Which of the following best explains why selective COX-2 inhibitors (coxibs) carry a higher cardiovascular risk compared to non-selective NSAIDs?
- A Coxibs directly activate protein kinase C in vascular smooth muscle causing vasoconstriction
- B COX-2 inhibitors increase circulating angiotensin II by reducing renal prostaglandin synthesis
- C COX-2 inhibition reduces prostacyclin (PGI2) in endothelium while leaving platelet thromboxane A2 (TXA2) production intact, shifting the balance toward thrombosis ✓
- D Selective COX-2 blockade increases leukotriene production causing coronary vasospasm
Correct answer: C. COX-2 inhibition reduces prostacyclin (PGI2) in endothelium while leaving platelet thromboxane A2 (TXA2) production intact, shifting the balance toward thrombosis
Explanation
Vascular endothelium uses predominantly COX-2 to generate prostacyclin (PGI2), which inhibits platelet aggregation and causes vasodilation. Platelets rely on COX-1 for thromboxane A2 (TXA2) synthesis, which promotes aggregation and vasoconstriction. Selective COX-2 inhibitors suppress endothelial PGI2 without affecting platelet TXA2, tipping the haemostatic balance toward a prothrombotic, vasoconstrictive state, increasing MI and stroke risk.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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