SEVERE ACETAMINOPHEN TOXICITY IN A PATIENT RECEIVING ISONIAZID

Persons with alcoholism are at increased risk for acetaminophen liver toxicity. Two complementary theories have been proposed to explain this phenomenon. The first is that the livers of persons with alcoholism are depleted in glutathione and are therefore incapable of detoxifying the electrophilic metabolite of acetaminophen produced by the liver's mixed-function oxidase system. The second theory is that ethanol consumption stimulates, or 'induces,' a mixed-function oxidase enzyme (P-450IIE1) that appears to generate the toxic metabolite. We report the case of a woman who developed life-threatening hepatic and renal toxicity after ingesting not more than 11.5 g of acetaminophen and whose initial acetaminophen blood level was not in the usual toxic range. This patient did not drink ethanol but was being treated with isoniazid. Isoniazid does not appear to deplete liver glutathione stores but does induce P-450IIE1. The data support the hypothesis that induction of P-450IIE1 may predispose patients to acetaminophen toxicity in the absence of glutathione depletion.