Hematology and Oncology Book

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Direct Thrombin Inhibitor

Aka: Direct Thrombin Inhibitor, Hirudin, Lepirudin, Refludan, Bivalirudin, Angiomax, Desirudin, Ipravask, Argatroban, Acova
  1. Indications
    1. Thrombus prophylaxis, treatment or Unstable Angina and
    2. Heparin-Induced Thrombocytopenia
  2. Dosing: Hirudins (peptide derivatives)
    1. Lepirudan (Refludan)
      1. See other references for dosing
    2. Bivalirudin (Angiomax)
      1. Used in Unstable Angina if Heparin contraindicated
      2. Coadminister with Aspirin
      3. Initial: 0.75 mg/kg IV bolus
      4. Later: 1.75 mg/kg/hour for 4 hours
      5. Maintenance: 0.2 mg/kg/hour for up to 20 hours
    3. Desirudin (Ipravask)
      1. DVT Prophylaxis: 15 mg SQ q12 hours after hip surgery
  3. Dosing: L-Arginine derivatives
    1. Argatroban (Acova)
      1. Initial: 2 mcg/kg/minute
      2. Maintenance: Adjusted per PTT
  4. Pharmacokinetics
    1. Clearance
      1. Renal clearance for Hirudins
      2. Hepatic clearance for L-Arginine derivatives
  5. Precautions
    1. Serious Allergic Reactions may occur to Hirudins

argatroban (C0048470)

Definition (NCI) A synthetic derivative of L-arginine with antithrombotic activity. Argatroban is a univalent and direct inhibitor of fibrin-bound thrombin. This agent reversibly binds to the thrombin active site thereby preventing the thrombin-dependent reactions, which include conversion of fibrinogen to fibrin; the activation of factors V, VIII and XI; the activation of protein C; and platelet aggregation. Argatroban is highly selective for thrombin and is able to inhibit the action of both free and clot-associated thrombin. As a result, stabilization of blood clots and coagulation is inhibited.
Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C031942
SnomedCT 116508003, 398738008
English 2-Piperidinecarboxylic acid, 1-(5-((aminoiminomethyl)amino)-1-oxo-2-(((1,2,3,4-tetrahydro-3-methyl-8-quinolinyl)sulfonyl)amino)pentyl)-4-methyl-, 4-methyl-1-(N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl)-2-piperidinecarboxylic acid, MMTQAP, MPQA, 1-[5-guanidino-2-[(3-methyl-1,2,3,4-tetrahydroquinolin-8-yl)sulfonylamino]pentanoyl]-4-methyl-piperidine-2-carboxylic acid, ARGATROBAN, Argatroban (medication), argatroban [Chemical/Ingredient], Argatroban, Argatroban (product), Argatroban (substance), Argipidine, argatroban
Spanish argatrobano (sustancia), argatroban, argatroban (producto), argatrobán (producto), argatroban (sustancia), argatrobán, argatrobano
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Hirudins (C1451270)

Definition (MSH) Single-chain polypeptides of about 65 amino acids (7 kDa) from LEECHES that have a neutral hydrophobic N terminus, an acidic hydrophilic C terminus, and a compact, hydrophobic core region. Recombinant hirudins lack tyr-63 sulfation and are referred to as 'desulfato-hirudins'. They form a stable non-covalent complex with ALPHA-THROMBIN, thereby abolishing its ability to cleave FIBRINOGEN.
Definition (CSP) active principle in the buccal gland secretion (saliva) of leeches; it acts as an antithrombin and as an antithrombotic agent.
Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH D006629
English hirudin, Hirudins [Chemical/Ingredient], Hirudins
Swedish Hirudiner
Czech hirudiny
Finnish Hirudiinit
Russian GIRUDIN, GIRUDINY, ГИРУДИН, ГИРУДИНЫ
Polish Hirudyny
French Hirudines
German Hirudine
Italian Irudine
Portuguese Hirudinas
Spanish Hirudinas
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Acova (C0939245)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C031942
English Acova, SmithKline Beecham brand of argatroban
Sources
Derived from the NIH UMLS (Unified Medical Language System)


desirudin (C0378366)

Definition (NCI) A synthetic recombinant form of the naturally occurring hirudin, the anticoagulant substance found in leech. Desirudin is a selective and almost irreversible inhibitor of thrombin, both free and clot-bound, by blocking its active site. This anticoagulant agent has no effect on other components of the hemostatic system. Desirudin is particularly used to prevent deep vein thrombosis in patients undergoing hip and knee replacement surgery.
Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C060225
SnomedCT 319718008, 407117009
English desulfatohirudin, desulphatohirudin, recombinant HV1 hirudin, desirudin, 63-Desulfohirudin(Hirudo medicinalis isoform HV1), desirudin (medication), DESIRUDIN, desirudine, Desirudin (product), Desirudin, Desirudin (substance), Desirudine, Desulfatohirudin
Spanish desirudina (producto), desirudina, desirudina (sustancia), desirudin
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Angiomax (C0939677)

Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C074619
English Angiomax, The Medicines Company brand of bivalirudin
Sources
Derived from the NIH UMLS (Unified Medical Language System)


lepirudin (C0772394)

Definition (NCI) A yeast cell-derived recombinant polypeptide related to the naturally occurring, leech-derived anticoagulant hirudin. Lepirudin directly binds to and inactivates thrombin, producing dose-dependent increases in the activated partial thromboplastin time (aPTT) and prothrombin time (PT). The mechanism of action of this agent is independent of antithrombin III and is not inhibited by platelet factor 4. Natural hirudin, a family of highly homologous isopolypeptides, is produced in trace amounts by the leech Hirudo medicinalis.
Definition (NCI) A drug that inhibits blood clotting. It is being studied in cancer treatment.
Definition (PDQ) A recombinant hirudin, a polypeptide naturally produced by the leech Hirudo medicinalis, derived from yeast cells and a highly specific inhibitor of thrombin. Lepirudin directly binds to thrombin, thereby inactivating the thrombogenic activity of thrombin. This anticoagulant produces dose-dependent increases in activated partial thromboplastin time (aPTT). Its action is independent of antithrombin III and it is not inhibited by platelet factor 4. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43356&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43356&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1839" NCI Thesaurus)
Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C083544
SnomedCT 108995001, 386955005
English Recombinant Hirudin, 1-Leu-2-Thr-63-desulfohirudin, lepirudin, lepirudin (medication), lepirudin (rDNA), LEPIRUDIN, lepirudin [Chemical/Ingredient], lepirudin,recombinant, Lepirudin, Lepirudin (product), Lepirudin (substance)
Spanish lepirudina (producto), lepirudina (sustancia), lepirudina
Sources
Derived from the NIH UMLS (Unified Medical Language System)


bivalirudin (C0168273)

Definition (NCI) A 20 amino acid long synthetic peptide with thrombin-specific anticoagulant properties. Bivalirudin reversibly binds thrombin, free as well as clot bound, at the catalytic site and the anion-binding exosite, thereby preventing the formation and activation of fibrin, factor XIIIa, and other coagulation factors. This drug is primarily used during coronary angioplasty procedures, in combination with aspirin, in patients with unstable angina.
Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C074619
SnomedCT 400610005, 129498009
English Phe-Pro-Arg-Pro-(Gly)4 desulfato-Tyr63'-hirugen, Phe-Pro-Arg-Pro-(Gly)4-desulfohirudin-(53-64), L-Leucine, D-phenylalanyl-L-prolyl-L-arginyl-L-prolylglycylglycylglycylglycyl-L-asparaginylglycyl-L-alpha-aspartyl-L-phenylalanyl-L-alpha-glutamyl-L-alpha-glutamyl-L-isoleucyl-L-prolyl-L-alpha-glutamyl-L-alpha-glutamyl-L-tyrosyl-, Phe-Pro-Arg-Pro-(Gly)4-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu, bivalirudin, bivalirudin (medication), BIVALIRUDIN, bivalirudin [Chemical/Ingredient], Bivalirudin (product), Bivalirudin (substance), Bivalirudin
Spanish bivalirrudina, bivalirudina (producto), bivalirudina, bivalirrudina (sustancia), bivalirudina (sustancia)
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Refludan (C0661608)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C083544
English Refludan, lepirudin (Refludan), refludan, Hoechst Brand of Lepirudin, Aventis Behring Brand of Lepirudin, Aventis Brand Lepirudin, Aventis Pharma Brand of Lepirudin, Berlex Brand of Lepirudin, Pharmion Brand of Lepirudin, Refludin, Schering Brand of Lepirudin
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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