NR566_Week_5_Study_Outline

• Pharmacodynamics Oral anticoagulants such as warfarin (Coumadin) inhibit the hepatic synthesis of several clotting factors, including factor X. The decline in clotting factors is a function of the half-life of each factor, which varies from 5 hours for factor VII to 72 hours for factor II. • Heparin inhibits the activity of several activated clotting factors by accelerating the activity of antithrombin III. LMWH enoxaparin (Lovenox) potentiates the activity of antithrombin III and inactivates factors Xa and IIa (thrombin). Dabigatran (Pradaxa) is a direct thrombin inhibitor. Thrombin is required for the conversion of fibrinogen to fibrin in the clotting cascade, thus dabigatran's inhibition of thrombin prevents thrombi from forming. Fondaparinux (Arixtra) is a selective inhibitor of antithrombin III and a factor Xa inhibitor. An anticoagulant, rivaroxaban (Xarelto), is a highly selective factor Xa inhibitor that inhibits thrombin formation and the development of thrombi. Apixaban (Eliquis) is a selective inhibitor of factor Xa. • Aspirin antagonizes the cyclooxygenase pathway and interferes with platelet aggregation. NSAIDs have this same action. NSAIDs are not used as antiplatelet drugs, but this explains why concurrent use with anticoagulants is contraindicated • Ticlopidine (Ticlid) and clopidogrel (Plavix) reduce platelet aggregation by inhibiting the ADP pathway of platelets. Unlike aspirin, they have no effect on prostaglandin metabolism. Ticagrelor (Brilinta) reversibly interacts with the platelet P2Y12 ADP- receptor to prevent platelet activation. Vorapaxar (Zontivity) is a protease-activated receptor-1 (PAR-1) antagonist, inhibiting thrombin-induced and thrombin receptor agonist peptide-induced platelet aggregation • Precautions and Contraindications All anticoagulants are contraindicated for patients who are hypersensitive to the drug or actively bleeding or who have hemophilia, thrombocytopenia, severe hypertension (HTN), intracranial hemorrhage, infective endocarditis, active tuberculosis, or ulcerative lesions of the GI tract. Heparins are contraindicated in advanced hepatic or renal disease. They may be used in patients who are actively bleeding to treat disseminated intravascular coagulation (DIC). Heparin is Pregnancy Category C.