What is colchicine and how does colchicine work Colchicine is a type of alkaloid medication used in managing gout flares. It is not entirely clear how colchicine exerts its effect although it may interfere with processes that lead to the activation of inflammatory markers known as interleukins. Colchicine may also interfere with neutrophil movement and activation as it pertains to producing symptoms of gout. When used for gout prophylaxis, the starting dose of colchicine is frequently colchicine 0.6 mg daily. The colchicine dose for gout prophylaxis can be titrated up at the discretion of the medical provider but usually should not exceed 1.2 mg daily. Colchicine sometimes used in conjunction with allopurinol (Zyloprim), indomethacin (Indocin) and probenecid as part of a gout treatment plan. Colchicine prescription medication is also used in treating some patients with Familial Mediterranean fever. Colchicine medication should not otherwise be considered an analgesic. Other uses for colchicine prescription medication are being investigated.
Colchicine is an oral medication that can be taken without regard to meals. After being administered orally, colchicine is absorbed well, reaching peak concentrations in the plasma in under 3 hours in healthy adults with an elimination half-life of roughly 30 hours. Colchicine is largely excreted in the urine. Colchicine is available as colchicine 0.6 mg tablets. Colchicine itself is a pale yellow powder that dissolve in water. Colchicine tablets are moderately expensive, with a price of colchicine 0.6 mg tablets at just over $2 per tablet. Colchicine coupons may be available online to help cover the cost of the medication and some insurance plans may also cover any costs associated with colchicine tablets. Colchicine 0.6 mg tablets are purple, film-coated tablets shaped like a capsule and scored on one side. Colchicine tablets should be stored at 20 C to 25 C.
Colchicine is a prescription medication in the United States. Colchicine OTC (over the counter) is not available at pharmacies and one cannot just buy colchicine online. People who need a colchicine prescription, however, can use Push Health to connect with a medical provider who can prescribe colchicine tablets, including generic colchicine 0.6 mg medication, when appropriate to do so.
Colchicine prescription medication can cause a variety of side effects when used, including diarrhea, throat pain, nausea, vomiting, and abdominal pain. Colchicine can cause blood dyscrasias and can interact with other medications. Muscle disorders such as rhabdomyolysis have been reported in association with colchicine use. Colchicine and alcohol should not be used at the same time. Questions about side effects related to colchicine medication use should be discussed with one's medical provider and pharmacist.
It preferentially concentrates in neutrophils, possibly related to their low expression of ABCB1 (ATP Binding Cassette Subfamily B Member 1), a drug transporter gene. Mutation of this gene leads to colchicine resistance.
Through microtubule depolymerization, colchicine inhibits cell proliferation, chemotaxis, adhesion, mobilization, signal transduction, gene expression, and neutrophil secretion of granule contents. It also inhibits the deformability of neutrophils, which affects the extravasation during inflammation.
Furthermore, Cronstein et al. have shown that colchicine may also alter the distribution of adhesion molecules (E selectin) on the surface of both neutrophils and endothelial cells, leading to a significant inhibition of the interaction between white blood cells (WBC) and endothelial cells interfering with their transmigration.
The clinical experience is that colchicine is ineffective in relieving ongoing acute Familial Mediterranean fever (FMF) attacks while being very efficient in preventing the attacks when given chronically. This is because colchicine exerts its prophylactic activity through gene suppression of loci involved in neutrophil migration or other inflammatory processes which requires 12-24 h and a higher dose.
In macrophages, it activates the nutritional biosensor AMP activated protein kinase, which transduces multiple anti-inflammatory effects of colchicine. It also blunts TNF-α--induced activation of macrophages and reduces TNF-α receptors on the surface of macrophages and endothelial cells.[1,11] Thus TNF-α-induced activation of NF-κB and signal transduction of the TNF-α-NF-κB pathway is inhibited by colchicine. These effects are medicated by its destabilization of the microtubule network.
Its action in amyloidosis is via a direct suppression of genes, like fibronectin, which inhibits the assembly and deposition of fibers such as amyloid. Also, colchicine has been found to inhibit transforming growth factor (TGF)-β1 activity. This can explain the beneficial effect of colchicine in other conditions of fiber deposition such as in scleroderma and cirrhosis where no direct relationship with the intensity or chronicity of an underlying inflammation exists.
An interesting off label use of this drug is as a re-purposed drug for COVID-19 via its action on IL-6 & inflammasomes, which may help in ameliorating the cytokine storm and is being actively researched in COVID-19. Recently the GRECCO-19 trial; an open-label RCT comparing colchicine with control group was carried out among 105 patients. The end point was to analyze difference in peak high-sensitivity troponin levels between the 2 groups. It was found that even though the authors did not see a significant reduction in troponin levels with colchicine, the group who received colchicine had significantly less clinical deterioration which was judged by requirement for mechanical ventilation. The patients treated with colchicine had significantly lower prothrombotic background as suggested by low levels of dimerized plasma fragment D levels.
Also, a role of Colchicine as a prophylactic agent in patients with high cardiovascular risk has been elicited. A retrospective cohort study done by Solomon et al. found that among 501 patients diagnosed with gout that were treated with colchicine; a protective effect signified by 49% relative risk reduction in the combined outcomes of transient ischemic attack, stroke, and MI was noted; along with 73% relative risk reduction of all-cause mortality.
INTRODUCTION: 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. METHODS: We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included \"colchicine\" and \"poisoning\" or \"overdose\" or \"toxicity\" or \"intoxication.\" TOXICOKINETICS: 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. DRUG INTERACTIONS: CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy. MECHANISMS OF TOXICITY: 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. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation. CLINICAL FEATURES: 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. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness. DIAGNOSIS: History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia). MANAGEMENT: Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent ( 59ce067264