Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain.
Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.
The abbreviation TNK is common for referring to tenecteplase, but abbreviating drug names is not best practice in medicine, and in fact "TNK" is one of the examples given on the Institute for Safe Medication Practices do-not-use list.
Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug.[1] The findings were published in the New England Medical Journal. Though safety has been established through previous clinical trials, there is ongoing debate about whether this is an effective treatment for ischemic stroke, and significant ongoing discussion between emergency physicians, neurologists and pharmacists about whether this treatment should be used for that indication.
The American Heart Association/American Stroke Association 2019 update to the 2018 guidelines for the Early Management of Acute Ischemic Stroke supports considering tenecteplase over alteplase in patients without contraindication to intravenous thrombolytics.[2]
Here is TNK-tPA. It is very similar to t-PA, but the glycosylation occurring in Kringle 1 is manipulated. The mutation T103N means that glycosylation occurs at that point. The mutation N117Q means that the high mannose sugar residue is absent at that point
In TNK-tPA, these amino acids have been replaced by four Alanines. This mutation is responsible for increased resistance to PAI-1.
Referencesedit
^Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. (March 2012). "A randomized trial of tenecteplase versus alteplase for acute ischemic stroke". The New England Journal of Medicine. 366 (12): 1099–1107. doi:10.1056/NEJMoa1109842. hdl:1959.13/1039697. PMID 22435369.
^Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. (December 2019). "Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association". Stroke. 50 (12): e344–e418. doi:10.1161/str.0000000000000211. PMID 31662037. S2CID 204973899.
Further readingedit
Gurbel PA, Hayes K, Bliden KP, Yoho J, Tantry US (January 2005). "The platelet-related effects of tenecteplase versus alteplase versus reteplase". Blood Coagulation & Fibrinolysis. 16 (1): 1–7. doi:10.1097/00001721-200501000-00001. PMID 15650539. S2CID 44664652.
Melzer C, Richter C, Rogalla P, Borges AC, Theres H, Baumann G, Laule M (August 2004). "Tenecteplase for the treatment of massive and submassive pulmonary embolism". Journal of Thrombosis and Thrombolysis. 18 (1): 47–50. doi:10.1007/s11239-004-0174-z. PMID 15744554. S2CID 10947258.
Ohman EM, Van de Werf F, Antman EM, Califf RM, de Lemos JA, Gibson CM, et al. (July 2005). "Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial". American Heart Journal. 150 (1): 79–88. doi:10.1016/j.ahj.2005.01.007. PMID 16084152.
De Luca G, Suryapranata H, Chiariello M (December 2005). "Tenecteplase followed by immediate angioplasty is more effective than tenecteplase alone for people with STEMI. Commentary". Evidence-Based Cardiovascular Medicine. 9 (4): 284–287. doi:10.1016/j.ebcm.2005.09.021. PMID 16380055.
"Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial". Lancet. 367 (9510): 569–578. February 2006. doi:10.1016/S0140-6736(06)68147-6. PMID 16488800. S2CID 23972378.
Bozeman WP, Kleiner DM, Ferguson KL (June 2006). "Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions". Resuscitation. 69 (3): 399–406. doi:10.1016/j.resuscitation.2005.09.027. PMID 16563599.
Hull JE, Hull MK, Urso JA, Park HA (April 2006). "Tenecteplase in acute lower-leg ischemia: efficacy, dose, and adverse events". Journal of Vascular and Interventional Radiology. 17 (4): 629–636. doi:10.1097/01.RVI.0000202751.74625.79. PMID 16614145.
Peacock M (22 March 2012). "Stroke patients make 'Lazarus-like' recovery". The World Today.
Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. (March 2012). "A randomized trial of tenecteplase versus alteplase for acute ischemic stroke". The New England Journal of Medicine. 366 (12): 1099–1107. doi:10.1056/NEJMoa1109842. hdl:1959.13/1039697. PMID 22435369.
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This article includes a list of general references but it lacks sufficient corresponding inline citations Please help to improve this article by introducing more precise citations September 2012 Learn how and when to remove this message Tenecteplase sold under the trade names TNKase Metalyse and Elaxim is an enzyme used as a thrombolytic drug TenecteplaseClinical dataTrade namesTNKaseAHFS Drugs comMonographLicense dataEU EMA by INNATC codeB01AD11 WHO Legal statusLegal statusIn general Prescription only Pharmacokinetic dataExcretionLiverIdentifiersIUPAC name Human tissue plasminogen activatorCAS Number191588 94 0 YDrugBankDB00031 YChemSpidernoneUNIIWGD229O42WKEGGD02837 YChemical and physical dataFormulaC 2561H 3919N 747O 781S 40Molar mass58951 37 g mol 1 N Y what is this verify Tenecteplase is a tissue plasminogen activator tPA produced by recombinant DNA technology using an established mammalian cell line Chinese hamster ovary cells Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA for natural human tPA a substitution of threonine 103 with asparagine and a substitution of asparagine 117 with glutamine both within the kringle 1 domain and a tetra alanine substitution at amino acids 296 299 in the protease domain Tenecteplase is a recombinant fibrin specific plasminogen activator that is derived from native t PA by modifications at three sites of the protein structure It binds to the fibrin component of the thrombus blood clot and selectively converts thrombus bound plasminogen to plasmin which degrades the fibrin matrix of the thrombus Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor PAI 1 compared to native t PA The abbreviation TNK is common for referring to tenecteplase but abbreviating drug names is not best practice in medicine and in fact TNK is one of the examples given on the Institute for Safe Medication Practices do not use list Contents 1 Research 2 Pharmacokinetics 3 Gallery 4 References 5 Further reading 6 External linksResearch editResearchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug 1 The findings were published in the New England Medical Journal Though safety has been established through previous clinical trials there is ongoing debate about whether this is an effective treatment for ischemic stroke and significant ongoing discussion between emergency physicians neurologists and pharmacists about whether this treatment should be used for that indication The American Heart Association American Stroke Association 2019 update to the 2018 guidelines for the Early Management of Acute Ischemic Stroke supports considering tenecteplase over alteplase in patients without contraindication to intravenous thrombolytics 2 Pharmacokinetics editDistribution approximates plasma volumeMetabolism Primarily hepaticHalf life elimination Biphasic Initial 20 24 minutes Terminal 90 130 minutesExcretion Clearance Plasma 99 119 mL minuteGallery edit nbsp Here is TNK tPA It is very similar to t PA but the glycosylation occurring in Kringle 1 is manipulated The mutation T103N means that glycosylation occurs at that point The mutation N117Q means that the high mannose sugar residue is absent at that point nbsp In human t PA the amino acids at position 296 299 are Lysine Histidine and two Arginines nbsp In TNK tPA these amino acids have been replaced by four Alanines This mutation is responsible for increased resistance to PAI 1 References edit Parsons M Spratt N Bivard A Campbell B Chung K Miteff F et al March 2012 A randomized trial of tenecteplase versus alteplase for acute ischemic stroke The New England Journal of Medicine 366 12 1099 1107 doi 10 1056 NEJMoa1109842 hdl 1959 13 1039697 PMID 22435369 Powers WJ Rabinstein AA Ackerson T Adeoye OM Bambakidis NC Becker K et al December 2019 Guidelines for the Early Management of Patients With Acute Ischemic Stroke 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association American Stroke Association Stroke 50 12 e344 e418 doi 10 1161 str 0000000000000211 PMID 31662037 S2CID 204973899 Further reading editGurbel PA Hayes K Bliden KP Yoho J Tantry US January 2005 The platelet related effects of tenecteplase versus alteplase versus reteplase Blood Coagulation amp Fibrinolysis 16 1 1 7 doi 10 1097 00001721 200501000 00001 PMID 15650539 S2CID 44664652 Melzer C Richter C Rogalla P Borges AC Theres H Baumann G Laule M August 2004 Tenecteplase for the treatment of massive and submassive pulmonary embolism Journal of Thrombosis and Thrombolysis 18 1 47 50 doi 10 1007 s11239 004 0174 z PMID 15744554 S2CID 10947258 Ohman EM Van de Werf F Antman EM Califf RM de Lemos JA Gibson CM et al July 2005 Tenecteplase and tirofiban in ST segment elevation acute myocardial infarction results of a randomized trial American Heart Journal 150 1 79 88 doi 10 1016 j ahj 2005 01 007 PMID 16084152 De Luca G Suryapranata H Chiariello M December 2005 Tenecteplase followed by immediate angioplasty is more effective than tenecteplase alone for people with STEMI Commentary Evidence Based Cardiovascular Medicine 9 4 284 287 doi 10 1016 j ebcm 2005 09 021 PMID 16380055 Primary versus tenecteplase facilitated percutaneous coronary intervention in patients with ST segment elevation acute myocardial infarction ASSENT 4 PCI randomised trial Lancet 367 9510 569 578 February 2006 doi 10 1016 S0140 6736 06 68147 6 PMID 16488800 S2CID 23972378 Bozeman WP Kleiner DM Ferguson KL June 2006 Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions Resuscitation 69 3 399 406 doi 10 1016 j resuscitation 2005 09 027 PMID 16563599 Hull JE Hull MK Urso JA Park HA April 2006 Tenecteplase in acute lower leg ischemia efficacy dose and adverse events Journal of Vascular and Interventional Radiology 17 4 629 636 doi 10 1097 01 RVI 0000202751 74625 79 PMID 16614145 Peacock M 22 March 2012 Stroke patients make Lazarus like recovery The World Today Parsons M Spratt N Bivard A Campbell B Chung K Miteff F et al March 2012 A randomized trial of tenecteplase versus alteplase for acute ischemic stroke The New England Journal of Medicine 366 12 1099 1107 doi 10 1056 NEJMoa1109842 hdl 1959 13 1039697 PMID 22435369 External links editMedlinePlus DrugInfo uspdi 500145 Retrieved from https en wikipedia org w index php title Tenecteplase amp oldid 1190946228, wikipedia, wiki, book, books, library,
