Anticoagulants

Roman Numerical Nomenclature of Blood-Clotting Factors and Some Common Synonyms Fibrinogen II Prothrombin III Thromboplastin, tissue factor IV Calcium V Proaccelerin, accelerator globulin, labile factor VI (this number is not used) VII Proconvertin, stable factor, autoprothrombin I, SPCA VIII Antihemophilic factor, Antihemophilic globulin, platelet cofactor II, Antihemophilic II. IX Plasma thromboplastin component (PTC), Christmas factor, platelet cofactor II, autoprothrombin II, antihemophilic factor B. X Stuart-Power factor, Stuart factor, autoprothrombin III XI Plasma thromboplastin antecedent (PTA), antihemophilic factor C. Hageman factor Fibrin-stabilizing factor, fibrinase, Laki-Lorand factor

Uses of anticoagulants:- in blood transfusion (maintain blood fluidity) To avoid thromboses. Drugs used to prevent thromboses are classified into:- Anticoagulants Antiplatelets drugs (Inhibitors of platelet aggregation, Prostaglandin inhibitors) Antifibrinolytic agents.

1-Anticoagulants

Agents which inhibit thrombin formation (Heparin)

Heparin is known as heparinic acid. It is a mucopolysaccharide isolated from liver. It is acidic polysaccharide molecule comprised of sulfated D-glucosamine and D-glucuronic acid residue.

Anticoagulant Mechanism

Vitamin K antagonists are classified chemically as 4-Hydroxycoumarin derivatives Indandione derivatives.

1. 4-Hydroxycoumarin derivatives

3,3̀-methylene bis[4-hydroxycoumarin] Dicumarol 3,3̀-methylene bis[4-hydroxycoumarin] Dicumarol is used alone or with heparin in the prophylaxis and treatment of intravascular clotting.

Synthesis of Dicumarol

Ethyl bis coumacetate (Tremoxan) 3,3̀-Ethoxy carbonyl methylene bis[4-hydroxycoumarin]

Warfarin Sodium (Coumadin) 3-(α-Acetonylbenzyl)-4-hydroxycoumarin By virtue of its great potency, warfarin sodium at first was considered unsafe for use in human and was used effectively as rodenticide. At the proper dose, however, it can be used in humans especially by the intravenous rout.

Synthesis

Phenprocoumon (Liquamar) 3-(α-Ethylbenzyl)-4-hydroxycoumarin Phenprocoumon has been shown to possess marked and prolonged anticoagulant activity.

2- Indandione derivatives.

Phenandione (Dindivan) 2-Phenyl-1,3indandione

Synthesis

Anisindione (Miradon) 2-(p-Methylphenyl)-1,3indandione Anisindione is a p-methoxy congener of phenandione.

2-Antiplatelets drugs

Aspirin Acetylsalicylic acid

Indomethacin

Dipyridamol (Persantin)

3-Antifibrinolytic Drugs

Streptokinase It is a protein purified from culture broths of Group C β-hemolytic streptococci bacteria. Alone it has no intrinsic enzymatic activity. To be active: It forms 1:1 complex with plasminogen. This complex acts to convert uncomplexed plasminogen to the active fibrinolytic enzyme plasmin which degrades fibrin clot.