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Pathway Description
Argatroban Action
Homo sapiens
Drug Action Pathway
Argatroban is a univalent direct thrombin inhibitor, which means that it binds directly to the active site of thrombin, preventing it from catalyzing the activation of coagulation factors V, XIII and fibrinogen.
The drug is injected intravenously, where it can bind any thrombin within the blood stream. This direct binding prevents any other molecules from using thrombin as an enzyme. It prevents catalyzation of factor V to factor Va, which would form the prothrombinase complex and create more thrombin. It also prevents the catalysis fibrinogen or factor I to fibrin, which then polymerizes to form the blood clot. The lack of useable thrombin also prevents the catalysis of factor XIII to factor XIIIa, which is necessary to crosslink the polymerized fibrin to form a water insoluble clot.
References
Argatroban Action References
Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. doi: 10.1056/NEJMra044440.
Pubmed: 16148288
Kawada T, Okada Y, Hoson M, Endo S, Yokoyama M, Kitanaka Y, Kimura K, Abe H, Yamate N: Argatroban, an attractive anticoagulant, for left heart bypass with centrifugal pump for repair of traumatic aortic rupture. Jpn J Thorac Cardiovasc Surg. 1999 Mar;47(3):104-9.
Pubmed: 10226408
Sakai M, Ohteki H, Narita Y, Naitoh K, Natsuaki M, Itoh T: Argatroban as a potential anticoagulant in cardiopulmonary bypass-studies in a dog model. Cardiovasc Surg. 1999 Mar;7(2):187-94.
Pubmed: 10353669
Jang IK, Brown DF, Giugliano RP, Anderson HV, Losordo D, Nicolau JC, Dutra OP, Bazzino O, Viamonte VM, Norbady R, Liprandi AS, Massey TJ, Dinsmore R, Schwarz RP Jr: A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study. J Am Coll Cardiol. 1999 Jun;33(7):1879-85. doi: 10.1016/s0735-1097(99)00107-2.
Pubmed: 10362188
Matsuo T, Kario K, Matsuda S, Yamaguchi N, Kakishita E: Effect of Thrombin Inhibition on Patients with Peripheral Arterial Obstructive Disease: A Multicenter Clinical Trial of Argatroban. J Thromb Thrombolysis. 1995;2(2):131-136.
Pubmed: 10608016
Serebruany VL, Jang IK, Giugliano RP, Massey TJ, Schwarz Jr RP: A Randomized, Blinded Study of Two Doses of Novastan(R) (Brand of Argatroban) Versus Heparin as Adjunctive Therapy to Recombinant Tissue Plasminogen Activator (Accelerated Administration) in Acute Myocardial Infarction: Rationale and Design of the Myocardial Infarction using Novastan(R) and T-PA (MINT) Study. J Thromb Thrombolysis. 1998;5(1):49-52.
Pubmed: 10608050
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
Pubmed: 11752352
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