Colchicine as medicine
In 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.
Colchicine has a relatively low therapeutic index. A high therapeutic index is preferable to a low one: this corresponds to a situation in which one would have to take a much higher dose of a drug to reach the lethal threshold than the dose taken to elicit the therapeutic effect.
Long term (prophylactic) regimens of oral colchicine are absolutely contraindicated in patients with advanced renal failure (including those on dialysis). 10-20% of a colchicine dose is excreted unchanged by the kidneys. Colchicine is not removed by hemodialysis. Cumulative toxicity is a high probability in this clinical setting. A severe neuromyopathy may result. The presentation includes a progressive onset of proximal weakness, elevated creatine kinase, and sensorimotor polyneuropathy. Colchicine toxicity can be potentiated by the concomitant use of cholesterol lowering drugs (statins, fibrates). This neuromuscular condition can be irreversible (even after drug discontinuation). Accompanying dementia has been noted in advanced cases. It may culminate in hypercapnic respiratory failure and death. (Minniti-2005)
Side effects include gastro-intestinal upset and neutropenia. High doses can also damage bone marrow and lead to anemia. Note that all of these side effects can result from hyper-inhibition of mitosis.
Colchicine 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.
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