血栓心血管基础精要.ppt

Slide * Slide E 1: Targets of Antiplatelet Therapy Platelets possess multiple receptors for pro-aggregatory stimuli including collagen, adenosine diphosphate (ADP) and thrombin on their surface. Binding of the ligands to these receptors triggers a cascade of intracellular signals. Thereby, the activation finally leads to the conversion of the platelet surface glycoprotein IIb/IIIa complex (GP IIb/IIIa) to a binding site for fibrinogen, von Willebrand factor and other adhesion molecules which anchor adjacent platelets into aggregates. Antithrombotic agents target different steps in this cascade of prothrombotic signals. Acetylsalicylic acid (ASA) irreversibly inhibits the cyclooxygenase and thus prevents the conversion of arachidonic acid to thromboxane A2 (TxA2). This effect translates into the inhibition of thromboxane A2-dependent platelet aggregation and vasoconstriction. Ticlopidine and Clopidogrel interfere with the signal transduction triggered by binding of adenosine diphosphate (ADP) to its platelet receptor. ADP released from activated platelets is rapidly metabolized to adenosine monophosphate (AMP) and adenosine. Adenosine is a potent inhibitor of platelet aggregation similar to prostacyclin (PgI2). Dipyridamole effectively inhibits the uptake of adenosine into cells (red blood cells, platelets, endothelial cells). Thus dipyridamole increases the local concentration of adenosine which accumulates in the microenvironment of a growing thrombus. GP IIb/IIIa antagonists block the binding of fibrinogen and other ligands to the platelet GP IIb/IIIa receptor. They inhibit platelet aggregation independently of the nature of the proaggregatory stimuli. 花生四西酸代谢产物TXA2 (platelet)PGI2(EC) Slide * 75mg即可抑制血小板聚集 血小板无合成蛋白能力 Cox失活后在血小板生存期不能得到补偿，半衰期20分钟每天一粒即可有效 100mg完全抑制TXA2的生物合成 不影响内皮细胞合成PGI2 Slide * Reference: 1. Jarvis B, Simpson K. Drugs 2000; 60: 347–77. Clopidogrel is a potent, non-competitive inhibitor of adenosine diphosphate- (ADP) induced platelet aggregat