Thrombolytics urokinase

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

For patients who demonstrate continued neurological deterioration despite anticoagulation, local intrathrombus thrombolysis may be beneficial. In case series in which most patients received urokinase, favorable outcome with no major therapeutic morbidity has been described.In one study, 29 patients with angiogram-proven CVST were reviewed retrospectively. Of the 18 who received local urokinase, 17 recovered completely, and 1 was left with a mild neurological deficit. Heparin was given to four patients, three of whom made a complete recovery. Six presented in a comatose state with severe CVST and only supportive measures were used. It is difficult to draw conclusions from these data, as only patients with mild or moderately severe disease were selected for thrombolytic treatment. 

Pharmacologic management of thrombosis includes local administration of thrombolytic agents. Alteplase (2 mg per port) and reteplase (0.5 unit per port) are the two most commonly used agents today. Urokinase has been used in the past, but after its reintroduction to the United States market, the larger dosed vial size makes it less cost effective than the newer agents. 

Concomitant use with thrombolytic therapy Clinical trials in HIT patients have provided only limited information on the combined use of lepirudin and thrombolytic agents. The following dosage regimen of lepirudin was used in 9 HIT patients in the studies who presented with TECs at baseline and were started on both lepirudin and thrombolytic therapy (alteplase, urokinase, or streptokinase). 

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

Thrombolytic agents such as streptokinase, urokinase, and recombinant tissue-type plasminogen activator... 

Urokinase (UK) was the first of the thrombolytic agents to appear in widespread use in the 1990s (20). UK is a naturally occurring thrombolytic produced by renal parenchyma and is therefore found in human urine. It has a plasma half-life of 15 minutes and when administered intravenously, it is rapidly removed from circulation by hepatic clearance. 

Tepes et al. reported the first clinical experience with abcix-imab and urokinase combination therapy in the peripheral circulation (44). Schweizer et al. used abciximab and rt-PA versus rt-PA with ASA in an 84 patient trial and found a significantly shorter duration of thrombolytic infusion was required to achieve lytic success in the combination group as well as improved clinical endpoints of less re-hospitalization, re-intervention, and amputation compared to ASA and heparin (45),... 

Urokinase, the activator of fibrinolysis, excreted with the urine, has already been used as thrombolytic agent for sane time It is isolated either as low molecular weight urokinase (LMW-UK, MW 3,300 dahons) or high molecular weight urokinase (HMW-UK, MW 54,000 daltons). To prepare a urokinase delivery... 

For thrombolytic studies, bcnzoyl-urokinasc was chosen. The thrombolytic effect of acylated urokinase as compared to the free enzyme was measured in vitro and in vivo. The in vitro experiments were carded out in an artificial circulating system composed of a 1 -fibrin-labeled clot suspended in human plasma. The degree of thrombolysis was estimated from the released radoaedvity (fig, 12). From these experiments we concluded that the thrombolytic effect of benzoyl-urokinase is higher than that of urokinase. 

Urokinase is also a thrombolytic agent, used for treating pulmonary embolism. Two variants of this protease have already been isolated one of 54 kDa and another of 33 kDa, both displaying proteolytic activity over plasminogen. Until recently, the only exogenous source for this enzyme was urine. However, in 2002 the product called Abbokinase, which is produced in neonatal kidney tissue culture, was approved in the USA. 

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