Thrombolytics alteplase

Clark WM, Albers GW, Madden KR Hamilton S. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part a (a0276g) results of a double-bhnd, placebo-controlled, multicenter study. Thrombolytic Therapy in Acute Ischemic Stroke Study Investigators. Stroke. 2000 31 811-816. 

Alteplase (rt-PA Activase) is an IV thrombolytic (fibrinolytic) that was approved for acute stroke treatment in 1996 based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial.10 The current American Stroke Association guidelines include alteplase as the only Food and Drug Administration (FDA) approved acute treatment for ischemic stroke and strongly encourage early diagnosis and treatment of appropriate patients.11... 

Streptokinase is not indicated for use in acute ischemic stroke treatment. Three large randomized controlled trials evaluating streptokinase were stopped early due to a high incidence of hemorrhage in the streptokinase-treated patients.14-16 At the present time, there is no indication for the use of streptokinase or thrombolytics other than alteplase in the acute treatment of ischemic stroke. 

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. 

In the case of thrombosis-related SVCS, anticoagulation is controversial because there is a lack of survival benefit. However, thrombolytics (e.g., alteplase) and anti coagulation with heparin and warfarin may be beneficial in patients with thrombosis owing to indwelling catheters if it is used within 7 days of onset of symptoms, although catheter removal maybe required. 

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

Tissue plasminogen Thrombolytic activator (Activase, t-PA, Alteplase)... 

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). 

Intracranial bleeding Following concomitant thrombolytic therapy with alteplase (tPA) or streptokinase may be life-threatening. Carefully assess the risk of lepirudin administration vs its anticipated benefit in patients with increased risk of bleeding. In particular, this includes the following conditions ... 

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. 

F. Role in therapy Reteplase is a novel thrombolytic agent. It has a longer half-life than alteplase, which allows bolus administration. Its administration technique is much simpler than that of alteplase. In addition reteplase has achieved more rapid, complete, and sustained thrombolysis of the infarct-related artery compared to standard doses of alteplase with comparable safety. Reteplase is at least as effective as streptokinase and alteplase in AMI. 

E Role in therapy Thrombolytic agents currently licensed for the treatment of AMI in the United States include streptokinase, tissue plasminogen activator, anistreplase, reteplase, and tenecteplase. TNKase and alteplase have similar clinical efficacy for thrombolysis after myocardial infarction (i.e., similar mortality and intracranial hemorrhage rates). However, advantages of TNKase include ease and rapidity of administration, longer half-life, greater fibrin specificity, and lower noncerebral bleeding rates. Reteplase shares some characteristics of tenecteplase (e.g., similar half-life, rapid onset, and ease of administration). 

Hacke W, Kaste M, Fieschi C (1998) Randomised double-blind placebo controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 352 1245-1251... 

Davis SM, Donnan GA, Parsons MW for the EPITHET Investigators (2008). Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) a placebo-controlled randomised trial. Lancet Neurology 7 299-309... 

GLYCOPROTEIN lib/ Ilia INHIBITORS THROMBOLYTICS 1. t risk of major haemorrhage when co-administered with alteplase 2. Possible t risk of bleeding complications when streptokinase is co-administered with eptifibatide 1. Uncertain other thrombolytics do not seem to interact 2. Additive effect 1. Avoid co-administration 2. Watch for bleeding complications. Risk-benefit analysis is needed before co-administering this will involve the availability of alternative therapies such as primary angioplasty... 

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