Anticoagulants Course: Pharmacology I Course Code: PHR 213 Course Instructor: Sabiha Chowdhury Lecturer Department of Pharmacy BRAC University

Blood Coagulation Process Haemostasis (arrest of blood loss) and blood coagulation involve complex interactions between the injured vessel wall, platelets and coagulation factors.

Anticoagulants These are drugs used to reduce the coagulability of blood. They may be classified into: I. Used in vivo A. Parenteral anticoagulants Heparin, Low molecular weight heparins (ii) Direct thrombin inhibitors: Lepirudin, Bivalirudin, Argatroban B. Oral anticoagulants (i) Coumarin derivatives: Bishydroxycoumarin (dicumarol), Warfarin sod (ii) Indandione derivative: Phenindione. II. Used in vitro A. A. Heparin B. Calcium complexing agents: Sodium citrate Sodium oxalate Sodium edetate

Heparin

Antiplatelet Heparin in higher doses inhibits platelet aggregation and prolongs bleeding time. Antiplatelet drugs are the agents which can interfere with the platelet aggregation and platelet adherence and thus inhibit thrombus formation. E.g. aspirin, dihydrochloropuin, dextran. Aspirin is used in lower dose 75mg/day for heart patient but normally 300 mg/tablet Therapeutic indications: Cerebrovascular accident/ brain stroke Venous thrombosis Chronic hypertension Pulmonary embolism Coronary Thrombosis Atherosclerosis Angina Pectoris

Heparin Antagonists Protamine sulfate: It is a strongly basic, low molecular weight protein obtained from the sperm of certain fish. Given I.V. It neutralises heparin weight for weight, i.e. 1 mg is needed for every 100 U of heparin. However, it is needed infrequently because the action of heparin disappears by itself in a few hours, and whole blood transfusion is needed to replenish the loss when bleeding occurs. Protamine is more commonly used when heparin action needs to be terminated rapidly, e.g. after cardiac or vascular surgery. In the absence of heparin, protamine itself acts as a weak anticoagulant by interacting with platelets and fibrinogen. Being basic in nature it can release histamine in the body. Hypersensitivity reactions have occurred. Rapid i.v. injection causes flushing and breathing difficulty. PROTA, PROTAMINE SULFATE 50 mg in 5 ml inj.

Uses of Anticoagulants 1. Deep vein thrombosis (DVT) and pulmonary embolism (PE) 2. Myocardial infarction (MI) 3. Unstable angina 4. Rheumatic heart disease; Atrial fibrillation (AF) 5. Cerebrovascular disease 6. Vascular surgery, prosthetic heart valves, retinal vessel thrombosis, extracorporeal circulation, haemodialysis 7. Defibrination syndrome

Oral Anticoagulants (e.g. dicoumarol/ warferin) Mechanism of Action of oral anticoagulants: Dicoumarol has structural similarity with Vit-K. So this drug competitively inhibits Vit-K-epoxide reductase enzyme which is responsible for conversion of Vit-K epoxide into Vit-K. Dicoumarol (-) Vitamin-K epoxide reductase Vit-K epoxide Vitamin K Activation of factor VIII, IX, X Blood coagulation

Oral Anticoagulants (Cont.) Vitamin-K epoxide in time causes activation of coagulation factors VIII, IX, and X. So inhibition of Vit-K-epoxide conversion results in anti coagulant activity of the drug. Therapeutic Indications of Oral anti-coagulant: -Venous thrombosis -Pulmonary embolism -Acute MI patient -Ischemic heart disease/ Angina Pectoris patient -Brain stroke/ Cerebral infraction patient -Arterilal embolism -Frost bite -Acute Gangrena