Vincristine (/'v?n'kr?sti:n/) (marketed under the brandname Oncovin/'?:?ko?v?n/) is a chemotherapy medication used to treat a number of types of cancer. It is given intravenously and works by inhibiting mitosis (stopping cells from dividing properly), causing the cells to die. The drug accomplishes this by binding to the tubulin protein, stopping the cell from separating its chromosomes during the metaphase; the cell then undergoes apoptosis. Because cancer cells divide more rapidly than healthy cells, they are affected more by the drug.
Most people experience some side effects from vincristine treatment. Commonly it causes a change in sensation, hair loss, constipation, difficulty walking, and headaches. It will likely cause harm to an infant if given during pregnancy.
Vincristine is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system. It was formerly known as leurocristine, sometimes abbreviated "VCR", and is a vinca alkaloid from the Madagascar periwinkle Catharanthus roseus (formerly named Vinca rosea).
Medical uses
Vincristine is delivered via intravenous infusion for use 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, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen in acute lymphoblastic leukemia (ALL), and in treatment for nephroblastoma. It is also used to induce remission in ALL with dexamethasone and L-Asparaginase, and in combination with prednisone to treat childhood leukemia. Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP).
Vincristine Side Effects Video
Side effects
The main side effects of vincristine are chemotherapy-induced peripheral neuropathy, hyponatremia, constipation, and hair loss.
Chemotherapy-induced peripheral neuropathy can be severe, and may be a reason to reduce or avoid using vincristine. The symptoms of this are progressive and enduring tingling numbness, pain and hypersensitivity to cold, beginning in the hands and feet and sometimes affecting the arms and legs. 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.
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. 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. 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.
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.
Pharmacology
Vincristine is created by the coupling of indole alkaloids vindoline and catharanthine in the vinca plant.
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.
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).
Research
In 2012 the FDA approved a Liposomal formulation of Vincristine. A novel nano-particle bound version of Vincristine is under development.
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