A patient with acute coronary syndrome is loaded with ticagrelor rather than clopidogrel. A key pharmacological advantage of ticagrelor over clopidogrel relevant to CYP2C19 polymorphism is:
- A Ticagrelor is a more potent irreversible P2Y12 blocker than the active metabolite of clopidogrel
- B Ticagrelor is an active drug that does not require metabolic activation by CYP2C19, providing consistent P2Y12 inhibition regardless of CYP2C19 genotype ✓
- C Ticagrelor additionally inhibits the P2Y1 receptor, providing synergistic ADP-independent platelet inhibition
- D Ticagrelor is a prodrug converted by CYP3A4 to an active metabolite; CYP2C19 poor metabolisers convert more ticagrelor via CYP3A4 compensating for reduced CYP2C19 activity
Explanation
Clopidogrel is a prodrug requiring hepatic oxidation to its active thiol metabolite — primarily by CYP2C19. CYP2C19 loss-of-function polymorphisms (e.g. *2, *3 alleles) present in ~25–30% of patients reduce active metabolite formation, leading to inadequate P2Y12 inhibition and higher rates of stent thrombosis and MACE (shown in TRITON and PLATO). Ticagrelor (a cyclopentyl-triazolo-pyrimidine) is itself an active drug and does not require bioactivation — it binds P2Y12 receptors directly and reversibly, providing consistent inhibition independent of CYP2C19 status. Ticagrelor does not inhibit P2Y1.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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