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Chapter 19: Drug Therapy of Thromboembolic Disorders

A patient diagnosed with acute coronary syndrome is prescribed clopidogrel. What is the mechanism of action of this agent?

a. It vasodilates coronary arteries.

b. It irreversibly blocks ADP receptors.

c. It blocks thrombin receptors on platelets.

d. It inhibits thrombin.

Answer is b. Clopidogrel and the other thienopyridines (ticlopidine, prasugrel) irreversibly block P2Y12 (ADP) receptors on platelets, which inhibits platelet activation and aggregation. A patient with acute coronary syndrome is at high risk of acute myocardial infarction caused by platelet thrombus formation at the site of ruptured coronary artery plaques (see Chapter 16). Antiplatelet therapy will reduce the risk of myocardial infarction in such patients.

Following a trans-Pacific flight from Australia, a 57-year-old man develops deep vein thrombosis in his right leg. He receives heparin to treat the DVT but after 6 days of heparin therapy he develops heparin-induced thrombocytopenia (HIT). What drug is he likely to receive instead of heparin?

a. Argatroban

b. Warfarin

c. Activated protein C (drotrecogin alpha)

d. Dabigatran

e. Rivaroxaban

Answer is a. The patient is most likely to receive argatroban which is a parenterally administered small molecule direct thrombin inhibitor. Alternatives to argatroban for patients with HIT include bivalirudin or fondaparinux. Warfarin should not be used initially to replace heparin because there is a risk of developing venous limb gangrene, but can be started after the patient has been stably anticoagulated with argatroban and his platelet count has increased. Activated protein C would not be an effective anticoagulant in this setting. The oral anticoagulants dabigatran (oral direct thrombin inhibitor) and rivaroxaban (oral direct factor Xa inhibitor) are theoretically good alternatives to heparin in patients with DVTs, but have not yet been tested clinically for this indication.

A 52-year-old woman with atrial fibrillation is prescribed apixaban. What is the mechanism of action of this oral anticoagulant?

a. It indirectly inhibits thrombin by activating antithrombin.

b. It directly inhibits thrombin.

c. It indirectly inhibits factor Xa by activating antithrombin.

d. It directly inhibits factor Xa.

e. It blocks the synthesis of active clotting factors.

Answer is d. Apixaban is an oral direct inhibitor of factor Xa. Inhibition ...

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