Acetaminophen and its Toxicity

Acetaminophen (APAP) is considered one of the safest of all minor analgesics, but when taken in large doses (> 10 g) toxicity occurs. Severely poisoned patients experience hepatic and/or renal failure. The major metabolic pathway of APAP is formation of glucuronide and sulfate conjugates. A minor pathway is formation of a reactive metabolite that conjugates with glutathione (GSH). When GSH is depleted, the reactive metabolite causes necrosis of hepatic and other tissues. Treatment of APAP toxicity involves supplying alternate sulfhydryl donors or inhibiting oxidative formation of the reactive metabolite. Estimation of plasma APAP levels is necessary for effective treatment.