Anticoagulant, Antithrombotic and Anti-Platelet Drugs

Anticoagulant, Antithrombotic and Anti-Platelet Drugs
By:Robert Taylor, MD, Ph.D.
Department of Pharmacology, Howard University

Clinical Thrombosis
Indications For Antithrombotic Therapy
* Venous thromboembolic disease
o Deep venous thrombosis (DVT)
o Pulmonary embolism (PE)
o Primary prophylaxis of DVT or PE
* Arterial thromboembolic disease
o Prosthetic heart valves
o Mitral valve disease, especially with atrial fibrillation
o Congestive cardiomyopathies, especially with atrial fibrillatio
o Atrial fibrillation
o Mural cardiac thrombi
o Transient ischemic attacks
o Stroke in evolution
* Disseminated intravascular coagulation
* Maintenance of patency of vascular grafts, shunts, bypasses

Recombinant Human Activated Protein C
* Drotrecogin alfa (activated)- Xigris
* Indicated for Severe Sepsis in Adults with Acute Organ Dysfunction with High Risk of Death
* Reduction in Death as Primary End Point
* Antithrombotic, Antiinfammatory, Profibrinolytic Properties
* Serious Bleeding is Major Side Effect

Antithrombin III Inhibits the Following Serine Proteases
* Coagulation
* Factor XIIa
* Factor XIa
* Factor IXa
* Factor Xa
* Thrombin
* Fibrinolysis
* Plasmin

Inhibitory activity against all these enzymes is substantially accelerated by heparin

Heparin
Anticoagulant Properties of Heparin
* Inhibits the thrombin-mediated conversion of fibrinogen to fibrin
* Inhibits the aggregation of platelets by thrombin
* Inhibits activation of fibrin stabilizing enzyme
* Inhibits activated factors XII, XI, IX, X and II
* Biologic Sources
* Bioavailability
* Metabolism
* Elimination
* Side Effects
* Overdose
* Contraindications
* Pregnancy- YES

Unfractionated Heparin
* High Dose
Monitoring of Anticoagulant Therapy
Heparin
Low Dose Unfractionated Heparin
Indications for and Contraindications to Parenteral Anticoagulant Agents
Regional anesthesia
Pregnancy
Prosthetic Heart Valves
Regional anesthesia
Antithrombin III inhibitor
Low-molecular-weight heparin
Unfractionated heparin
Enoxaparin(Lovenox)
Dalteparin(Fragmin)
Tinzaparin(Innohep)
Contraindication
Approved & Appropriate Indications
Class
Anticoagulant Agent
Thrombocytopenia other than heparin-induced thrombocytopenia
Direct thrombin inhibitor
Heparinoid
Hirudin derivative
Synthetic factor Xa inhibitor
Ardeparin
Lepirudin
Argatroban
Danaparoid
Bivalirudin
Fondaparinux(Arixtra)
Heparin-Antibiotic Interactions
Mechanisms of HIT
Therapy of HIT
Warfarin
* Bioavailability
* Metabolism
* Serum Protein Binding
* Vitamin K Status
* Protein C Effects
* Elimination
* Side Effects
* Overdose
* Contraindications
* Pregnancy- NO
Contraindications to Antithrombotic Therapy
Platelet Receptor Mediated Pathways: Drugs
GP IIB/IIIA Inhibitors
Abciximab (ReoPro)
Eptifibatide (Integrilin)
Tirofiban
Thrombin
-Final Common Pathway
-Promotes Platelet Adhesion (Fibrinogen, vWF)
Ticlopidine
Clopidogrel
ADP
ASA
NSAIDs
Arachidonic Acid
Anti Platelet Drugs
CAD
Stroke-TIAs
Permanently inhibits COX-1 and COX-2
Aspirin
TIAs;Stroke
CAD;PVD
Inhibits ADP PlatAg;active metabolite
Ticlopidine
Clopidrgrel
TIAs
Inhibits PDE; increases cAMP
Dipyridamole
Limited Reversibly inhibits COX-1
NSAIDs
Uses
Mechanism
Drug

Anticoagulant, Antithrombotic and Anti-Platelet Drugs.ppt