Download - Drug-Induced Liver Disease-semester 4
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DRUG-INDUCED LIVER DISEASE
HENOCH AWALOEI
BAGIAN FARMAKOLOGI DAN TERAPI
FK UNSRAT MANADO.
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DRUG-INDUCED HEPATOTOXICITY
- SUATU KERUSAKAN HATI AKIBAT INDUKSI OBAT.
- 50% KASUS GAGAL HATI DI AS, AKIBAT
BAHAN TOKSIK DAN OBAT-OBATAN
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PERMUKAAN ABSORPSI TRAKTUS GI
H A T I
ORGAN TARGET
HATI : PUSAT METABOLISME DARI OBAT/ ZAT TOKSIK
METABOLIT/ZAT AKTIF KERUSAKAN HATI REVERSIBLE ATAU IRREVERSIBLE
(NECROSIS, CELL DEATH, OR CARCINOGENESIS,DLL)
BIOTRANSFORMASII. OKSIDASI cypP450, lipofilik, nonpolar II. ESTERIFIKASI hidrofilik, polar
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OBAT HEPATOTOXIC
- DIPERKIRAKAN ADA 1000 JENIS OBAT
BERPOTENSI HEPATOTOXIC
- SELAIN OBAT, TOXIN ALAMIAH, BAHAN KIMIA SINTETIK DALAM MAKANAN ATAU MINUMAN
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TIPE REAKSI OBAT PADA HATI
I. HEPATOCELLULAR REACTION
II. CHOLESTATIC REACTIONS
III. IMMUNOALLERGIC REACTIONS
IV. STEATOHEPATITIS
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DRUG-INDUCED HEPATOTOXICITY DENGAN IKTERUS KERUSAKAN HATI BERAT ATAU
FATAL.
3% - 5% PENDERITA IKTERUS YG Masuk RS, DISEBABKAN REAKSI OBAT.
- 10 % AKAN ALAMI GAGAL HATI AKUT
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FAKTOR YG MEMPENGARUHINASIB METABOLIT OBAT
1. USIA
2. ALKOHOL : AKUT DAN KRONIK
3. GENDER
4. KEHAMILAN
5. PENYAKIT HATI PENYERTA
6. PENYAKIT GINJAL
7. BAHAN MAKANAN
8. PEMAKIAIAN OBAT BERSAMAAN
9. GENETIK
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I. HEPATOCELLULAR REACTIONS
JENIS OBAT:
- ASPIRIN - AMPHOTERICIN B
- AZAPROPAZONE - ETHACRYNIC ACID
- FUROSEMIDA - GOLD SALTS
- GRISEOFULVIN - HALOTHANE
- HYDANTOINS - ISONIAZID
- METHYLDOPA - MAO-INHIBITORS
- NITROFURANTOIN - PROPILTHIOURACYL
- PYRAZINAMIDE - QUINIDINE
- RIFAMPICIN - SULFONAMIDES
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(HEPATOCELLULAR REACTIONS)
- 90 % DRUG INDUCED LIVER DISEASE- SERUM LIVER TEST HEPATOCELLULAR
INJURY- HISTOLOGI : NEKROSIS SEL HATI,
INFILTRASI SEL RADANG- NEKROSIS MASIF GAGAL HATI DEATH- CONTOH : ACETAMINOPHENE / PARASETAMOL
- PERCOBAAN BUNUH DIRI 20% FATAL
- PEMAKAIAN DOSIS TINGGI
- PEMAKAIAN DOSIS TERAPETIK
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(ACETAMINOPHENE / PARASETAMOL)
- EFEK TOKSIK MENINGKAT OLEH :
- PUASA
- ALKOHOL KRONIK
* ANTIDOTE :
- N-ACETYLCYSTEINE
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II. CHOLESTATIC REACTIONS- CHOLESTATIC KEGAGALAN EMPEDU
MENCAPAI DUODENUM (STASIS, Batu Empedu)- GEJALA UMUM: IKTERUS dan GATAL- Pure Cholestasis no hepatocellular damage
Oral contraceptives, anaolic steroids, tamoxifen- Acute Cholestatic Histo : cell necrosis,
bile duct inj., infiltration PMN
-Carbamazepine,Trimetho-Sulfamethoxazole,
Captopril.
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JENIS OBAT:
- CHLORZOXASON - IMIPRAMINE
- ETHCHLORVYNOL - NALIDIXIC ACID
- NITROFURANTOIN - PHENOTHIAZINE
- SULFAMETHOXAZOLE
- SULFONYLUREA - TROLEANDOMYCINE
- ERYTHROMYCINE ESTOLATE
- ORAL CONTRASEPTIVES
- ANABOLIC STEROIDS
- TAMOXIFEN - CHLORPROMAZINE
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IMMUNOALLERGIC REACTIONSOBAT REAKSI ALLERGIK SEL HATIKOMBINASI : TOXIC-IMMUNOLOGIC
KERUSAKAN HATI OBAT-OBAT : - HALOTHANE - ISOFLURANE
- DESFLURANE- FLUORINATED H-C ANESTHETICPaparan berulang kerusakan hati fatalPhenitoin efek sama. Steven Johnson
drug eruption. STOP OBAT KERUSAKAN HATI
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• Steatosis Hati
Mikrovesikular dan makrovesikuler
1.Mikro
Hepatosit mengandung banyak fat vesicle
obat2 valproat, tetracycline, flaluridine
Aspirin fleye’s sindrom (child)
2. Makro
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V. OTHER DRUG REACTIONS
- GRANULOMATOUS, FIBROSIS, ISCHEMIC INJURY, CHRONIC AUTOIMMUNE INJURY.
ZAT TOKSIK;- CARBONTETRACHLORIDE,- TRICHLOROETYLENE,- YELLOW PHOSPHORUS
KEMBANG API, RACUN TIKUS- MUSHROOM POISONING AMANITA PHYLOIDES
Prognois : poor, liver trasplantation.