Colchicine
Classification:
Musculoskeletal Agents
» Antiinflammatory Agents
» Antigout agents
Description: Colchicine is an ancient remedy for the treatment of articular pain. Use of Colchicum alkaloid for the treatment of acute gout occurred as early as 1810, and reports of its medicinal value exist from the first century AD. Colchicine is the preferred agent in the treatment of acute gouty arthritis. It also has been used in the management of amyloidosis, Behcet’s disease, dermatitis herpetiformis, familial Mediterranean fever, Paget’s disease, pericarditis, and pseudogout. Colchicine has also been beneficial in the treatment of biliary and hepatic cirrhosis. Colchicine was first approved by the FDA in December 1939. Colchicine is available in oral and intravenous dosage forms, but the parenteral route should be avoided due to the potential for serious toxicity.
Mechanism of Action: Colchicine possesses antiinflammatory properties. Although it is highly effective in treating acute gouty arthritis, it is not effective for other types of pain. It is not an analgesic and does not affect uric acid clearance. Instead, colchicine binds to proteins in microtubules of neutrophils. This binding, in turn, inhibits the migration of neutrophils into the area of inflammation, thereby interfering with the inflammatory response to urate crystal deposition. Although colchicine does not inhibit phagocytosis of uric acid crystals, it does appear to prevent the release of an inflammatory glycoprotein from phagocytes.
Colchicine arrests metaphase due to two separate antimitotic effects: disruption of mitotic spindle formation and disruption of sol-gel formation. These actions also may contribute to its antigout properties. Toxic effects of colchicine are related to its antimitotic activity within proliferating tissues such as the skin, hair, and bone marrow. Colchicine exhibits other diverse pharmacological actions including decreasing body temperature, suppressing the respiratory center, and vasomotor stimulation leading to hypertension. As a result, acute overdoses of colchicine are extremely serious and can be fatal. Intravenous use of colchicine should be avoided.
Colchicine Tablets (Tab 0.6 mg)
Pharmacokinetics: Although colchicine can be administered orally or intravenously, parenteral use should be avoided due to its toxicity. Oral colchicine is rapidly absorbed, with peak serum concentrations occurring at 0.5 - 2 hours. The onset of action is within 12 hours, with the peak antiinflammatory effect occurring within 24 - 48 hours. Relief of swelling may take several days. Enterohepatic recirculation occurs to a large extent and can lead to adverse GI effects with larger dosages. Colchicine distributes to the kidney, liver, spleen, and intestinal tissues, and concentrates primarily in the leukocytes. Colchicine can be found in leukocytes for 10 days after administration.
Colchicine is metabolized by the liver and other tissues. The distribution half-life in plasma is 3 - 5 minutes. Elimination half-life has ranged from 1.7 - 20.9 hours in patients with normal renal function. Plasma half-life may be extended in patients with renal impairment, so dosage reductions are recommended (see Dosage). Colchicine and its metabolites are excreted primarily in the feces, with 10 - 20% eliminated unchanged in the urine. Renal elimination may increase in patients with hepatic disease.
[1 of 3 - Click here to see more photos]
References
. Putterman C, Ben-Chetrit E, Caraco Y et al. Colchicine intoxication: Clinical pharmacology, risk factors, features, and management. Sem Arth Rheum 1991;21:143 - 55.
. Kaplan MM, Alling DW, Zimmerman HJ et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986;315:1448 - 54.
. Kershenobich D, Vargas F, Garcia-Tsao G et al. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 1988;318:1709 - 13.
. Freeman DL. Frequent doses of intravenous colchicine can be lethal. N Engl J Med 1983;309:310.
[ Revised 3/5/2006 2:19:00 PM ]
Related entries
Monthly Archives
Syndicate
Allergies
