N-acetylcysteine is used to prevent paracetamol hepatotoxicity. Its mechanism involves:

• A Inhibiting CYP2E1 to reduce conversion of paracetamol to NAPQI
• B Replenishing hepatic glutathione stores by acting as a cysteine precursor, allowing conjugation and detoxification of NAPQI ✓
• C Directly binding NAPQI in the blood stream before it reaches the liver
• D Activating hepatic aldehyde dehydrogenase to convert NAPQI back to paracetamol

Explanation

Paracetamol overdose saturates sulfation and glucuronidation, diverting it through CYP2E1/3A4 to NAPQI. Normally, NAPQI is detoxified by conjugation with hepatic glutathione; in overdose, glutathione is depleted and NAPQI covalently binds hepatocyte proteins causing necrosis. N-acetylcysteine provides cysteine (a glutathione precursor), rapidly restoring hepatic glutathione and enabling continued NAPQI detoxification. Direct NAPQI binding by NAC also contributes.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.