APAP overdose mechanism statement.

• A. Acetaminophen is excreted unchanged in urine
• B. Acetaminophen overdose increases glutathione synthesis
• C. Acetaminophen is converted to NAPQI by cytochrome P450
• D. Acetaminophen does not affect the liver

Answer: (C)

The key idea is how acetaminophen is detoxified and what happens when that detoxification pathway is overwhelmed. Most of the drug is safely processed through sulfate and glucuronide conjugation and excreted, but a portion is oxidized by liver cytochrome P450 enzymes to a reactive metabolite called NAPQI. Normally, NAPQI is rapidly neutralized by conjugation with glutathione and eliminated. In an overdose, glutathione stores become depleted, allowing NAPQI to accumulate and bind to cellular proteins, causing oxidative damage and hepatocellular injury. This is why the mechanism involving conversion to NAPQI by cytochrome P450 is the correct description of how acetaminophen overdose causes liver toxicity. Other statements aren’t the primary cause: not all acetaminophen is excreted unchanged, overdose actually depletes glutathione rather than increasing it, and acetaminophen does affect the liver.