NABP NAPLEX Exam - Topic 4 Question 114 Discussion

Clopidogrel and ticlopidine are ADP receptor pathway inhibitors. The irreversible inhibition of the ADP- dependent pathway of platelet activation is thought to be the result of covalent modification and inactivation of the platelet P2Y ADP receptor. This receptor is coupled to the inhibition of adenylyl cyclase. Both drugs are prodrugs and undergo conversion to active metabolites in the liver. However, clopidogrel must undergo oxidation by hepatic P450 enzymes to its active form. This is significant because many drugs are metabolized the hepatic P450 enzymes, including statins, and clopidogrel may interact with these medications. Clopidogrel is a second-generation thienopyridine and ticlopidine is a first-generation thienopyridine. Both drugs are indicated in combination with aspirin to prevent stent thrombosis. Eptifibatide is a GPIIb-IIIa receptor antagonist that is used to treat unstable angina and non-ST segment elevation myocardial infarction. Eptifibatide is also used to reduce ischemic events in patients who are undergoing percutaneous coronary intervention. The drug is a synthetic peptide that directly antagonizes the GPIIb-IIIa receptor on the platelet. Aspirin is an antiplatelet drug that works by inhibition of synthesis of prostaglandins. Prostaglandin G2 is the result of a synthesis pathway that is activated by platelets and endothelial cells, and results in localized

vasoconstriction and induction of platelet aggregation, as well as causing release of platelet granules. Warfarin is an anticoagulant that acts on vitamin K-dependent reactions in the coagulation pathway. Vitamin K is necessary for hepatic synthesis of coagulation factors II, VII, IX and X, protein C and protein S. Vitamin K- dependent carboxylation is necessary for induction of enzymatic activity of these coagulation factors. Take- home message: Clopidogrel, a second-generation thienopyridine ADP receptor pathway inhibitor, is indicated in combination with aspirin to prevent stent thrombosis in patients who undergo percutaneous coronary intervention after myocardial infarction. Clopidogrel is a prodrug that must undergo oxidation by hepatic P450 enzymes, and therefore may affect the activity of statins and other drugs dependent on the hepatic P450 enzymes.