Coxibs (selective COX-2 inhibitors) increase cardiovascular risk primarily because:

• A They directly activate platelet ADP receptors, increasing platelet aggregation
• B They inhibit endothelial nitric oxide synthase, reducing vasodilator NO production
• C They increase leukotriene synthesis by shunting arachidonic acid to the 5-lipoxygenase pathway
• D They inhibit prostacyclin (PGI2) synthesis in endothelial cells (COX-2 dependent) while sparing platelet thromboxane A2 production (COX-1 dependent), shifting the haemostatic balance toward thrombosis ✓

Explanation

Vascular endothelium synthesises PGI2 (prostacyclin) via COX-2, which is vasodilatory and anti-aggregatory. Platelets produce TXA2 via COX-1, which is vasoconstrictive and pro-aggregatory. Selective COX-2 inhibitors suppress PGI2 without affecting TXA2, tipping the balance toward thrombosis, hypertension, and increased MI risk. This is the established mechanism behind the cardiovascular toxicity of rofecoxib and other coxibs.

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

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