Description

Colchicine is an alkaloid derived from the autumn crocus plant (Colchicum autumnale). It is an oral medication that has been used for centuries for its potent anti-inflammatory effects. Colchicine is not an analgesic and does not affect serum uric acid levels. Its therapeutic effects are due to its unique mechanism of action on inflammatory cells, which makes it particularly effective in treating gout and other inflammatory conditions.

Indication

Colchicine is indicated for the treatment and prevention of certain inflammatory conditions. Its primary indications include:

• Gout: It is a first-line treatment for the prevention of acute gout flares and for the treatment of an acute gout attack.
• Familial Mediterranean Fever (FMF): It is the cornerstone of treatment for FMF, a genetic inflammatory disorder, to prevent acute attacks and amyloidosis.
• Pericarditis: It is used as a treatment for recurrent pericarditis, an inflammation of the sac-like tissue surrounding the heart.

Mechanism of Action

Colchicine’s mechanism of action is distinct from other anti-inflammatory drugs like NSAIDs or corticosteroids. Its anti-inflammatory effect is primarily achieved by disrupting the function of inflammatory cells, particularly neutrophils, which are key players in acute inflammatory responses like a gout attack. The process is as follows:

1. Binding to Tubulin: The primary action of colchicine is to bind to a protein called tubulin. Tubulin is a building block for microtubules, which are essential components of the cellular cytoskeleton.

2. Inhibition of Microtubule Polymerization: By binding to tubulin, colchicine prevents it from polymerizing into functional microtubules. This has a profound effect on cellular processes that depend on microtubules, such as cell division, motility, and intracellular transport.
3. Disruption of Neutrophil Function: In the context of gout, the inflammatory response is triggered by the deposition of uric acid crystals in the joints. This triggers a massive influx of neutrophils to the joint. By disrupting microtubule formation, colchicine interferes with several critical functions of neutrophils:

• • Inhibition of Chemotaxis: It prevents neutrophils from migrating to the site of inflammation.

• • Inhibition of Phagocytosis: It impairs the ability of neutrophils to engulf the uric acid crystals.

3. • Inhibition of Degranulation: It prevents neutrophils from releasing pro-inflammatory mediators that would otherwise amplify the inflammatory response.
4. Reduction of Inflammation: By crippling the inflammatory response of neutrophils, colchicine effectively reduces the pain, swelling, and redness associated with the gout attack. Its action is to break the inflammatory cycle, not to directly affect uric acid levels.