Paper I
2022 July (Supplementary) (2019 Scheme) · 100 marks · 180 min

Question

Selective COX-2 inhibitors (merits and demerits).

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Answer

Selective COX-2 inhibitors (Celecoxib, Etoricoxib) selectively inhibit the inducible COX-2 isoform responsible for inflammatory prostaglandin synthesis, while sparing constitutive COX-1, which maintains gastric mucosal protection and normal platelet thromboxane function.

Merits:

  • Substantially lower risk of GI ulceration/bleeding than non-selective NSAIDs, since gastroprotective COX-1-derived prostaglandins are spared.
  • No antiplatelet effect (COX-1/thromboxane A2 spared), so no added bleeding risk from platelet dysfunction.
  • Equivalent analgesic and anti-inflammatory efficacy to non-selective NSAIDs.

Demerits:

  • Increased cardiovascular (thrombotic) risk with prolonged use — COX-2 inhibition suppresses vascular endothelial prostacyclin (an antiplatelet, vasodilator mediator) without the offsetting COX-1/thromboxane suppression that non-selective NSAIDs provide, shifting the hemostatic balance toward thrombosis.
  • Some renal toxicity, similar to non-selective NSAIDs (both COX-1 and COX-2 contribute to renal prostaglandin-mediated blood flow autoregulation).
  • Higher cost than non-selective NSAIDs.
  • Rofecoxib was withdrawn from the market specifically for excess cardiovascular risk, a cautionary example for the whole class.

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