Drug Induced Liver Disease Flashcards
Intrinsic drug induced liver disease
Drugs that cause liver injury predictably in humans and animal models when given at a high dose
Ex: acetaminophen
Idiosyncratic drug induced liver disease
Affects susceptible individuals
Variable presentation
Less consistent relationship to dose
Most of the drugs we are exposed to
Non-immune drug induced liver disease (idiosyncratic)
Aberrant metabolism of the drug in susceptible individuals
Duration of exposure varies from weeks to months
Reactions can develop weeks after discontinuation
No hypersensitivity features
MOA: metabolites binding to cellular elements = ox stress
Ex: amiodarone, diclofenac, isoniazid
Immune mediated drug induced liver disease (idiosyncratic)
Duration of exposure 1-8 weeks Hypersensitivity features Recurrence after rechallenge Modification of proteins due to covalent binding with the drug Activation of immune system Ex: amoxicillin, diclofenac, phenytoin
Autoimmune like drug induced liver disease (idiosyncratic)
Elevated IgG, ANA, ASMA Once resolved there is no relapse Eosinophilia or granulomatous inflam on liver biopsies Responds to GCs Ex: minocycline, nitrofurantoin
R value
ALT/ULN divided by ALP/ULN
Hepatocellular if R > 5
Cholestatic if R < 2
ULN = upper limit of normal
Antidote for acetaminophen
N-acetylcysteine
Risk factors for acetaminophen-induced hepatotoxicity
Chronic excessive alcohol ingestion Fasting Concomitant medications Late presentation Underlying liver disease Concomitant alcohol ingestion may be protective
Criteria to refer for transplant with tylenol overdose
Arterial pH < 7.3 Or all 3 of: INR > 6.5 Creatinin > 3.3 Hepatic encephalopathy grade 3-4
Anabolic steroid drug induced liver disease
Cholestasis without hepatitis
Bilirubin levels > 20x ULN
Very slow resolution to normal levels
Antibiotic drug induced liver disease
Amox-clav and fluoroquinolines
Cholestasis with hepatitis
Onset can be delayed by several weeks after the use of the drug
