TRNG I HC CN TH KHOA NNG NGHIP V SINH HC NG DNG B MN CHN NUI- TH Y

Chuyn dc l th y

THUC KHNG SINH NHM PHENICOLS THUC KHNG SINH NHM CYCLINES
Nhm thc hin: u Tng Dng 3082782

GIO VIN HNG DN:

Tin S:

Hunh Kim Diu

Nguyn Th Thy Hng 3082787 Ng Th M Phng Nguyn Ngc Thun Phm Ngc Trn 3082812 3082827 3082834

MC LC
I.T VN : 2 II.NI DUNG: 3 1. KHNG SINH NHM PHENICOLS: 3 1.1 Ngun gc, Cu to ha hc:.....................................................................................3 -Ngun gc: Nm 1947, Chloramphenicol c c lp t Streptomyces venezuelae. Do c ph khng khun rng v kh nng phn tt b vo cc m trong c th nn Chloramphenicol rt c a chung trong tr liu. Tuy nhin t khi pht hin nhng c tnh ng k trn c quan to mu, vic s dng cht ny c gii hn trong nhng qui nh quc t v khu vc Thiamphenicol l dn cht tng hp ca Chloramphenicol..............................................................................................................3 1.3 C ch tc ng ca khng sinh nhm Cyclines:......................................................3 1.5 Dc ng hc:..........................................................................................................4 .........................................................................................................................................4 Thi gian bn hy ca Cloramphenicols ty gia sc: ngn nht nga (1 gi), di......4 nht mo (5-6 gi): Thiamphenicols: 2,5-3,5 gi, Florphenicols: 5-18 gi ty loi....4 1.6 Ch nh:.....................................................................................................................4 Do c tnh cao, Phenicol ch gii hn s dng trong cc trng hp:...........................4 1.7 Tc dng ph - c tnh: ..........................................................................................4 1.9.4 Mt s thuc khng sinh nhm cyclines trn th trng:.......................................7 2. KHNG SINH NHM CYCLINES: 7 2.1 Ngun gc, cu to:...................................................................................................7 2.2 Phn loi:...................................................................................................................7 2.3 C ch tc ng ca khng sinh nhm Cyclines:......................................................9 2.4 Dc ng hc:..........................................................................................................9 2.5 Hot tnh khng khun:..............................................................................................9 2.6 Ch nh:...................................................................................................................10 2.7 Tc dng ph - c tnh:.........................................................................................10 III. KT LUN: 11 Ti liu tham kho 12

I.T VN :
Khng sinh (antibiotics) l nhng cht c to ra bi cc sinh vt sng (nm men, nm mc, vi khun v mt s loi thc vt) c c tnh dit vi khun hoc km hm s pht trin ca chng (Ensminger, 1990). Vic s dng khng sinh trong thc n (TA) chn nui c nh du bng mt th nghim ca Stokstad v Juke (1949) khi cho gia cm n TA c b sung
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aureomycin, nhn thy tc sinh trng v hiu qu s dng TA ca gia cm tng r rt. T rt nhiu cng trnh nghin cu v khng sinh nh cht b sung trong TA chn nui c thc hin v bt u t nhng nm 1950 v 1960 ca th k 20 to ra kt qu tt trong chn nui.Ngoi vic iu tr bnh do vi khun khng sinh cn c dng kch thch tng trng. Tuy nhin vic s dng khng sinh trn lan dn n tc hi l hin tng khng thuc, v khng sinh cng gy ra nhiu tc dng ph. Nn s vic s dng khng sinh cn phi thn trng v theo hng dn ca ngi c chuyn mn. Nhm khng sinh Cyclines ng vai tr rt quan trng,c nhiu ng dng trong thc tin. Phenicols l nhm khng sinh c tc dng khng khun rng c s dng ph bin hin nay.

II.NI DUNG: 1. KHNG SINH NHM PHENICOLS:

1.1 Ngun gc, Cu to ha hc : -Ngun gc: Nm 1947, Chloramphenicol c c lp t Streptomyces venezuelae.
Do c ph khng khun rng v kh nng phn tt b vo cc m trong c th nn Chloramphenicol rt c a chung trong tr liu. Tuy nhin t khi pht hin nhng c tnh ng k trn c quan to mu, vic s dng cht ny c gii hn trong nhng qui nh quc t v khu vc Thiamphenicol l dn cht tng hp ca Chloramphenicol. -Cu to: Hai cu t c bit: - para- nitrophenil, cacbongemdiclor.

1.2 L ha tnh:
- Tinh th khng mu, v rt ng, bn 1000 C, pH=2-9, tan nhiu trong alcohol. - B mt hot tnh bi tc nhn oxyha (nhm alcohol nh cp), kh (nhm nitro).

1.3 C ch tc ng ca khng sinh nhm Cyclines:

Tc ng ca phenicols l c ch s tng hp ca protein ca vi khun bng cch gn vo tiu n v 50S ca ribosom vi khun, ngn chn s thnh lp cu ni peptid ca cc amin do phong b tc ng ca enzyme peptidytransferase. Phenicols cng tc ng trn t bo ty xng ca ng vt hu nh.

1.4 C ch khng ca vi khun:

C ch khng ca vi khun i vi phenicols c ngun gc plasmid v do vi khun tit enzyme acetyltranferase lm mt hot tnh khng sinh. Ngoi ra i vi E.coli, Pseudomonas aeruginosa cn lm gim thm tnh ca mng.

1.5 Dc ng hc:
Phenicols hp thu qua ng ung ( Cloramphenidols: 75-90%, thiamphenicols: hon ton), t nng ti a trong huyt thanh sau 30 pht s dng thuc. khi nng ti a trong mu cao nht, 60% thuc s gn kt vi albumin huyt tng. Th tch phn b ca Cloramphenicols rng (>1L/kg). thuc tan mnh trong lipid, xm nhp tt vo nhiu m v dch trong c th: dch no ty (35-50%), no, xng, khpv c bn trong t bo. Thuc qua nhau thai (70-80% nng trong mu nh). Cloropham ch yu b chuyn ha gan ( glucuro hp) thnh dn cht mt hot tnh v thi qua mt, phn khc bi thi qua nc tiu dng c hot tnh ( ch: 10%, mo 20%); Thiamphenicols v Florphenicols khng b chuyn ha v bi tit qua nc tiu(70%) v mt (5%) dng khng i Thi gian bn hy ca Cloramphenicols ty gia sc: ngn nht nga (1 gi), di nht mo (5-6 gi): Thiamphenicols: 2,5-3,5 gi, Florphenicols: 5-18 gi ty loi.

1.6 Ch nh:
Do c tnh cao, Phenicol ch gii hn s dng trong cc trng hp: - Thng hn, ph thng hn do Salmonella - Vim mng no, vim thanh kh qun, vim phi do Haemophilus - Nhim trng k kh (thay th Metronidazol, Clindamycin) - Nhim rickettsia - Vim nhim tuyn prostate - S dng ti ch: thuc nh mt, tai, kem bi da. *Chng ch nh: trong thc n gia sc, thuc iu tr trn gia sc sn xut thc phm cho ngi (b sa, g trng, ong mt...), ph n mang thai, cho con b, tr di 6 thng (h thng kh c gan cha hon chnh)

1.7 Tc dng ph - c tnh:

- Ri lon ty xng: suy ty khng hi phc (thiu mu bt sn). - Try tim mch khi dng liu cao tr thng hn (c th do vi khun cht hng lot, phng thch c t) - R lon tiu ha: tiu chy, i ma - Tc dng ph: suy gim min dch. Do khi ang chng nga cho gia sc, nu
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phi s dng khng sinh th chn cc khng sinh khc.

1.8 Liu lng :

Th ln 500- 1000mg/ ngy 2-4mg / kgP / 8-12h. Th nh 250-500mg/ ngy 4-10mg / kgP.

1.9 Phn loi:

1.9.1 Cloramphenicols (C11H12Cl2N2O5): a. Tnh cht. Bt trng, v ng, t tan trong nc, tan trong cn, Propylen Glycol. Dung dch 37C gi c 1 thng. Bn vng vi nht , PH:2 9, gi c v hn nh, PH>9 h. b.Tc dng: Chloramphenicol c ph khng khun rt rng. Tc ng trn vi khun G+ v G-, tt c Rickettsiae, xon khun v nhng vi khun khng Penicilins, Streptomycin v Sulfonamides. c bit tc ng trn Pasteurella, E.coli, Salmonella c nng thp. c. Cng dng: Dng tr: Bnh ng rut: tiu chy, thng hn. Nhim trng tai, mi, hng, sinh dc, da. Bnh ng h hp. Bnh vim v. d. c tnh: Thuc gn tren tiu phn 50S (ch c trn VSV), cn gn trn c tiu phn 70S hin din c VSV v tb vt ch. Gy chng thiu mu v to. Khng s dng liu tn cng v git nhiu vi khun thi ra nhiu c t c hi cho gia sc.

Kch ng nim mc ng tiu ha gy nn v gy lon khun. i khi xut hin d ng ton thn hay cc b. Trong nhng nm trc y, hu ht ngi chn nui u bit n hiu qu iu tr thn k ca Chloramphenicol, mt khng sinh ca nhm Phenicol. Nhng, bn cnh cng nng iu tr hiu qu nhiu bnh do vi khun th Chloramphenicol li c khng t nhc im, trong ng ch nht l nh hng n sc khe ca ngi tiu dng khi s dng tht cn tn d mt lng ln thuc. Chnh v th m B Nng nghip v Pht trin nng thn Vit Nam ra Quyt nh 29/2002/QBNN ngy 24/04/2002 v vic cm s dng Chloramphenicol trong phng, iu tr bnh trn gia sc-gia cm. Chloramphenicol ch gii hn s dng cc gia sc khng cung cp thc phm cho ngi:ch, mo, nga. 1.9.2 Thiamphenicols : (C12H15Cl2NO5S) Thiamphenicol l dn xut ca Chloramphenicol c ph khng khun ging Chloramphenicol, hot tnh km 1-2 ln nhng c tnh hn.

1.9.3 Florfenicols: (C12H14ClFNO4S) Florfenicol tc dng mnh hn Chloramphenicol (invitro) v Thiamphenicol, khng c tnh nh Chloramphenicol, khng c s v hot ca vi khun c trn nhng vi khun khng Chloramphenicol (c bit vi khun gy bnh ng rut). c khuyn co s dng cho gia sc cung cp thc phm cho ngi, thay th nhng khng sinh ph rng m c c tnh v tn d trong sn phm ng vt. Vic thay th nhm p-NO2 bng CH3SO2 gip loi c tnh gy thiu mu v to v thay th nhm OH bng F hn ch s pht trin khng ca Vi khun. Do , c

Thiamphenicol v Florfenicol khng gy thiu mu v to, nhng li c ch s to mu c hi phc nhiu hn Chloramphenicol. Florfenicol (khng sinh nhm Phenicol) ra i, khng nhng c nhng tnh nng thn k nh Chloramphenicol m cn khc phc c cc nhc im gy nguy him n sc khe con ngi. Florfenicol l khng sinh th h mi nht ca nhm Phenicol, c hiu qu trong iu tr cc bnh do vi khun Gram m, Gram dng. Khi Florfenicol ra i, mt s bnh nh vim phi, thng hn c iu tr mt cch nhanh chng v rt hiu qu nhng a s cc cng ty u sn xut dng dung dch tim vi thi gian ko di trong 3 n 5 ngy, gy tn km chi ph, nhn cng v c bit l lm cho heo b stress. Nhu cu cn c mt sn phm dung dch tim cha Florfenicol nhng ch cn tim 1 n 2 liu l chn ng ngay bnh v ch s dng mt lng nh khi tim gip hn ch stress trn heo.

1.9.4 Mt s thuc khng sinh nhm cyclines trn th trng:

Bocin-pharm (Florphenicol 15%, Doxycyclin 7,5%) : Suyn, t huyt trng, MMA . Bocinvet-L.A (Florfenicol 15%) : Suyn, vim v, t cung . Pharm-flor ( Florfenicol 4%) : Phng bnh bi nhim trong Hi chng h hp sinh sn ln. Pharthiocin ( Thiamphenicol 20%,Oxytetraxyclin 10%) : Ph thng hn, lin cu khun, lepto .

2. KHNG SINH NHM CYCLINES:

2.1 Ngun gc, cu to:
- Ngun gc: Ly t Streptomyces aureofaciens ( Clotetracyclin, 1947), hoc bn tng hp. - Cu to: Cyclines dng tinh th lng tnh, ha tan trong nc km ( pH = 7,0), dng mui Chlohydrate ha tan nhiu nht . u l khng sinh c 4 vng 6 cnh,. Minocycline v Doxycycline ha tan trong lipid nhiu hn cc cht khc.

2.2 Phn loi:

y l nhm khng sinh km khun, ty theo thi gian tc ng: ngn, trung bnh hoc chia lm cc th h sau: Th h I (thi gian bn hy 6-8h):

Oxytetracycline (Terramycin) (C22H24N2O9) Chlortetracycline (Aureomycin) (C22H23ClN2O8) Rolitetracycline (Transcycline) (C27H33N3O8) Tetracycline (Hexacyclin, Florocyclin) (C22H24N2O8)

Th h II (thi gian bn hy khong 12h): - Demeclocycline (Lysocline) (C22H21ClN2O8) - Lymecycline (Tetralysal) (C22H23ClN2O8) - Methacycline (Lysoclin) (C22H22N2O8) Th h III (thi gian bn hy 16h): - Doxycycline (Doxy 100, Spanor, Vibramycin) (C22H24N2O8) - Minocycline (Mynocine, Mestacine) (C23H27N3O7) - Tigecycline (Tygacil) (C29H39N5O8) Cc Cyclones hoc c ngun gc thin nhin (Chlortetracycline t Streptomyces aureofaciens, Oxytetracycline t Streptomyces rimosus) hoc bn tng hp (Doxycycline, Minocycline). Ngoi ra cn c Tigecycline l mt Cyclones mi (dn xut cu Minocycline v c cho l cht duy nht c nhm nh Glycylcyclines), chng li c s khng ca vi khun i vi Cyclones, tc ng c trn Staphylococcus aureus khng Meticillin.

Tetracycline

Oxytetracycline

Chlortetracycline

Doxycycline

Minocycline

2.3 C ch tc ng ca khng sinh nhm Cyclines:

Cyclines tc ng bng cch gn vo tiu phn 30S ca ribosome vi khun ngn tr RNA vn chuyn ribosome-RNA thng tin, nn c ch tng hp protein ca vi khun. S khng thu nhn ca Cyclones xy ra ph bin cc vi khun gram m v gram dng v Mycoplasma, lm gim i s hu dng ca nhm ny, c ch do vi khun khng l: + Ngn chn khng sinh i qua mng hoc y khng sinh ra ngoi mng bng vn chuyn tch cc. + To enzyme bt hot Cyclones (cc protein bo v ribosome lm khng sinh khng th gn kt c). + S khng c ngun gc nhim sc th v plasmid.

2.4 Dc ng hc:
S hp thu cc Cyclones qua ng tiu ha khc nhau (Chlortetracycline; 30%, Oxytetracycline, Tetracycline: 60-80%, Doxycycline: 100%). Hu ht cc thuc thuc nhm Cyclones (ngoi tr Doxycycline, Minocycline) b gim hp thu khi ung chung vi thuc hay thc phm c cation ha tr II hoc III nh Ca++, Mg++, Fe+ + , Ag++,. (c bit sa v cc ch phm ca n) do to dng chalate ha. Vo mu cc Cyclines phn b tt cc m (tr dch no ty v dch khp), c kh nng xm nhp vo bn trong t bo, qua c nhau thai v sa nhng vt hng ro mu no km. Tch ly gan, t tng, xng v rng. Chuyn ha: i qua chu trnh gan-rut khong b chuyn ha, ngoi tr Doxycycline, Monicycline chuyn ha gan. Thi gian bn hy: 5-19h. o thi ch yu qua ng tiu (60%) dng khng i, ngoi tr Doxycycline v Minocycline qua phn dng khng hot tnh.

2.5 Hot tnh khng khun:

Ph khng khun rt rng. Tc ng trn vi khun gram dng v gram m cng cc vi khun ni bo nh Mycoplasma, Rickettsia, Chlamydia. Tuy nhin Mycobacterium, Proteus v Pseudomonas th khng vi Cyclines. Hiu lc mnh nht l Minocycline, k n Doxycycline. Tetracycline v Oxytetracycline hiu lc yu nht. Ngoi tc ng trn vi khun, Cyclines cn c tc ng khng vim, c bit Minocycline v Doxycycline.

2.6 Ch nh:
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iu tr nhiu bnh nhim trng: - Nhim khun ng rut, tiu chy do E.coli, Salmonella, Shigella. - Nhim khun ng h hp do Chlamydia, Mycoplasma. - Bnh sy thai truyn nhim. - Nhim khun ng sinh dc, tit niu. - Nhim khun da.

2.7 Tc dng ph - c tnh:

Cyclines ni chung l nhm khng sinh t c, tuy nhin cng c nhng tc dng ph sau:
-

Do ph khng rng, Cyclines d gy ri lon tiu ha: nn ma, tiu chy, vim rut, bnh do nm Candida. Suy gan thn khi s dng liu cao. Gy bt thng xng v rng. Gy nhy cm quang hc lm tn thng da, bong mng. Phn ng d ng v gy kch thch ni tim (rt au).

2.8 Tng tc:

Cyclines tc ng hip ng vi cc nhm km khun nh Macrolides (Tetracycline + Tylosin tr Pasteurella), Phenicols, Sulfonamides. Cyclines l nhm km khun, nhng cng c tc dng hip ng khi dng chung vi cc nhm st khun nh polypeptides do lm tng hp thu nhm Cyclines; Doxycycline vi Rifampin hoc Streptomycin trong iu tr bnh do Brucella.

Liu khuyn co s dng ca nhm Cyclines: Gia sc Thuc Tetracycline, Oxytetracycline Tetracycline, Oxytetracycline Doxycycline Chlotetracycline Minocycline Oxytetracycline Tetracycline Liu cp (mg/kg) 10 20 5-10 20 5-15 3-5 10 ng cp IM, IV PO IV, PO PO PO IV IM, Nhp cp (gi) 12 8 12 8 12 12 12-24

Ch, mo

Nga Tru, b

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Oxytetracycline Tetracycline tc dng ko di Heo Tetracycline Oxytetracycline Chlotetracycline Tetracycline Chlotetracycline Doxycycline Oxytetracycline

IV 20 Nh tru, b 10-30 1% 100 250ppm IM IM PO T PO T 24 Nga (45 ngy) 12 (20 ngy) 48

Gia cm

2.9 Mt s thuc khng sinh nhm cyclines trn th trng:

- Tetracyclin: ung 1- 2 g/ ngy, chia 3 - 4 ln. Vin 250500 mg; dch treo 125 mg/ 5mL - Clotetracyclin (Aureomycin): ung, tim t/m 1 - 2 g. - Oxytetracyclin (Terramycin): ung 1 - 2 g; tim bp, tnh mch 200 mg - 1g. - Minocyclin (Mynocin): ung 100 mg 2 ln; tim bp hoc tnh mch 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 - Bocin-pharm (Florphenicol 15%, Doxycyclin 7,5%): Tr Suyn,t huyt trng, MMA . - Phar-D.O.C ( Oxytetraxyclin 4%, Colistin 1% ) :Tr tiu chy, phn trng, Sng ph u, T huyt trng . - Pharthiocin (Thiamphenicol 20%,Oxytetraxyclin 10%) :Tr ph thng hn, lin cu khun, lepto .

III. KT LUN:
Vic pht hin ra khng sinh ni chung v nhm khng sinh Cyclines Phenicols ni ring to ra mt cuc cch mng trong y hc v cu loi ngi thot khi nhiu thm dch do vi trng gy ra. Mt k nguyn mi ca ngnh chn nui c m ra khi khng sinh c coi nh mt yu t khng th thiu v to nn mt bc t ph v nng sut v hiu qu chn nui nhiu nc trn th gii.

Ti liu tham kho

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1.Gio trnh dc l Th y TS. Hunh Kim Diu. 2. S dng thuc v bit dc Th y Nguyn Phc Tng. 3. Khng sinh trong Th y V Vn Minh.

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