Potentiation by Previous Drug Therapy of Hepatotoxicity following Paracetamol Overdosage

Abstract

Patients developing hepatic necrosis following intoxication with paracetamol were classified as either ‘potentially induced’ or ‘non-induced’ according to their consumption during the previous 3 weeks of drugs likely to cause liver microsomal enzyme induction. Despite uncontrolled differences between the two groups the ‘potentially induced’ group developed statistically significantly more severe hepatic necrosis than the ‘non-induced’ patients. The greater severity of liver damage in the former group was accompanied by a higher incidence of death and acute renal failure. This is consistent with the observation that paracetamol-induced hepatic necrosis in animals is mediated by toxic intermediate metabolites.