Vincristine

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Vincristine

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

Alkaloid

Alkaloids are naturally occurring chemical compounds containing base nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base....
from the Catharanthus roseus
Catharanthus roseus

Catharanthus roseus is a species of Catharanthus native and endemism to Madagascar. Synonyms include Vinca rosea , Ammocallis rosea, and Lochnera rosea; other English names occasionally used include Cape Periwinkle, Rose Periwinkle, Rosy Periwinkle, and "Old-maid"....
(Madagascar periwinkle), formerly Vinca rosea and hence its name. It is a mitotic inhibitor

Mitotic inhibitor

A mitotic inhibitor is a type of drug derived from natural substances such as plant alkaloids and primarily used in cancer treatment and certain types of cancer research including cytogenetics....
, and is used in cancer chemotherapy

Chemotherapy

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
.

a class="link1" onMouseover='showByLink("m2992912",this)' onMouseout='hide("m2992912")'href="http://www.absoluteastronomy.com/topics/Tubulin">Tubulin

Tubulin

Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are a-tubulin and ?-tubulin, the proteins that make up microtubules....
is a structural protein which polymer

Polymer

A polymer is a large molecule composed of repeating structural units typically connected by covalent chemical bonds. While polymer in popular usage suggests plastic, the term actually refers to a large class of natural and synthetic materials with a variety of properties....
ises to form microtubule

Microtubule

Microtubules are one of the components of the cytoskeleton. They have a diameter of 25 Nanometre and length varying from 200 nanometers to 25 micrometers....
s. The cell cytoskeleton

Cytoskeleton

The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within the cytoplasm. The cytoskeleton is present in all cells; it was once thought this structure was unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton....
and mitotic spindle

Mitotic spindle

In cell biology, the spindle apparatus is the structure that separates the chromosomes into the daughter cells during cell division. It is part of the cytoskeleton in eukaryote....
, amongst other things, are made of microtubules. Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures.

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Mode of action

Tubulin
Tubulin

Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are a-tubulin and ?-tubulin, the proteins that make up microtubules....
is a structural protein which polymer

Polymer

Microtubule

Microtubules are one of the components of the cytoskeleton. They have a diameter of 25 Nanometre and length varying from 200 nanometers to 25 micrometers....
s. The cell cytoskeleton

Cytoskeleton

Mitotic spindle

Mitosis

Mitosis is the process in which a eukaryotic cell separates the chromosomes in its cell nucleus, into two identical sets in two daughter nuclei....
in metaphase

Metaphase

Metaphase, from the ancient Greek ?et? and f?s?? , is a stage of mitosis in the Eukaryote cell cycle in which condensed chromosomes, carrying DNA sequence, align in the middle of the cell before being separated into each of the two daughter cells....
. The vinca alkaloids therefore affect all rapidly dividing cell types including cancer cells, but also intestinal epithelium

Epithelium

In biology and medicine, epithelium is a Biological tissue composed of cell s that line the cavities and surfaces of structures throughout the body....
and bone marrow

Bone marrow

Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells....
.

Uses

Vincristine is delivered via intravenous infusion

Route of administration

In pharmacology and toxicology, a route of administration is the path by which a medication, fluid, poison or other substance is brought into contact with the body....
for use in various types of chemotherapy regimens

Chemotherapy regimens

Chemotherapy regimens are often identified with acronyms, identifying the agents used in combination. Unfortunately, the letters used are not consistent across regimens, and in some cases the same letter is used to represent two different treatments....
. Its main uses are in non-Hodgkin's lymphoma

Lymphoma

Lymphoma is a type of cancer that originates in lymphocytes of the immune system. They often originate in lymph nodes, presenting as an enlargement of the node ....
as part of the chemotherapy regimen CHOP

Chop

Chop can refer to:* CHOP, a chemotherapy treatment for non-Hodgkin's lymphoma* Meat chop, a cut of meat usually containing a rib and served as an individual portion....
, Hodgkin's lymphoma

Hodgkin's lymphoma

Hodgkin's lymphoma, also known as Hodgkin's disease is a type of lymphoma . It was named after Thomas Hodgkin, who first described abnormalities in the lymph system in 1832....
as part of MOPP, COPP, BEACOPP, or the less popular Stanford V

Stanford V

Stanford V is a chemotherapy regimen designed for Hodgkin's lymphoma that consists of the following:* Mechlorethamine * Doxorubicin* Vinblastine...
chemotherapy regimen, in acute lymphoblastic leukemia

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia , is a form of leukemia, or hematological malignancy characterized by excess lymphoblasts.Malignant, immature lymphoblasts continuously multiply and are overproduced in the bone marrow....
, and in treatment for nephroblastoma (Wilms tumor, a kidney tumor common in children). Vincristine is occasionally used as an immunosuppressant

Immunosuppressant

An immunosuppressant is a substance that performs immunosuppression of the immune system. They may either be exogenous, as immunosuppressive drugs, or endogenous, as e....
, for example, in treating thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura is a rare disease of the coagulation system, causing extensive microscopic blood clots to form in the small blood vessels throughout the body ....
(TTP) or chronic idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura is the condition of having a low platelet platelet count of no known cause . As most causes appear to be related to antibody against platelets, it is also known as immune thrombocytopenic purpura or immune-mediated thrombocytopenic purpura....
(ITP).

Side effects

The main side-effects of vincristine are peripheral neuropathy

Peripheral neuropathy

Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the Adverse effect of systemic illness....
, hyponatremia

Hyponatremia

Hyponatremia is an electrolyte disturbance in which the sodium concentration in the blood plasma is too low .Severe or rapidly progressing hyponatremia can result in swelling of the brain , and the symptoms of hyponatremia are mainly neurology....
, constipation

Constipation

Constipation, costiveness, or irregularity, is a condition of the digestive system in which a person experiences hard feces that are difficult to expel....
and hair loss

Alopecia

Alopecia or hair loss is the medical description of the loss of hair from the head or body, sometimes to the extent of baldness. Unlike the common cosmetic depilation of body hair, alopecia tends to be involuntary and unwelcome, e.g., androgenic alopecia....
.

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

Foot drop

Foot drop is a dorsiflexion in turning the ankle and toes upward, known as dorsiflexion. Conditions leading to foot drop may be neurology, muscular or anatomy in origin, often with significant overlap....
: a person with a family history of foot drop and/or Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease , known also as Hereditary Motor and Sensory Neuropathy , Hereditary Sensorimotor Neuropathy , or Peroneal Muscular Atrophy, is a heterogeneous inherited disorder of nerves that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands...
(CMT) may benefit from genetic testing for CMT before taking vincristine.

Accidental injection of vinca alkaloids into the spinal canal (intrathecal

Intrathecal

Intrathecal is an adjective that refers to something that happens inside the spinal canal. For example, intrathecal immunoglobulin production means production of this substance in the spinal cord....
administration) is highly dangerous, with a mortality rate approaching 100%. The medical literature documents cases of ascending paralysis

Paralysis

Paralysis is the complete loss of muscle function for one or more muscle groups. Paralysis can cause loss of feeling or loss of mobility in the affected area....
due to massive encephalopathy

Encephalopathy

Encephalopathy /?n?s?f?'l?p??i/ literally means Disorder or disease of the brain. ...
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

Cerebrospinal fluid

Cerebrospinal fluid , Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain....
and administration of protective medications. A significant series of inadvertent intrathecal vincristine administration occurred in China

China

China is a Culture of China, an ancient civilization, and, depending on perspective, a national or multinational entity extending over a large area in East Asia....
in 2007 when batches of cytarabine

Cytarabine

Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of hematological malignancy such as acute myeloid leukemia and non-Hodgkin lymphoma....
and methotrexate

Methotrexate

Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug used in treatment of cancer and autoimmune diseases....
(both often used intrathecally) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine.

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

Diabetes mellitus

Diabetes mellitus , often referred to simply as diabetes , is a syndrome of disordered metabolism, usually due to a combination of genetic disorder and environmental causes, resulting in abnormally high blood sugar levels ....
were disappointing, the discovery that it caused myelosuppression (decreased activity of the bone marrow) led to its study in mice with leukemia

Leukemia

Leukemia is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation of blood Cell , usually white blood cells ....
, 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

Aluminium oxide

Aluminium oxide is an amphoteric oxide of aluminium with the chemical formula 23. It is also commonly referred to as alumina or aloxite in the mining, ceramic and materials science communities....
, chromatography

Chromatography

Chromatography is the collective term for a family of laboratory techniques for the separation of mixtures. It involves passing a mixture dissolved in a "mobile phase" through a stationary phase, which separates the analyte to be measured from other molecules in the mixture and allows it to be isolated....
, trichloromethane

Chloroform

Chloroform, also known as trichloromethane and methyl trichloride, is a chemical compound with chemical formula CarbonHydrogenChlorine3....
, benz-dichloromethane and separation by pH to yield vincristine.

Vincristine was approved by the United States

United States

The United States of America is a Federal government constitutional republic comprising U.S. state and a federal district. The country is situated mostly in central North America, where its Contiguous United States and Washington, D.C., the Capital districts and territories, lie between the Pacific Ocean and Atlantic Oceans, Borders of the U...
Food and Drug Administration

Food and Drug Administration

The U.S. Food and Drug Administration is an Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, dietary supplements, Medications, vaccines, Biopharmaceutical, blood transfusion, medical devices, Electromagnetic radiation-emitting devices, veteri...
(FDA) in July 1963 as Oncovin. The drug was initially discovered by a team lead by Dr. J.G. Armstrong; it was then marketed by Eli Lilly and Company

Eli Lilly and Company

Eli Lilly and Company is a global pharmaceutical company and one of the world's largest corporations. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States....
.

Suppliers

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

Teva Pharmaceutical Industries

Teva Pharmaceutical Industries Ltd. , is an international pharmaceutical company headquartered in Petah Tikva, Israel. It specializes in generic drug and proprietary pharmaceuticals and active pharmaceutical ingredients....
).

Vincristine

Mode of action

Uses

Side effects

History

Suppliers

See also

External links