Vincristine



Vincristine
Systematic (IUPAC) name
 ?
Identifiers
CAS number 57-22-7
ATC code L01CA02
PubChem 5978
DrugBank APRD00495
Chemical data
O10 
Mol. mass 824.958 g/mol
Pharmacokinetic data
Bioavailability n/a
Protein binding ~75%
Metabolism Hepatic
Half life 19 to 155 hours
Excretion Mostly biliary, 10% in urine
Therapeutic considerations
Pregnancy cat.

D(AU) D(US)

Legal status

℞ Prescription only

Routes Exclusively intravenous

Vincristine (brand name, Oncovin), also known as leurocristine, is a vinca chemotherapy.

Contents

Mode of action

Tubulin is a structural protein which 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.

Uses

Vincristine, injected Stanford V chemotherapy regimen, and in acute lymphoblastic leukemia. It is occasionally used as an immunosuppressant, e.g. in thrombotic thrombocytopenic purpura (TTP).

Side effects

The main side-effects of vincristine are peripheral neuropathy, hyponatremia, constipation and hair loss.

Peripheral neuropathy 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) may benefit from genetic testing for CMT before taking vincristine.[1]

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.[2]

History

Having been used as a folk remedy for centuries, studies in the 1950s revealed that trichloromethane, benz-dichloromethane and separation by pH to yield vincristine.[3]

Vincristine was approved by the United States Eli Lilly and Company.

Suppliers

Three generic drug makers supply vincristine in the United States - APP, Mayne, and Sicor (Teva).

See also

References

  1. ^ Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD (1996). "Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A". Cancer 77 (7): 1356–62. doi:10.1002/(SICI)1097-0142(19960401)77:7%3C1356::AID-CNCR20%3E3.0.CO;2-%23. PMID 8608515.
  2. ^ Qweider M, Gilsbach JM, Rohde V (2007). "Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report". J Neurosurg Spine 6 (3): 280–3. PMID 17355029.
  3. ^ Johnson IS, Armstrong JG, Gorman M, Burnett JP (1963). "The vinca alkaloids: a new class of oncolytic agents". Cancer Res 23: 1390-427. PMID 14070392.
 
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