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CLINICAL PHARMACOLOGY 2003 (PART 29)

Occlusive vascular disease is a major cause of morbidity and mortality.There is now better understanding of the mechanisms by which the haemostatic system ensures blood remains fluid within vessels, yet forms a solid plug when a vessel is breached, and of the ways in which haemostasis may be altered by drugs to prevent or reverse (lyse) pathological thrombosis. | SECTION BLOOD AND NEOPLASTIC DISEASE This page intentionally left blank r ION Drugs and haemostasis SYNOPSIS Occlusive vascular disease is a major cause of morbidity and mortality.There is now better understanding of the mechanisms by which the haemostatic system ensures blood remains fluid within vessels yet forms a solid plug when a vessel is breached and of the ways in which haemostasis may be altered by drugs to prevent or reverse lyse pathological thrombosis. Coagulation system the mode of action of drugs that promote coagulation and that prevent it anticoagulants and their uses Fibrinolytic system the mode of action of drugs that promote fibrinolysis fibrinolytics and their uses to lyse arterial and venous thrombi thrombolysis Platelets the ways that drugs that inhibit platelet activity are used to treat arterial disease The haemostatic system is complex but can be separated into the following major components Formation of fibrin coagulation which stabilises the platelet plug Dissolution of fibrin fibrinolysis Platelets which form the haemostatic plug Bloodvessels. Drugs that interfere with the haemostatic system anticoagulants thrombolytics antiplatelet agents are valuable in the management of pathological thrombus formation within blood vessels or of pathological bleeding. They are classified according to which component of the system they affect. The blood coagulation system is shown in simplified form in Figure 28.1. It consists of glycoprotein components that circulate in necessarily inactive pro-enzyme or pro-cofactor factors V and VIII form. The activated enzymes are serine proteases. Physiological coagulation the extrinsic pathway begins when tissue factor TF tissue thromboplastin exposed by vascular injury activates and complexes with factor VII to activate factors IX and X which complex with Villa and Va respectively on membrane surfaces which provide phospholipid PL . The Xa Va complex converts prothrombin to thrombin which converts fibrinogen to .