Anticoagulants, Thrombolytic Agents and Antiplatelet Drugs

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Presentation transcript:

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 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

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

Coumarin Derivatives Antiplatelet Drugs Warfarin Dicumarol 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™)

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

Development of Atherosclerotic Plaques

Anticoagulant Therapy - Coagulation Mechanism Intrinsic System XII XIIa XI XIa IX IXa X Xa II Thrombin XIII XIIIa HMW kininogen Kallikrein HMW kininogen Extrinsic System TPL VIIa VII PL Ca++ VIII PL Ca++ VIII Fibrinogen Fibrin PL Ca++ VIII Stabilization

X-Linked Fibrin XIII XIIIa Surface XII, HK, Prekallikrein VIIa VII Tissue Factor XI XIa VIIa X IX IXa X-Linked Fibrin VIII X Xa V Prothrombin Thrombin XIII XIIIa Fibrinogen Fibrin

Thrombin

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

Thrombin Direct & Indirect Thrombin Inhibitors Direct Inhibitors Indirect Inhibitors Hirudin ATIII Hirulog Heparin Argatroban LMWHs Lepirudin [rDNA] -dalteparin -enoxaparin Other Agents Danaparoid Dermatan Sulfate

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