TRNG I HC DC H NI

NG C PARACETAMOL
Trng Thanh Tng A5K62

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1.i cng - Dch t

- T khi c a vo s dng nm 1950, Acetaminophen (Nacetyl-p-aminophenol = APAP) c s dng rng ri gim au v h st, v l mt trong 100 thuc s dng khng cn toa. - Mc d thuc kh an ton vi liu iu tr, qu liu acetaminophen c cng nhn l nguyn nhn ca hoi t t bo gan t 1966. - Acetaminophen c th gy c cho gan ngay c liu iu tr lp li nhng ngi nghin ru. - Ng c Acetaminophen l nguyn nhn suy gan cp thng gp M. - iu tr ng c Acetaminophene ch yu bng than hot v N-Acetylcysteine.

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1. Dc ng hc: ACP c dng: phng thch nhanh v phng thch chm. Liu iu tr: + 10- 15 mg/kg/liu tr em + 325 1000mg/liu ngi ln, cho mi 4-6 gi; Liu khuyn co ti a 80mg/kg/ngy tr em v 4 g/ngy ngi ln.

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1. Dc ng hc:
-Liu c thay i theo tng c th tng ng vi nng Glutathione v nhng yu t khc + c tnh t khi vi liu n c < 150mg/kg tr em hoc 7,5- 10g ngi ln trong 24gi. c tnh xy ra vi liu n c > 250mg/kg, hoc > 12g trong 24 gi. Tt c Bn dng > 350mg/kg gy c cho gan nng (AST hoc ALT > 1000UI/L tr khi c iu tr thch hp). + Liu c trn BN s dng liu lp li trn liu iu tr (RSI: repeated supratherapeutic ingestion) cn bn ci. Liu lp li trn liu iu tr (ng c mn tnh) c nh ngha l trn 01t s dng Acetaminophene trong khong thi gian > 8 gi, vi tng liu > 4g/ ngy.

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1. Dc ng hc:

Acetaminophen hp thu nhanh v hon ton qua ng tiu ho. - Nng nh gi- 4 gi sau ung liu iu tr. - Nng iu tr trong huyt thanh l: 10-20 mcg/mL. - Nng nh trong vng 4 gi sau qu liu thuc dng phng thch nhanh, nhng c th chm hn 4gi dng phng thch chm hoc c dng ng thi vi nhng thuc lm trng d dy chm (thuc anticholinergic, thuc phin). - Thi gian bn hu o thi l 2 4 gi nhng c th chm nhng sn phm phng thch chm. Thi gian bn hu chm > 4 gi Bn c tn thng gan.

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C ch gy c

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Chuyn ha ACP

Hnh 1: Chuyn ha acetaminophen

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Chuyn ha ACP
- Hu ht Acetaminophen chuyn ho ti gan (90%) gn kt vi Sulfate v Glucuronide, ri thi ra nc tiu. - Phn cn li: + Mt na (5%) thi ra nc tiu di dng nguyn vn, + mt na c oxy ho thnh Nacetyl-p-benzoquinone imine (NAPQI) qua cytochrome P450 gan (CYP2E1, CYP1A2, CYP3A4). NAPQI l cht c cho t bo gan
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Chuyn ha ACP

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C ch gy tn thng gan sau ng c

Vi liu Acetaminophen thch hp lng nh NAPQI kt hp vi Glutathione ca gan Cysteine v mercapturic acid khng c nc tiu. Vi liu c con ng gn kt vi Sulfate v Glucuronide b bo ha, nhiu Acetaminophen c chuyn thnh NAPQI qua men cytochrome P450. Khi d tr Glutathione gan gim gn 70%, NAPQI bt u phn ng vi cu trc t bo gan v tn thng t bo gan xy ra.

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C ch gy tn thng gan sau ng c

NAPQI gn ng ho tr vi phn t t bo gan gy tn thng do oxy ho (oxidative injury), v hoi t t bo gan trung tm thu. S tn thng ty th v s peroxi ho lipid c vai tr trong qu trnh tn thng t bo gan. S phng thch nhng cytokines v nhng cht oxy phn ng t tn thng t bo gan c vai tr trong tn thng t bo gan lan rng. Cytokines phng thch t t bo gan c th khi pht p ng vim th pht t t bo Kupffer v nhng t bo vim khc, lm lan rng tn thng t bo gan .Tn thng th pht ny xy ra trong giai on II ca biu hin ng c trn lm sng.

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C ch gy tn thng gan sau ng c

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Triu chng lm sng

Gm 4 giai on:
Giai oan 1 (0.5-24h): (Ngay sau ung,thng khng c triu chng) + C th gp chn n, nn , bun nn. + V m hi, kh chu. + C th tng AST,ALT. + Khm LS thy BT Giai on 2: 24-72 h: + Chn n, bun nn, nn t ni bt. + AST, ALT, bilirubin, thi gian PT, chc nng thn gim. Giai on 3: (72-96h): + Hoi t TB gan: vng da, RLM. bnh no gan. + Sinh thit gan thy hoi t trung tm tiu thu..Nu suy gan ti cp xy ra c th gy TV, bnh no gan, thi gian PT ( tin lng xu). + Suy thn cp: i khi gp c th phi hp hoc khgn phi hp vi suy gan. + Suy a tng Giai on 4: t 4-14 ngy: nu BN sng th chc nng gan hi phc hon ton khng li x ho.
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X tr

Nguyn tc: +Gim ACP c trong d dy (cha hp thu) +Hn ch s tch t NAPQI trong t bo gan v tc dng ca n ln t bo

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X tr Bin php hin nay l: Loi cht c bng than hot v cht i vn N-acetylcysteine (NAC). (Khng nn ra d dy v gy nn t nhin v c th lm gim tc dng ca than hot, NAC)

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Tc dng ca NAC
Khng vim Tng kt hp vi Glutathione

antioxidant

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Tc dng ca NAC

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