Fibrinolytic enzyme drugs

An important application of fibrinolytic drugs has been to dissolve thrombi in acutely occluded coronary arteries, thereby to restore blood supply to ischaemic myocardium, to limit necrosis and to improve prognosis. The approach is to give a plasminogen activator intravenously by infusion or by bolus injection in order to increase the formation of the fibrinolytic enzyme plasmin. Those currently available include ... 

Figure 34—3. Diagram of the fibrinolytic system. The useful thrombolytic drugs are shown on the left in bold type. These drugs increase the formation of plasmin, the major fibrinolytic enzyme. The activator shown in the shaded box is a complex of streptokinase and plasminogen. Aminocaproic acid, a useful inhibitor of fibrinolysis, is shown on the right. (Reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill. 2001.)...

Such clots—also known as emboli—present a serious hazard by their potential for blocking circulation of blood to vital organs. The considerable research devoted to agents that will lyse the fibrin in clots has led to the development of the clinically useful agent, uj-okinase. This drug is a fibrinolytic proteinaceous enzyme isolated from human urine. The difficulty involved in isolation of significant amounts and the antigenicity of urokinase and a related... 

Although most of the enzyme-based drugs are inhibitors of enzymes, a number of enzyme preparations have also been developed as drugs for the treatment of a number of diseases. The development of enzymes as therapeutics has been made easier due to the advances in biotechnology. Most successful example of enzyme therapy includes various preparations of plasminogen activators (thrombolytic or fibrinolytic agents) such as a bacterial protein streptokinase and two plasminogen activators... 

A study in coronary patients has shown that fibrinogen levels are Increased over normal controls ° and that fibrinolytic activity is also decreased in these patients.The rate of degradation of fibrinogen is inhibited in rats fed an atherogenic diet. It would seem reasonable then that some control over the clinical outcome of atherosclerosis could be had by the use of fibrinolytic agents. The enzymes streptokinase and urokinase continue to be evaluated with some benefits reported in the therapy of acute Thromboembolism.Phenformin is still the only drug of interest as a fibrinolytic agent other than the enzymes and CPIB mentioned earlier. 

Fibrinolytic drugs are all proteins which act to promote the formation of plasmin, which is the enzyme in the body responsible for breaking down fibrin, the protein... 

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