A 16-year-old girl ingests an estimated 12 g of paracetamol in a suicide attempt. She reaches hospital 4 hours after ingestion and is asymptomatic. Serum paracetamol concentration plots above the treatment line on the Rumack-Matthew nomogram. Which drug should be started, and through which mechanism does it act?

• A Activated charcoal alone, adsorption of circulating drug
• B Naloxone, competitive antagonism at mu receptors
• C N-acetylcysteine, replenishes hepatic glutathione stores ✓
• D Silymarin, inhibition of cytochrome P450 2E1

Explanation

Paracetamol is metabolized to NAPQI, a toxic intermediate normally detoxified by glutathione. In overdose, glutathione is depleted and NAPQI causes centrilobular hepatic necrosis. N-acetylcysteine acts as a glutathione precursor and surrogate, detoxifying NAPQI, and is most effective within 8 hours of ingestion. C level above the treatment line on the nomogram drawn at 4 hours or later mandates NAC. Charcoal is useful only within 1 to 2 hours and never replaces the antidote.

Reference: Katzung Basic and Clinical Pharmacology / Nelson Textbook of Pediatrics, 15th / 21st ed.

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