Low-dose aspirin is prescribed for cardiovascular prophylaxis. Although aspirin has a half-life of only about 15 to 20 minutes, its antiplatelet effect persists for 7 to 10 days. The reason for this prolonged effect is:

• A Aspirin is stored in platelet granules and released slowly
• B Competitive inhibition with a Ki far below the plasma drug concentration
• C Irreversible acetylation of cyclooxygenase in anucleate platelets that cannot resynthesize the enzyme ✓
• D Slow dissociation from the prostaglandin receptor on the platelet surface

Explanation

Aspirin covalently and irreversibly acetylates a serine residue of cyclooxygenase-1, permanently inactivating it. Platelets are anucleate and cannot synthesize new COX-1, so the effect lasts for the platelet lifespan of 7 to 10 days until fresh platelets are released from marrow. Competitive inhibitors act only while drug is present and would vanish with the short half-life, so option B is killed by the pharmacokinetics. This irreversibility distinguishes aspirin from reversible NSAIDs like ibuprofen.

Reference: Katzung Basic and Clinical Pharmacology, 16th ed.

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