Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptokinase and urokinase are the two thrombolytic agents currently available in the United States. These drugs promote dissolution of thrombi by stimulating the conversion of plasminogen to plasmin, resulting in an overall "lytic state" in the blood. Recent clinical trials in patients with pulmonary emboli, deep vein thrombosis, arterial thrombosis, and arteriovenous cannula occlusions demonstrated significantly greater lysis with thrombolytics than with heparin alone. However, because of the increased risk of bleeding, the use of these agents is reserved for patients in whom the therapeutic advantages outweigh the disadvantages. Contraindications are numerous and include any preexisting condition that may render the patient more susceptible to bleeding.
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PMID:Advances in thrombolytic therapy. 704 63

Fibrinolytic treatment of acute myocardial infarction with streptokinase and urokinase has now been under investigation for almost 20 years. Initially encouraging reports of beneficial effects of streptokinase were not substantiated by carefully controlled studies performed on coronary care and intensive care units. Studies carried out during the last tne years were characterized by non-uniform trial conditions and results. Similarly, to date no clearly beneficial effects of urokinase could be established. In order to provide more concise analysis, the "European Cooperative Study Group for Streptokinase Treatment in Myocardial Infarction" conducted a multi-center controlled trial. Patients were allocated to risk-groups. Three-hundred fifteen patients with medium and high risk were randomized to a 24-hour infusion of streptokinase or glucose. The overall mortality within six months was significantly lower in the streptokinase group (p less than 0.01) contributed primarily by eight of the eleven centers. Only 13.5% of patients with myocardial infarction, however, were eligible for the study. Interpretation of the results yielded no indication of the nature of the fibrinolytic effects nor how the benefit could be explained pathophysiologically. Furthermore, it remains questionable whether systemically-administered streptokinase can lyse coronary thrombosis or reduce the size of myocardial necrosis. An indirect effect of streptokinase through lowering of blood viscosity and subsequently, peripheral capillary resistance may represent a theoretical possibility. the indication of routine systemic administration of streptokinase has not yet been established. Recent reports of promising results obtained by direct, intracoronary infusion of thrombolytic agents indicate that this alternative may lead to realization of a specific effect in reduction of coronary thrombosis and, consequently, myocardial necrosis.
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PMID:[Fibrinolytic treatment of acute myocardial infarction (author's transl)]. 721 22

In patients with acute myocardial infarction (MI), quick initiation of thrombolytic therapy is the best strategy for improvement of survival and reduction of morbidity. Streptokinase, a purified product of haemolytic streptococci, is the most commonly administered agent. The compound anistreplase (a complex of streptokinase to plasminogen), is available but currently not often used. The non-antigenic competitor for these two compounds for the indication of MI is alteplase (recombinant tissue plasminogen activator, rt-PA). Due to former use of streptokinase or its derivative anistreplase, patients may develop specific antibodies to the foreign protein, whereas cross-reacting antibodies may be due to streptococcal infections. These antibodies may neutralise streptokinase or its derivative in case of (re)administration and may mediate adverse events, sometimes serious. Since advanced age by itself is certainly not a contraindication to thrombolytic therapy, and because reinfarction occurs frequently, the benefit-risk ratio of re-exposure to streptokinase or its derivative is decreased in the elderly who present with reinfarction. In the framework of tailored thrombolytic therapy, alteplase or urokinase appear to be the drugs of choice in these patients.
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PMID:Does the potential for development of streptokinase antibodies change the risk-benefit ratio in older patients? 757 82

Streptokinase remains the most widely used agent worldwide, largely because it is the cheapest. Because of cost considerations when the incremental cost of the use of accelerated TPA exceeds $35,000 (US) per life year added, and because an iatrogenically induced stroke in a patient who is otherwise likely to have a good outcome is unacceptable, streptokinase may be used in patients with small to moderate-sized infarctions and those aged less than 60 years. Streptokinase is the agent of choice in patients who have an increased risk of stroke and may be used in patients presenting after 6 hours. Streptokinase also may have a role in patients with cardiogenic shock. Administration of accelerated TPA is the treatment of choice in patients at high risk such as those with large anterior infarctions, the elderly, and patients with bypass grafts, and it is an alternative to urokinase when streptokinase has been administered previously. The most important approach is to treat as many patients as early as possible with thrombolytic therapy regardless of which agent is used. Thrombolytic therapy still is widely underused. More lives will be saved, regardless of which thrombolytic drug is used, by encouraging patients to present early, improving on the "door-to-needle" time, and treating more patients with a therapy that can save thousands of lives worldwide.
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PMID:Selecting a thrombolytic agent. 758 72

Radioactively labeled human fibrin clots were placed into veins of Macaca arctoides monkeys. Thrombolysis was recorded by the disappearance of radioactivity and by angiography. Streptokinase (SK) and urokinase (UK) induced thrombolysis was potentiated by low dose aspirin (ASA) and pentoxifylline (PE). Studies on the mechanisms of action revealed that PE inhibits platelet aggregation, releases tissue plasminogen activator (t-PA) from the endothelium, increases red cell deformability and inhibits white cell adhesion. Thrombolysis by pro-urokinase (pro-UK) was potentiated by low dose SK probably because of streptokinase-plasmin activation of pro-UK to UK. Platelet aggregation inhibitory effects, disaggregation of platelet aggregate inducing effects, and the t-PA releasing activity of PE was demonstrated in patients with obstructive cardiovascular disease. Pharmacodynamic studies suggested that PE metabolites one and five are most effective from this point of view. These metabolites are currently studied in combination with thrombolytic enzymes.
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PMID:Potentiation of thrombolytic therapy by enzyme combinations and with aspirin or pentoxifylline. 799 60

Catheter-directed thrombolytic therapy has become an important part of the treatment of patients with acute arterial and graft occlusion. The underlying pharmacologic principle is the activation of plasminogen, bound to fibrin within the thrombus. Guide-wire passage reliably predicts success of catheter-directed thrombolysis. The underlying disease process leading to thrombosis should be accurately identified and promptly corrected to reduce the probability of recurrent occlusion. Streptokinase (SK), urokinase (UK) and recombinant tissue plasminogen activator (rt-PA) are the three agents used to treat peripheral arterial occlusive disease. The evolution from SK to UK and rt-PA and improvements in techniques and delivery systems have led to improved success rates and lower complication rates. Patient selection, basic technical considerations and overall results are discussed here. The currently available thrombolytic agents, as well as those being developed, are reviewed to provide background information for current and future applications.
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PMID:Thrombolytic therapy in peripheral arterial occlusive disease: mechanisms of action and drugs available. 837 15

The 4 widely available thrombolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase), streptokinase and urokinase have revolutionised the treatment of acute myocardial infarction and are also effective in treating pulmonary embolism and peripheral arterial thrombosis. Therapeutic efficacy of the agents appears to be similar. Choice of a thrombolytic agent depends more on patient characteristics, availability and familiarity with the drug, cost and differences in tolerability. While overall thrombolytic therapy is relatively safe, these 4 agents differ in their tolerability profiles. Streptokinase has the lowest cerebral haemorrhage rate, anistreplase an intermediate and alteplase the highest rate. The incidence of total stroke is also higher with alteplase and anistreplase than with streptokinase, translating to an actual difference in patient risk of 4 extra strokes per 1000 patients treated. Risk of major bleeding is dependent on predisposing factors and seems to be similar with each agent. The incidence of hypotension with alteplase (4.3% in ISIS-3) is less than with streptokinase or anistreplase (6.8 and 7.2%, respectively in ISIS-3). The incidence of major anaphylactic reactions with streptokinase and anistreplase is low (< 1%). Urokinase and alteplase may be preferred for readministration of thrombolytic therapy and anistreplase is the agent of choice where rapid completion of therapy is desirable. The various agents may have different tolerability profiles with different adjunctive therapies and further data are therefore required.
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PMID:Comparative tolerability profiles of thrombolytic agents. A review. 847 Nov 85

Tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and streptokinase were evaluated for their ability to reduce postsurgical adhesion formation in a rat uterine horn devascularization and serosal injury model in a blinded, randomized study. Small doses of tPA, uPA, or streptokinase were delivered over approximately a 4-day period either from a biodegradable hydrogel matrix or as four daily intraperitoneal injections. The hydrogel was formed upon the uterine horns by photopolymerization of an aqueous precursor solution containing dissolved drug. A control group that received no treatment had an average extent of adhesion formation of 72 +/- 15% (mean +/- SEM, percentage of the length of the uterine horns involved in adhesions). Application of this formulation of the hydrogel alone reduced the extent of adhesion formation to 22 +/- 10% by functioning as a mechanical barrier. When tPA was released from the hydrogel, adhesion formation was reduced to 4 +/- 3%, while when tPA was given by intraperitoneal injection, adhesion formation was only reduced to 49 +/- 8%. Local delivery of urokinase reduced adhesion formation to 6 +/- 6%, but intraperitoneal injection of urokinase did not reduce adhesion formation. Streptokinase did not reduce adhesion formation when administered by intraperitoneal injection and increased adhesion formation to 45 +/- 9% when locally released relative to the hydrogel alone. These results suggest that both tPA and uPA may be used to prevent adhesion formation when delivered locally.
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PMID:Local release of fibrinolytic agents for adhesion prevention. 853 78

Intraarterial thrombolysis is used increasingly for management of arterial and bypass graft occlusions. Current research has been directed at the indications for and methods of catheter-directed thrombolysis. Streptokinase, urokinase, and tissue plasminogen activator (t-PA) are the most commonly used agents. They are administered by a variety of techniques and in various doses involving intrathrombic infusions, thrombus lacing, high-dose bolus therapy, and pulse-spray lysis. The latter methods appear to produce thrombolysis within a few hours, so this chemical therapy has the potential to become the first-line management for all episodes of acute limb ischemia. The role of thrombolysis is to return patients to their prethrombotic or preembolic state, so the underlying condition can be treated by radiologic intervention, surgery, or anticoagulation. Intraarterial thrombolysis is indicated for occlusions of less than 2 weeks' duration where the limb is able to withstand a period of further ischemia. Older occlusions should be treated by surgery, reserving intraoperative lysis for specific situations.
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PMID:Lower limb intraarterial thrombolysis as an adjunct to the management of arterial and graft occlusions. 866 48

Fibrinolytic therapy has become an accepted treatment modality for recent peripheral arterial and bypass graft occlusions and, in some cases, for chronic arterial occlusions. Streptokinase, urokinase, and tissue plasminogen activator have all been used for intraarterial infusion with varying protocols and results. This review focuses on dosing variables and clinical results for the various thrombolytic agents in peripheral arterial and bypass graft occlusions. Also discussed are new thrombolytic agents and the effects of concomitant use of other drugs as part of the treatment regimen.
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PMID:Drug variables in thrombolytic therapy. 877 Aug 44


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