Celecoxib selectively inhibits COX-2. However, selective COX-2 inhibition increases cardiovascular risk because of which mechanistic imbalance?

• A Increased prostacyclin (PGI2) production from COX-1 in endothelium causing vasoconstriction
• B Reduced prostacyclin (PGI2) from endothelial COX-2 without reducing thromboxane A2 (TXA2) from platelet COX-1, favoring thrombosis ✓
• C Direct inhibition of platelet COX-1, impairing thromboxane A2 production
• D Increased leukotriene B4 via shunting of arachidonic acid to the 5-LOX pathway

Explanation

Vascular endothelial cells express COX-2 constitutively, producing prostacyclin (PGI2), which is vasodilatory and anti-aggregatory. Platelets express only COX-1, producing thromboxane A2 (TXA2), which promotes vasoconstriction and platelet aggregation. Selective COX-2 inhibition reduces endothelial PGI2 without affecting platelet TXA2, tipping the balance toward a prothrombotic, vasoconstrictive state and increasing the risk of MI and stroke. This is the VIGOR/APPROVe trial finding with rofecoxib and celecoxib.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.