Dicumarol

Jump to: navigation, search
Dicumarol
Dicumarol svg.png
Clinical data
ATC code
Pharmacokinetic data
Protein bindingplasmatic proteins
Metabolismhepatic
Excretionfaeces, urine
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC19H12O6
Molar mass336.295 g/mol

WikiDoc Resources for Dicumarol

Articles

Most recent articles on Dicumarol

Most cited articles on Dicumarol

Review articles on Dicumarol

Articles on Dicumarol in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Dicumarol

Images of Dicumarol

Photos of Dicumarol

Podcasts & MP3s on Dicumarol

Videos on Dicumarol

Evidence Based Medicine

Cochrane Collaboration on Dicumarol

Bandolier on Dicumarol

TRIP on Dicumarol

Clinical Trials

Ongoing Trials on Dicumarol at Clinical Trials.gov

Trial results on Dicumarol

Clinical Trials on Dicumarol at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Dicumarol

NICE Guidance on Dicumarol

NHS PRODIGY Guidance

FDA on Dicumarol

CDC on Dicumarol

Books

Books on Dicumarol

News

Dicumarol in the news

Be alerted to news on Dicumarol

News trends on Dicumarol

Commentary

Blogs on Dicumarol

Definitions

Definitions of Dicumarol

Patient Resources / Community

Patient resources on Dicumarol

Discussion groups on Dicumarol

Patient Handouts on Dicumarol

Directions to Hospitals Treating Dicumarol

Risk calculators and risk factors for Dicumarol

Healthcare Provider Resources

Symptoms of Dicumarol

Causes & Risk Factors for Dicumarol

Diagnostic studies for Dicumarol

Treatment of Dicumarol

Continuing Medical Education (CME)

CME Programs on Dicumarol

International

Dicumarol en Espanol

Dicumarol en Francais

Business

Dicumarol in the Marketplace

Patents on Dicumarol

Experimental / Informatics

List of terms related to Dicumarol

For patient information, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Dicoumarol (INN) or dicumarol (USAN) is a naturally occurring anticoagulant that functions as a functional vitamin K depleter (similar to warfarin, a drug that dicoumarol inspired). It is also used in biochemical experiments as an inhibitor of reductases.

Dicoumarol is a natural chemical substance of combined plant and fungal origin. It is a derivative of coumarin, a bitter tasting but sweet-smelling substance made by plants that does not itself affect coagulation, but which is (classically) transformed in mouldy feeds or silages by a number of species of fungi, into active dicoumarol. Dicoumarol does affect coagulation, and was discovered in mouldy wet sweet-clover hay, as the cause of a naturally occurring bleeding disease in cattle.[1] See warfarin for a more detailed discovery history.

Identified in 1940, dicoumarol became the prototype of the 4-hydroxycoumarin derivative anticoagulant drug class. Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative warfarin, and other 4-hydroxycoumarin drugs.

It is given orally, and it acts within two days.

Mechanism of Action

Like all 4-hydroxycoumarin drugs it is a competitive inhibitor of vitamin K epoxide reductase, an enzyme that recycles vitamin K, thus causing depletion of active vitamin K in blood. This prevents the formation of the active form of prothrombin and several other coagulant enzymes.

These compounds are not direct antagonists (in the pharmaceutical sense) of vitamin K itself, but rather act to deplete reduced vitamin K in tissues. For this reason vitamin K antagonizes their effect (rather than the reverse), and this has led to the loose terminology of vitamin K antagonism.

Administration of vitamin K is therefore the antidote for dicoumarol toxicity. The action and toxicity of the drug and the antidote effectiveness are measured with the prothrombin time (PT) blood test.

Uses

Dicoumarol was used along with heparin, for the treatment of deep venous thrombosis. Unlike heparin, this class of drugs may be used for months or years.

Poisoning

Overdose results in serious, sometimes fatal uncontrolled hemorrhage.

References

  • Cullen J, Hinkhouse M, Grady M, Gaut A, Liu J, Zhang Y, Weydert C, Domann F, Oberley L (2003). "Dicumarol inhibition of NADPH: quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism". Cancer Res. 63 (17): 5513–20. PMID 14500388.
  • Mironov A, Colanzi A, Polishchuk R, Beznoussenko G, Mironov A, Fusella A, Di Tullio G, Silletta M, Corda D, De Matteis M, Luini A (2004). "Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport". Eur J Cell Biol. 83 (6): 263–79. doi:10.1078/0171-9335-00377. PMID 15511084.
  • Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz L (2005). "Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication". Arch Biochem Biophys. 434 (2): 241–7. doi:10.1016/j.abb.2004.11.002. PMID 15639223.
  • Thanos C, Liu Z, Reineke J, Edwards E, Mathiowitz E (2003). "Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride". Pharm Res. 20 (7): 1093–100. doi:10.1023/A:1024474609667. PMID 12880296.]
  1. Nicole Kresge, Robert D. Simoni and Robert L. Hill (2005-02-25). "Sweet clover disease and warfarin review". Jbc.org. Retrieved 2012-09-26.

External Links


Linked-in.jpg