A 22-year-old woman is brought 10 hours after ingesting paracetamol 12 g. She has right upper quadrant tenderness and her ALT is markedly elevated. The antidote works by:
- A Competitively blocking cytochrome P450-mediated conversion of paracetamol to NAPQI
- B Enhancing glucuronidation of paracetamol in the liver
- C Replenishing hepatic glutathione stores, allowing detoxification of NAPQI ✓
- D Chelating paracetamol metabolites in the circulation
Correct answer: C. Replenishing hepatic glutathione stores, allowing detoxification of NAPQI
Explanation
Paracetamol hepatotoxicity results from CYP2E1-generated N-acetyl-p-benzoquinone imine (NAPQI), which depletes glutathione and binds hepatocyte proteins. N-acetylcysteine replenishes glutathione (and provides cysteine substrate), permitting conjugation and excretion of NAPQI. It does not inhibit CYP2E1 competitively, and benefit is greatest within 8 to 10 hours of ingestion, though late administration still helps established liver injury.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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