Chapter 10. Thrombolytic Agents

摘要: Publisher Summary lntravascular thrombi, leading to myocardial infarction, stroke, pulmonary embolism, or peripheral occlusion are the major cause of mortality and much morbidity in economically advanced countries. Administration thrombolytic agents, that currently plasminogen activators, is an efficient means restore blood flow, preserving life limb. This chapter discusses new molecular clinical progress, activators under study, problems remaining thrombolysis. Fibrin-specificity a activator refers relative activation clot-bound versus free depends on many factors. Free adopts compact conformation resistant activate exists more open accessible structure, like lys-plasminogen. The most specific use tPA prourokinase (proUK) least streptokinase. Fibrin specificity does not lead greater safety, but enhances efficacy, via preservation circulating plasminogen, needs sustain activity systemically administered activators. Partial degradation fibrinogen, by leads accumulation clottable truncated fibrinogen known as X-fragment (XF). Plasminogen has higher affinity for polymerized XF than fibrin, binding their end-to-end junctions. Resistance lysis affected, presence natural inhibitors. Anisoylated plasminogen-SK complex prodrug form SK, which essential active site serine complexed SKlys-plasminogen blocked, hydrolytically labile group.