Paracetamol (Acetaminophen)

Abstract

Paracetamol is a weak analgesic and antipyretic found in many proprietary pain killers. It is well absorbed and widely distributed. Metabolism is by hydroxylation and methylation but is mainly by conjugation to glucuronic acid and sulphate. The half-life in plasma is 1.5-3 hours after therapeutic doses. An important small fraction of drug is oxidized to a reactive metabolite which is normally detoxified by conjugation with glutathione. In overdose with as little as 10 g paracetamol, the pool of available glutathione is insufficient and the free active metabolite binds covalently with liver cell proteins some 10-12 hours after dosing leading to hepatic necrosis. Sulphur-containing amino acids such as acetylcysteine or methionine administered within 15 hours are antidotes against hepatic damage by acting as substrates for detoxification of the active metabolite. Plasma concentrations can be used as a guide for antidote administration. Liver damage is possible if plasma concentrations are > 200 μg/ml at 4 hours or > 30 μg/ml 15 hours after dosing.