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| {{drugbox | IUPAC_name = | image = Vincristin.svg | width = 218 | CAS_number = 57-22-7 | ATC_prefix = L01 | ATC_suffix = CA02 | ATC_supplemental = | PubChem = 5978 | DrugBank = APRD00495 | C = 46 | H = 56 | N = 4 | O = 10 | molecular_weight = 824.958 g/mol | bioavailability = n/a | protein_bound = ~75% | metabolism = [[Liver|Hepatic]] | elimination_half-life = 19 to 155 hours | pregnancy_AU= D | pregnancy_US= D | legal_status = Rx-only | routes_of_administration = '''Exclusively''' [[Intravenous therapy|intravenous]] | excretion = Mostly biliary, 10% in urine }}
| | #redirect:[[Vincristine sulfate]] |
| {{SI}}
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| {{CMG}}
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| {{EH}}
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| ==Overview==
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| '''Vincristine''' (Oncovin®), also known as '''leurocristine''', is a vinca [[alkaloid]] from the [[Madagascar periwinkle]] (''Catharanthus roseus'', formerly ''Vinca rosea'' and hence its name). It is a [[mitotic inhibitor]], and is used in cancer [[chemotherapy]].
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| ==Mode of action==
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| ''[[Tubulin]]'' is a structural protein which [[polymer]]ises to form [[microtubule]]s. The cell [[cytoskeleton]] and [[mitotic spindle]], amongst other things, are made of microtubules. ''Vincristine'' binds to tubulin dimers, inhibiting assembly of microtubule structures. Disruption of the microtubules arrests [[mitosis]] in [[metaphase]]. The vinca alkaloids therefore affect all rapidly dividing cell types including cancer cells, but also intestinal [[epithelium]] and [[bone marrow]].
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| ==Uses==
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| Vincristine, injected [[intravenous]]ly only, is used in various types of [[chemotherapy regimens]]. Its main uses are in non-Hodgkin's [[lymphoma]] as part of the chemotherapy regimen [[CHOP]], [[Hodgkin's lymphoma]] as part of MOPP or COPP, or the less popular [[Stanford V]] chemotherapy regimen, and in [[acute lymphoblastic leukemia]]. It is occasionally used as an immunosuppressant, e.g. in [[thrombotic thrombocytopenic purpura]] (TTP).
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| ==Side effects==
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| The main side-effects of vincristine are [[peripheral neuropathy]], [[hyponatremia]], and [[constipation]].
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| Peripheral neuropathy can be severe, hence reason to avoid, reduce, or stop the use of vincristine. One of the first symptoms of peripheral neuropathy is [[foot drop]]: a person with a family history of foot drop and/or [[Charcot-Marie-Tooth disease]] (CMT) may benefit from genetic testing for CMT before taking vincristine.<ref>{{cite journal |author=Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD |title=Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A |journal=Cancer |volume=77 |issue=7 |pages=1356–62 |year=1996 |pmid=8608515 |doi=10.1002/(SICI)1097-0142(19960401)77:7%3C1356::AID-CNCR20%3E3.0.CO;2-%23}}</ref>
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| Accidental injection of vinca alkaloids into the spinal canal ([[intrathecal]] administration) is highly dangerous, with a mortality rate approaching 100%. The medical literature documents cases of ascending [[paralysis]] due to massive [[encephalopathy]] and spinal nerve [[demyelination]], accompanied by intractable pain, almost uniformly leading to death; a handful of survivors were left with devastating neurological damage with no hope of recovery. Rescue treatments consist of washout of the [[cerebrospinal fluid]] and administration of protective medications.<ref>{{cite journal |author=Qweider M, Gilsbach JM, Rohde V |title=Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report |journal=J Neurosurg Spine |volume=6 |issue=3 |pages=280–3 |year=2007 |pmid=17355029 |doi=}}</ref>
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| == History ==
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| Having been used as a folk remedy for centuries, studies in the 1950s revealed that ''[[Vinca_rosea|C. roseus]]'' contained 70 alkaloids, many of which are biologically active. While initial studies for its use in [[diabetes mellitus]] were disappointing, the discovery that it caused [[myelosuppression]] (decreased activity of the bone marrow) led to its study in mice with [[leukemia]], whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skelly-B defatting agent and an acid benzene extract led to a fraction termed "fraction A". This fraction was further treated with [[aluminium oxide]], [[chromatography]], [[Chloroform|trichloromethane]], benz-dichloromethane and separation by pH to yield vincristine.<ref>{{cite journal |author=Johnson IS, Armstrong JG, Gorman M, Burnett JP |title=The vinca alkaloids: a new class of oncolytic agents |journal=Cancer Res |volume=23 |issue= |pages=1390-427 |year=1963 |pmid=14070392 |url=http://cancerres.aacrjournals.org/cgi/reprint/23/8_Part_1/1390}}</ref>
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| Vincristine was approved by the [[United States]] [[Food and Drug Administration]] (FDA) in July 1963 as Oncovin. The drug was initially marketed by [[Eli Lilly and Company]]. | |
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| == Suppliers ==
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| Three generic drug makers supply vincristine in the United States - APP, Mayne, and Sicor ([[Teva Pharmaceutical Industries|Teva]]).
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| == See also ==
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| * [[Rosy Periwinkle]]
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| == References ==
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| <references/>
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| == External links ==
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| * [http://www.cancerbackup.org.uk/Treatments/Chemotherapy/Individualchemotherapydrugs/Vincristine Vincristine chemotherapy]
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| * [http://www.chm.bris.ac.uk/webprojects2002/jjones/Content/vincristine.htm Vincristine and vinblastine]
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| * [http://biotech.icmb.utexas.edu/botany/perihist.html Description and Natural History of the Periwinkle]
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| * [http://www.organic-chemistry.org/Highlights/2006/05June.shtm The Boger Route to (-)-Vindoline]
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| {{Chemotherapeutic agents}}
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| {{SIB}}
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| [[Category:Chemotherapeutic agents]]
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| [[Category:Alkaloids]]
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| [[Category:Biopiracy and bioprospecting]]
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| [[de:Vincristin]]
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| [[fr:Vincristine]]
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| [[hu:Vinkrisztin]]
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| [[it:Vincristina]]
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| [[ja:ビンクリスチン]]
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| [[pl:Winkrystyna]]
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| [[sv:Vinkristin]]
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| {{WH}}
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| {{WS}}
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