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Anticoagulants, Thrombolytic Agents and Antiplatelet Drugs

Anticoagulants, Thrombolytic Agents and Antiplatelet Drugs. Management and Prevention of Vascular Thrombosis. Benedict R. Lucchesi, M.D., Ph.D. Department of Pharmacology University of Michigan Medical School. Revised 10/03. Anticoagulant Therapy .

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Anticoagulants, Thrombolytic Agents and Antiplatelet Drugs

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  1. Anticoagulants, Thrombolytic Agents and Antiplatelet Drugs Management and Prevention of Vascular Thrombosis Benedict R. Lucchesi, M.D., Ph.D. Department of Pharmacology University of Michigan Medical School Revised 10/03

  2. Anticoagulant Therapy • Areas of Concentration and Drugs to Know • Required Reading Goodman and Gilman 10 ed pages 1519-1536. • Mechanisms for hemostasis • Thrombus Formation • Role of platelets • Venous thrombosis • Arterial thrombosis • Biochemistry of coagulation • Role of vitamin K • Platelet Biology • Thrombolysis

  3. Drugs to Know • Anticoagulants and Adjuncts • Heparin • Protamine Sulfate • Low-molecular weight heparins - • Enoxaparin (Lovenox™) • Dalteparin (Fragmin™) • Danaparoid (Orgaran™) • Lepirudin [rDNA] (Refludan™) • Bivalirudin (Hirulog, Angiomax™) • Argatroban • Danaparoid (Orgaran™)

  4. Coumarin Derivatives • Warfarin • Dicumarol • Antiplatelet Drugs • Aspirin • Dipyridamole • Ticlopidine (Ticlid™) • Clopidogrel (Plavix™) • Abciximab (ReoPro™; Antibody to platelet GPIIb/IIIa receptor) • Tirofiban (Aggrastat™) Reversible, nonpeptide GPIIb/IIIa receptor antagonist • Eptifibatide (Integrilin™) cyclic peptide GPIIb/IIIa receptor blocker • Anagrelide (Agrylin™)

  5. Thrombolytic Agents • Streptokinase • Tissue plasminogen activator (rt-PA) • Alteplase (Activase™) • Reteplase (Retavase™) • Tenecteplase, TNK-tPA (TNKase™) • Urokinase • Anisoylated plasminogen streptokinase activator complex (APSAC)

  6. Development of Atherosclerotic Plaques

  7. Thrombin

  8. aPC Protein S aPC Inactivation Va & VIIIa INTRINSIC PATHWAY EXTRINSIC PATHWAY IXa VIIa / Tissue Factor VIIIa TFPI Platelet Aggregation aPC FACTOR Xa Fibrinogen ProthrombinThrombin Va XIIIa PC / Thrombomodulin Fibrin

  9. Direct & Indirect Thrombin Inhibitors Thrombin Direct InhibitorsIndirect Inhibitors HirudinATIII HirulogHeparin ArgatrobanLMWHs Lepirudin [rDNA] -dalteparin -enoxaparin Other Agents Danaparoid Dermatan Sulfate

  10. Anticoagulant Therapy • Reduce the formation of fibrin clots • Consist of two major types • Heparin and other Factor Xa, IIa inhibitors • LMWHs • Danaparoid • Lepirudin (Refludin™) • Bivalirudin (Angiomax™) • Argatroban • Warfarin

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