colchicine

A drug to treat gout and other diseases, taken by mouth.
The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells.
It works by decreasing inflammation.

It binds to tubulin which is essential to microtubule polymerization in mitosis, and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis.
It inhibits activation and migration of neutrophils to sites of inflammation, leading to a net anti-inflammatory effect to ease gout inflammation.

(Manifestation to treat)
• gout: Less preferred to NSAIDs or steroids.
• Behçet's disease
• pericarditis
• familial Mediterranean fever

It has a narrow therapeutic index, so overdosing is a significant risk.
Side effects can result from inhibition of mitosis.
The poisoning by overdose begins with a gastrointestinal phase occurring 10-24 hours after ingestion, followed by multiple organ dysfunction occurring 24 hours to 7 days after ingestion. After that, the affected person either declines into multiple organ failure or recovers over several weeks.

It interacts with the P-glycoprotein transporter and Cytochrome P450 3A4 (CYP3A4), which drugs such as erythromycin and clarithromycin inhibit, leading to death.
It should not be given to people taking macrolide antibiotics, ketoconazole, or cyclosporine, or those who have liver or kidney disease, as colchicine blood levels is raised because its metabolism is interfered, potentially increasing its toxicity abruptly.

(Side effects)
Moderate doses:
• gastrointestinal upset, diarrhea
• neutropenia
High doses:
• anemia caused by damage of bone marrow
• multiple organ dysfunction: kidney damage, low white blood cell counts, anemia, muscular weakness liver failure, hepatomegaly, bone marrow suppression, thrombocytopenia, ascending paralysis
• alopecia (hair loss)
• neuromuscular toxicity: seizures, confusion, delirium, hallucinations in children
• rhabdomyolysis: A life-threatening condition caused by muscle breakdown and muscle death.
• hypovolemic shock: Due to extreme vascular damage and fluid loss through the gastrointestinal tract, which can be fatal.