Coxibs (selective COX-2 inhibitors) have reduced GI adverse effects compared to non-selective NSAIDs but are associated with increased thrombotic cardiovascular events. The mechanistic explanation for increased cardiovascular risk with COX-2 inhibitors is:
- A They selectively inhibit prostacyclin (PGI2) synthesis in endothelium while sparing platelet TXA2, shifting the balance toward prothrombotic state ✓
- B They block TXA2 synthesis in platelets, impairing haemostasis
- C They enhance PAF (platelet activating factor) production
- D They cause sodium retention elevating blood pressure via direct renal COX-1 inhibition
Correct answer: A. They selectively inhibit prostacyclin (PGI2) synthesis in endothelium while sparing platelet TXA2, shifting the balance toward prothrombotic state
Explanation
COX-2 is constitutively expressed in vascular endothelium and is responsible for prostacyclin (PGI2) synthesis, which is vasodilatory and anti-platelet aggregating. Platelet TXA2 synthesis depends on COX-1 (not COX-2), which is unaffected by coxibs. Selective COX-2 inhibition thus suppresses endothelial PGI2 while leaving platelet TXA2 intact, shifting the TXA2/PGI2 balance toward vasoconstriction and platelet aggregation — increasing MI and stroke risk. This is the mechanism underlying rofecoxib withdrawal (VIGOR trial).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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