khng dng qu 1,5g/ ngy v khng qu 2 ngy. - Ch n t Ca v dng cortison: steroid tranh chp vi vitamin D receptor ca rut, lm gim hp thu Ca qua tiu ha v tng thi qua thn. Cn dng liu cao: Prednison 1mg/ kg/ ngy. Tc d ng h calci mu xut hin chm, sau 1- 2 tun dng thuc. Ngng thuc khi c du hiu nhim c. Mt s thuc lm gim tiu xng: - Mithracin (Plicamycin) l khng sinh gy c t bo, tc dng c ch trc tip cc hu ct bo (osteoclastes), lm gim h uy ng Ca t xng ra mu v gim ti hp thu Ca ti ng thn. Ch dng trong tng Ca - mu do ung th nng khng vi cc cch iu tr khc, v mithracin c nhiu tc dng ph, c bit l gim tiu cu, bch cu, gim prothrombin, gy chy mu c th dn n cht. ng trong l ng kh 2500 g Truyn tnh mch 25 g/ kg/ ngy. Pha trong 500 mL huyt thanh ngt ng trng. Cch 2-3 ngy, truyn li tuz thuc vo Ca - mu. - Cc diphosphonat: l thuc tng hp ca cc pyrophosphat v c c tc dng c ch tiu xng ca cc hu ct bo. Th d: Didronel (etidronat disodic): ch nh chnh trong bnh Paget hoc cc di cn ung th vo xng, gy tiu xng. Dng liu duy nht, ung 2 gi trc ba n vi liu 5 mg/ kg/ ngy, trong thi gian 6 thng. Khng dng cho ngi suy thn. Dng qu liu gy h Ca - mu (iu tr bng calci- gluconat tim tnh mch) Vin 200 mg - Calcitonin: l hormon ca t bo C tuyn gip trng, lm h calci mu do: . c ch hu ct bo (ngc vi PTH, kch thch) lm gimtiu x ng . Tng thi Ca v P qua thn do c ch ti hp thu Cc ch phm sn xut t ng vt (Staporos, Calcitar t ln, Calsyn, Miacalcic t c hi salmon) hoc tng p (Cibacalcin). Calcitonin ca c hi mnh hn ca ng hin i v ln 10 - 40 ln v tc dng lu h n 10 ln. Liu lng: 4- 8 n v quc t/ kg/ ngy chia lm 4 ln tim di da, tim bp hoc tim chm vo tnh mch. Tc dng xut hin nhanh 2. CC DCH THAY TH HUYT TNG Khi th tch huyt tng b gim do mt nc v mui n thun (tiu chy, nn nhiu) th ch cn truyn nc v in gii l . Nhng nu do mt nhiu mu hoc huyt tng nh trong sc xut huyt, bng nng, th phi truyn mu, huyt

tng hoc cc dch thay th c p lc keo cao. Cc sn phm thin nhin (mu, huyt tng ca n gi) l tt nht, nhng t v c nhiu nguy c (phn ng min dch, lan truyn vim gan siu vi khun B hoc C, lan truyn AIDS). V vy, cc dch thay th huyt tng c nghin cu v s dng. Cc dch ny cn phi c by tnh cht sau: - Tn ti trong tun hon lu, ngha l c p lc keo tng t vi huyt tng, c trng lng phn t tng ong vi albumin huyt tng ( 40.000). - Khng c tc dng dc l khc. - Khng c tc dng khng nguyn, khng c ch nhit t. - Khng c tng tc h oc phn ng cho vi nhm mu. - Gi n nh lu khi bo qun hoc thay i ca nhit mi trng. - D kh khun - nht thch hp vi s tim truyn. Di y l mt s dch truyn t tiu chun hin ang c dng: 2.1. Gelatin bin cht c sn xut t colagen ca xng, thu phn cho ti khi t c cc phn t protein c trng lng phn t khong 3.000. C nhiu dng: - Plasmion: cha 30g gelatin lng trong 1 lt, c thm thnh phn cc ion Na +, K+, Mg++ v Cl- tng t nh huyt tng, kh ng c Ca++. Cht m l lactat. ng trong l 500 mL. - Plasmagel: cha 30g gelatin lng trong 1 lt dung dch mui ng trng, thm 27 mEq Ca++ (cho nn khng c dng cho bnh nhn ang c iu tr bng digitalis). Khng c cht m. ng tro ng l 500 mL. - Plasmagel khng mui, c ng (Plasmagel dsod glucos): cha 25 g gelatin trong 1 lt dung dch glucose ng trng, khng c mui, Ca ++ v cht m (trnh b tha mui). ng trong l 500 mL. + u im ca gelatin lng l d bo qun, k hng cn xc nh nhm mu trc khi truyn. + Nhc im: . Khng gi c lu trong c th, khong 75% b thi tr qua nc tiu trong 24h. . Vn cn phn ng khng nguyn: d ng biu hin da, him gp phn ng

tim mch. . C ri lon ng mu: gim p rotrombin, fibrinogen, tiu cu, ko di thi gian chy mu. . Gy protein- niu gi. Nu dng Plasmagel, ch c th lm tng calci huyt. . Phi hm nng trc khi dng v rt qunh khi gp lnh. 2.2. polyvinyl- pyrrolidone (PVP) l cht tng hp, c tr ng lng phn t khong 40.000. ng trong l 500 mL (Subtosan) - u im: tng i d bo qun. - Nhc im: cn phn ng khng nguyn, gy protein niu gi v nht l b gi lu trong h lin vng ni mc. 2.3. Dextran L cht trng phn c trng l ng phn t rt cao, c to ra t glucose di tc ng ca vi khun Leuconostoc mesenteroides. Phn hai loi: 2.3.1. Loi c trong lng phn t cao Khong 80.000 . ng trong l 250 v 500 mL. Thi tr qua chuyn ha. - u im: d bo qun, gi khng t lm. - Nhc im: . To phc hp fibrinogen - dextran, gn vo hng cu, lm tng dnh tiu cu, v vy c th gy ri lon ng mu. Rt t c, nhng c th gy phn ng qu mn ngay t ln truyn u tin v mn cm vi dextran t nhin gp trong mt s thc n. 2.3.2. Loi c trng lng phn t thp . Khong 40.000. ng trong l 250 v 500 mL (Rheomacrodex). Thi tr bng chuyn ha v qua thn. - u im: lm d dng tun hon ca hng cu trong mao mch. - Nhc im: gi thnh cn cao v gy ri lon ng mu. Ch { l sau khi truyn, c th lm sai lc vic xc nh nhm mu v glucose mu. 2.4. Dung dch in gii C 5 loi hay dng 1g NaCl = 17 mmol Na= 400 mg Na. ASTT: p sut thm thu 2.4.1. Dung dch ng trng : 2.4.1.1. Dung dch nc mui sinh l (NaCl 0, 9%) - u: R, ph bin. - Nhc: d gy toan mu do lng Cl - cao. Truyn nhiu v nhanh d gy

nc ngoi bo v ph phi cp. 2.4.1.2. Ringer lactat (dung dch Hartman) - Vo c th, lactat chuyn thnh bicarbonat (do gan) v kim ha mu (chnh c t oan nh). - C thm K+ v Ca2+. - Truyn 1 lt s tng c 200 - 300 mL th tch tun hon, v vy cn truyn 1 lng gp 3 ln th tch b mt. Nhng khng c gi lu trong mu nn cn truyn lin tc. Ch truyn khi th tch tun hon mt 1 lt. Tng lng truyn khng qu 3 4 lt/ 24h. 2.4.2. Dung dch u trng - Cc loi dung dch: NaCl 1,2 - 1,8- 3,6- 7,2- 10 v 20%. Trn th trng c sn loi 10 - 20%, ng 10- 20 mL. Khi dng, pha vi glucose 5% t nng mong mun. - c im: . ASTT qu cao, d gy ph. . Lm gim kt tp tiu cu, tng nguy c chy mu. . Lm gin mch ni tng: thn, tim. Tng co bp tim. . Lm gim ph no, gim tng p lc ni s tt hn so vi dung dch keo. 3. CC DCH CUNG CP GLUCID, ACID AMIN V L IPID Dng cung cp nng lng khi khng dinh dng c qua ng tiu ha. Trong sc, nhu cu nng lng c cung cp giai on u ch yu bng glucid v c hp thu trc tip, sau l cc acid amin, v trong giai on hi phc l lipid. 3.1. Cc glucid d hp thu 3.1.1. Glucose (dextrose) - Dung dch ng trng 50g/ 1000 mL (5%) - Dung dch u trng 100g; 150g v 300g/ 1000 mL. ng trong l 500 - 1000 mL, 100g glucose cung cp 400 kilo calo. Ngoi ra cn dng iu tr v d phng cc trng hp mt nc nhiu hn mt mui. Truyn chm vo tnh mch. Cc dung dch u trng d lm vim tc tnh mch ti ni truyn v gy hoi t nu truyn ra ngoi tnh mch. Glucose huyt tng ph thuc khng nhng vo nng dung dch tim truyn m cn v o tc truyn v kh nng chuyn ha ca ngi bnh. Khi nui dng bng dch truyn, cn phn phi liu u trong ngy v gim

liu dn, trnh ngng t ngt d gy h ng huyt. C th b tr thm bng insulin v kali tuz thuc vo ng - niu, aceton- niu, kali- mu. 3.1.2. Sorbitol Sorbitol l hexa - alcol khng c chc kh, trong c th, b phn hu nhanh thnh fructose di tc dng ca sorbitol desh?ydrogenase gan. - Dung dch ng trng 50g/ 1000 mL - Dung dch u trng 100g/ 1000mL. ng trong l 500- 1000 mL. Tc dng v ch nh ging nh glucose, 100g sorbitl cung cp 400 Kcal. Dung dch u trng c th gy ri lon thn kinh hoc l do tng p lc thm thu, hoc l do tc dng c trc tip trn thn kinh. 3.2. Cc acid amin L dung dch c cha cc acid amin cn thit nh leucin, isoleucin, lysin, methionin, arginin di dng L d hp thu. Truyn chm tnh mch (khng vt qu 50 git/ pht). Khng dng trong giai on u ca sc. Thn trng khi c suy gan, suy thn nng, suy tun hon nng v dung dch cha nhiu m v u trng. C th gy ra hoc lm nng thm phn ng phn v. Tc dng khng mong mun: nim toan chuyn ha do qu liu acid amin, tng N mu ngi suy thn, mn cm, d ng, a niu do tng p lc thm thu. Cc ch phm: Alvesin 40, Amigreen - TPN, Proteolysat, Moriamin. Phi tuyt i v khun khi tim truyn v khng c trn bt kz mt thuc g vo dung dch truyn. L thuc dng tim truyn 100 - 250- 500- 1000mL. 3.3. Lipid L dung dch cung cp nng lng v cc a cid bo cn thit cho c th, khng gy u trng huyt tng. Cc phn ng khng mong mun sm c th gp l st, bun nn, nn, h ng huyt, m phi, gim tiu cu. Cc phn ng mun : gan to, vng da, do mt, lch to, gim tiu cu, gim bch cu, tng tm thi cc test chc phn gan. Ch phm: Intralipid, Lipofundin, Lipovenoes 10% PLR (du u tng - soja). - Dch nh tng 10% ng trong l 100 v 500 mL, cung cp 1100 Kcal/ lit. - Dch nh tng 20% ng trong l 100 - 250 v 500 mL, cung cp 2000 K cal/

lt Liu lng: tng lng lipid cho ngi ln trong 24 gi l 2 - 3g/ kg thn trng; cho tr em l 0,5- 4g/ kg. Trong 10 pht u truyn 10 git/ pht; trong 20 pht sau l 20 git/ pht, sau t ti 40 git/ pht. Khi m l phi dng ht trong 1 ln. BI 49. CC VITAMIN 1. I CNG - Vitamin l nhng hp cht hu c m t bo ngi v ng vt khng th t tng hp (tr vitamin D), c mt trong thc n vi s lng nh, cu trc hon ton khc vi glucid, protid v lipid nhng rt cn thit cho mt s phn ng chuyn ha gip duy tr s pht trin v s sng bnh thng, khi thiu ht s gy nn bnh l{ c hiu. - Tuz theo gii v giai on pht trin ca c th, nhu cu vitamin rt khc nhau. C th gp tha hoc thiu vitamin. S thiu ht vitamin d o nhiu nguyn nhn v ng thi c th thiu nhiu loi vitamin. Do vy, trong iu tr cn phi tm nguyn nhn v phi hp nhiu loi vitamin khc nhau. Thc t c th gp tha vitamin , c bit l cc vitamin tan trong du. Da vo tnh cht ha tan t rong nc hay du cc vitamin c xp thnh 2 nhm: - Cc vitamin tan trong du: vitamin A, D, E, K thi tr chm, tha s gy nn bnh l tha vitamin. - Cc vitamin tan trong nc: vitamin nhm B ( B 1, B2, B3, B5, B6, B8, B9, B12 )v vitamin C thi tr nhanh ra khi c th, nhng nu dng liu cao cng gy nn ng c. 2. CC VITAMIN TAN TRONG DU 2.1. Vitamin A 2.1.1. Ngun gc- cu trc v tnh cht Vitamin A c 3 dn?g: retinol, retinal v acid retionic. Retinol l mt ru di dng ester c nhiu trong gan, b, ph omat, sa, lng trng. Retinal dng aldehyd ca vitamin A. C 3 tin vitamin A: , , - caroten. - caroten c nhiu trong c, qu c mu nh gc, c rt hoc rau xanh, vo c th, ch c 1/6 lng - caroten chuyn thnh retinol.

1E.R = 6 g - caroten = 3,3 IU vitamin A; (E.R l equivalent Retinal). 2.1.2. Vai tr sinh l * Trn th gic: Vitamin A ch yu l retinol v retinal ng vai tr quan trng trong hot ng ca th gic. Thiu vitamin A s gy ra bnh qung g, kh mt, lot gic mc. Acid r etinoic khng c tc dng trn th gic. C ch: trong mu vitamin A c chuyn thnh trans - retinol v sau thnh 11 - cis- retinol v 11- cis- retinal. Trong bng ti 11 - cis- retinal kt hp vi opsin to thnh Rhodopsin. Rhodopsin l mt sc t nhy cm vi nh sng t bo hnh nn ca vng mc gip cho vng mc nhn c cc hnh nh khi thiu nh sng. Khi ra nh sng Rhodopsin b phn hu thnh opsin v trans - retinal. Transretinal c th c chuyn thnh cis - retinol hoc trans - retinol i vo mu tip tc chu kz ca s nhn. * Trn biu m v t chc da: c bit acid retinoic kch thch bit ha t bo biu m, sinh tit nhy, c ch s sng ha t bo biu m. Ngi thiu vitamin A d b mn cm vi cc cht gy ung th v cc t bo nn c a biu m nhng vng khc nhau tng sn r rt v gim kh nng bit ha. C ch tc dng chng ung th ca vitamin A vn cha c gii thch y . C th vitamin A iu ha s sinh tng hp protein c bit cn thit cho s bit ha t bo ca t ch c biu m v c ch s nhn ln ca t bo ung th. * Trn chc nng min dch: - Vitamin A tng sc khng ca c th. Thiu vitamin A kch thc ca t chc lympho thay i. -caroten lm tng hot ng ca t bo dit (Killer cell), tng s nhn ln ca t bo lympho B v T. * -caroten c tc dng chng oxy ha mnh c s dng trong phng v chng lo ha. Tham gia cu to ht vi th dng chp (Chylomicron). 2.1.3. Du hiu thiu ht vitamin A Nhu cu hng ngy ngi ln cn 4000 - 5000 n v/ ngy, tr em t 400 1000 n v/ ngy. Khi thiu vitamin A c cc triu chng: tng sng ha biu m, da kh, thoi ha tuyn m hi, nhim trng da, qung g, kh mng tip hp, kh gic mc c th gp

vim lot gic mc d dn n m lo v c th d b nhim trng h hp, tit niu, sinh dc v chm ln, chn n. 2.1.4. Du hiu tha vitamin A Ung liu cao ko di d gy tha vitamin A, biu hin: da kh, trc vy, nga, vim da, rng tc, au xng, tng p lc ni s, au u, chn n, mt mi, d b kch thch v c th gp xut huyt. 2.1.5. Dc ng hc Trn 90% retinol trong khu phn n di dng retinolpalmitat. Nh enzym lipase ca ty ester ny b thu phn gii phng retinol hp thu. Retinol c hp thu hon ton rut nh protein m ang retinol CRBP (cellular retinol binding protein). Trong mu retinol gn vo protein i vo cc t chc v c d tr gan, gii phng ra protein mang retinol. Vitamin A thi qua mt di dng lin hp vi acid glucuronic v c chu kz gan - rut. Khng thy dng? cha chuyn ha trong nc tiu. 2.1.6. Ch nh v liu dng * Ch nh: - Bnh kh mt, qung g, tr chm ln d mc cc bnh nhim trng, suy dinh dng, bnh Kwashiorkor. - Bnh trng c, da, tc, mng kh, bnh sng, bnh vy nn, cc vt thng, vt bang. - H tr trong iu tr ung th da, c t cung, i trng, phi v phng -chng lo ho . * Ch phm v liu dng: - Vin nang, vin n n 5000 ; 50000 n v. - Vin nang du c cha lng v itamin A khc nhau tuz tng ch phm v thng dao ng t 200-800 n v. - Ung 5000 n v mi ngy hoc cch 10 - 15 ngy ung 50.000 n v. - Ph n c thai ung di 2500 n v/ ngy. 2.2. Vitamin D 2.2.1. Ngun gc- cu trc- tnh cht - Vitamin D1 l hn hp chng ci xng, tn mang tnh cht lch s. - Ergocalciferol (D 2) c ngun gc tng hp thng c dng trong iu tr. - Cholecalciferol (D 3) c ngun gc t nhin c th chit xut t du gan c v mt s cy h c (Solanaceae) hoc c th t tng h p di tc dng ca tia cc tm.

- Vitamin D c coi nh mt hormon v: . c tng hp di da i vo mu n c quan ch to nn tc dng thng qua receptor c hiu. . Hot tnh enzym hydroxylase xc tc cho qu trnh chuyn ha vitamin D to thnh cht c hot tnh c iu ha theo c ch iu khin ngc thng qua nng ion calci trong mu. - Vitamin D2 v D3 d b phn hu bi nh sng, oxy, acid. 2.2.2. Vai tr sinh l - Tng hp thu calci rut v ti hp thu calci ng thn do kch thch tng si nh cc carrier vn chuyn calci. Phi hp vi hormon cn gip iu ha nng calci trong mu. - Tng tch t calci trong xng, gim bi tit phosphat v gip chuyn phosphat hu c thnh phosphat v c. - Oxy ha citrat gip cho s ha tan phc hp calc i v iu ha nng calci. 2.2.3. Du hiu thiu vitamin D Thiu Vitamin D c th do gim hp thu rut, suy cn gip, dng thuc c ch enzym gan, ngi t tip xc vi nng. Thiu vitamin D c du hiu gim calci v phosphat trong mu, c th gp cn h calc i mu. Thiu lu di dn n ci cng tr em v nhuyn xng ngi ln. 2.2.4. Du hiu tha vitamin Tr di 1 tui dng lin tc 400 n v/ ngy. Tr trn 1 tui dng lin tc trn 1000 n v / ngy c th gy ng c. Liu trn 50.000n v / ngy c t h gy ng c c tr em v ngi ln. Khi ng c c biu hin tng calci mu, chn n, mt mi, i nhiu, kht nc, nn, a chy, ri lon tm thn. Tng calci mu k o di gy calci ha cc tng v c th gp suy thn. Gp ng c phi ngng ung vi ta min D, c ch n t calci, dng glucocorticoid v truyn dch. 2.2.5. Dc ng hc Vitamin D c hp thu rut non; D 3 hp thu tt hn D 2. Trong mu vitamin D c gn vo - globulin v c tch lu gan v t chc m. to thnh cht c tc dng, vitamin D c hydroxyl ha qua 2 giai on. gan c chuyn thnh 25 - hydroxycalciferol hay calcifediol sau i vo mu n thn b hydroxyl ha ln th 2 to thnh 1 , 25 dihydroxylcalciferol hay calcitrol

c hot tnh. Enzym tham gia phn ng hydroxyl ha vitamin D gan v thn c th gy? cm ng hoc tng hot tnh bi s thiu vitamin D, calci, phosphat, hormon cn gip, prolactin v estrogen. Thi tr ch yu qua mt, phn nh thi qua nc tiu. Thuc ha c chu kz gan rut. 2.2.6. Ch nh- ch phm v liu dng * Ch nh: - Phng v chng ci xng tr em, phng v chng long xng, nhuyn xng ngi ln, ngi gy xng lu lnh. - Phng v chng co git trong suy cn gip. - Hi chng Fanconi. * Ch phm v liu dng Mt n v quc t vitamin D bng 25 nanogam ergocalciferol hoc colecalciferol. Hin nay c nhiu ch phm dng vin nang, vin nn, dung dch ung hoc tim bp cha ergocalciferol, colecalciferol, alfacalcidol, calcitriol, hoc dihydrotachysterol hm lng khc nhau. - Phng bnh (tr em): ung 500 - 1000 n v/ ngy hoc cch 6 thng ung liu duy nht 200.000 n v. - iu tr ci xng: ung 10.000 - 20.000 n v (chia 3 ln/ ngy). Ngi ln ung 400 800 n v/ ngy. - Chng co git do suy cn gip: ung hoc tim bp 50. 000- 200.000 n v/ ngy. Tun dng 2 ln. 2.3. Vitamin E 2.3.1. Ngun gc- cu trc- tnh cht Vitamin E gm 3 dng: , v - tocopherol c cu trc v tc dng dc l{ tng t nhau. Ring - tocopherol chim 90% lng tocopherol trong t chc v c tc dng sinh hc cao nht nn c s dng nhiu trn lm sng. D - - tocopherol c hot tnh mnh hn L - tocopherol, 1 mg d - - tocopherol = 1,5 n v vitamin E. Vitamin E c nhiu trong cc ht ng cc, la m, ng, u, gi , du lc, du olive, rau xanh, gan, m, b, lng trng, b t t mt tc dng trong khng kh, tia cc tm, nhit cao, FeCl3 v peroxid.

2.3.2. Vai tr sinh l - Tng sn xut tinh trng v kh nng th thai, lm t ca trng th thai. - Ngn cn s to thnh gc t do, lm vng bn mng t bo c bit khi c mt vitamin C v cc cht c cha nhm SH. - Tng hp thu v d tr vitamin A, nhng li lm gim mt s triu chng ca s tha vitamin A. 2.3.3. Du hiu thiu ht Nhu cu hng ngy ca ngi ln l 10 - 30 mg. Thiu ht ko di s gp m t s triu chng sau: gim phn x, tht iu, gim nhy cm xc gic, yu c, teo c ph i, gim sn xut tinh trng, gim kh nng th thai, do xy thai, non, tn thng c tim , thiu mu, tan mu v rung git nhn cu. 2.3.4. Du hiu tha vitamin Dng liu cao trn 300 n v/ ngy c th gy bun nn, nn, y hi, i lng, vim rut hoi t. Tim tnh mch c th gy ri lon chc nng gan - thn, do hin nay khng dng. 2.3.5. Dc ng hc Sau khi thu phn rut non, thng qua cc ht vi dng chp i vo dng bch huyt vo mu. Trong mu gn vo -lipoprotein v c phn phi vo hu ht cc t chc. D tr nhiu trong gan v t chc m. i qua hng ro rau thai k m. 2.3.6. Ch nh v liu dng * Ch nh: - Do xy thai, ph n b xy thai lin tip,v s inh - Teo c ; thiu mu, tan mu, bnh x cng b tr em v lipid mu cao. - Chng lo ha: vitamin E c phi hp vi coenzym Q, acid amin cha lu huznh hoc - caroten, vitamin C v selen. - Cn th tin trin do gim s oxy ho ca - caroten. - Chng i dm sau ho?c ri lon kinh nguyt. * Ch phm v liu dng: - Ch phm : Vin nang: 200, 400, v 600 mg;vin nn hoc vin bao ng: 10, 50, 100 v 200 mg; ng tim : 30, 50, 100 hoc 300 mg/mL - Liu lng: Thuc c th ung hoc tim bp. Liu thng dng cho ngi c biu hin thiu ht cao gp 4 - 5 ln nhu cu hoc 40 -50 mg/ngy. 2.4. Vitamin K (xem bi thuc tc dng trn qu trnh ng mu) 3. CC VITAMIN TAN TRONG NC

3.1. Vitamin B1 (thiamin, Aneurin) 3.1.1. Ngun gc, cu trc v tnh cht C nhiu trong men bia (6 - 10 mg/ 100g), cm go, u tng. Ngoi ra c lng nh vitamin B1 trong sa, trng, tht nc, gan, thn. Khng n nh vi nh sng v m. Mt hot tnh trong mi trng trung tnh v base. n nh tnh cht pH = 4. Enzym diphosphatk inase xc tc cho s chuyn ha thiamin thnh thiamin pyrophosphat b c ch bi cc cht khng thiamin: neopyrithiamin v oxythiamin. 3.1.2 . Vai tr sinh l - Dng hot tnh ca thiamin l thiaminpyrophosphat c vai tr mt coenzym ca decarboxylase, tr ansketolase gip cho qu trnh chuyn ha pyrurat, ketoglutarat thnh cc aldehyd v acid carboxylic v chuyn ha pentose trong chu trnh hexosemonophosphat. Khi thiu thiamin nng pyrurat trong mu tng cao v transketolase trong hng cu gim r rt. - Tham gia tng hp acetylcholin v kh carboxyl ca valin, leucin v isoleucin. 3.1.3.Du hiu thiu ht Khi thiu vitamin B1 c th lm cho c th mt mi, chn n, gim tr nh, au, vim dy thn kinh, gim trng lc c. Nu thiu nng v ko di c th dn n bnh t ph Beri -Beri v suy tim, ngy nay t gp. 3.1.4.Dc ng hc Hp thu rut nh qu trnh vn chuyn tch cc, liu cao c th khuch tn th ng qua nim mc rut. Bo ha ngng hp thu vi liu 8 - 15 mg nhng chia nh li u v ung ri rc cng vi thc n s tng s hp thu. Thiamin c tp trung cao nht gan, no, thn, tim. Khi cc m qu nhu cu thiamin s b thi tr qua nc tiu di dng cha chuyn ha, hoc dng pyrimidin. 3.1.5.Ch nh v liu dng * Ch nh: - Bnh t ph Beri Beri - Vim au dy thn kinh, c bit ngi nghin ru, ph n c thai. - Ri lon tiu ha: chn n, kh tiu, a chy ko di, vim lo t i trng. - Bnh tim mch, ngi c ch nui dng nhn to v nhc c. * Liu

dng: - Trung bnh ngi ln ung 0,04 - 0,1g/ ngy hoc tim bp 0,05 g/ ngy. - Liu cao 0,1- 1,0g/ ngy (chia 2 - 3 ln) dng iu t vim dy thn kinh, au khp, au mnh my. - Khi nhu cu s dng glucid tng th cn tng liu lng thiamin. C 1000 calo c ngun t glucid cn 0,5 mg thiamin. * Khng tim trc tip vitamin B 1 vo tnh mch gy shock c th dn n t vong. C th pha 100 mg thiamin trong 1 lt dung dch glucose nh git tnh mch. 3.2. Vitamin B2 (Riboflavin) v vitamin B 6 (Pyridoxin) - Vitamin B2: c mu vng v c mt trong hu ht cc thc phm, vi khun rut c kh nng tng hp vitamin B 2. t tan trong nc hn cc vitamin nhm B khc v d b phn hu trong mi trng nc v base, l thnh phn cu to nn Flavomononucleotid (FMN) v Flavoadenindinucleotid (FAD). FMN v FAD l cofactor ca cyt creductase, oxydase v dehydrogenase gip tng cng chuyn h i a glucid, lipid, protid v vn chuyn in t trong chui h hp t bo. t gp thiu ht ring r vitamin B 2. nhng ngi nu i dng nhn to, vim da, nim mc, thiu mu v ri lon th gic c th ung vitamin B 2 (5- 10 mg/ ngy). - Vitamin B6: c mt trong nhiu loi thc phm ging vitamin B 1 v rt d phn hu nhit cao hoc tip xc vi cht oxy ha hay tia cc tm. Di s xc tc ca pyridoxalkinase, vitamin B 6 chuyn thnh pyridoxalphosphat mt coenzym ca transaminase, decarboxylase v desaminase. Ngoi ra, vitamin B 6 cn tham gia tng hp GABA v chuyn ha acid oxalic, vitamin B 12, acid folic. C th gp thiu vitamin B6 ngi suy dinh dng hoc dng INH, hydralazin, pencilamin Thuc c dng ng ung, tim bp hoc di da 0,05 - 0,1g/ ngy cho nhng ngi c vim dy thn kinh ngoi vi, thn kinh th gic, x va ng mch, ng kinh, chng ma vn tr em, ngi say tu xe, vim nim mc ming, thiu mu, gim bch cu ht hoc khi dng km 1 s thuc. 3.3. Vitamin B 3 (acid nicotinic, Niacin, vitamin PP): Xin xem bi thuc h lipoprotein mu.

3.4. Vitamin B5 v B8 t gp thiu ht 2vitamin ny ring r Vitamin B5 (acid panthothenic) : C mt trong hu ht cc loi thc phm, l thnh phn rt quan trng cu to nn coenzym A, gip cho s chuyn ha glucid, lipid, tng hp cc sterol trong c hormon steroid v porphyrin. Thuc c ch nh trong ri lon chuyn ha do cc nguyn nhn khc nhau, bnh ngoi da, chng mt do khng sinh aminoglycosid gy ra, phng v chng sc sau m v vim nhim ng h hp. Vitamin B8 (vitamin H, Biotin): C nhiu trong cc ph tng, lng trng, c, cc loi ht v l cofactor ca enzym carboxylase tham gia phn ng kh carboxyl ca 4 c cht: Pyrurat CoA, acetyl- CoA, Propionyl- CoA v - methylcrotonyl - CoA gip cho s chuyn ha glucid v lipid. Tuy nhin, vitamin B8 thng c ch nh trong bnh da tng t it b nhn, bnh nhn c ch n nhn to v thiu ht enzym ph thuc biotin c tnh di truyn. 3.5. Vitamin C (acid ascorbic) 3.5.1. Ngun gc - tnh cht - C trong hu ht rau, qu c bit trong rau ci xoong, cam, qu{t, chanh, bi, c chua. Tan mnh trong nc nhng d b phn hu bi nhit , cc cht oxy ha v trong mi trng base. 3.5.2. Vai tr sinh l Trong c th, acid ascorbic b oxy ha to thnh acid dehydroascorbic vn cn y hot tnh v 2 in t. y l phn ng thun nghch. Nh c nhm endiol trong phn t nn vitamin C l cofactor ca nhiu phn ng oxy ha kh quan trng trong s tng hp collagen, carnitin, chuyn acid folic thnh acid folinic, c ch hyaluronidase lm vng bn thnh mch. - Chuyn dopamin thnh noradrenalin , tng hp serotonin t tryptrophan, tng hp hormon thng thn v s tng hp collagen, proteoglycan v cc thnh phn hu c khc rng, xng, ni m mao mch. - Gip chuyn Fe +3 thnh Fe+2 lm tng s hp thu st rut. - Ngoi ra, vitamin C cn c tc dng hip ng vi vitamin E, - caroten, selen lm ngn cn s to gc t do gy c t, bo tng tng hp interferon, gim nhy cm ca t bo vi histamin. 3.5.3. Du hiu thiu ht - Thiu trm trng vitamin C gy bnh Scorbut - ngy nay t gp, i n hnh c

du hiu: chy mu di da, rng ming, rng r?ng, tng sng ha nang lng, vim li . - Thiu va phi biu hin: mt mi, vim li, ming, thiu mu, gim sc khng d b nhim trng. 3.5.4. Du hiu tha vitamin C Tuy t tch lu, nhng khi dng liu cao trn 1g/ ngy v di ngy c th gp tha vitamin C, biu hin: mt ng, kch ng, i lng, vim lot d dy - rut, gim sc bn hng cu c th gy tan mu c bit ngi thiu G 6PD. Ph n mang thai dng liu cao di ngy c th gy bnh Scorbut cho con. C th gp si thn oxalat do dehydroascorbic chuyn thnh acid oxalic v tng huyt p. 3.5.5. Ch nh v liu dng * Ch nh: - Phng v iu tr bnh Scorbut, chy mu do thiu vitamin C. - Tng sc khng trong nhim trng, nhi m c, thai nghn. - Thiu mu, d ng v ngi nghin ru, nghin thuc l. * Liu dng: - Ung trung bnh 0,2 - 0,5g/ ngy, nn chia liu nh ung nhiu ln trong ngy. - Tim di da hoc tnh mch khng vt qu 1g/ ngy. Ch c th gp schock khi tim, c bit khi tim tnh mch. - Tr em dng mt na liu ngi ln. TI LIU THAM KHO: WEBSITES : BENHHOC.COM, YDUOCVN.NET, YHOCQUANY.COM, THUOCBIETDUOC.COM.VN, THUOC.NET.VN, CIMSI.ORG.VN, MIHBT.COM.VN,YKHOANET.COM, 1. DC L HC 2008 I HC Y H NI. NXB Y HC 2. BI GING DC L HC 2008 I HC Y DC THNH PH H CH MINH 3. The Hands-on Guide to Clinical Pharmacology - Christopher Tofield, Alexander Milson, Sukhdev Chatu - Publisher: Blackwell Publishing 4. Lange Pharmacology Flash Cards Suzanne J. Baron, MD and Christoph I. Lee, MD Publisher: The McGraw-Hill Companies, Inc. 5. Pocket Prescriber - Timothy R.J. Nicholson, MBBS, BSc, MSc, MRCP, MR-

CPsych, Ashan Gunarathne, MBBS, MRCP, and Donald R.J. Singer, BMedBiol, MD, FRCP Publisher: Hodder Arnold, an imprint of Hodder Education Edition: Based on the 3rd edition