COLCHICINE
Chemistry - An antigout drug possessing many other pharmacologic effects, colchicine occurs asa pale yellow, amorphous powder or scales. It is soluble in water and freely soluble in alcohol.
Pharmacology; Uses, Indications - Colchicine is best known for its antigout activity in humans.
The mechanism for this effect is not totally understood, but it probably is related to the drug'sability to reduce the inflammatory response to the disposition of monosodium urate crystals.
Colchicine inhibits cel division during metaphase by interfering with sol-gel formation and themitotic spindle.
In veterinary medicine, colchicine has been proposed as a treatment in small animals for amyloidosis. Colchicine apparently blocks the synthesis and secretion of serum amyloid A (SAA; anacute-phase reactant protein) by hepatocytes thereby preventing the formation of amyloid-enhancing factor and preventing amyloid disposition. For colchicine to be effective however, it mustbe given early in the course of the disease and it will be ineffective once renal failure has occurred.
Colchicine has also been proposed for treating chronic hepatic fibrosis presumably by decreasingthe formation and increasing the breakdown of collagen.
These metabolites and unchanged drug are re-secreted into the GI tract via biliary secretions whereit is reabsorbed. This "recycling" phenomena may explain the intestinal manifestations noted withcolchicine toxicity. Colchicine is distributed into several tissues, but is concentrated in leukocytes.
Plasma half-life is about 20 minutes, but leukocyte half-life is approximately 60 hours. Colchicineis deacetylated in the liver and also metabolized in other tissues. While most of a dose (ascolchicine and metabolites) is excreted in the feces, some is excreted in the urine. More may beexcreted in the urine in patients with hepatic disease. Patients with severe renal disease may haveprolonged half-lives.
Because colchicine has been demonstrated to be teratogenic in laboratory animals (mice andhamsters) it should be used during pregnancy only when its potential benefits outweigh its risks. Itis unknown if colchicine enters maternal milk; use cautiously in nursing mothers. Colchicine maydecrease spermatogenesis.
Prolonged administration has caused bone marrow depression. Severe local irritation has beennoted if extravasation occurs after intravenous administration; thrombophlebitis has also beenreported.
Deaths in humans have been reported with a single oral ingestion of as little as 7 mg, but 65 mg isconsidered the lethal dose in an adult human. GI manifestations are usually the presentingsymptoms seen. These can range from anorexia and vomiting to bloody diarrhea or paralytic ileus.
Renal failure, hepatotoxicity, pancytopenia, paralysis, shock and vascular collapse may also occur.
There is no specific antidote to colchicine. Gut removal techniques should be employed whenapplicable. Because of the extensive GI "recycling" of the drug, repeated doses of activated charcoal and a saline cathartic may reduce systemic absorption. Other treatment is symptomatic andsupportive. Dialysis (peritoneal) may be of benefit.
Laboratory Considerations - Colchicine may cause false-positive results when testing for erythrocytes or hemoglobin in urine. Colchicine may interfere with 17-hydroxycorticosteroiddeterminations in urine if using the Reddy, Jenkins, and Thorn procedure. Colchicine may causeincreased serum values of alkaline phosphatase.
Storage, Stability, Compatibility
Colchicine tablets should be stored in tight, light resistantcontainers. The injection should be diluted only in 0.9% sodium chloride for injection or sterilewater for injection. Do not use D5W or bacteriostatic sodium chloride for injection as precipitationmay occur. Do not use solutions that have become turbid.Pharmacology; Uses, Indications - Colchicine is best known for its antigout activity in humans.
The mechanism for this effect is not totally understood, but it probably is related to the drug'sability to reduce the inflammatory response to the disposition of monosodium urate crystals.
Colchicine inhibits cel division during metaphase by interfering with sol-gel formation and themitotic spindle.
In veterinary medicine, colchicine has been proposed as a treatment in small animals for amyloidosis. Colchicine apparently blocks the synthesis and secretion of serum amyloid A (SAA; anacute-phase reactant protein) by hepatocytes thereby preventing the formation of amyloid-enhancing factor and preventing amyloid disposition. For colchicine to be effective however, it mustbe given early in the course of the disease and it will be ineffective once renal failure has occurred.
Colchicine has also been proposed for treating chronic hepatic fibrosis presumably by decreasingthe formation and increasing the breakdown of collagen.
Pharmacokinetics - COLCHICINE
No information was located specifically for domestic animals, the followinginformation is human/lab animal data unless otherwise noted. After oral administration, colchicine isabsorbed from the GI tract. Some of the absorbed drug is metabolized in the liver (first-pass effect).These metabolites and unchanged drug are re-secreted into the GI tract via biliary secretions whereit is reabsorbed. This "recycling" phenomena may explain the intestinal manifestations noted withcolchicine toxicity. Colchicine is distributed into several tissues, but is concentrated in leukocytes.
Plasma half-life is about 20 minutes, but leukocyte half-life is approximately 60 hours. Colchicineis deacetylated in the liver and also metabolized in other tissues. While most of a dose (ascolchicine and metabolites) is excreted in the feces, some is excreted in the urine. More may beexcreted in the urine in patients with hepatic disease. Patients with severe renal disease may haveprolonged half-lives.
Contraindications, Precautions, Reproductive Safety
Colchicine is contraindicated in patientswith serious renal, GI, or cardiac dysfunction and should be used with caution in patients in earlystages of these disorders. It should also be used with caution in geriatric or debilitated patients.Because colchicine has been demonstrated to be teratogenic in laboratory animals (mice andhamsters) it should be used during pregnancy only when its potential benefits outweigh its risks. Itis unknown if colchicine enters maternal milk; use cautiously in nursing mothers. Colchicine maydecrease spermatogenesis.
Adverse Effects, Warnings
There has been very little experience with colchicine in domesticanimals. There are reports that colchicine can cause nausea, vomiting and diarrhea in dogs. Thefollowing adverse effects have been noted in humans and may not accurately reflect its use in dogsor cats. GI effects have been noted (abdominal pain, anorexia, vomiting, diarrhea). Because thesesymptoms are an early sign of toxicity it is recommended to discontinue therapy should they occur.Prolonged administration has caused bone marrow depression. Severe local irritation has beennoted if extravasation occurs after intravenous administration; thrombophlebitis has also beenreported.
Overdosage, Acute Toxicity
Colchicine can be a very toxic drug after relatively small overdoses.Deaths in humans have been reported with a single oral ingestion of as little as 7 mg, but 65 mg isconsidered the lethal dose in an adult human. GI manifestations are usually the presentingsymptoms seen. These can range from anorexia and vomiting to bloody diarrhea or paralytic ileus.
Renal failure, hepatotoxicity, pancytopenia, paralysis, shock and vascular collapse may also occur.
There is no specific antidote to colchicine. Gut removal techniques should be employed whenapplicable. Because of the extensive GI "recycling" of the drug, repeated doses of activated charcoal and a saline cathartic may reduce systemic absorption. Other treatment is symptomatic andsupportive. Dialysis (peritoneal) may be of benefit.
Drug Interactions
Non-steroidal anti-inflammatory agents, especially phenylbutazonemay increase the risks of thrombocytopenia, leukopenia or bone marrow depression developmentwhen used concurrently with colchicine. Many antineoplastics and other bone marrow depressant drugs (e.g., chloramphenicol, flucytosine, amphotericin B) may cause additivemyelosuppression when used with colchicine. Colchicine may enhance the activity of sympathomimetic agents and CNS depressants; clinical significance is unknown.Laboratory Considerations - Colchicine may cause false-positive results when testing for erythrocytes or hemoglobin in urine. Colchicine may interfere with 17-hydroxycorticosteroiddeterminations in urine if using the Reddy, Jenkins, and Thorn procedure. Colchicine may causeincreased serum values of alkaline phosphatase.