Dicumarol: Difference between revisions

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Dicumarol
Clinical data
ATC code	B01AA01 (WHO) ;
Pharmacokinetic data
Protein binding	plasmatic proteins
Metabolism	hepatic
Excretion	faeces, urine
Identifiers
	IUPAC name 3,3'-methylenebis(4-hydroxy-2H-chromen-2-one);
CAS Number	66-76-2;
PubChem CID	653;
DrugBank	APRD00761;
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
Formula	C19H12O6
Molar mass	336.295 g/mol

VisualWikitext

Revision as of 00:25, 26 July 2014

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 Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative warfarin, and other 4-hydroxycoumarin drugs.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.]

↑ 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

Template:DiseasesDB

[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.

[1]

@@ Line 24: / Line 24: @@
 | routes_of_administration =
 }}
+__NOTOC__
 {{SI}}
+'''For patient information, click [[Dicumarol (patient information)|here]].'''
 {{CMG}}
+==Overview==
+'''Dicoumarol''' ([[International Nonproprietary Name|INN]]) or '''dicumarol''' ([[United States Adopted Name|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.<ref>{{cite web|author=Nicole Kresge, Robert D. Simoni and Robert L. Hill |url=http://www.jbc.org/content/280/8/e5.full |title=Sweet clover disease and warfarin review |publisher=Jbc.org |date=2005-02-25 |accessdate=2012-09-26}}</ref> 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.
-===[[Dicumarol (patient information)|For patient information, click here]]===
+== 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.
-'''Dicumarol''' (or '''Dicoumarol''') is an [[anticoagulant]] that functions by as a [[Vitamin K]] antagonist (similar to [[warfarin]]).
+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.
-It is a derivative of [[coumarin]].
+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.
-==External links==
+== 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 ==
+* {{cite journal | author = Cullen J, Hinkhouse M, Grady M, Gaut A, Liu J, Zhang Y, Weydert C, Domann F, Oberley L | title = Dicumarol inhibition of NADPH: quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. | journal = Cancer Res | volume = 63 | issue = 17 | pages = 5513–20 | year = 2003 | pmid = 14500388}}
+* {{cite journal | author = Mironov A, Colanzi A, Polishchuk R, Beznoussenko G, Mironov A, Fusella A, Di Tullio G, Silletta M, Corda D, De Matteis M, Luini A | title = Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport. | journal = Eur J Cell Biol | volume = 83 | issue = 6 | pages = 263–79 | year = 2004 | pmid = 15511084 | doi = 10.1078/0171-9335-00377}}
+* {{cite journal | author = Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz L | title = Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication. | journal = Arch Biochem Biophys | volume = 434 | issue = 2 | pages = 241–7 | year = 2005 | pmid = 15639223 | doi = 10.1016/j.abb.2004.11.002}}
+* {{cite journal | author = Thanos C, Liu Z, Reineke J, Edwards E, Mathiowitz E | title = Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride. | journal = Pharm Res | volume = 20 | issue = 7 | pages = 1093–100 | year = 2003 | pmid = 12880296 | doi = 10.1023/A:1024474609667}}]
+{{reflist|2}}
+== External Links ==
 * {{DiseasesDB|30166}}
-* {{cite journal | author = Cullen J, Hinkhouse M, Grady M, Gaut A, Liu J, Zhang Y, Weydert C, Domann F, Oberley L | title = Dicumarol inhibition of NADPH: quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. | journal = Cancer Res | volume = 63 | issue = 17 | pages = 5513-20 | year = 2003 | id = PMID 14500388}}
-* {{cite journal | author = Mironov A, Colanzi A, Polishchuk R, Beznoussenko G, Mironov A, Fusella A, Di Tullio G, Silletta M, Corda D, De Matteis M, Luini A | title = Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport. | journal = Eur J Cell Biol | volume = 83 | issue = 6 | pages = 263-79 | year = 2004 | id = PMID 15511084}}
-* {{cite journal | author = Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz L | title = Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication. | journal = Arch Biochem Biophys | volume = 434 | issue = 2 | pages = 241-7 | year = 2005 | id = PMID 15639223}}
-* {{cite journal | author = Thanos C, Liu Z, Reineke J, Edwards E, Mathiowitz E | title = Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride. | journal = Pharm Res | volume = 20 | issue = 7 | pages = 1093-100 | year = 2003 | id = PMID 12880296}}
+{{Antithrombotics}}
-{{Antithrombotics}}
 [[Category:Drug]]
-[[Category:Cardiology]]
+[[Category:Cardiovascular Drugs]]
-{{WikiDoc Help Menu}}
-{{WikiDoc Sources}}

Clinical data

ATC code	B01AA01 (WHO)
Pharmacokinetic data
Protein binding	plasmatic proteins
Metabolism	hepatic
Excretion	faeces, urine
Identifiers
IUPAC name 3,3'-methylenebis(4-hydroxy-2H-chromen-2-one)
CAS Number	66-76-2
PubChem CID	653
DrugBank	APRD00761
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
Formula	C₁₉H₁₂O₆
Molar mass	336.295 g/mol