Colchicine Pharmacology!

Colchicine Pharmacology

Colchicine has been used since at least 1500BC; its extracts taken from the Autumn crocus plant (Colchicum autumnale) to treat joint swelling and pain. Today, colchicine use has been expanded to treat a variety of other inflammatory disease states.

Indications of colchicine include:

• Gout
• Familial Mediterranean fever – a hereditary inflammatory disorder
• Behçet’s disease
• Pericarditis

Colchicine is sold under names such as Colcrys and Mitigare, among others.

Below, we review in more detail both the common and uncommon side effects of colchicine, as well as its notable drug interactions and must-know clinical pharmacology and toxicology.

However, let’s first begin by learning more about the mechanism of action of colchicine; how the drug works to achieve its therapeutic effects.

Mechanism of Action

There are a variety of mechanisms by which colchicine works:

• Binds to tubulin to inhibit microtubule polymerization.
• Inhibits neutrophil chemotaxis migration to sites of inflammation.
• Interrupts mast cell and lysosome degranulation and break-up.

Gout is caused by an accumulation of uric acid, which reaches levels that exceed its solubility in blood. As a result, uric acid crystallizes around joints. White blood cells such as neutrophils are drawn to these sites, which contributes to the inflammatory response – causing inflammation, redness, and pain. Colchicine works to inhibit these mechanisms and alleviate inflammation and pain at the site of gout attacks.

For the same anti-inflammatory reasons, colchicine is also effective in the treatment of inflammatory conditions such as pericarditis, familial Mediterranean fever, and Behçet’s disease.

In familial Mediterranean fever, colchicine is believed to work by interfering with the inflammasome complex which is present in neutrophils and monocytes. This complex mediates the activity of the pro-inflammatory interleukin-1 β.

Side Effects

Common side effects with colchicine include:

• Gastrointestinal upset
• Diarrhea
• Neutropenia
• Anemia
• Fatigue
• Headache

Less commonly, colchicine can cause muscle pain, paresthesias, pale/gray appearance of skin or the tongue, or flu-like symptoms.

Colchicine may cause other side effects not listed in this guide.

Clinical Pharmacology

When we think about the clinical pharmacology of colchicine, we must consider the following factors:

• Colchicine is contraindicated in patients with advanced kidney disease. Up to one-fifth of colchicine is eliminated unchanged in the urine. Renal disease increases the risk of toxicity and adverse effects such as neuromyopathy.
• CYP 3A4 inhibitors, particularly strong inhibitors, should be avoided with colchicine as they increase the risk of toxicity. Examples include clarithromycin, protease inhibitors, nefazodone, chloramphenicol, and some azole antifungals such as ketoconazole or voriconazole.
• Statins increase the risk of colchicine toxicity.
• Grapefruit juice increases the risk of colchicine toxicity.
• Colchicine toxicity is serious and includes symptoms such as fever, abdominal pain, vomiting and diarrhea – which may progress to hypovolemia, nephrotoxicity, hepatotoxicity, thrombocytopenia, ascending paralysis, multi-organ failure, and death. Neurological symptoms such as seizures may also present. There is no antidote for colchicine toxicity, so treatment remains supportive.
• Elimination half-life = approximately 31 hours.
• Patients are counselled to maintain adequate fluid intake whilst taking colchicine.

That concludes our review of colchicine pharmacology! Check back to our pharmacy blog soon for more exclusive content to help you master the science behind drugs and medicines!