Paracetamol NAPQI Mechanism — FRCA Primary MCQ
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Correct answer: A — NAPQI formed at therapeutic doses is normally detoxified by conjugation with reduced glutathione
Explanation lettering: B = shown as A · C = shown as B · A = shown as C
B is correct. Most paracetamol undergoes hepatic glucuronidation or sulfation. A small fraction—less than 4% in the cited SmPC—is oxidised by cytochrome P450 to the reactive metabolite NAPQI. At therapeutic doses, NAPQI is rapidly detoxified by conjugation with reduced glutathione and is subsequently excreted as cysteine and mercapturic acid conjugates. A is therefore false because CYP-mediated oxidation is a minor pathway. C is false because small quantities of NAPQI are formed during normal metabolism. D is false because NAPQI is detoxified rather than excreted unchanged as the major metabolite. E is false: saturation of the principal conjugation pathways during overdose is associated with increased NAPQI production and depletion of hepatic glutathione, permitting toxic metabolite accumulation and hepatic injury.
Reference: Electronic Medicines Compendium, Paracetamol ALTAN 10 mg/mL solution for infusion, SmPC sections 5.1–5.2, updated 23 January 2026. https://www.medicines.org.uk/emc/product/13649/smpc