BLOOD COAGULATION, ANTICOAGULANT, THROMBOLYTICS & ANTIPLATELET DRUGS .

1. BLOOD COAGULATION, ANTICOAGULANT, THROMBOLYTICS & ANTIPLATELET DRUGS. PRESENTED BY:- DR. MARWASHAALAN PHARM-D

2. Physiology and Pathophysiology of Coagulation • Hemostasis • Stage 1—formation of platelet plug • Platelet aggregation • Stage 2—coagulation • Intrinsic coagulation pathway • Extrinsic coagulation pathway • Keeping hemostasis under control • Physiologic removal of clots • Thrombosis • Arterial thrombosis • Venous thrombosis .

3. A Blood Clot • Consists of platelets meshed into fibrin • A web-like accumulation of strands with RBCs • There are two major facets of the clotting mechanism – the platelets, and the thrombin system

4. Anticoagulants – General Overview • Drugs that help prevent the clotting (coagulation) of blood • Coagulation will occur instantaneously once a blood vessel has been hurt. • Blood begins to solidify to prevent excessive blood loss and to prevent invasive substances from entering the bloodstream

5. MECHANISM OF PLATELET AGGREGPATION . Mechanism of platelet aggregation and actions of antiplatelet drugs

6. Mechanism of platelet aggregation and actions of antiplatelet drugs.

7. Anticoagulant Use • Anticoagulant drugs help prevent the development of harmful clots in the blood vessels by lessening the blood's ability to cluster together • The function of these drugs is often misunderstood because they are sometimes referred to as blood thinners; they do not in fact thin the blood • These drugs will not dissolve clots that already have formed, but it will stop an existing clot from becoming worse and prevent future clots

8. 1-Anticoagulant Drugs • Heparin and warfarin are the two traditional anticoagulants • Anticoagulants are used for acute coronary syndromes, deep-vein thrombosis (DVT), pulmonary embolism (PE), and heart surgery • Thrombus - A blood clot that forms abnormally within the blood vessels • Embolus - When a blood clot becomes dislodged from the vessel wall and travels through the bloodstream • It is also given to certain people at risk for forming blood clots, such as those with artificial heart valves or who have atrial fibrillation (AF)

9. A-Parenteral Anticoagulants 1-Heparin and Related Drugs 1-Heparin (unfractionated) • Sources • Lungs of cattle • Intestines of pigs • Rapid-acting anticoagulant • Uses • Pulmonary embolism (PE) • Stroke evolving • Massive deep venous thrombosis (DVT) .

10. A-Parenteral Anticoagulants I:1-Heparin and Related Drugs (cont’d) • Adverse effects – Hemorrhage – Heparin-induced thrombocytopenia – Hypersensitivity reactions • Protamine Sulfate[ antidote] • Activated partial thromboplastin time (APTT) for monitoring.

11. 2-Low-Molecular-Weight Heparins • Heparin preparations composed of molecules that are shorter than those found in unfractionated heparin as ENOXAPARIN. • Therapeutic use • Prevention of DVT following surgery • Treatment of established DVT • Prevention of ischemic complications • Adverse effects and interactions • Bleeding • Immune-mediated thrombocytopenia • Cost .

12. 3-Fondaparinux [Arixtra] • Synthetic anticoagulant • Selective inhibition • Therapeutic use • Prevention of DVT following surgery • Treatment of acute PE (in conjunction with warfarin) • Treatment of acute DVT (in conjunction with warfarin) • Adverse effects • Bleeding • Patients weighting less than 50 kg • Thrombocytopenia • Spinal or epidural hematoma

13. 4-Direct Thrombin Inhibitors • Bivalirudin [Angiomax], Lepirudin • Argatroban • Desirudin • Therapeutic use • Prevent clot formation (combined with aspirin) • Mechanism of action • Facilitates the actions of antithrombin • Prevents the conversion of fibrinogen into fibrin • Prevents the activation of factor XIIIa • Adverse effects • Back pain • Nausea • Headache

14. B-Oral Anticoagulant1-WARFARIN • Oral anticoagulant • Antagonist to vitamin K • Blocks the biosynthesis of factors VII, IX, X, and prothrombin • Therapeutic uses • Long-term prophylaxis of thrombosis • Prevention of venous thrombosis and associated pulmonary embolism • Prevention of thromboembolism (in patients with prosthetic heart valves) • Prevention of thrombosis during atrial fibrillation

15. Warfarin, an Oral Anticoagulant (cont’d) • Adverse effects • Hemorrhage • Fetal hemorrhage and teratogenesis from use during pregnancy • Not to be Used during lactation WARNING? .

16. Warfarin, an Oral Anticoagulant (cont’d) • Drug interactions • Drugs that increase anticoagulant effects[ CYT P450 inhibitors as cimetidine] • Drugs that promote bleeding • Drugs that decrease anticoagulant effects[CYT P 450 INDUCERS AS PHENYTOIN] • Heparin • Aspirin • Acetaminophen

17. 2-Dabigatran etexilate • Dabigatranetexilate is a new oral direct thrombin inhibitor and the prodrug of dabigatran • Dabigatran is a small molecule that reversibly inhibits both free and clot-bound thrombin by binding to exosite 1 and/or the active site of thrombin

18. The future for anticoagulants • Molecular targets are factor IIa (thrombin) and factor Xa • The two candidate compounds, one direct thrombin inhibitor (dabigatran etexilate) and one direct factor Xa inhibitor (rivaroxaban) are hoping to be approved as new oral anticoagulants in the near future

19. 2-Antiplatelet Drugs • Aspirin (ASA) • Inhibition of cyclooxygenase • Adverse effect • Increase risk of GI bleeding • Ticlopidine [Ticlid] • Inhibits ADP-mediated aggregation • Adverse effects • Hematologic effects • Clopidogrel [Plavix] • ADP receptor antagonist

20. Antiplatelet Drugs (cont’d) • Glycoprotein (GP) IIb/IIIa receptor antagonists • Most effective antiplatelet drugs esp. in acute coronary syndromes. • Reversible blockade of platelet GP IIb/IIIa receptors • EXAMPLE: ABCIXIMAB

21. 3-Thrombolytic Drugs Drugs that break down, or lyse, preformed clots Older drugs streptokinase and urokinase Newer drugs Tissue plasminogen activator (t-PA) Anisoylated plasminogen-streptokinase activator complex (APSAC)

22. Thrombolytic Drugs (cont’d) • Streptokinase • Binds plasminogen • Uses • Myocardial infarction • Deep vein thrombosis • Massive pulmonary emboli • Adverse effects • Bleeding – Antibody production • Hypotension • Fever

23. Thrombolytic Drugs (cont’d)NEW COMPOUNDS anistreplase (Eminase) alteplase (t-PA, Activase) reteplase (Retavase) tenecteplase (TNKase)

24. Thrombolytic Drugs Indications Acute MI Arterial thrombolysis DVT Occlusion of shunts or catheters Pulmonary embolus Acute ischemic stroke

25. Thrombolytic Drugs: Adverse Effects Bleeding Internal Intracranial Superficial Other effects Nausea, vomiting, hypotension, anaphylactic reactions Cardiac dysrrhythmias; can be dangerous

26. Thank you !