This article is about the cancer chemotherapy drug vinCRIStine. It is not to be confused with vinBLAStine, a chemotherapy drug with a different chemical formula.
Vincristine
|
|
| Systematic (IUPAC) name |
| (3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-ethyl-9-((5S,7S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-6-formyl-5-hydroxy-8-methoxy-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate |
| Clinical data |
| Trade names |
Oncovin |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682822 |
| Pregnancy cat. |
D (AU) D (US) |
| Legal status |
Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US) |
| Routes |
intravenous |
| Pharmacokinetic data |
| Bioavailability |
n/a (not reliably absorbed by the GI tract)[1] |
| Protein binding |
~44%[2] |
| Metabolism |
Liver, mostly via CYP3A4 and CYP3A5[1] |
| Half-life |
19 to 155 hours (mean: 85 hours)[1] |
| Excretion |
Faeces (70-80%), urine (10-20%)[1] |
| Identifiers |
| CAS number |
57-22-7 Y |
| ATC code |
L01CA02 |
| PubChem |
CID 5978 |
| DrugBank |
DB00541 |
| ChemSpider |
5758 Y |
| UNII |
5J49Q6B70F Y |
| KEGG |
D08679 Y |
| ChEBI |
CHEBI:28445 Y |
| ChEMBL |
CHEMBL303560 N |
| Chemical data |
| Formula |
C46H56N4O10 |
| Mol. mass |
824.958 g/mol |
SMILES
- O=C(OC)[C@]4(c2c(c1ccccc1n2)CCN3C[C@](O)(CC)C[C@@H](C3)C4)c5c(OC)cc6c(c5)[C@@]89[C@@H](N6C=O)[C@@](O)(C(=O)OC)[C@H](OC(=O)C)[C@@]7(/C=C\CN([C@@H]78)CC9)CC
|
InChI
-
InChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28) N
Key:OGWKCGZFUXNPDA-XQKSVPLYSA-N Y
|
| N (what is this?) (verify) |
Vincristine (brand name, Oncovin), formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus (Madagascar periwinkle), formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy. Vincristine is created by the coupling of indole alkaloids vindoline and catharanthine in the vinca plant.[3]
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[4]
Contents
- 1 Medical uses
- 2 Side-effects
- 3 Mechanism of action
- 4 History
- 5 Suppliers
- 6 See also
- 7 References
- 8 External links
Medical uses
Vincristine is delivered via intravenous infusion for use in various types of chemotherapy regimens.[1] Its main uses are in non-Hodgkin's lymphoma as part of the chemotherapy regimen CHOP, Hodgkin's lymphoma as part of MOPP, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen in acute lymphoblastic leukemia (ALL), and in treatment for nephroblastoma.[1] It is also used to induce remission in ALL with dexamethasone and L-Asparaginase, and in combination with prednisone to treat childhood leukemia.[1] Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP).[1]
Side-effects
The main side-effects of vincristine are chemotherapy-induced peripheral neuropathy, hyponatremia, constipation, and hair loss.
Chemotherapy-induced peripheral neuropathy, a progressive, enduring, often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs,[5] can be severe, and hence a 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) should avoid the taking of vincristine.[6]
Accidental injection of vinca alkaloids into the spinal canal (intrathecal administration) is highly dangerous, with a mortality rate approaching 100 percent. 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. Several patients have survived after aggressive and immediate intervention. Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications.[7] Children may do better following this injury. One child, who was aggressively treated at the time of the injection, recovered almost completely with only mild neurological deficits.[8] A significant series of inadvertent intrathecal vincristine administration occurred in China in 2007 when batches of cytarabine and methotrexate (both often used intrathecally) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine.[9]
Mechanism of action
Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures and arresting mitosis in metaphase. Because vincristine's mechanism of action targets all rapidly dividing cell types, it not only inhibits cancerous cells but can also affect the intestinal epithelium and bone marrow.[citation needed]
History
Having been used as a folk remedy for centuries, studies in the 1950s revealed that 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, trichloromethane, benz-dichloromethane, and separation by pH to yield vincristine.[10]
Vincristine was approved by the United States Food and Drug Administration (FDA) in July 1963 as Oncovin. The drug was initially discovered by a team led by Dr. J.G. Armstrong, then marketed by Eli Lilly and Company.
Suppliers
Three generic drug makers supply vincristine in the United States - APP, Mayne, and Sicor (Teva).
See also
References
- ^ a b c d e f g h Brayfield, A, ed. (13 December 2013). "Vincristine". Martindale: The Complete Drug Reference. Pharmaceutical Press. Retrieved 15 April 2014.
- ^ "Oncovin, Vincasar PFS (vincristine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 16 April 2014.
- ^ "Pharmacognosy of Vinca Alkaloids".
- ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010;7(4):6.
- ^ Graf, W. D.; Chance, P. F.; Lensch, M. W.; Eng, L. J.; Lipe, H. P.; Bird, T. D. (1996). "Severe Vincristine Neuropathy in Charcot-Marie-Tooth Disease Type 1A". Cancer 77 (7): 1356–1362. doi:10.1002/(SICI)1097-0142(19960401)77:7<1356::AID-CNCR20>3.0.CO;2-#. PMID 8608515.
- ^ Qweider, M.; Gilsbach, J. M.; Rohde, V. (2007). "Inadvertent Intrathecal Vincristine Administration: A Neurosurgical Emergency. Case Report". Journal of Neurosurgery: Spine 6 (3): 280–283. doi:10.3171/spi.2007.6.3.280. PMID 17355029.
- ^ Zaragosa, M.; Ritchey, M.; Walter, A. (1995). "Neurological Consequences of Accidental Intrathecal Vincristine: A Case Report.". Medial and Pediatric Oncology 24: 61–62. PMID 7968797.
- ^ Jake Hooker and Walt Bogdanich (January 31, 2008). "Tainted Drugs Tied to Maker of Abortion Pill". New York Times.
- ^ Johnson, I. S.; Armstrong, J. G.; Gorman, M.; Burnett, J. P. (1963). "The Vinca Alkaloids: A New Class of Oncolytic Agents" (pdf). Cancer Research 23 (8 Part 1): 1390–1427. PMID 14070392.
External links
- Vincristine chemotherapy
- Vincristine and vinblastine
- Description and Natural History of the Periwinkle
- The Boger Route to (-)-Vindoline
- U.S. National Library of Medicine: Drug Information Portal - Vincristine
