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Colchicine

 

is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF).

 

It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians.

 

Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome.

 

Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements.

 

Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys.

 

THERAPEUTIC AND TOXIC DOSES:

 

The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.

 

Colchicine’s toxicity is an extension of its mechanism of action – binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility.

 

The culmination of these mechanisms leads to multi-organ dysfunction and failure.

 

Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion – gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion – multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis.

 

 

 

 

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