Aspirin at low dose selectively inhibits platelet COX-1 but not vascular endothelial COX-2 prostacyclin synthesis. This selectivity at low doses is explained by:
- A Aspirin's shorter half-life means it reaches endothelium at sub-inhibitory concentrations
- B Platelets lack a nucleus and cannot regenerate acetylated COX-1; endothelial cells can synthesise new COX-2 de novo ✓
- C Low-dose aspirin selectively acetylates Ser529 of COX-1 but not Ser516 of COX-2
- D Gastric first-pass acetylation of platelet COX-1 occurs before systemic absorption reaches endothelium
Explanation
Aspirin irreversibly acetylates the serine residue of both COX-1 and COX-2. At low doses, platelets (which are anucleate) cannot synthesise new COX protein; once COX-1 is permanently inhibited, platelets remain inhibited for their 8–10 day lifespan. Endothelial cells, being nucleated, regenerate COX-2 within hours, restoring prostacyclin (PGI2) production. This asymmetry in recovery explains why low-dose aspirin selectively inhibits thromboxane A2 synthesis (platelet aggregation) while largely preserving endothelial prostacyclin (antiaggregation, vasodilator). The portal theory (option D) has some supporting data but option B is the primary, textbook-accepted explanation.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.