Therapeutic Applications

Marketed since 1960, streptokinase is one of the oldest and most cost-effective thrombolytic agents in routine clinical use. It is indicated for use by either the intravenous or intra-coronary route in the management of acute myocardial infarction, for the lysis of intracoronary thrombi, and for the improvement of ventricular function. Early administration of streptokinase is correlated with greater clinical benefit, the greatest benefit being evident when streptokinase is administered within the first 4 h of symptom onset. Streptokinase is also employed for the lysis of pulmonary emboli, acute arterial thrombi, and emboli, as well as the lysis of acute and extensive thrombi of the deep veins [51,54]. Along with urokinase, it is also utilized for degrading fibrin clots in arteriovenous catheters, including clots in external arteriovenous shunts of patients on hemodialysis. Varidase (Wyeth) is another commercial preparation containing streptokinase, and is indicated for use in treating wounds and ulcers. This preparation also contains streptodornase, which helps the liquefaction of the components of dead cells and pus. The action of the two enzymes together results in clotted blood, fibrous and infected matter covering a wound to be liquefied, which helps to clean the wound. This process is called desloughing and allows new healthy tissue to grow and the wound to heal more rapidly [55].

Comparative clinical trials of the three major thrombolytic agents available (i.e., tPA, urokinase plasminogen activator, and streptokinase plasminogen activator) show that there are few advantages of using one over the other in certain clinical situations [56,57]. However, on considering the cost of the thrombolytic agents, streptokinase is the least expensive (US$200 per treatment). A major disadvantage of streptokinase is that it elicits an immune response on its introduction into the circulatory systems, which can lead to anaphylactic shock and death. The severity of the immunogenicity is dependent on the level of antibodies against streptokinase in circulation, which restricts multiple administrations of streptokinase [35]. The analysis of three trials reporting the frequency of immune response (ISI-2, ISIS-3, and GUSTO-1) revealed a rate of 4.8% of patients displaying immu-nogenicity. Allergic symptoms reported ranged from skin reactions and slight temperature elevation to rash and shivering [51]. These symptoms were not deemed severe enough to prevent continuation of streptokinase therapy. Current research on streptokinase has focused on reducing its immunogenicity, prolonging its half-life in plasma, and improving plasminogen activation [35]. Other adverse effects associated with streptokinase are hypotension, arrhythmia, and bleeding. The analysis of published data of five megatrials with almost 70,000 streptokinase patients revealed a frequency of hypotension of 11.3%, arrhythmia 9.4%, and bleeding 6.8%. The rate of intracranial hemorrhage was below 1% for all thrombolytics tested with streptokinase, the lowest rates of all [51].

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