ABSTRACT
Thrombolysis consists of the pharmacological dissolution of a blood clot by intravenous infusion of plasminogen activators that activate the fibrinolytic system. The fibrinolytic system includes a proenzyme, plasminogen, which is converted by plasminogen activators to the active enzyme plasmin, which in turn digests fibrin to soluble degradation products. Inhibition of the fibrinolytic system occurs by plasminogen activator inhibitors (mainly plasminogen activator inhibitor-1, PAI-1) and by plasmin inhibitors (mainly 2-antiplasmin) (Fig. 1.1). Thrombolytic agents that are either approved or under clinical investigation in patients with acute myocardial infarction include streptokinase, recombinant tissue-type plasminogen activator (rt-PA or alteplase), rt-PA derivatives, such as reteplase, lanoteplase and tenecteplase, anisoylated plasminogen-streptokinase activator complex (APSAC or anistreplase), two-chain urokinase-type plasminogen activator (tcu-PA or urokinase), recombinant single-chain u-PA (scu-PA or pro-urokinase, saruplase), and recombinant staphylokinase and derivatives. Fibrin-selective agents (rt-PA and derivatives, staphylokinase and derivatives and to a lesser extent scu-PA), which digest the clot in the absence of systemic plasminogen activation, are distinguished from non-fibrin-selective agents (streptokinase, tcu-PA and APSAC), which activate systemic and fibrin-bound plasminogen relatively indiscriminately (Fig. 1.1).1,2 In this chapter, we will review the physicochemical properties, mechanism of action and pharmacodynamics of presently available thrombolytic agents.
