Celecoxib selectively inhibits COX-2 but still carries cardiovascular risk. The mechanism of this cardiovascular risk is:
- A Inhibition of COX-2-derived TXA2 in platelets, reducing platelet aggregation
- B Direct sodium retention and increased blood pressure via COX-2 inhibition in renal collecting duct
- C Inhibition of COX-2-derived PGI2 in endothelium without inhibiting COX-1-derived TXA2 in platelets, shifting balance towards prothrombotic state ✓
- D Reduced prostacyclin production from both COX-1 and COX-2 in vascular endothelium
Correct answer: C. Inhibition of COX-2-derived PGI2 in endothelium without inhibiting COX-1-derived TXA2 in platelets, shifting balance towards prothrombotic state
Explanation
Vascular endothelium produces anti-aggregatory, vasodilatory prostacyclin (PGI2) primarily via COX-2. Platelets produce pro-aggregatory, vasoconstrictive thromboxane A2 (TXA2) via COX-1. Selective COX-2 inhibitors (celecoxib, rofecoxib) suppress endothelial PGI2 without inhibiting platelet TXA2 (platelet COX-1 is unaffected), creating a prothrombotic imbalance. This mechanism explains the increased risk of MI and stroke with coxibs. Aspirin, by inhibiting both, causes a different but overall less prothrombotic state.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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