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Toxic and drug induced hepatitis
 

Toxic and drug induced hepatitis

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    Toxic and drug induced hepatitis Toxic and drug induced hepatitis Presentation Transcript

    •  
      • Inhalation, Ingestion, parenteral administration
      • Industrial toxins (CCl4, yellow phosphorus)
      • Mushroom poisoning (Amenita, Galerina)
      • Pharmacologic agents
      • Direct toxic
      • Carbon tetrachloride
      • Acetaminophen
      • Halothane
      • Idiosyncratic
      • Hepatitis occurs with predictable regularity
      • Dose-dependent
      • Latent period short (several hours)
      • Clinical manifestations may be delayed (24- 48 hours)
      • CCl4, phosphorus, Amanita mushroom, Tetracycline
      • Liver injury may go unrecognized until the onset of jaundice
      • Hepatitis is infrequent (1 in 1000-10000 px)
      • Unpredictable
      • Response is not dose-dependent
      • Liver injury may occur during or shortly after exposure to the drug
      • Isoniazid, phenytoin, statins, oral contraceptives
      • Extrahepatic manifestations: rash, fever, arthralgia, leukocytosis, eosinophilia
      • Cholestasis
      • Fatty liver
      • Hepatitis
      • Mixed hepatitis/cholestasis
      • Toxic (necrosis)
      • Grnulomas
      • Methyl testosterone
      • Erythromycin
      • Rifampin
      • Amoxicillin-clavulanic
      • Oxacillin
      • Clopidogrel
      • Irbersartan
      • Nifedipine
      • Verapamil
      • Methimazole
      • Sulindac
      • Ezetimibe
      • Tamoxifen
      • Mestranol
      • Chlorpropamide
      • Chlorpromazine
      • Amiodarone
      • Tertracycline (high dose IV)
      • Valproic acid
      • Antiviral protease inhibitors (indinavir, ritonavir)
      • Methorexate
      • Halothane
      • Isoniazid (INH)
      • Rifampin
      • Pyrazinamide (PZA)
      • Phenytoin
      • Carbamazine
      • Ketoconazole
      • Fluconazole
      • Itraconazole
      • Methyldopa
      • Captopril
      • Losartan
      • Ibuprofen
      • Diclofenac
      • Indomethacin
      • Sulindac
      • Nifedipine
      • Verapamil
      • Diltiazem
      • Chlorothiazide
      • Troglitazone
      • Acarbose
      • Antiviral Protease inhibitors (ritnavir, idinavir)
      • Amoxicillin/Clavulanic acid
      • Trimethoprim/Sulfamethoxazole
      • Azathioprine
      • Nicotinic acid
      • Lovastatin
      • Ezetimibe
      • Acetaminophen
      • Carbon tetrachloride
      • Yellow phosphorus
      • Amanita phalloides
      • Dimethylformamide
      • Quinidine
      • Sulfonamides
      • Carbamazine
      • Allopurinol
      • Direct toxin
      • Common in US and UK
      • Single dose of 10-15 grams  liver injury
      • >25 grams  fatal
      • Pain, nausea, vomiting, diarrhea in 4-12 hrs
      • Liver failure in 24-48 hrs
      • Aminotranferase levels app 10,000 units
      • In alcoholics, toxic dose may be 2 grams
      • Supportive measures
      • Gastric lavage
      • Activated charcoal or cholestyramine (prevent absorption); should be given within 30 mins
      • N-acetylcysteine given within 8 hrs; loading dose-140/kg, ff by 70mg/kg q 4 hrs x 15-20 doses
      • Survivors have no evidence of hepatic sequelae
      • Idiosyncratic type
      • 1% of cases: hepatitis-like syndrome
      • Aminotransferases < 200 units; return to normal in few weeks whether INH is continued or not
      • Liver morphology: hepatitis-like
      • Toxicity increases wit age; > 50 yrs old
      • Enhanced by alcohol, rifampin, pyrazinamide
      • Idiosyncratic type
      • Steven Johnson’s syndrome: exfoliative dermatitis, fever, lymphadenopathy; leukocytosis, eosinopilia  immune mediated hypersensitivity mechanism
      • Liver morphology: hepatitis-like picture (majority); cholestasis (rare)
      • Toxic and idiosyncratic reaction
      • 15-50% have modest elevations of aminotransferases, which may remain stable or decrease despite continuation of the drug
      • Liver morphology: fatty liver
      • Direct hepatoxic effect
      • Liver injury may persist for months after discontinuation ( long half-life)
      • More common in children
      • Cholestatic type
      • Idiosyncratic reaction
      • Nausea, vomiting, fever, RUQ pain, jaundice, leukocytosis, elevated aminotransferases
      • Clinical improvement upon drug withdrawal
      • No evidence of CLD on follow up
      • Combination of estrogenic and progestational steroids; estrogen is primarily responsible
      • Intrahepatic cholestasis
      • Pruritus and jaundice
      • Susceptible patients: idiopathic jaundice of pregnancy, family history
      • Focal nodular hyperplasia, adenomas
      • Jin Bu Huan
      • Xiao chai hu tang
      • Senna
      • Mistletoe
      • Skull cap
      • Ma huang
      • Bee pollen
      • Valerian root
      • Kava
      • Caelandine
      • Impila
      • Herbal tea
      • Pyrrolizidine alkaloids may contaminate Chinese herbal meds  venoocclusive disease  sinusoidal hepatic vein obstruction
      • Active metabolites, which maybe potentiated by alcohol and drugs that stimulate cytochrome P450
      • Alternative meds may also stimulate cytochrome P450  amplify the hepatotoxicity of drug hepatotoxins
    •