Coxibs (selective COX-2 inhibitors) increase the risk of myocardial infarction and stroke. The biochemical imbalance responsible for this prothrombotic state involves which eicosanoid imbalance?
- A Increased leukotriene B4 from arachidonic acid diversion through lipoxygenase pathway
- B Decreased prostacyclin (PGI2) synthesis from endothelium with preserved thromboxane A2 (TXA2) production from platelets ✓
- C Increased thromboxane A2 without change in prostacyclin production
- D Decreased thromboxane A2 and proportionally decreased prostacyclin maintaining hemostatic balance
Explanation
Vascular endothelial cells express COX-2 constitutively to synthesize prostacyclin (PGI2), which is antithrombotic (inhibits platelet aggregation, causes vasodilation). Platelets express only COX-1 to produce thromboxane A2 (TXA2), which is prothrombotic (promotes platelet aggregation and vasoconstriction). Selective COX-2 inhibition reduces endothelial PGI2 production without affecting platelet TXA2 (which is COX-1 derived), creating an imbalance favoring thrombosis. Non-selective NSAIDs inhibit both, partially preserving the balance. Leukotriene involvement is the mechanism of aspirin-exacerbated respiratory disease, not cardiovascular risk.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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