CHNG 3.

THU C KHNG KHU N

1. KHI NI M Vuillemin (1889) c p n t antibiosis v i ngha l s khng gi a cc sinh v t s ng. Sau , vo nm 1942, Waksman nh ngha antibiotics l nh ng ch t c t o b i cc vi sinh v t, n ch ng l i s pht tri n ho c tiu di t cc vi sinh v t khc m t n ng nh . Xt v m t t ng , antibiotics c ngha l khng sinh (anta = khng, bios = sinh v t). ngha ny qu r ng , c th bao g m c thu c st trng ng th i khng nu ln c tc ng chuyn bi t trn vi sinh v t gy b nh v tnh khng c cho c th sinh v t h u nh li u i u tr . Theo quan ni m m i ngy nay, thu c khng sinh l t t c nh ng ch t ha h c, khng k ngu n g c (chi t xu t t mi tr ng nui c y vi sinh v t, bn t ng h p hay t ng h p) c kh nng km hm s pht tri n c a vi khu n (bacteriostatic) ho c tiu di t vi khu n (bactericidal) b ng cch tc ng chuyn bi t trn m t giai o n chuy n ha c n thi t c a vi sinh v t. V i nh ngha ny, nhi u thu c tr c y x p vo lo i ch t khng khu n t ng h p (nh sulfamid, quinolone) by gi cng c x p vo lo i khng sinh 2. PHN LO I 2.1. Theo c u trc ha h c -Nhm beta-Lactam: penicillin, ampicillin, amoxicillin, cephalosporin... -Nhm aminoglycosid: streptomycin, gentamicin, kanamycin, neomycin... -Nhm polypeptid: colistin, bacitracin, polymyxin... -Nhm tetracyclinee: tetracyclinee, oxytetracyclinee, chlotetracyclinee, doxycycline.. - Nhm phenicol: chloramphenicol, thamphenicol - Nhm macrolide: erythromycin, spiramycin, tylosin... - Nhm khng sinh g n gi v i macrolide: lincomycin, virginiamycin... - Nhm sulfamid: sulfaguanidin, sulfacetamid, sulfamethoxazol... - Nhm diaminopyrimidin: trimethoprim, diaveridin - Nhm quinolonee: acid nalidixic, flumequin, norfloxacin... - Nhm nitrofuran: nitrofurazol, furazolidon, furaltadon... - Cc nhm khc: glycopeptid, pleuromutilin, polyether ionophore... 2.2. Theo c ch tc ng 2.2.1. Tc ng ln thnh t bo vi khu n T t c cc t bo s ng (vi khu n v ng v t h u nh) u c mng t bo c c u trc lipid ph c t p, do u b tiu h y b i ch t st trng. Nhng khc v i t bo ng v t h u nh, t bo vi khu n c p su t th m th u bn trong t bo cao hn nn chng cn c thnh t bo bn ngoi mng t bo. Thnh t bo ny c c u t o t ch t peptidoglycan (= mucopeptid = murein) g m nhi u dy polysaccharid th ng d c v nh ng o n ngang pentapeptid. Polysaccharid g m nhi u phn t ng mang amin: N-acetyl-glucosamine v N-acetylmuramic (ch c vi khu n). - Ti n trnh hnh thnh thnh t bo b t u b ng s chuy n i L. Alanin thnh D. Alanin. Sau 2 D. Alanin k t h p v i nhau. Cycloserin c ch c nh tranh giai o n ny, nn n tc ng n c vi khu n G+ v G-. 20

- Ti p n D-alanin dipeptid n i v i 3 acid amin khc v 1 ng N-acetyl muramic acid t o thnh ng Pentapeptid. n l t n, n l i c p i v i m t ng mang amin khc l N- etylglucosamin. Ton b c u trc ny l i k t h p v i 1 phn t mang lipid l Isoprenyl phosphate r i di chuy n t t bo ch t ra ngoi mng t bo. T i y chng k t h p v i nhau ko di thnh chu i peptidoglycan. Bacitracin ngn c n ti n trnh ny b ng cch g n v i Isoprenyl phosphate t o ph c h p v d ng. Vancomycin ngn c n s di chuy n ng pentapeptid thnh chu i a phn t bn ngoi mng t bo. - Giai o n cu i l hnh thnh dy ngang gi a cc dy peptidoglycan b ng cch n i D-alanin c a 1 chu i v i diaminopimelic acid c a chu i k c n nh enzym transpeptidase. Penicillin c ch giai o n ny do c u trc c a n gi ng D-alanylalanin (1 v tr trn peptidoglycan m enzym g n vo) 2.2.2. Khng sinh tc ng ln mng t bo ch t (mng bo tng) - Mng ny c nhi m v bao b c v ngn cch d ch tng bo v i v t bo. N c tnh th m ch n l c, i u ha s trao i v i mi tr ng bn ngoi. C t bo ng v t v t bo vi khu n u c cc y u t nh protein, lipid nhng lipid c a vi khu n l phospholipid cn n m m c l sterol. - Khng sinh thu c nhm polypeptid (colistin, polymyxin) v polyens (ch t khng n m) g n k t trn cc ch t ha h c ring bi t lm xo tr n ch c nng th m th u khi n cc ch t trong bo tng nh Mg2+, K+, Ca2+ thot ra ngoi (tc ng nh m t ch t t y lo i Cation) 2.2.3. Khng sinh tc ng ln s t ng h p acid nucleic - S nhn i DNA b t u b ng ph n ng tch hai chu i DNA ra, m i chu i l m t khun g n cc nucleotid thch h p theo nguyn t c b sung. DNA polymerase xc tc s t ng h p cc lin k t gi a cc nucleotid; DNA gyrase gip n i cc DNA trong qu trnh t h p v t o thnh cc vng xo n. - S sao m l qu trnh t ng h p RNA do DNA lm khun theo nguyn t c b sung nh enzym RNA polymerase v ion Mg2+ - Qu trnh t ng h p acid nucleic b t u t vi c t ng h p acid folic r i thnh purin nh vo m t s enzym: Dihydroteroat synthetase, dihydrofolat reductase... - Quinolonee (acid nalidixic, norfloxacin: Quinolonee c fluor ha) c ch m nh s t ng h p DNA trong giai o n nhn i do c ch DNA gyrase. - Rifampin c ch t ng h p RNA do c ch RNA polymerase. - Sulfamides i khng c nh tranh v i PABA (p-aminobenzoic acid) m t ti n ch t t ng h p acid folic ( ng v t h u nh dng folat c s n trong th c ph m cn vi khu n ph i t ng h p folat). PABA k t h p v i pteroic acid ho c glutamic acid t o pteroylglutamic acid (PGA), ch t ny gi ng nh 1 coenzym trong s t ng h p purin v timin. PGA cng l 1 ph n c a phn t B12 c lin quan n s bi n d ng acid amin v purin. Do khi thi u PABA s gy thi u purin, acid nucleic. i u ny cng gi i thch t i sao cc vi khu n t t ng h p c PABA th khng v i sulfamid v t i sao thymin, purin, methionin, v m t s acid amin khc l i i khng v i hi u qu sulfamid. Sulfamides ch c tc ng km khu n. - Trimethoprim c ch dihydrofolat reductase ngn qu trnh chuy n ha dihydrofolat thnh tetrahydrofolat (d ng ho t ng c a acid folic). 2.2.4. Khng sinh tc ng n qu trnh t ng h p protein c a t bo vi khu n Qu trnh ny x y ra thng qua vi c chuy n giao thng tin di truy n c m ha trn mRNA. n v ch c nng c a qu trnh ny l ribosome. Khc v i t bo ng v t (ribosome 80S), t bo vi khu n c ribosome 70S, g m 2 ti u n v 30S v 50S.

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* Giai o n kh i u: nh nhi u y u t kh i u khc nhau m ti u n v 30S s g n v i mRNA v tRNA c mang acid amin (amino acyl-t.RNA). Sau g n v i ti u n v 50S hnh thnh nn ribosom 70S. t.RNA t v tr A (amino acyl) d ch chuy n sang v tr P (peptidyl) gi i phng v tr A cho tRNA k ti p. * Giai o n ko di: ti n trnh trn c l p l i n khi c h t o n di truy n v protein c hnh thnh. * Giai o n k t thc: cc y u t k t thc khc nhau lin quan n s phng thch chu i protein. Cc ti u n v 30S v 50S tch r i nhau ra, tham gia vo t p h p nh ng ti u n v t do tr c khi ti k t h p v i m t o n gene m i. - Khng sinh aminoglycoside (aminoglycosid: streptomycine...) g n ch t v i ti u n v 30S, phong b ho t ng bnh th ng c a ph c h p kh i u, can thi p ti p c n tRNA , lm sai o n gen t hnh thnh cc protein khng c ch c nng. - Khng sinh tetracycline cng g n vo ti u n v 30S v phong b s k t h p c a tRNA v i mRNA. - Khng sinh chloramphenicol g n v i ti u n v 50S, c ch enzym peptidyl transferase khng cho amino acid g n vo chu i polypeptid - Khng sinh macrolide (erythromycin...) tranh ginh v tr g n ribosom v ngn c n v tr d ch chuy n cc acid amin 2.3. Theo tc ng khng khu n Chia lm hai nhm: Khng sinh km khu n (hay tnh khu n) khng c tc d ng h y di t m m b nh m ch c tc d ng c ch s nhn ln c a chng Khng sinh st khu n (hay di t khu n) c ho t tnh tiu di t vi khu n S phn bi t ny ch c tnh tng i v b t k khng sinh no cng c tc d ng km khu n v st khu n ty theo li u l ng cung c p. Tuy nhin, i v i nh ng khng sinh ch c tc d ng st khu n n ng r t cao trong mu (c th gy c tnh ho c tai bi n) th ch c s d ng v i m c ch km khu n li u th p hn. 2.3.1. Nhm cc khng sinh km khu n - Tetracycline - Macrolide - Lincosamid - Synergistin - Phenicol - Sulfamid - Diaminopyrimidin 2.3.2. Nhm cc khng sinh st khu n 2.3.2.1. Khng sinh st khu n ph thu c n ng T c st khu n ph thu c n ng t c trong mu. Hi u l c c a nh ng khng sinh ny th ng r t nhanh chng - Nhm aminoglycoside - Nhm fluoroquinolone tc ng trn vi khu n G- Polypeptid - Sulfamid + diaminopyrimidin ngha: Ch c n c p khng sinh 1-2 l n trong ngy

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2.3.2.2. Khng sinh st khu n ph thu c th i gian T c st khu n ph thu c th i gian vi khu n ti p xc khng sinh n ng l n hn hay b ng n ng c ch t i thi u (MIC). Hi u l c st khu n c a nh ng khng sinh ny th ng x y ra ch m - Nhm beta-Lactam - Nhm glycopeptid - Nhm quinolone trn Staphylococcus - Nhm rifampicin ngha: chia t ng li u thnh nhi u li u nh trong ngy (MIC: l n ng t i thi u khng sinh c kh nng c ch s nhn ln c a vi khu n invitro) 3. S KHNG C A VI KHU N

3.1. S khng t nhin y cng l gi i h n kh nng khng khu n c a khng sinh V d : Streptococcus khng t nhin v i aminoglycosidee do thnh vi khu n khng cho thu c qua 3.2. khng thu nh n khng do t bi n nhi m sc th khng do plasmid - Quinolone, nitrofuran, polypeptid - Cc nhm khc - T n xu t th p: 10-9 -10-10 - T n xu t cao hn: 10-6 -10-7 - Hi m x y ra (10-20%) - Th ng x y ra (80-90%) - khng 1 lo i khng sinh - khng nhi u KS, nhi u nhm - Di truy n theo chi u d c - C d c v ngang 3.3. C ch c a s khng - Vi khu n s n xu t cc enzym lm bi n i ho t v ho t khng sinh V d : vi khu n sinh betalactamase ph h y cc betalactam - Thay i c u trc i m ti p nh n (receptor) V d : Thay i ribosom 30S khng cho aminoglycoside g n vo - Ngn c n s v n chuy n khng sinh vo trong t bo V d : vi khu n khng v i tetracycline - Thay i qu trnh bi n d ng V d : vi khu n khng v i sulfamide 4. S D NG KHNG SINH

4.1. Ch n khng sinh: d a vo - K t qu ch n on b nh - Tnh nh y c m c a 1 hay nhi u vi khu n gy b nh i v i 1 khng sinh (d a vo khng sinh ho c nh ng hi u bi t v th ng k d ch t ). - Kh nng i t i b nh c a khng sinh (d a vo hi u bi t v tc ng d c l). - C a c a th (c mang, b nh gan th n, th non...) 4.2. Nguyn t c c a li u php khng sinh - Nhanh: trnh pht tn m m b nh - M nh: b t u b ng li u c hi u l c (tng i cao) v ti p theo l li u duy tr (th p hn). - Lu: m b o duy tr n ng khng sinh c hi u l c trong 5 ngy.

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4.3. Bi n php h n ch s khng thu c - Khng s d ng khng sinh c ph r ng ho c khng sinh th h m i trong khi khng sinh c ph h p, khng sinh c v n c hi u qu - Th ng xuyn n m b t thng tin v tnh hnh d ch t v kh nng nh y c m khng sinh c a h vi khu n - Khi k t h p khng sinh v i m c ch ngn khng, cc khng sinh thnh ph n ph i s d ng nguyn li u l ng 5. PH I H P KHNG SINH 5.1. M c ch - M r ng ph khng khu n V d : Penicillin + Streptomycin - Tng hi u l c st khu n V d : Sulfamid + Trimethoprim - Ngn s khng thu c V d : Amoxcillin + acid clavulanic 5.2. Cc nguyn t c ph i h p khng sinh

NHM BETA LACTAM

Cc penicillin
1. Ngu n g c Alexander Fleming (1929) pht hi n trn mi tr ng nui c y n m Penicillinum notatum, P.chrysogenum. 2. C u t o ha h c Vng betalactam (amid n i vng) Vng thiazolidin -RCO: s thay i R cho cc khng sinh khc nhau trong nhm 3. L ha tnh Km b n nh t trong cc lo i khng sinh. R t ht m v b th y gi i nhanh. pH t i u t 6-6,5, mi tr ng acid, ki m s ph h y penicillin. S h h ng cng gia tng theo nhi t . Penicillin b cc tc nhn oxyha, kh ph h y (KMnO4). Cc ha ch t c kim lo i n ng cng lm m t tc d ng c a penicillin (thu c ). Alcohol v cc h p ch t c ch a -SH cng i khng v i penicillin. Vi khu n tr c trng c kh nng ti t penicillinase, m vng betalactam cng ph h y penicillin. 4. D c ng - H p thu: Ch nh ng penicillin b n trong mi tr ng acid m i c h p thu vo ng tiu ho (nhm A, nhm M, penicillin V). Penicillin G ch dng ng tim chch (IM, SC, t dng ng IV). - Phn b : d ch ngo i bo. Khu ch tn t t vo ph i, kh khuy ch tn vo mng no t y, nhau thai tr khi nh ng ni ny vim. Vo s a khi tim nh ng li u l n. - Chuy n ha: 24

- Bi th i: nhanh v ch y u qua ng th n. Ng i ta th ng ko di tc d ng c a penicillin b ng cch: + Ph i h p v i procain, benzathin phng thch d n + Dng penicillin trong d u + T o mu i c a penicillinc phn t l ng cao th y gi i ch m + Ph i h p v i probenecid c nh tranh o th i 5. Ho t tnh d c l c: - Tc ng st khu n - Ph khng khu n: thay i ty t ng nhm penicillin 5.1. Nhm G: penicillin G (Benzyl penicillin), penicillin V (penoxymethyl penicillin) y l cc khng sinh c ho t l c cao i v i vi khu n G+ v khng khng penicillinase. 5.2. Nhm A: ampicillin, amoxcillin Cc khng sinh ny c ph khng khu n m r ng trn vi khu n G+ v G- nhng v n khng khng c penicillinase. Ampicillin c n ng cao trong m t. Amoxcillin c h p thu t t hn, n ng trong mu cao hn ampicillin g p 2 l n. 5.3. Nhm M: (methicillin) oxacillin, cloxacillin, floxacillin Cc penicillin bn t ng h p ny c ph khng khu n r ng, trn vi khu n G+ v G-, b n trong mi tr ng acid v khng penicillinase. 6. Ch nh B nh nhi t thn, d u son heo, vim v do Staphylococcus, Streptococcus, b nh do Leptospira, vim nhi m ph i... Ch ng ch nh: th , chu t hamster 7. c tnh L nhm khng sinh t c nh t. Tuy nhin c n phng tnh tr ng d ng:penicillin c vai tr nh 1 hapten. Khi vo c th l n th nh t, chng s b bi n i thnh acid penicilloic v acid penicillenic. Cc ch t ny k t h p v i protein thnh m t ph c h p c tnh sinh khng th ch ng l i chnh ph c h p ny. Cc Ig (ch y u l IgE) bm trn cc t bo b ch c u v Mastocyte. Khi penicillin vo c th l n th hai, chng mang tnh khng nguyn, k t h p v i khng th c. Ph n ng k t h p khng nguyn khng th d n n v cc t bo Mast v b ch c u, phng thch histamin gy cc tri u ch ng: , s n, ph, co th t kh ph qu n, co th t c tim... 8. Li u l ng: - penicillin G (IM)10.000-20.000 U.I/kgP 1mg=1695 USP unit - Na penicillin G: 4 gi /1li u 1mg=1211 - procain penicillin: 24 gi / 1 li u 1mg= 1667 - benzathin penicillin: 2 tu n/1 li u 1mg =1009 9. Tng tc thu c: Hi p l c: Aminoglycoside (penicillin+streptomycin); quinolone; polypeptid (ampicillin +colistin); ch t c ch betalactamase (amoxcillin + acid clavulanic) i khng: Tetracycline, macrolide

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Cc cephalosporin
Cc khng sinh ny c vng dihydrothiazin n i v i vng betalactam cephalosporin th h Ph khng khu n I G+ II III

G+, G- ng ru t G+, G- k kh + + + ceftriazon

khng cephalosporinase vo d ch no t y i di n -

cefalexin cefamandol

NHM AMINOGLYCOSIDE (AMINOSIDE)

1. Ngu n g c -Streptomycin c chi t t Streptomyces griseus - Kanamycin c chi t t Streptomyces kanamycetius - Gentamicin c chi t t Micromonospora purpurea - Spectinomycin c chi t t Streptomyces spectabilis - Neomycin chi t t S. fradiae - Dihydrostreptomycin, apramycin l khng sinh bn t ng h p 2. C u t o ha h c G m c c u trc vng aminocyclitol (aminocyclohexanol) n i v i 1 hay nhi u phn t amin. ng

3. L ha tnh - pH t i u t 6-8, pH 8 c th ph h y thu c. Do ng i ta th ng dng ch t m citrat Na - Nhi t v cc tc nhn oxyha kh cng lm h h ng streptomycin. - Cc h p ch t c nhm -SH c th tc ng ln nhm aldehyd t do, h h ng thu c. - Mu i Na, K, phodphate, tartrate lm gi m ho t tnh. 4. D c ng H p thu: do tnh phn c c, cc aminoglycoside tan t t trong n c, khng h p thu qua ng tiu ha. ng u ng ch cho tc ng t i ch . C th tim b p ho c tnh m ch (tr DHS), khng tim d i da Phn b : d ch ngo i bo. t n ng tr li u kh p, ph i, d ch phc m c th n v tai trong: thu c t p trung v i n ng cao Vo d ch no t y: kh v ch m Qua c nhau thai v nh h ng bo thai Bi th i: ch m qua th n d ng c ho t tnh 5. Ho t tnh d c l c - Tc ng st khu n ngoa tr spectinomycin

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- Ph khng khu n: * Streptomycin c ph khng khu n h p, tc ng trn vi khu n G- (tr c khu n G- hi u kh), Leptospira, Mycobacterium. t tc d ng trn vi khu n k kh do s th m ph thu c O2 v c n nng l ng. * Gentamicin, kanamycin, neomycin tc ng trn c vi khu n G- v G+ (Streptococcus), ring gentamicin cn c hi u qu trn Proteus v Pseudomonas * Spectinomycin ch c tc ng km khu n nhng c hi u qu trn vi khu n G-, G+ v Mycoplasma (tr c CRD trn gia c m). Khng sinh ny t c trn th n nh t. Ho t tnh c a streptomycin< kananycin<gentamicin<apramycin - Tinh th l ng tnh, ho tan trong n c km, d ng mu i Chlohydrat tan nhi u hn. Trong , Oxytetracycline tan nhi u nh t (nhm OH) - Tnh b y b t (kelate ha) v i cc ion kim lo i ha tr II (Ca, Mg...) lm cho cc tetracycline b gi m h p thu khi th c n c cc kim lo i ny (ngo i tr Doxycyclin), ng th i gi i thch i l c t n tr m xng, rng. 4. D c ng: - H p thu: qua ng tiu ha, t l h p thu khc nhau gi a cc tetracycline Chlotetracycline: 30% ; tetracycline, oxytetracycline 60-80%; doxycyclin 100% Chlotetracycline khng c s d ng tim b p v d gy kch ng, th ng dng trong thu c m tra m t. Doxycyclin, tetracycline th ng s d ng d ng u ng (thu c b t, vin) nhng khng dng cho loi nhai l i v s nh h ng h vi sinh v t d c ng tim chch cho tc ng nhanh chng hn - Phn b : ng u bn trong v bn ngoi t bo (homogene). Kh nng phn tn t t n cc m trong c th nh ph i, gan, th n, lch, xng (tr d ch no t y v d ch kh p). Qua c nhai thai v tuy n s a, gy nh h ng bo thai. Tch ty m xng v rng - Chuy n ha gan - o th i: qua phn 40% (m t) v n c ti u 60%. Ring Doxycyclin o th i qua phn d ng khng ho t tnh nn t nh h ng h vi khu n ng ru t , an ton tr nhi m trng ngoi th n cho th suy th n. 5. Ho t tnh d c l c - Tc ng tnh khu n - Ph khng khu n r ng: G+ (Staphylococcus, Streptocoocus, Corynebacterium, c vi khu n k kh G+ nh Clostridium), G- (E.coli, Salmonella, Actinobacillus, vi khu n n i bo nh Mycoplasma (M. hyopneumonia, M galisepticum, M.synoviae, M. bovis), Brucella abortus, Ricketsia (Ehrlichia canis), Chlamydia (C. psitaci), Leptospira (L. canicola). Mycobacterium, Proteus, Pseudomonas... khng v i tetracycline

6. Ch nh Nhi m trng mu, nhi m trng ng h h p, ti t ni u, tiu ha do cc vi khu n nh y c m gy ra. 7. c tnh - Tc d ng ph : r i lo n tiu ha khi dng lu ngy, b i nhi m n m m c, thi u vitamin B,K - Nh y c m quang h c (photosensitive): doxycyclin lm t n thng da khi ti p xc nh sng, n i m n, vim da. - Trn xng v rng: do s thnh l p ph c h p tetracycline calcium- orthophosphat v i xng v rng. Ch t ny l ng ng gy i mu men rng, ch m pht tri n . Ch ng ch nh

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ng i mang thai v tr em d i 8 tu i. 8. Li u l ng: Ty theo lo i gia sc v ng c p: U NG TIM - Gia sc l n: 500-1000mg/ngy 2-4mg/kgP/8h - Gia sc nh : 1000-2000mg/ngy 2-8mg/kgP/8h - Ch mo: 50mg/kgP 2-10mg/kgP/8h - Gia c m: 1g/4,5L nu c 9. Tng tc thu c: - i khng . Lactam, Barbituratesv i - Hi p ng v i cc khng sinh khc: . Aminoglycoside: Neomycin + Oxytetracycline . Macrolide: Ery +Tetra; Spira + Oxytetra . Polypeptid: Polymyxin B+ Oxytetra . Sulfamid: Sulfamethoxypyridazin+ Chlortetra .Phenicol: tetracycline+chloramphenicol - K t h p v i khng vim, khng histamin: Colistin+ Oxytetracycline + Prednisolon + Chlorpheramin

NHM PHENICOL
1. Ngu n g c Nm 1947, chloramphenicol c c l p t Streptomyces venezuelae. Do c ph khng khu n r ng v kh nng phn t t b vo cc m trong c th nn chloramphenicol r t c a chu ng trong tr li u. Tuy nhin t khi pht hi n nh ng c tnh ng k trn c quan t o mu, vi c s d ng ch t ny c gi i h n trong nh ng qui nh qu c t v khu v c Thiamphenicol l d n ch t t ng h p c a chloramphenicol. 2. C u t o ha h c 2c ut c bi t: - para- nitrophenil - Carbongemdiclor 3. L ha tnh - Tinh th khng mu, v r t ng, b n 1000 C, pH=2-9, tan nhi u trong alcohol - B m t ho t tnh b i tc nhn oxyha (nhm alcohol nh c p), kh (nhm nitro) 4. D c ng - H p thu: t t qua ng tiu ha (chloramphenicol 75-90%; thiamphenicol 100%) v ngo i tiu ha (IM, IV, IP). Cc d ng mu i palmitat v sucsinat khng ho t tnh, khi vo c th c th y gi i thnh d ng c ho t tnh - Phn b : ng u trong d ch n i v ngo i bo. Do tnh khng ionha, chloramphenicol tan t t trong lipid, c phn ph i r ng kh p cc m trong c th : nhau thai, s a, d ch m t, ph i, tuy n prostate, k c d ch no t y - Chuy n ha: chloramphenicol chuy n ha gan (k t h p v i a. glucuronic) d ng khng ho t tnh. mo v gia sc non, ph n ng lin h p ny r t km nn khi dng c n ch gi m li u.Thiamphenicol khng b chuy n ha, cn nguyn v n do c dng tr nhi m trng gan m t v ng ti u. 28

- Bi th i: ch y u qua th n 5. Ho t tnh d c l c: - Tc d ng tnh khu n. Nhng i v i Haemophilus th c tc d ng st khu n - Ph khng khu n: G+, G-, vi khu n n i bo (Ricketsia, Chlamydia) vi khu n k kh (Clostridium, Bacteroides...) . Mycoplasma t nh y c m 6. Ch nh Do c tnh cao, phenicol ch gi i h n s d ng trong cc tr ng h p: - Thng hn, ph thng hn do Salmonella - Vim mng no, vim thanh kh qu n, vim ph i do Haemophilus - Nhi m trng k kh (thay th Metronidazol, Clindamycin) - Nhi m rickettsia - Vim nhi m tuy n prostate - S d ng t i ch : thu c nh m t, tai, kem bi da Ch ng ch nh: trong th c n gia sc, thu c i u tr trn gia sc s n xu t th c ph m cho ng i (b s a, g tr ng, ong m t...), ph n mang thai, cho con b, tr d i 6 thng (h th ng kh c gan cha hon ch nh) 7. c tnh - R i lo n t y xng: suy t y khng h i ph c (thi u mu b t s n) - Tr y tim m ch khi dng li u cao tr thng hn (c th do vi khu n ch t hng lo t, phng thch c t ) - R lo n tiu ha: tiu ch y, i m a - Tc d ng ph : suy gi m mi n d ch. Do khi ang ch ng ng a cho gia sc, n u ph i s d ng khng sinh th ch n cc khng sinh khc 8. Li u l ng U NG TIM (IM) Th l n 500- 1000mg/ngy 2-4mg/kgP/8-12h Th nh 250-500mg/ ngy 4-10mg/kgP 9. Tng tc thu c .- i khng v i -Lactam, Aminoglycoside, Lincomycin - Hi p l c v i Tetracycline (Chloramphenicol + Oxytetracycline +Prednisolon) - Dng chung chloramphenicol+ sulfamethoxypyridazin s lm t n thng gan - Khng dng chung v i pentoibarbital, codein, NSAID, coumarin v lm ko di tc c ch chuy n ha cc ch t ny.

ng do

NHM MACROLIDE
1. Ngu n g c Chi t xu t t n m Streptomyces (Erythromycin t S. erythreus, Spriramycin t S.ambofacient) 2. C u t o ha h c G m m t vng Lacton l n (c t 12-16 nguyn t ) g n v i cc phn t k t glycosid - Lo i 12nguyn t : khng s d ng trong lm sng - 14 nguyn t : Erythromycin, Oleandomycin ng b ng cc lin

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- 16 nguyn t : Spiramycin, Tylosin 3. L ha tnh - pH t i u =7,8-8, pH10 lm h h ng thu c, do ng i ta b c vin nh ng khi dng ng u ng - Kh b n, km tan trong n c , tan t t trong dung mi h u c. - Th ng d ng mu i: lactobionat, thiocyanate (erythromycin); adipate (spiramycin); chlohydrate (oleandomycin); tartrate, phosphate (tylosin)... 4. D c ng - H p thu: Erythromycin base b h y b i acid d ch v nn s d ng ng u ng ph i d ng capsul ho c mu steroat, propionate. Cc macrolide m i th ng h p thu t t hn v t b nh h ng b i th c n trong d dy - Phn b : d ch n i bo, khuy ch tn vo kh p cc m nh t l ph i, xng, gan , nhau thai tr d ch no t y (khng n ng tr li u) - Bi th i: ch y u qua m t (khc penicillin), tuy n s a, n c b t d ng cn ho t tnh 5. Ho t tnh d c l c - Tc ng tnh khu n - Ph khng khu n: vi khu n G+, Mycoplasma, Rickettsia, Chlamydia. 6. Ch nh u tin ch nh cc b nh ng h h p (CRD, PPLO gia c m, suy n heo, vim ph i b ngh), tiu ch y (h ng l heo do Treponema) vim v (do l i i m bi th i nhanh, t gy t n d trong s a), d u son, nhi m trng tai mi h ng ... Thay th penicillin tr nhi m trng do Staphylococcus * Ch ng ch nh loi ng a 7. c tnh th p nh t: s t, nn m a, d ng da

9. Tng tc thu c: - i khng v i - Lactam, chloramphenicol, lincomycin ngo i tr Tylosin c th ph i h p v i chloramphenicol - Hi p l c v i: polypeptid, tetracycline, sulfamid

NHM SULFONAMIDE
1. Ngu n g c y l nhm khng khu n c t lu nh t (th p nin 1940). B t ngu n t phn t Protonsil (m t lo i thu c nhu m azo), cc sulfamid c t ng h p, l nh ng chuy n ha ch t c a sulfanilamid v i cc v tr th N1 v N4 2. C u t o ha h c C nhm sulfamoil (-SO2NH2) trong phn t 3. L ha tnh - D ng b t tinh th , tan t t pH=9-10, t tan trong n c v mi tr ng acid y u. C khuynh h ng k t tinh trong mi trng n c ti u pH acid. 30

- Tnh ha tan c a h n h p nhi u sulfamid cao hn c a t ng ch t ring l . 4. D c ng - H p thu: qua ng tiu ha t t, ngo i tr cc sulfamid co tc ng t i ch ng tim d i da: dung d ch tim c n ph i c ch t m v mu i Na c a sulfamid c tnh gy kch ng. Tim b p v tim tnh m ch th ng s d ng hn nhng n ng h u hi u trong mu th ng ng n, ph i b sung b ng cch cho u ng Tim vo v cc h n d ch sulfamid trong d u. t vo t cung, m o nh ng vin nang sulfamid+ urea (tng tnh ha tan) ho c ph i h p v i cc khng sinh khc - Phn b : d ch ngo i bo, phn tn n kh p c th bao g m cc m m m c h th n kinh trung ng (d ch no t y) v kh p (d ch kh p). Vo c tuy n v nhng cha t n n ng tr li u - Chuy n ha: x y ra gan v i 2 ph n ng chnh - Ph n ng lin h p v i acid glucuronic thnh d ng b t ho t nhng c tnh ha tan - Ph n ng acetyl ha t o thnh d ng b t ho t v khng tan nn th ng gy c (hnh thnh d ng tinh th th n) - Bi th i: Qua th n l ch y u (tr cc sulfamid khng khu n ng ru t), m t t qua phn, s a S l c qu n c u th n: khu ch tn th ng, t t c cc sulfamid u qua S ti h p thu ng th n: qu trnh ny c s ch n l c. i u ny gi i thch t i sao m t s sulfamid c duy tr trong c th lu hn cc sulfamid khc V sulfamid c tnh acid y u nn vi c ki m ha n c ti u b ng NaHCO3 s lm tng tnh ha tan, trnh t o tinh th gy h h i th n. 5. Ho t tnh d c l c - Tc ng khng khu n:ch c tc ng tnh khu n nn h mi n d ch gi vai tr ch y u trong vi c lo i tr t n g c s nhi m trng. Sulfamid c hi u qu cao trong giai o n u c a nhi m trng c p tnh v giai o n ny vi khu n c m c bi n d ng cao, d k t h p v i sulfamid, thm vo kh nng th c bo cn m nh m v s khuy ch tn c a thu c cha b c n tr b i qu trnh x ha trong vim mn tnh. - Ph khng khu n: r ng, tc ng trn vi khu n G+, G-, Protozoa (Coccidia, Toxoplasma) 6. Ch nh -Nhi m trng ng h h p, tiu ha, ti t ni u - Vim v, vim t cung, vim a kh p - Tr c u trng, toxoplamosis * sulfamid tc ng ton thn + sulfamid tc ng nhanh (3-6h), bi th i nhanh: sulfamerazin, sulfadimidin, sulfathiazol... + sulfamid n a ch m (6-10h): sulfapyridin, sulfamethxazol, sulfadiazin... + sulfamid bi th i ch m (10-12h) (long-acting): sulfamethoxypyridazin, sulfadimethoxin, sulfadoxin... * sulfamid khng khu n ng ru t: sulfaguanidin, phtalylsulfathiazon... * sulfamid tc ng t i ch (thu c nh m t): sulfacetamid, sulfadiazin b c... * sulfamid tr c u trng (th ng k t h p v i nhm diaminopyrimidin): sulfadimidin, sulfaquinoxalin, sulfadimethoxin, sulfadoxin... 7. c tnh: - Trn th n: s n th n, ti u ra mu do t qu n c u th n n ng d n ti u, sulfamid c lm m c 50 l n, s bi ti t H+ vo ng th n lm n c ti u cng acid hn, gi m tnh tan c a sulfamid t t o thnh tinh th trong ng th n.

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 phng c tnh trn th n khi s d ng sulfamid: . Nn s d ng d ng d ha tan . Dng d ng h n h p nhi u sulfamid (2-3) . m b o cung c p n c trong th i gian i u tr . C p thm cc ch t ki m trong n c u ng (Na2CO3, NaHCO3, Na lactate...) - ng ru t: m t cn b ng h vi khu n ch,h vi sinh v t d c , gy thi u vitamin nhm B,K - Trn c quan t o v tr ng: tr ng khng v ho c c v m ng do c ch carbonic anhydrase - Gic m c (ch): s ng ho gic m c, nh h ng n vi c ti t n c m t - Trn mu: gi m prothombin mu (sulfaquinoxalin) do c ch vitamin K reductase - Nh y c m da, suy t y, ung th tuy n gip... 8. Li u l ng li u ban sulfadimethoxin sulfamerazin sulfadiazin sulfamethoxypyrimidin sulfapyridin 55 220 50 110 132 u li u duy tr (mg/kgP/24h P.O) 27.5 110 50 55 66

9. Tng tc thu c - Hi p l c b i tng v i nhm diaminopyrimidin (t l 5:1 hay 3:1). S ph i h p ny cho tc ng st khu n m nh g p 20-100 l n so v i tc d ng c a t ng thu c ring l sulfamethoxazol (5) +trimethoprim (1): Bactrim sulfaquinoxalin (3) +trimethoprim (1) - K t h p v i cc sulfamid khc: sulfamerazin+sulfamethazin+sulfadiazin - V i cc khng sinh tnh khu n khc: sulfamerazin+ tylosin, sulfamethazin+chlotetracycline - V i penicillin G procain

NHM DIAMINOPYRIMIDINE
1. Ngu n g c Ch t khng khu n t ng h p: Trimethoprim (1956) Pyrimethamin (1951) Diaveridin Ormethoprim 2. C u t o ha h c 3. L ha tnh - Tnh base, tan trong lipid 4. D c ng -H p thu nhanh qua ng tiu ha v tim chch - Phn b : n i bo, khp c th (ph i, th n gan, nh tuy n) c khuynh h ng t p trung m c tnh acid hn huy t tng (prostate) - Bi th i qua th n (45-75%) v phn 5. Ho t tnh d c l c 32

cc

- Tc ng tnh khu n khi dng m t mnh. R t t khi dng n c do s gia tng tnh khng. Th ng ph i h p v i sulfamid, lc ny s ph i h p cho tc ng st khu n - Ph khng khu n: vi khu n G+,G-, c u trng. Khng tc ng n Pseudomonas v Mycobacterium 6. Ch nh - Ph i h p v i sulfamid trong i u tr cc b nh nhi m trng do cc vi sinh v t nh y c m gy ra. S ph i h p 1:5 s cho n ng t i a trong huy t tng v i t l 1:20 l t l di t khu n t i u trn h u h t cc vi khu n. S ph i h p ny cn gip thu c phn tn t t vo d ch no t y, d ch tai gi a, ph qu n ph i, tuy n ti n li t. 7. c tnh - Thi u mu do thi u folate. C th ch a b ng cch cung c p acid folic - Tiu ch y, i m a Pyrimethamin g n v i h enzym c a ng v t h u nh m nh hn Trimethoprim nn n hn.

NHM QUINOLONE
1. Ngu n g c y l nhm khng sinh nhn t o g m nh ng d n xu t c a quinolein c pht tri n trong nh ng th p k g n y. Ban u chng c ph st khu n h p v i cc vi khu n Gram m, nhng cc quinolone hi n nay c pht tri n (fluor ha), chng gi vai tr quan tr ng trong s nh ng ch t khng khu n. Chng c u i m l c tnh r t th p, pht sinh tnh khng khng ng k v t gy t n ng trong sc s n Th h 1: acid nalidixic (1960s), acid oxolinic Th h 2: flumequin Th h 3: norfloxacin, ciprofloxacin, enrofloxacin, pefloxacin... 2. C u t o ha h c Nhn quinolein, nhm ceton tr C3 v tr paraso v i phn t nitrogen n i vng, nhm -COOH v

3. L ha tnh - C tnh l ng tnh, tan y u trong n c pH 6-8 (trong n c ti u ch mo d thy nh ng tinh th quinolone hnh kim) - Ho t tnh gi m khi ti p xc nh sng - Tnh acid (do nhm -COOH) cho php t o mu i Na, d ion ha, d tan hn trong n c - Tnh b y b t (tng t tetracycline) v i cc ion ha tr II nhng quan tr ng nh t l Mg2+ 4. D c ng - H p thu: t t qua ng tiu ha v ngo i tiu ha - Phn b : cc quinolone th h I ch phn b ngo i bo, chng khu ch tn vo cc m c m ch mu phong ph. Cc quinolone c fluor ha th phn b ng u c trong d ch n i v ngo i bo, phn b n h u h t cc c quan: ph i, xng, tuy n ti n li t, d ch no t y, d ch tai, mi, h ng... - Chuy n ha: 2 ph n ng qun tr ng l: Th y phn t o cc ch t chuy n ha v n cn ho t tnh sinh h c 33

Lin h p v i acid glucuronic t o cc ch t d tan v o th i ra ngoi - Bi th i: cc quinolone bi th i ch y u qua ng ti t ni u v i n ng d c ph m cn ho t tnh cao hn c trong huy t thanh, do chng c ch nh trong cc nhi m khu n ng ti t ni u. Cc quinolone c ti h p thu th ng th n. i v i th n th t, pH acid c a n c ti u c tc d ng lm ch m s bi th i d d n n tnh tr ng k t tinh th . i v i th n c , pH ki m c a n c ti u gip cc quinolone c bi th i nhanh hn. Ring pefloxacin c bi th i ch y u qua m t. 5. Ho t tnh d c l c: - Tc ng khng khu n: st khu n - Ph khng khu n: Cc quinolone th h I, II (acid oxolinic, flumequin...) ch c tc ng trn vi khu n G-, c bi t l vi khu n ng ru t. Cc quinolone th h III c ph khng khu n r ng hn trn vi khu n G-, G+, Mycoplasma v Clamydia 6. Ch nh Cc quinolone th h I: nhi m trng ng ti t ni u do vi khu n G- gy ra Cc quinolone th h II: nhi m trng ng tiu ha do vi khu n E.coli, Salmonella, Shigalla, Proteus... gy ra Cc quinolone th h III: nhi m trng ton thn, ng tiu ha, ng h h p, vim mng no, xng, kh p, tuy n prostate. 7. c tnh R t th p: - Nh y c m quang h c - R t lo n pht tri n xng, s n (gt asin

ng i) do ho t tnh b t gi cc kim lo i

8. Li u l ng Cho Ch mo - Acid nalidixic: 3mg/kgP/P.O X 3 l n - Norfloxacin: 10-20mg/kgP/P.O X 2 l n - Enrofloxacin: 2,5mg/kgP/ P.O, S.C X 2 l n Cho heo con, b ngh con: Enrofloxacin: 2,5mg/kgP/ P.O, S.C/ngy 9. Tng tc thu c: - Hi p l c v i: beta-lactam, aminoglycoside, clindamycin, metronidazole - i khng: nitrfuran (lm tng c tnh v nguy c r i lo n th n kinh)

CC KHNG SINH KHC

NHM LINCOSAMIDE
LINCOMYCIN V CLINDAMYCIN: c ho t tnh gi ng macrolide 1. Ngu n g c: Lincomycin c chi t t Streptomyces linconensis Clindamyclin l d n xu t bn t ng h p 7. Chlor c a Lincomycin. Ho t tnh c a Clindamycin m nh hn Lincomycin

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2. D c ng: - H p thu: t t qua ng tiu ha (tan trong lipid) - Phn b : d ch n i bo c bi t c kh nng qua s a, ph i, gan, xng, rng. - Bi th i: qua m t (80%) v n c ti u 3. D c l c: - Ho t l c: tnh khu n - Ph khng khu n: G+ (m t vi vi khu n k kh), Mycoplasma 4. Ch nh: - Vim ph i, ng h h p do vk G+, Mycoplasma - Vim v do Staphylococci - Vim da (m n), rng, mi ng 5. Tng tc: - C ng h ng v i spectinomycin (T l 2:1) - i khng: - Lactam, macrolide, chloramphenicol

NHM SYNERGISTIN
VIRGINIAMYCIN 1. Ngu n g c: - T n m S. virginiae. - C c u trc vng lacton (peptolid) tng t macrolide 2. c i m d c l: - Km h p thu qua ng tiu ha, ch c tc ng t i ch - Khuy ch tn trong da, ph i. Bi th i qua ru t v m t t qua th n - Tc d ng trn vi khu n G+ v Protozoa (Toxoplasma) - C ch c ch t ng h p Protein t i ti u n v 23S c a ribosom 3. Ch nh: - i u tr t i ch : vim da, vim v (pomade) - Tr n trong th c n: kch thch tng tr ng:50-100ppm 4. Ch ng ch nh: gia sc ci th i k mang thai

NHM PLEUROMUTILIN
TIAMUTILIN 1. Ngu n g c: - T n m Pleurotus mutilis. C c u trc c a base diterpen - Tan trong cac dung mi h u c, th ng s d ng d ng fumarate. 2. c i m d c l: - Tc ng km khu n . - Ph khng khu n: h p , gi i h n trn vi khu n G+, Mycoplasma, Treponema (Treponema hyodysenteria), Haemophylus, Campylobacter 35

- C ch tc ng: c ch sinh t ng h p protein do g n vo ti u th 50S c ch Peptidyltranferase 3. Ch nh: - Gia c m: Cc b nh ng h h p do Mycoplasma (CRD) 100mg/kg th c n /8-10 ngy - Heo: B nh vim ph i, h ng l (vim ru t xu t huy t do Treponema) 4. Ch ng ch nh: gia c m: ch ng ch nh s d ng chung v i cc polyether ionophore v c nguy c lm ch t sau m t hi n t ng tng tranh o th i.

NHM POLYETHER IONOPHORE MONENSIN, SALINOMYCIN, AVOPARCINE, NARASIN...

1. Ngu n g c t n m Streptomyces cinnamonensis 2. D c l: - Tc ng: st khu n i v i vi khu n G+ v c u trng - C ch : Do lm thay i tnh th m i v i cc ion mng t bo vi khu n, c ch s t ng h p ATP (mitochondria) c a c u trng gia o n sinh s n 3. S d ng: tr c u trng, kch thch tng tr ng 4. Ch ng ch nh: g mi , g ty, nh t l ng a. - Ngng thu c tr c khi gi t m 3-5 ngy.

NHM NITROFURAN
NITROFURAL, FURAZOLIDON, FURALTADONE, NITROFURANTOIN 1. Ngu n g c: Nhm khng sinh t ng h p 2. c i m d c l: - Thu c b t k t tinh mu vng ti, kh tan trong n c, km h p thu qua ru t nhng c ho t tnh cao pH ng tiu ha nn n c vai tr nh ch t khng khu n ng ru t. Phn b d ch ngo i bo. Bi th i g n nh hon ton qua phn . - Ho t tnh: km khu n G+, G- (tr Proteus v Pseudomonas), Coccidia 3. Ch nh: + Vim ru t tiu ch y do E. Coli, Salmonella (thng hn, ph thng hn, B ch l ): 30-40mg/kgP ; 100-400g/ t n th c n + C u trng g, th 0,4% /th c n ho c 3%/ n c u ng 4. c tnh: - Th n kinh (t li t, m t i u ha) - Ch y mu ru t - Nguy c ung th

36

5. Ch ng ch nh: - Khng s d ng cho loi th y c m v gia sc non do - Khng dng lm ch t b sung trong th c n c a b

c tnh cao

NHM NITROIMIDAZOLE
METRONIDAZOLE 1. Ngu n g c: Nhm khng sinh t ng h p 2. D c ng: - H p thu t t qua ng tiu ha - Phn b : n i bo, kh p cc ni trong c th - Bi th i qua: n c ti u v m t 3. D c l c: - Tc ng tnh khu n. C ch : xo tr n bi n i nng l ng - Ph khng khu n: h p: G+, vi khu n k kh (thay cho Vancomycin), Treponema (xo n khu n), Trichomonas (Protozoa) 4. c tnh: th n kinh v nguy c gy ung th

NHM GLYCOPEPTIDE
VANCOMYCIN - Ngu n g c: Chi t t S orientalis - Tc ng khng khu n: st khu n do c ch t ng h p thnh t bo - Ph khng khu n: c u khu n G+ ( c bi t l Staphylococcus), Clostridium - H p thu: km qua ng tiu ha , t s d ng trong th y - c tnh cao trn th n, gi m tr ng trn ch, h huy t p, nn m a

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