Streptokinase action

Tissue Plasminogen Aetivator (tPA). While streptokinase and urokinase can effectively induce clot dissolution in the majority of patients if given early, they lack clot specificity. Treatment with these enzymes results in a systemic lytic state attributable to their degradative action on circulating fibrinogen. Tissue plasminogen activator (tPA) was developed to achieve rapid and specific thrombolysis. 

Figure 51-7. Scheme of sites of action of streptokinase, tissue plasminogen activator (t-PA), urokinase, plasminogen activator inhibitor, and Kj-antiplasmin (the last two proteins exert inhibitory actions). Streptokinase forms a complex with plasminogen, which exhibits proteolytic activity this cleaves some plasminogen to plasmin, initiating fibrinolysis. 

Mammahan blood will clot spontaneously if allowed to stand however, on further standing, this clot may dissolve as a result of the action of a proteolytic enzyme called plasmin. Plasmin is normally present as its inactive precnrsor, plasminogen. Certain strains of streptococci were fonnd to produce a substance which was capable of activating plasminogen (Fig. 25.3), a phenomenon that suggested a potential use in liquefying clots. This snbstance was isolated, found to be an enzyme and called streptokinase. 

A 47-year-old female comes to the emergency department (ED) with severe crushing chest pain of one hour s duration Electrocardiogram and blood chemistries are consistent with a diagnosis of acute ME Streptokinase is chosen as part of the therapeutic regimen. What is its mechanism of action ... 

The need for a rapid onset of action (and/or clearance) usually requires that an IV route be used, although at a certain stage of cardiopulmonary resuscitation (for example), the need for an even more rapid effect may require the use of an intracardiac injection. The required site of action may influence the choice of route of administration (e.g., certain radiopaque dyes are given intraarterially near the site being evaluated streptokinase is sometimes injected experimentally into the... 

Urokinase 411 aa two-chain Cultured human Similar action as streptokinase... 

At present, the binary water-soluble preparation of heparin and proteolytic enzymes is being applied for the treatment of thromboses. For instance, injection into the bloodstream of heparin-plasmin complex or a heparin-plasmin-streptokinase preparation leads to the total dissolution of the thrombus, while if introduced separately, heparin and streptokinase do not display the lytic action at all, and plasmin, alone or together with streptokinase, dissolves the thrombus only partially 132>. The treatment of acute thrombophlebitis with trypsin resulted in a full dissolution of the thrombus and in an increase of antithrombin III in the blood 133). Administration of trypsin together with heparin has an effect similar in efficiency to the action of the heparin-plasmin complex 134>. The use of a mix of heparin and urokinase for improving tbrom-boresistance of polymeric materials was also described 13S). These substances were immobilized by preliminary coating of the surface of a polymer with a graphite layer and subsequent adsorption of heparin and the enzyme. 

UK is nonantigenic and its mechanism of action is much more direct compared with that of streptokinase. UK cleaves plasminogen, by first-order reaction kinetics, to form plasmin. It is pH and temperature stable. The lack of circulating neutralizing antibodies and its direct mechanism of action allow for a predictable dose response relationship. 

Urokinase is an endogenous plasminogen activator that occurs in different organs. Urokinase used therapeutically is obtained from human cultured kidney cells. Circulating antibodies are not expected. The substance is more expensive than streptokinase and also does not depend on fibrin in its action. 

Q8 Explain why thrombolytic therapy may be necessary and the pharmacological actions of streptokinase. 

Anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC), is the plasminogen-streptokinase complex (above) in which the enzyme centre that converts plasminogen to plasmin is protected from deactivation, so prolonging its action. 

Acylated (or anisoylated) plas minogen streptokinase Effective, prolonged action, modest cost Antigenic, allergic reactions... 

Streptokinase is removed from circulation by antibodies and the reticuloendothelial system. Its half-life is biphasic initially it is 18 minutes (from antibody action) and then extends up to 83 minutes. Anticoagulant effects may persist for 12 to 24 hours after infusion is discontinued. 

F. 45.7. Regulation of plasmin activation. Plasminogen can be activated by either t-PA or scu-PA (+). PAI-1 blocks t-PA action (-). Streptokinase binding to plasminogen allows autocatalysis to form plasmin. Circulating a2-antiplasmin blocks (—) the activity of any soluble plasmin that may be in the blood. 

Anistreplase Prodrug streptokinase plus recombinant human plasminogen 1-2 hours Slowly releases streptokinase-activated plasminogen single bolus administration provides bng duration of action... 

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