Alteplase activator

The answer is c. (Katzung, pp 572—574.) Alteplase is an unmodified tPA. Alteplase activates plasminogen that is bound to fibrin. The plasmin... 

Tissue plasminogen activator (alteplase t-PA) is a serine protease that is released into the circulation from vascular endothelium under conditions of injury or... 

Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999 282 2019-2026 [see comment]. 

Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke The Standard Treatment with Alteplase to Reverse stroke (STARS) study. JAMA. 2000 283 1145-1150. 

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

With alteplase, another endogenous plasminogen activator (tissue plasminogen activator, tPA) is available. With physiological concentrations this activator preferentially acts on plasminogen bound to fibrin. In concentrations needed for therapeutic fibrinolysis this preference is lost and the risk of bleeding does not differ with alteplase and streptokinase. Alteplase is rather short-Liillmann, Color Atlas of Pharmacology... 

Alteplase Alteplase is a drag that activates human tissue plasminogen (t-PA). It is a glycoprotein of molecular mass 68,000 that is synthesized by vascular endothelial cells. t-PA cells were first isolated from cultured human melanoma cells [56-58], but currently a genetically recombined form of rt-PA is genetically engineered. 

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. 

The Arst therapeutic sAategy attempted for sAoke victims was to disrupt the embolus and thus attack the cause of ischaemia/hypoxia. This approach appeared in 1996 with the advent of a tissue plasminogen activator, alteplase, to be administered... 

Currently, in both arterial and venous occlusion, newer products such as alteplase which is recombinant human tissue-type plasminogen activator where 10 mg is given as an intitial bolus and a further 90 mg infused over 2 hours are offering alternative regimens. Although costly they have apparent benefit in stroke and acute coronary syndromes. 

Two genetically engineered variants of human t-PA have better pharmacological properties than alteplase. Reteplase (Retavase) contains only the peptide domains required for hbrin binding and protease activity. These... 

The advent of recombinant DNA technology has allowed the isolation of genes and expression of proteins that are found in biologic tissues in exceedingly small quantities. This has permitted large-scale production of enzymes such as tissue plasminogen activator (i.e., tPA, alteplase) that cannot be extracted from tissues in quantities required for therapeutic use. Table 9.2... 

Disposition Tenecteplase is metabolized in the liver, but the extent of metabolism is unknown. It is also inactivated in plasma by circulating plasminogen activator inhibitor-1. The degree of inactivation may be less than that of alteplase. 

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). 

Plasminogen can also be activated endogenously by tissue plasminogen activators (t-PAs). These activators preferentially activate plasminogen that is bound to fibrin, which (in theory) confines fibrinolysis to the formed thrombus and avoids systemic activation. Human t-PA is manufactured as alteplase by means of recombinant DNA technology. 

Activase (Alteplase) [CHO-expressed glycoprotein-recombinant human tissue plasminogen activator] Genentech Lyophilized (50 mg single-dose vial 100 mg single dose vial) 50 and 100 mg doses to be reconstituted with 50 or lOOmL of WFI, respectively Per 50 mg vial 1.7 g L-arginine 0.5 g phosphoric acid < 4 mg polysorbate 80 (under vacuum) Per 100 mg vial 3.5 g L-arginine 1 g phosphoric acid <11 mg polysorbate 80 (without vacuum) IV... 

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