第29章 作用于血液及造血器官的药物.pptVIP

Drugs used in Disorders of coagulation治疗凝血功能障碍的药物 Chen Nana Institute of Pharmaceutical Sciences , College of Pharmaceutical Sciences Excessive bleeding and thrombosis may represent altered states of hemostasis（止血）. Impaired hemostasis results in spontaneous bleeding; stimulated hemostasis results in thrombus（血栓)formation. The drugs used to arrest abnormal bleeding and to inhibit thrombosis（血栓形成） are the subjects of this chapter. Hemostasis: Cessation of bleeding from an injured blood vessel Primary Hemostasis The process occurs within seconds Vasospasm: Vasoconstriction of the blood vessel by Thromboxane A2 (TXA2) and serotonin (5-HT). Slows down the bleeding. Platelet Plug: Platelet aggregation and Adherence of platelets to collagen of damaged endothelial cells. Secondary Hemostasis This process takes several minutes. Stabilizes the soft clot and maintains vasoconstriction. Fibrin Clot: Conversion of prothrombin to thrombin. Thrombin stimulates the conversion of fibrinogen (Blood protein) to polymerized fibrin (mesh). Dissolution of the clot by fibrinolysis: Plasminogen is converted to plasmin, the enzyme that dissolves the fibrin. Coagulation Factors: The active heparin molecules bind tightly to antithrombin Ⅲ and cause a conformational change in this inhibitor. The conformational change of antithrombin exposes its active site for more rapid interaction with the proteases (the activated clotting factors). Pharmacokinetics: Administration: Not absorbed from the gut; i.v. and s.c.. Hepatic elimination and excretion，some excreted unchanged in urine. Dosage is determined by the activated partial thromboplastin time (aPTT; 1.5-2 times is normal). Clinical Use: Prevention and treatment of thrombosis and embolism (i.e., post-op or following myocardial infarction), deep vein thrombosis, pulmonary embolism、brain thrombosis , peripheral arterial thrombosis, etc. DIC (disseminated intravascular coagulation，弥散性血管内凝血): If use heparin early