What is the mechanism of acetaminophen and its primary safety risk?

• A. It reduces central prostaglandin synthesis via weak COX inhibition in CNS; hepatotoxicity risk with overdose.
• B. It blocks peripheral COX enzymes and causes nephrotoxicity risk.
• C. It inhibits COX-2 selectively and carries risk of GI bleeding.
• D. It antagonizes NMDA receptors and risks serotonin syndrome.

Answer: (A)

Acetaminophen relieves pain and fever mainly by reducing prostaglandin synthesis in the brain through weak COX inhibition, so it has little peripheral anti-inflammatory effect. The primary safety risk is hepatotoxicity with overdose: the liver metabolizes acetaminophen to a highly reactive metabolite (NAPQI), which is normally neutralized by glutathione. In overdose, glutathione stores are overwhelmed, NAPQI accumulates, and liver cells can be damaged, with higher risk in chronic alcohol use or preexisting liver disease.

Other options describe mechanisms that don’t apply to acetaminophen. Peripheral COX inhibition and GI bleeding risk are characteristic of NSAIDs, not acetaminophen. Nephrotoxicity is more associated with NSAIDs and certain contrast agents. NMDA receptor antagonism is not how acetaminophen works.