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

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 .

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 Causes a plug for bloodstream

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

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

Mechanism of platelet aggregation and actions of antiplatelet drugs.

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

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) intravascular coagulation of the blood in any part of the circulatory system, as in the heart, arteries, veins, or capillaries

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) .

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.

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 .

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

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

B-Oral Anticoagulant 1-WARFARIN 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

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

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

2-Dabigatran etexilate Dabigatran etexilate 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

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

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

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

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)

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

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

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

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

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