Chapter 41 DRUGS AND LIVER DISEASE
INTRODUCTION
The liver also has a sophisticated series of metabolic enzymes, which, in general, convert drugs from lipophilic substances to hydrophilic substances that can be more easily eliminated. The cytochrome P450 enzymes, which play the major role in drug metabolism, may produce reactive metabolites during this process and these are thought to be the mechanism by which many adverse hepatic reactions occur.
RISK FACTORS FOR DRUG HEPATOTOXICITY
Age: older persons appear to be more susceptible to drug-induced hepatotoxicity.
Gender: women are more affected by the toxic adverse effects on the liver than men.
PRESENTATION
Drug-related hepatotoxicity can mimic clinically and histologically almost any type of liver disease (Table 41.1). Presenting symptoms are similarly diverse, from asymptomatic elevations of liver function tests to coma secondary to fulminant hepatic failure. Anorexia and tiredness can be the presentations of hepatitic reactions while itch, dark urine and jaundice occur in more severe cholestatic syndromes.
Condition | Drug |
---|---|
Acute hepatocellular necrosis | Isoniazid, cloxacillin, halothane, methyldopa, paracetamol |
Fatty liver | Tetracycline, valproic acid, corticosteroids, non-steroidal antiinflammatory drugs, perhexiline, amiodarone |
Granulomatous reactions | Hydralazine, allopurinol, carbamazepine |
Acute cholestasis | Oral contraceptive steroids, anabolic androgens, chlorpromazine, flucloxacillin |
Chronic cholestasis | Chlorpromazine, flucloxacillin, amitriptyline |
Chronic hepatitis/necrosis | Methyldopa, nitrofurantoin, dantrolene |
Fibrosis and cirrhosis | Methotrexate |
Vascular disorders | Oral contraceptive steroids, anabolic androgens, azathioprine |