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Namespace Prefixes

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Statements

Subject Item
n2:DB00682
rdf:type
n3:Drug
n3:description
Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Although originally marketed as a pesticide (d-Con, Rodex, among others), Warfarin has since become the most frequently prescribed oral anticoagulant in North America. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.
n3:dosage
n11:271B43F2-363D-11E5-9242-09173F13E4C5 n11:271B43F3-363D-11E5-9242-09173F13E4C5 n11:271B43F4-363D-11E5-9242-09173F13E4C5 n11:271B43F0-363D-11E5-9242-09173F13E4C5 n11:271B43F1-363D-11E5-9242-09173F13E4C5 n11:271B43F6-363D-11E5-9242-09173F13E4C5 n11:271B43F7-363D-11E5-9242-09173F13E4C5 n11:271B43F8-363D-11E5-9242-09173F13E4C5 n11:271B43F9-363D-11E5-9242-09173F13E4C5 n11:271B43F5-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15383473 # Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/646989 # Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/14765195 # Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/14765194 # Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12742309 # Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS: Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005 May 23;165(10):1095-106. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15911722 # Macina, Orest T.; Schardein, James L. (2007). "Warfarin". Human Developmental Toxicants. Boca Raton: CRC Taylor & Francis. pp. 193–4 # Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):160S-198S. doi: 10.1378/chest.08-0670. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18574265 # Freedman MD: Oral anticoagulants: pharmacodynamics, clinical indications and adverse effects. J Clin Pharmacol. 1992 Mar;32(3):196-209. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/1564123 # Loftus, Christopher M. (1995). "Fetal toxicity of common neurosurgical drugs". Neurosurgical Aspects of Pregnancy. Park Ridge, Ill: American Association of Neurological Surgeons. pp. 11–3.
n3:group
approved
n3:halfLife
R-warfarin t<sub>1/2</sub>=37-89 hours; S-warfarin t<sub>1/2</sub>=21-43 hours.
n3:indication
For the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis.
n3:manufacturer
n5:271B439D-363D-11E5-9242-09173F13E4C5 n5:271B439E-363D-11E5-9242-09173F13E4C5 n5:271B43A7-363D-11E5-9242-09173F13E4C5 n5:271B43A5-363D-11E5-9242-09173F13E4C5 n5:271B43A6-363D-11E5-9242-09173F13E4C5 n5:271B43A4-363D-11E5-9242-09173F13E4C5 n5:271B43A3-363D-11E5-9242-09173F13E4C5 n5:271B43A1-363D-11E5-9242-09173F13E4C5 n5:271B43A2-363D-11E5-9242-09173F13E4C5 n5:271B439F-363D-11E5-9242-09173F13E4C5 n5:271B43A0-363D-11E5-9242-09173F13E4C5
owl:sameAs
n13:DB00682 n24:DB00682
dcterms:title
Warfarin
adms:identifier
n15:Warfarin n16:10033 n17:DB00682 n18:50088240 n19:0056-0169-70 n20:PA451906 n21:C01541
n3:mechanismOfAction
Warfarin inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
n3:packager
n5:271B4388-363D-11E5-9242-09173F13E4C5 n5:271B4387-363D-11E5-9242-09173F13E4C5 n5:271B4385-363D-11E5-9242-09173F13E4C5 n5:271B4384-363D-11E5-9242-09173F13E4C5 n5:271B4376-363D-11E5-9242-09173F13E4C5 n5:271B4378-363D-11E5-9242-09173F13E4C5 n5:271B4374-363D-11E5-9242-09173F13E4C5 n5:271B4375-363D-11E5-9242-09173F13E4C5 n5:271B4372-363D-11E5-9242-09173F13E4C5 n5:271B4373-363D-11E5-9242-09173F13E4C5 n5:271B4370-363D-11E5-9242-09173F13E4C5 n5:271B4371-363D-11E5-9242-09173F13E4C5 n5:271B436E-363D-11E5-9242-09173F13E4C5 n5:271B436F-363D-11E5-9242-09173F13E4C5 n5:271B4386-363D-11E5-9242-09173F13E4C5 n5:271B4389-363D-11E5-9242-09173F13E4C5 n5:271B4381-363D-11E5-9242-09173F13E4C5 n5:271B4383-363D-11E5-9242-09173F13E4C5 n5:271B437F-363D-11E5-9242-09173F13E4C5 n5:271B4380-363D-11E5-9242-09173F13E4C5 n5:271B437D-363D-11E5-9242-09173F13E4C5 n5:271B437E-363D-11E5-9242-09173F13E4C5 n5:271B437B-363D-11E5-9242-09173F13E4C5 n5:271B437C-363D-11E5-9242-09173F13E4C5 n5:271B4379-363D-11E5-9242-09173F13E4C5 n5:271B437A-363D-11E5-9242-09173F13E4C5 n5:271B438B-363D-11E5-9242-09173F13E4C5 n5:271B4394-363D-11E5-9242-09173F13E4C5 n5:271B4382-363D-11E5-9242-09173F13E4C5 n5:271B438A-363D-11E5-9242-09173F13E4C5 n5:271B436D-363D-11E5-9242-09173F13E4C5 n5:271B4377-363D-11E5-9242-09173F13E4C5 n5:271B436B-363D-11E5-9242-09173F13E4C5 n5:271B436C-363D-11E5-9242-09173F13E4C5 n5:271B436A-363D-11E5-9242-09173F13E4C5 n5:271B438E-363D-11E5-9242-09173F13E4C5 n5:271B438F-363D-11E5-9242-09173F13E4C5 n5:271B438C-363D-11E5-9242-09173F13E4C5 n5:271B438D-363D-11E5-9242-09173F13E4C5 n5:271B439B-363D-11E5-9242-09173F13E4C5 n5:271B439C-363D-11E5-9242-09173F13E4C5 n5:271B4399-363D-11E5-9242-09173F13E4C5 n5:271B439A-363D-11E5-9242-09173F13E4C5 n5:271B4397-363D-11E5-9242-09173F13E4C5 n5:271B4398-363D-11E5-9242-09173F13E4C5 n5:271B4395-363D-11E5-9242-09173F13E4C5 n5:271B4396-363D-11E5-9242-09173F13E4C5 n5:271B4392-363D-11E5-9242-09173F13E4C5 n5:271B4393-363D-11E5-9242-09173F13E4C5 n5:271B4390-363D-11E5-9242-09173F13E4C5 n5:271B4391-363D-11E5-9242-09173F13E4C5
n3:routeOfElimination
The elimination of warfarin is almost entirely by metabolism. Very little warfarin is excreted unchanged in urine. The metabolites are principally excreted into the urine; and to a lesser extent into the bile.
n3:synonym
Coumafene Zoocoumarin 4-Hydroxy-3-(3-oxo-1-phenylbutyl)coumarin
n3:toxicity
LD<sub>50</sub>=374 (orally in mice)
n3:volumeOfDistribution
* 0.14 L/kg
n6:hasAHFSCode
n27:20-12-04-08
n3:foodInteraction
Limit garlic, ginger, gingko, and horse chestnut. Avoid St. John's Wort. Consult your doctor before ingesting large amounts of dietary Vitamin K (e.g. from green leafy vegetables). Avoid alcohol. Avoid drastic changes in dietary habit.
n3:proteinBinding
99% bound primarily to albumin
n3:salt
n3:synthesisReference
Nasri W. Badran, "Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin (warfarin) and methods of making." U.S. Patent US4113744, issued April, 1960.
n25:hasConcept
n26:M0022871
foaf:page
n9:warfarin.html n22:warfarin.htm
n3:IUPAC-Name
n10:271B43FE-363D-11E5-9242-09173F13E4C5
n3:InChI
n10:271B4404-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n10:271B4403-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n10:271B4400-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n10:271B4401-363D-11E5-9242-09173F13E4C5
n3:SMILES
n10:271B4402-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n10:271B43FC-363D-11E5-9242-09173F13E4C5 n10:271B4414-363D-11E5-9242-09173F13E4C5
n3:logP
n10:271B43FD-363D-11E5-9242-09173F13E4C5 n10:271B43FA-363D-11E5-9242-09173F13E4C5 n10:271B4416-363D-11E5-9242-09173F13E4C5
n3:logS
n10:271B43FB-363D-11E5-9242-09173F13E4C5 n10:271B4417-363D-11E5-9242-09173F13E4C5
n3:pKa
n10:271B4419-363D-11E5-9242-09173F13E4C5
n6:hasATCCode
n7:B01AA03
n3:H-Bond-Acceptor-Count
n10:271B440A-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n10:271B440B-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n10:271B4405-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n10:271B4406-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n10:271B4408-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n10:271B4407-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n10:271B4409-363D-11E5-9242-09173F13E4C5
n3:absorption
Rapidly absorbed following oral administration with considerable interindividual variations. Also absorbed percutaneously.
n3:affectedOrganism
Humans and other mammals
n3:caco2-Permeability
n10:271B4418-363D-11E5-9242-09173F13E4C5
n3:casRegistryNumber
81-81-2
n3:category
n3:clearance
* 0.065 +/- 0.025 mL/min/kg [CYP2C9 Genotype *1/*1] * 0.041 +/- 0.021 [CYP2C9 Genotype *1/*2 or *1/*3] * 0.020 +/- 0.011 [CYP2C9 Genotype *2/*2, *2/*3, or *3/*3]
n3:containedIn
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n3:Bioavailability
n10:271B4410-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n10:271B4412-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n10:271B4413-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n10:271B4415-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n10:271B440F-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n10:271B440E-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n10:271B4411-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n10:271B43FF-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-acidic-
n10:271B440C-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n10:271B440D-363D-11E5-9242-09173F13E4C5