Celecoxib is a selective COX-2 inhibitor. The mechanism underlying its increased risk of cardiovascular thrombotic events compared to non-selective NSAIDs is:

• A COX-2 inhibition in platelets reduces TXA2 and promotes platelet aggregation
• B COX-2 inhibition raises blood pressure by reducing renal prostaglandin E2
• C Increased platelet COX-1 activity unmasked when COX-2 is blocked
• D Selective suppression of endothelial prostacyclin (PGI2) production without affecting platelet TXA2, tipping the balance toward thrombosis ✓

Explanation

Prostacyclin (PGI2) is produced by vascular endothelium primarily through COX-2, and it inhibits platelet aggregation and causes vasodilation. Thromboxane A2 (TXA2) is produced by platelets through COX-1, promoting platelet aggregation and vasoconstriction. Non-selective NSAIDs inhibit both COX-1 (reducing TXA2) and COX-2 (reducing PGI2), maintaining a rough balance. Selective COX-2 inhibitors suppress endothelial PGI2 without reducing platelet TXA2, thus tipping the hemostatic balance toward platelet aggregation and vasoconstriction, increasing cardiovascular thrombotic risk. This was the pharmacological basis for the withdrawal of rofecoxib (Vioxx) in 2004.

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

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