Myocardial infarction Alteplase

Alteplase is a recombinant tissue plasminogen activator (rt-PA). As a result of its production in eukaryotic Chinese hamster ovary (CHO) cells, carbohydrate residues are present as in the native substance. At the therapeutically used dosage, alteplase loses its fibrin dependence and thus also activates circulating plasminogen. In fresh myocardial infarctions, alteplase appears to produce better results than does streptokinase. 

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. 

Gillis, J. et al. (1995). Alteplase. A reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction. Drugs 50(1), 102-136. 

Activase (Alteplase, rh-tPA produced in CHO cells) Genentech Acute myocardial infarction 1987 (USA)... 

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. 

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). 

Doggrell SA. Alteplase descendancy in myocardial infarction, ascendancy in stroke. Expert Opin Investig Drugs. 2001 10 2013-2029. 

Genentech Activase (alteplase) Acute myocardial infarction 2005, 2010 2005... 

Vermeer R Vahanian A, Fels PW, et al. Argatroban and alteplase in patients with acute myocardial infarction the ARGAMI study. J Thromb Thrombolysis 2000 10 233-240. 

Alteplase was the first commercially available recombinant tissue-type plasminogen activator (rt-PA) (25), It has a plasma half-life of less than five minutes and is metabolized by the liver, This agent was initially hailed as fibrin-specific unlike its precursors (urokinase and streptokinase). It was thought that this would result in a better safety profile, but this has not been born out in either the coronary or the peripheral experience, where actually there may be a higher bleeding risk as infusion time increases. Alteplase is currently indicated for use in the treatment of myocardial infarction, acute ischemic stroke, and pulmonary embolism. 

Acute myocardial infarction (MI) Fibrinolytic therapy Streptokinase Alteplase Reteplase Heparin Aspirin Reduced coronary and all-cause mortality GISSI-1 ISIS-2 GISSI-2/ISG ISIS-3 GUSTO >120,000 10... 

Therapeutic Activase /Alteplase tPA Acute myocardial infarction... 

Alteplase and Tenecteplase ) are used in the treatment of acute myocardial infarction. 

Therapeutic uses Currently alteplase is approved for the treatment of myocardial infarction, massive pulmonary embolism, and acute ischemic stroke. Alteplase seems to be superior to streptokinase and urokinase in dissolving older clots, and may ultimately be approved for other applications. Alteplase administered within 3 hours of the onset of ischemic stroke significantly improves clinical outcome, that is, the patients ability to perform activites of daily living. 

Protein manipulation for enzyme proteins can serve as a good example of several possible manipulations. Alteplase is a thrombolysis enzyme protein used to prevent death in acute myocardial infarction. The protein has 527 amino acids, 5 disulfide bridges, glycosylation at several amino acids, and 5 peptide domains. Truncation of most domains leaving intact the protease domain resulted in a new biological, reteplase (Retevase), with quite similar thrombolytic activity. Another set of... 

Alteplase (r-TPA) Activase (Genentech) Acute myocardial infarction pulmonary embolism stroke CVT clot removal... 

There were no differences in the activities of serum transaminases, lactate dehydrogenase, or creatine kinase in patients with myocardial infarction who received an 18-hour infusion of urokinase compared with patients who received glucose alone (38), but subacute alterations of liver function tests have been described with streptokinase and anistreplase (39). Unexplained increases in transaminase activities have been reported in almost 25% of patients treated with streptokinase (40). In view of the greater prominence of liver dysfunction with streptokinase than with alteplase it could be wiser to choose alteplase rather than streptokinase in patients with previous impaired hepatic function (41). 

The combination of thrombolytic agents with an anticoagulant and/or aspirin has been said to be life-threatening. An excess of major bleeding episodes with combined subcutaneous heparin and streptokinase or alteplase treatments (1.0% with heparin versus 0.5% without heparin) has been reported in the International Study Group Trial (103) in patients with suspected acute myocardial infarction. 

The International Study Group. In-hospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet 1990 336(8707) 71-5. 

The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators. A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Med 1997 337 1118-1123. 

Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction The ASSENT-2 double-blind, randomized trial. Lancet 1000 354 716-722. 

Gruppo ItaUoano per Lo Studio della Sopravvivenza NelPinfarcto Myio-cardio. GISSI-2 A factorial randomised trial of alteplase versus streptokinase andheparin versus no heparin among 12,490 patients with acute myocardial infarction. Lancet 1990 336 65-71. 

Cannon CP, Gibson CM, McCabe CH, et al. TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators. Circulation 1998 98(25) 2805-14. 

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