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USMLE STEP 1 REVIEW QUESTIONS: COX INHIBITORS

USMLE STEP 1 REVIEW QUESTIONS: COX INHIBITORS

 

QUESTION: Which drugs irreversibly inhibits platelet COX (cyclooxygenase)? What is the mechanism of action of ibuprofen, celebrex, clopidogrel, and aspirin.

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ANSWER:

– Arachidonic acid released from the platelet membranes is converted by COX to prostaglandin G2 (PGG2) and then to prostaglandin H2 (PGH2), which, in turn, is converted to TXA2.

– TXA2 has potent vasoconstriction and platelet aggregation effects.

– Arachidonic acid may also be shuttled to adjacent endothelial cells and converted to prostacyclin (PGI2), which is a vasodilator and acts to inhibit platelet aggregation.

– Platelet COX is irreversibly inhibited by aspirin and reversibly blocked by NSAIDs but is not affected by COX-2 inhibitors.

– Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) and reversibly affects platelet COX.

– Both aspirin and clopidogrel irreversibly inhibit platelet function, clopidogrel through selective irreversible inhibition of ADP-induced platelet aggregation and aspirin through irreversible acetylation of platelet prostaglandin synthase.

– Celebrex is a COX-2 inhibitor and therefore does not affect platelet COX.

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