Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alteplase (t-PA), a recombinant analogue of human tissue plasminogen activator, became the first genetically engineered thrombolytic approved by the Food and Drug Administration in 1987 for acute myocardial infarction (AMI). In addition to AMI, alteplase is currently approved for the treatment of acute ischemic stroke and pulmonary embolism, and we anticipate approval for catheter clearance in late 2001 in a 2-mg vial configuration. With the withdrawal of human neonatal kidney cell-derived urokinase, alteplase has become an alternative agent in peripheral vascular applications. Because few interventionalists had prior experience with the handling and dosage of alteplase, the Advisory Panel to the Society of Cardiovascular and Interventional Radiology established practice guidelines for use in noncoronary applications. Emerging clinical experience with contemporary dosing regimens shows a safety and efficacy profile similar to urokinase but with significantly reduced drug costs. Tenecteplase (TNK) is a genetically modified version of alteplase. TNK is the only plasminogen activator available that has shown a significantly enhanced safety profile versus alteplase in AMI. Approved for a 5-second, single-bolus injection in AMI, TNK possesses a longer half-life, increased resistance to plasminogen activator inhibitor, and improved fibrin specificity compared with alteplase. Because of its enhanced safety profile, TNK may be a desirable agent for peripheral vascular applications. Initial clinical studies with TNK in acute arterial and venous disease are ongoing. This article outlines the Advisory Panel guidelines for using alteplase and highlights features of tenecteplase.
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PMID:Alteplase and tenecteplase: applications in the peripheral circulation. 1198 95

(1) Alteplase is the standard thrombolytic agent for treating patients under 75 years with myocardial infarction if they are seen within 6 hours. It is given as an intravenous infusion over 90 minutes in combination with aspirin and unfractionated or low-molecular-weight heparin. (2) Tenecteplase has been authorized for use in myocardial infarction as an intravenous bolus over 5 to 10 seconds. (3) The evaluation file on tenecteplase contains data from three dose-finding studies and one double-blind trial against alteplase in nearly 17 000 patients. The trial found no difference in mortality between the two treatments (6% at 30 days). Nor was there any substantial difference in serious adverse events (stroke, intracranial haemorrhage or heart failure). (4) Major haemorrhage was slightly less frequent in patients given tenecteplase, but there was no difference between groups in the incidence of intracranial haemorrhage or stroke. (5) A comparative trial suffering from a number of biases suggests that combined treatment with tenecteplase + enoxaparin has a similar risk-benefit ratio to combined treatment with tenecteplase + unfractionated heparin. The combination of tenecteplase and enoxaparin makes treatment simpler, which could be particularly useful prior to hospital admission. A smaller trial of alteplase + enoxaparin against alteplase + unfractionated heparin gave similar findings. (6) In practice, tenecteplase has the advantage of a more convenient administration; a very large trial strongly suggests that its effects are almost identical to those of alteplase.
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PMID:Tenecteplase: new preparation. Another thrombolytic agent for myocardial infarction: a slightly simpler treatment. 1206 43

Several studies since 1998 have shown the efficacy of catheter-directed thrombolytic therapy with reteplase. Reteplase is a plasminogen activator that penetrates the thrombus and causes lysis. This catheter-directed approach has been used to treat both arterial and venous occlusions, with a success rate of 72% to 88%. The most serious complication associated with thrombolytic therapy is intracranial hemorrhage. Patients should be admitted to the intensive care unit for monitoring of neurological status, vital signs, laboratory values (hematocrit, hemoglobin level, activated partial thromboplastin time, and fibrinogen concentration), and bleeding or oozing at puncture sites. Staff nurses in the intensive care unit must be aware of this important thrombolytic therapy, its indications, and its implications for nursing interventions.
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PMID:Reteplase: nursing implications for catheter-directed thrombolytic therapy for peripheral vascular occlusions. 1238 13

Hemodialysis patients frequently require temporary venous catheters until suitable arteriovenous (AV) access can be placed and used for cannulation. However, these temporary catheters often occlude before the AV access has matured. The National Kidney Foundation (NKF) recommends using urokinase to clear the thrombus before progressing to the more invasive and costly procedure of catheter replacement, but urokinase is not currently available. The recombinant tissue-plasminogen activator, reteplase (Retavase, Centocor, Inc., Malvern, PA) was used to clear catheters in 62 patients (a total of 199 doses) at two for-profit outpatient hemodialysis centers with an overall success rate of 91.4% and a minimal cost of $44 per dose. Reteplase was found to be an efficacious and cost-effective alternative to urokinase in the treatment of occluded dialysis venous catheters.
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PMID:The efficacy of reteplase in the treatment of thrombosed hemodialysis venous catheters. 1214 62

The effectiveness of alteplase and urokinase in restoring adequate hemodialysis blood-flow rates was examined. A retrospective review of the medical records of hemodialysis patients with central venous catheters receiving alteplase or urokinase for presumed catheter thrombosis between June 1997 and December 2000 was conducted. Patients received 1 mL of alteplase 1 mg/mL or 1 mL of urokinase 5000 units/mL in each catheter port. The choice of the thrombolytic agent was left to the prescriber. Effectiveness of thrombolysis was defined as achieving a posttreatment hemodialysis blood-flow rate of > 300 mL/min, maintained for at least 30 minutes during the dialysis session. Inclusion criteria included adherence to the thrombolytic protocol and the inability to achieve a hemodialysis blood-flow rate of > 300 mL/min during the first 60 minutes of the hemodialysis session despite at least one attempt to reposition the catheter. Both thrombolytic agents significantly increased the hemodialysis blood-flow rates. Patients with alteplase-treated catheters were twice as likely to achieve hemodialysis blood-flow rates of > 300 mL/min (p = 0.0134) and were more likely to complete hemodialysis during that session (93% versus 70%, p = 0.0234). The percentage of functioning catheters at a subsequent hemodialysis session did not significantly differ between groups (p = 0.0806). The majority of patients in both treatment groups required no further interventions. Hemodialysis blood-flow rates increased after either alteplase 1 mg/mL per port or urokinase 5000 units per port was used to clear presumed catheter thrombosis. Alteplase was more likely than urokinase to result in a hemodialysis blood-flow rate of > 300 mL/min.
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PMID:Alteplase versus urokinase in restoring blood flow in hemodialysis-catheter thrombosis. 1216 43

The field of intravenous and intra-arterial thrombolysis for the treatment of acute ischemic stroke is rapidly advancing. Limitations of existing thrombolytic agents have prompted the development of new thrombolytic agents over the last decade. These new agents are broadly classified as third generation thrombolytics. Two of the several third generation thrombolytic agents have been investigated for the treatment of acute ischemic stroke and include tenecteplase (Genentech Inc) and reteplase (Roche Holding AG). By virtue of structural modifications, third generation thrombolytics have longer half-lives and greater penetration into the thrombus matrix. Tenecteplase has been evaluated in experimental models of ischemic stroke. These experimental studies have observed faster and more complete recanalization of occluded arteries compared with second-generation thrombolytics. The first prospective human clinical trial evaluated the safety and efficacy of intra-arterial reteplase in 16 patients with ischemic stroke who were poor candidates for intravenous alteplase therapy. Near complete or complete recanalization was observed after treatment in 88% of the patients. The development and use of third generation thrombolytics is expected to increase the rate of recanalization and clinical recovery in patients with ischemic stroke. Clinical trials are required to determine the appropriate dose and patient selection for these emerging pharmacological agents.
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PMID:Third generation thrombolytics for the treatment of ischemic stroke. 1252 7

Tenecteplase, a new fibrinolytic with longer plasma half-life and greater specificity for fibrin than alteplase, achieves rapid thrombolysis in patients with acute myocardial infarction. Similar TIMI grade 3 flow rates at 90 minutes have been observed with tenecteplase and alteplase. The efficacy and safety of tenecteplase have been confirmed in a large trial, ASSENT-2, demonstrating similar mortality rates at 30 days and a lower rate of noncerebral bleeding complications when compared with alteplase. The convenience of a single bolus treatment may facilitate the initiation of early and efficient reperfusion. (c) 2001 Prous Science. All rights reserved.
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PMID:Tenecteplase (TNK tissue plasminogen activator): A new fibrinolytic for the acute treatment of myocardial infarction. 1273 71

The use of intravenous thrombolytic agents has revolutionised the treatment of acute myocardial infarction. However, the improved mortality achieved with these drugs is tempered by the risk of serious bleeding complications, especially intracranial haemorrhage (ICH). Tenecteplase (TNKase, Genetech Inc.) is an engineered variant of alteplase (Activase, Genentech Inc.) designed to have increased fibrin specificity, greater efficacy and a longer half-life. The longer half-life of tenecteplase compared to alteplase allows for convenient single bolus administration of the drug. In addition, tenecteplase dosing is based on actual or estimated patient weight, which enhances both the safety and efficacy outcomes. Large clinical trials have demonstrated equivalence in mortality and ICH between tenecteplase and alteplase. Compared to alteplase, tenecteplase use leads to lower rates of bleeding complications and a decreased risk of ICH among low weight, elderly women.
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PMID:Safety and efficacy of tenecteplase in acute myocardial infarction. 1274 1

Previous studies have shown that Japanese taxi drivers are exposed to more risk factors and have a higher mortality rate due to cardiovascular disease than other occupational groups. We investigated the effect of night taxi driving with a view to preventing acute events of cardiovascular disease among aged taxi drivers. Twenty-nine taxi drivers (41-67 years old) were examined for urine normetanephrine/creatinine, von Willebrand factor, anti-thrombin III, t-plasminogen activator-plasminogen activator inhibitor 1-complex, hematocrit, blood glucose and blood pressure in the morning and at midnight during a duty day and in the following morning. At the same time, the blood pressure and blood glucose of 46 taxi drivers (43-67 years old) in the morning after a night duty with little sleep and in the morning after daytime work and subsequent night sleep were compared. The results obtained indicate that the aggravation of sympathetic nervous system functions with disturbed circadian rhythms, increased blood coagulation and blood concentration, endothelial injury and the elevation of blood glucose at midnight or the next morning were induced by their night work. These conditions are supposed to favour acute vascular events in aged taxi drivers. Preventive measures considered include social support for anticoagulant food and water intake, short exercise and walking as well as taking a rest and a nap during night work.
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PMID:Searching for preventive measures of cardiovascular events in aged Japanese taxi drivers--the daily rhythm of cardiovascular risk factors during a night duty day. 1456 2

Amediplase (K(2) tu-PA) is a hybrid plasminogen activator, consisting of the kringle 2 domain of alteplase and the protease domain of urokinase. The objective of this study was to determine the in vitro clot penetration of amediplase in relation to its fibrin binding and to compare the properties with those of alteplase. The clot lysis activity of amediplase in internal clot lysis models (both purified system and plasma system) was about 10 times less than that of alteplase. The clot lysis activity of amediplase in an external clot lysis model (plasma system) was similar to that of alteplase at therapeutic concentrations around 1 micro g/ml. The fibrin-clot binding properties of amediplase and alteplase were studied in a purified system as well as in a plasma system. In both systems amediplase bound to fibrin although to a significantly lower extent than alteplase. The binding of amediplase or alteplase did not increase during plasmin-mediated degradation of fibrin. The binding of amediplase was fully inhibited by epsilon-aminocaproic acid, indicating that the observed binding was specific and occurred via the lysine binding site in the kringle of amediplase. Clot penetration was studied during pressure-driven fluid permeation using syringes containing plasma clots. Amediplase was able to enter the clot without significant hindrance, while alteplase was concentrated on the top of the plasma clot and hardly entered into the inner parts of the clot. Diffusion-driven clot penetration was studied during clot lysis using confocal microscopy. Alteplase was detected on or close to the clot surface, while two-chain urokinase, which has no affinity to fibrin, was also detected deep inside the clot. Amediplase showed a penetration behaviour, which was distinct from that of alteplase and similar to that of two-chain urokinase. We concluded that the fibrin binding of amediplase is moderate and does not hinder clot penetration under permeation-driven or diffusion-driven transport conditions. Enhanced clot penetration, especially in large clots, could allow a more efficient lysis during thrombolytic therapy.
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PMID:Clot penetration and fibrin binding of amediplase,a chimeric plasminogen activator (K2 tu-PA). 1469 68


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