Aspirin at low dose (75–150 mg/day) selectively inhibits platelet TXA2 synthesis more than endothelial prostacyclin (PGI2) synthesis. The pharmacological basis for this selectivity is:
- A Anucleate platelets cannot synthesise new COX-1 protein, while endothelial cells regenerate COX-1 from existing mRNA ✓
- B Platelets lack CYP450 isoenzymes needed to regenerate COX-1 after aspirin acetylation
- C Aspirin preferentially inhibits platelet COX-1 at lower doses due to higher COX-1 concentration in platelets
- D Aspirin is selectively cleaved by platelet esterases to salicylate, which irreversibly inhibits platelet COX-1 only
Correct answer: A. Anucleate platelets cannot synthesise new COX-1 protein, while endothelial cells regenerate COX-1 from existing mRNA
Explanation
Aspirin irreversibly acetylates serine-530 on both COX-1 and COX-2. The selective platelet-sparing endothelial effect at low dose is explained by the fact that platelets are anucleate (no nucleus, no protein synthesis capability); once their COX-1 is acetylated, they cannot regenerate the enzyme for their 7–10 day lifespan. Endothelial cells are nucleated and can rapidly resynthesise COX-1, recovering PGI2 production. Low-dose aspirin given as a once-daily formulation ensures platelet COX-1 is acetylated in portal circulation before systemic dilution.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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