Streptokinase, urokinase, and tissue plasminogen activator: pharmacokinetics, relative advantages, and methods for maximizing rates and consistency of lysis.
Early reperfusion of occluded coronary arteries offers great promise as a method for minimizing myocardial damage after acute myocardial infarction. Such reperfusion is usually attempted via administration of fibrinolytic agents. Urokinase may hold marginal advantages over streptokinase, especially in patients with high preexisting titers of antistreptokinase antibodies. These minor differences, however, pale in comparison to important advantages demonstrated by the newly developed agent, tissue plasminogen activator (t-PA). The advantages of t-PA derive primarily from its property of binding to, and being activated by, fibrin. Consequently the generated plasmin is also fibrin-bound, the bound plasmin is protected from circulating antiplasmin and therefore more efficiently utilized, and circulating fibrinogen is spared. Preliminary clinical experience indicates that the frequency of favorable response after intravenous administration of t-PA is considerably greater than after SK. A major determinant of clinical benefit after reperfusion is the brevity of ischemia. Selective intracoronary infusion of fibrinolytic agent produces faster lysis than does intravenous infusion, and rate of lysis may be further accelerated by transcatheter disruption of clot and intrathrombic injections of highly concentrated urokinase or t-PA. Even maximally accelerated lysis, however, cannot fully compensate for the inherent delay imposed by catheterization. For that reason, prompt intravenous infusion of fibrinolytic agents, presumably t-PA, seems preferable to the intracoronary route. In the effort to initiate fibrinolytic therapy at the earliest feasible time after infarction, administration by paramedics, or even home administration after training, is a program worthy of exploration.
D003328:Coronary Thrombosis / Q000188:drug therapy; D006801:Humans; D007700:Kinetics; D009203:Myocardial Infarction / Q000188:drug therapy*; D013300:Streptokinase / Q000378:metabolism / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism / Q000627:therapeutic use*
D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator