Direct Thrombin Inhibitor Anticoagulants

Two drugs that are direct inhibitors of thrombin but that do not involve antithrombin III or vitamin K in their mechanism of action have been approved to provide intravenous anticoagulation in patients with he-parin-induced thrombocytopenia. Lepirudin (Refludan) and bivalirudin (Angiomax), which are analogues of the leech peptide anticoagulant hirudin, bind in a 1:1 complex with thrombin to inhibit its protease activity. Argatroban (Acova, Novastan), a synthetic analogue of arginine, interacts reversibly with and inhibits throm-bin's catalytic site. Both drugs have a short half-life. Lipuridin is cleared following metabolism and urinary excretion of changed and unchanged drug; hepatic metabolism of argatroban is a therapeutic advantage in patients with renal insufficiency. No antagonists for these drugs are available.

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