colchicine
08 »
colchicine
ColchicineSystematic (IUPAC) nameN-heptalen-7-yl]acetamideIdentifiersCAS number64-86-8ATC codeM04AC01PubChem6167ChemSpider5933Chemical dataFormulaC22H25NO6 Mol. mass399.437Pharmacokinetic dataBioavailability ?Metabolism ?Half life9.3 - 10.6 hoursExcretionPrimarily feces, urine 10-20%Therapeutic considerationsPregnancy cat.XLegal statusRX/POMRoutesOral tabletsColchicine is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum (Autumn crocus, Colchicum autumnale, also known as the "Meadow saffron"). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Its present medicinal use is mainly in the treatment of gout; as well, it is being investigated for its potential use as an anti-cancer drug. It can also be used as initial treatment for pericarditis and preventing recurrences of the condition. In neurons, axoplasmic transport is disrupted by colchicine.// HistoryColchicum extract was first described as a treatment for gout in De Materia Medica by Pedanius Dioscorides in the first century CE. Colchicine, an alkaloid, was first isolated in 1820 by the two French chemists P.S. Pelletier and J. Caventon. The alkaloid was later identified as a tricyclic alkaloid, and its pain-relieving and anti-inflammatory effects for gout were linked to its ability to bind with tubulin. Pharmacology Biological functionColchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules. Availability of tubulin is essential to mitosis, and therefore colchicine effectively functions as a "mitotic poison" or spindle poison. Since one of the defining characteristics of cancer cells is a significantly increased rate of mitosis, this means that cancer cells are significantly more vulnerable to colchicine poisoning than are normal cells. However, the therapeutic value of colchicine against cancer is (as is typical with chemotherapy agents) limited by its toxicity against normal cells.Apart from inhibiting mitosis, a process heavily dependent on cytoskeletal changes, colchicine also inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect. Colchicine also inhibits uric acid (urate) crystal deposition, which is enhanced by a low pH in the tissues, probably by inhibiting oxidation of glucose and subsequent lactic acid production in leukocytes. The inhibition of uric acid crystals is a vital aspect on the mechanism of gout treatment. Colchicine as medicineIn the United States colchicine by itself is not FDA approved, however it is still prescribed for the treatment of gout and also for familial Mediterranean fever, secondary amyloidosis(AA), and scleroderma. It is also used as an anti-inflammatory agent for long-term treatment of Behçet's disease.The Australian biotechnology company Giaconda has developed a combination therapy to treat constipation-predominant irritable bowel syndrome which combines colchicine with the anti-inflammatory drug olsalazine.The British drug development company Angiogene is developing a prodrug of colchicine, ZD6126 (also known as ANG453) as a treatment for cancer.Colchicine has a relatively low therapeutic index.Colchicine is "used widely" off-label by naturopaths for a number of treatments, including the treatment of back pain. Side effectsSide effects include gastro-intestinal upset and neutropenia. High doses can also damage bone marrow and lead to anaemia. Note that all of these side effects can result from hyper-inhibition of mitosis. ToxicityColchicine poisoning has been compared to arsenic poisoning: symptoms start 2 to 5 hours after the toxic dose has been ingested and include burning in the mouth and throat, fever, vomiting, diarrhea, abdominal pain and kidney failure. These symptoms may set in as many as 24 hours after the exposure. Onset of multiple-system organ failure may occur within 24 to 72 hours. This includes hypovolemic shock due to extreme vascular damage and fluid loss through the GI tract, which may result in death. Additionally, sufferers may experience kidney damage resulting in low urine output and bloody urine; low white blood cell counts (persisting for several days); anemia; muscular weakness; and respiratory failure. Recovery may begin within 6 to 8 days. There is no specific antidote for colchicine, although various treatments do exist. Botanical useSince chromosome segregation is driven by microtubules, colchicine is also used for inducing polyploidy in plant cells during cellular division by inhibiting chromosome segregation during meiosis; half the resulting gametes therefore contain no chromosomes, while the other half contain double the usual number of chromosomes (i.e., diploid instead of haploid as gametes usually are), and lead to embryos with double the usual number of chromosomes (i.e. tetraploid instead of diploid). While this would be fatal in animal cells, in plant cells it is not only usually well tolerated, but in fact frequently results in plants which are larger, hardier, faster growing, and in general more desirable than the normally diploid parents; for this reason, this type of genetic manipulation is frequently used in breeding plants commercially. In addition, when such a tetraploid plant is crossed with a diploid plant, the triploid offspring will be sterile, which may be commercially useful in itself by requiring growers to buy seed from the supplier, but also can often be induced to create a "seedless" fruit if pollinated (usually the triploid will also not produce pollen, therefore a diploid parent is needed to provide the pollen). This is the method used to create seedless watermelons, for instance. On the other hand, colchicine's ability to induce polyploidy can be exploited to render infertile hybrids fertile, as is done when breeding triticale from wheat and rye. Wheat is typically tetraploid and rye diploid, with the triploid hybrid infertile. Treatment with colchicine of triploid triticale gives fertile hexaploid triticale.When used to induce polyploidy in plants, colchicine is usually applied to the plant as a cream. It has to be applied to a growth point of the plant, such as an apical tip, shoot or sucker. Seeds can be presoaked in a colchicine solution before planting. As colchicine is so dangerous, it is worth noting that doubling of chromosome numbers can occur spontaneously in nature, and not infrequently. The best place to look is in regenerating tissue. One way to induce it is to chop off the tops of plants and carefully examine the lateral shoots and suckers to see if any look different. If there is no visual difference flow cytometry can be used for analysis. See alsoProbenecid and colchicine
.On April 30, 2007, the Food and Drug Administration, in conjunction with drug manufacturer ApothéCure, have issued an immediate drug recall for compounded Injectable Colchicine .Nearly identical deaths of patients at hospitals in Portland and Washington state recently have health officials suspecting a highly toxic medication used primarily by naturopaths.Colchicine is a nitrogen-based and highly toxic chemical that doctors use to relieve a number of extremely painful and debilitating physical conditions such as: Gout: Gout is a condition that causes uric acid to build up in the cartilage of joints and tendons, causing extremely painful inflamed tissues..5mg/ml, 4ml vials, lot number 20070122@26 due to a number of deaths associated with the product..Articles and information about colchicineThe FDA is cracking down on unapproved injectable colchicine following 23 deaths... While state authorities are investigating the deaths, which occurred within days of each other the Oregon Poison Center has issued an alert about the drug .WASHINGTON - Take the generic drug clonidine for high blood pressure? Double-check that you didn't leave the drugstore with Klonopin for seizures, or the gout medicine colchicine. Colchicine gout treatment side effect .Take the generic drug clonidine for high blood pressure? Double-check that you didn't leave the drugstore
Even more about colchicine
colchicine
Colchicine is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum (Autumn crocus, Colchicum autumnale, also known as the ...
Colchicine - Wikipedia, the free encyclopedia
Learn about the prescription medication Colchicine (Colchicine), drug uses, dosage, side effects, drug interactions, warnings, and patient labeling.
Colchicine (Colchicine) Drug Information: Uses, Side Effects, Drug ...
Colchicine of acetyltrimethylcolchicine, een alkaloïde uit de herfsttijloos, is een heel oud middel dat goed tegen jicht werkt. Ook werd de stof vroeger bij de behandeling van ...
Colchicine - Wikipedia
Read about colchicine, a drug prescribed for the pain of gouty arthritis. Side effects, drug interactions, dosage, and preagnancy information is also included in the information.
Colchicine Drug Information on MedicineNet.com
лекарственное вещество, получаемое из лугового шафрана (Colchicum autumale); применяется для уменьшения ...
Comment:
