Pharmacology of thrombolytic drugs

Streptokinase and urokinase have proved to be useful in a limited number of clinical conditions. Mainly because of the risk and unpredictability of bleeding with this first generation of thrombolytic agents, thrombolysis has not been ingrained in medical practice. In the interim, more fibrin-specific thrombolytic agents have been developed such as acylated streptokinase-human plasminogen complex, tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator (scu-PA or pro-urokinase). Only the latter two drugs do not induce major systemic fibrinogenolysis at thrombolytic effective doses. These two agents, obtained by recombinant techniques, as well as acylated streptokinase-plasminogen complex are available for clinical investigations. The first results of systemic administration of recombinant tissue-type plasminogen activation (t-PA) in patients with acute myocardial infarction were published and are promising. Continued experimentation with t-PA and pro-urokinase in evolving myocardial infarction and other thrombotic disorders is essential to better delineate their therapeutic index.