Paracetamol is an effective analgesic and antipyretic but has negligible anti-inflammatory activity at therapeutic doses. The accepted explanation for its poor anti-inflammatory action is:
- A It does not cross the blood brain barrier to reach inflamed tissues
- B It selectively inhibits COX-1, which mediates pain but not inflammation
- C High peroxide concentrations at sites of inflammation destroy the reduced form of its COX target, so it cannot inhibit COX there ✓
- D It is rapidly glucuronidated in plasma before reaching inflamed joints
Correct answer: C. High peroxide concentrations at sites of inflammation destroy the reduced form of its COX target, so it cannot inhibit COX there
Explanation
Paracetamol only inhibits cyclooxygenase when the enzyme is in a reduced state. At inflammatory lesions, peroxide levels generated by neutrophils are high enough to keep COX oxidised, so paracetamol cannot act there, while centrally the lower peroxide tone permits COX inhibition and explains analgesic and antipyretic effects. Poor brain penetration is false since central action underlies its benefit, and its action is not explained by selective COX-1 inhibition.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
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