Hepatotoxicity in patients with liver disease.

The biochemical and physiological disturbances caused by liver disease may enhance the toxicity of drugs. Besides alterations in liver blood flow and drug binding, a decreased rate of drug metabolism is an important phenomenon. Studies with phenazone, a model drug, demonstrates that the rate of microsomal drug metabolism is related to the degree of metabolic hepatic impairment. Individual dosage adjustments in patients with liver disease are complicated for many drugs, because of the counteracting influences of a decreased hepatic blood clearance and an increased free fraction of drug which may enhance drug metabolism and drug action. Moreover, many drugs owe part of their pharmacological action to active metabolites formed in the liver. Finally, little is known about altered receptor sensitivity in patients with liver disease. Non-predictable hepatotoxic reactions appear not to occur more frequently in patients with liver disease than in other patients. However, hepatotoxicity may be masked by the liver disease or by the intake of ethanol.