Jaundice cholestatic, drug-induced

Hepatotoxicity Prolonged use of high doses of androgens has been associated with the development of potentially life-threatening peliosis hepatis, hepatic neoplasms, and hepatocellular carcinoma. Cholestatic hepatitis and jaundice occur with fluoxymesterone and methyltestosterone at relatively low doses. Drug-induced jaundice is reversible when the medication is discontinued. 

The incidence of drug-induced liver injury with rosiglitazone has been calculated at 0.02% for alanine transaminase activity 10 times the upper end of the reference range and 0.001% for jaundice (120). The above case report is unusual because, although liver damage is rare, hepatic necrosis occurs more commonly than cholestatic hepatitis. 

Dose-independent, drug-induced liver dysfunction (cholestatic jaundice) is not an unusual adverse reaction. Caused by a number of different, commonly used drugs, cholestasis is a hypersensitivity reaction that primarily affects the biliary canaliculi, causing an intrahepatic obstructive jaundice. An alteration in... 

Ockner RK (1979) Drug-induced liver disease. West J Med 131 36 Ohman L, Wahlberg I (1975) Ocular side-effects of clofazimine. Lancet 11 933 Ogilvie AL, Toghill PJ (1980) Cholestatic jaundice due to co-trimoxazole. Postgrad Med J 56 202... 

Hepatitis and jaundice caused by the combination of amoxicillin and clavulanic acid were first identified in 1988. The combination of the two drugs is associated with a higher incidence of liver injury than the administration of amoxicillin alone. The risk of this drug-induced liver injury, mostly cholestatic in nature, increases with age and by about a factor of 3 after 2 or more consecutive courses of drug. 

Several cases of ticlopidine-induced hepatotoxicity have been reported (27). Between 10 days and 12 weeks after the start of treatment, patients develop jaundice, usually without fever, eosinophilia, or pain. Laboratory tests show a cholestatic or mixed cholestatic-hepatocellular pattern of injury. There is usually clinical and biochemical recovery within 1-11 months. Frank ticlopidine-associated liver injury is uncommon, but in one study, 44% of patients had abnormal liver function tests and about one-half of them had to stop taking the drug (22). 

Other side effects of sulfonylureas include nausea and vomiting, cholestatic jaundice, agranulocytosis, aplastic and hemolytic anemias, generalized hypersensitivity reactions, and rashes. About 10-15% of patients who receive these drugs, particularly chlorpropamide, develop an alcohol-induced flush similar to that caused by disulfiram see Chapter 23). Sulfonylureas, especially chlorpropamide, may induce hyponatremia by potentiating the effects of vasopressin on the renal collecting duct see Chapter 29), and this effect on water retention has been used to therapeutic advantage in patients with mild forms of central diabetes insipidus. 

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