Aspirin at low doses (75–100 mg/day) selectively inhibits platelet COX-1 over vascular endothelial COX-1/COX-2. The pharmacological basis for this selectivity is:

• A Low doses block only the COX-1 isoform; higher doses are required to block the inducible COX-2 isoform
• B Platelets lack nuclei and cannot re-synthesize acetylated COX-1 after irreversible inactivation; endothelial cells continuously synthesize new COX-2 (PGI2 synthase), recovering prostacyclin production within hours
• C Low-dose aspirin acetylates the COX-1 serine 530 only in platelets, where it encounters higher local drug concentrations in the portal circulation before first-pass metabolism
• D Both B and C are correct mechanisms contributing to selective platelet inhibition ✓

Explanation

Both mechanisms operate: (1) Presystemic (portal circulation) aspirin exposure causes irreversible platelet COX-1 acetylation before substantial hepatic first-pass metabolism reduces aspirin bioavailability in systemic circulation. (2) Platelets are anucleate and cannot synthesize new COX-1, making inhibition permanent for their 8–10-day lifespan; vascular endothelial cells can synthesize new COX-2 within 4–6 hours, restoring PGI2 (prostacyclin) production. The net effect is selective suppression of TXA2 (platelet aggregation) with relative preservation of PGI2 (antiplatelet/vasodilatory), conferring antithrombotic benefit at low doses.

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

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