First Generation Thrombolytic Drugs

Streptokinase (Streptase, Kabikinase), a nonenzymatic protein from Lancefield group C (-hemolytic strepto cocci, is an indirectly acting activator of plasminogen. It forms a 1:1 complex with plasminogen, which results in a conformational change and exposure of an active site that can convert additional plasminogen into plasmin. The systemic administration of streptokinase can produce significant lysis of acute deep vein and pulmonary emboli and acute arterial thrombi. Intravenous or intra-coronary artery (IC) streptokinase is effective in establishing recanalization after myocardial infarction and in increasing short-term survival. The greatest benefit of streptokinase appears to be achieved by early intravenous drug administration. Complications associated with the administration of streptokinase include hemorrhage, pyrexia, and allergic or anaphylactic reactions. Patients may be refractory to streptokinase during therapy because of preexisting or streptokinase-induced antibodies. Streptokinase has two half-lives. The faster one (11 to13 minutes) is due to drug distribution and inhibition by circulating antibodies, and the slower one (23 to 29 minutes) is due to loss of enzyme activity.

Urokinase (Abbokinase) is a two-polypeptide chain serine protease that does not bind avidly to fibrin and that directly activates both circulating and fibrin-bound plas-minogen. The plasma half-life of urokinase is approximately 10 to 20 minutes. Urokinase is derived from human cells and thus is not antigenic. Urokinase produces a significant resolution of recent pulmonary emboli.

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