TABULATE THE DIFFERENCES BETWEEN RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR ( r t PA ) AND TENECTEPLASE ?
A 9 INTRODUCTION
1 Tissue plasminogen
activator (abbreviated tPA orPLAT) is a protein involved in the breakdown of bloodclots.
2 It is a serine protease found on endothelial cells, the cells that line the blood vessels.
3 As an enzyme, it catalyzes the conversion ofplasminogen to plasmin, the major enzyme responsible for clot breakdown.
4 Because it works on the clotting system, tPA (such as alteplase, reteplase, and tenecteplase) is used in clinical medicine to treat embolic or thrombotic stroke.
5 Use is contraindicated in hemorrhagic stroke and head trauma.
6 The antidote for tPA in case of toxicity is aminocaproic acid.
7 Should be used within 3 hours of ischemic stroke not the hemorrhagic stroke *** vv imp
8 Streptokinase is a first generation thrombolytic agent.
A ) Streptokinase is an antigenic compound isolated and derived from purified streptococci bacteria.
B ) Therefore streptokinase is not a protease but binds to plasminogen for the generation of plasmin and is not restricted at the site of thrombus formation.
C ) Because of its non lysine specificity, Streptokinase, produces more fibrin degradation products (fibrinogensis) as a result of widespread lytic action in the body.
D ) Fibrinogensis occurs when there are high levels of fibrin in the blood and can cause thrombosis, haemorrhage or tissue oedema.
E ) Although much less expensive, this makes Streptokinase a less attractive agent for acute treatments in ischemic stroke than tPA products.
F ) Studies of streptokinase in acute stroke were stopped due to an increase in mortality compared to placebo due to increased haemorrhage rates
Thus , specificity of tPA drugs (Alteplase, Retaplase, Tenecteplase and desmoteplase) for plasminogen bound fibrin means that conversion of plasminogen to plasma occurs in clots with minimal circulating plasma.
DIFFERENCES
1 Tenecteplase has fewer bleeding complications as compared to alteplase ( 0.9 mg / kg ) since it has greater fibrin specificity
2 In pilot testing, tenecteplase ( 0.1 to 0.5 mg / kg ) seemed to offer therapeutic benefit among stroke patients at doses that were lower than those used for acute coronary syndromes as compared to alteplase
So , Tenecteplase has lower dose requirement or adjustment as compared to alteplase
3 Tenecteplase has longer half life as compared to alteplase
4 Tenecteplase has a better ability to achieve reperfusion compared with alteplase
5 Tenecteplase is also called the TNK-mutant of alteplase
A ) The molecule does not constitute a deletion mutant of alteplase (as reteplase does)
B ) Instead, it consists of the alteplase molecule with the exception of three point mutations
1 At position 103 of the polypeptide the aminoacid threonine has been replaced by asparagine leading to a new glycosylation site.
2 The carbohydrate chain that is linked to this site enlarges the molecule, thereby reducing its elimination and prolonging its plasma half life.
3 At position 117 asparagine has been replaced by glutamine. By the exchange of this amino acid the carbohydrate side chain that facilitates hepatic elimination has been removed.
4 The amino acids that were replaced at the three positions are called T, N, and K according to the one letter code for amino acids, which leads to the expression TNK-mutant.
6 Tenecteplase has been tested extensively in clinical trials. In the ASSENT-1 (assessment of safety and efficacy of a new thrombolytic agent) trial in patients with acute myocardial infarction, single bolus tenecteplase proved to be as safe as the gold standard of thrombolytic therapy as compared to the accelerated regimen of alteplase (initial bolus followed by an infusion over 90 minutes)
7 Tenecteplase in comparison with alteplase is equal in efficacy and superior in its application as a single bolus that also facilitates prehospital initiation of reperfusion therapy.
8 Tenecteplase, used in conjunction with advanced imaging selection, resulted in more effective reperfusion than alteplase, which translated into increased clinical benefit.
9 Tenecteplase is of 3rd generation as compared to alteplase which is of 2nd generation
10 Reocclusion of a coronary vessel is high with alteplase ( 30 % ) than tenecteplase