What is the role of colchicine in the treatment of cyclosporine nephrotoxicity?
Li C, Yang CW, Ahn HJ, Kim WY, Park CW, Park JH, et al. Colchicine decreases apoptotic cell death in chronic cyclosporine nephrotoxicity. J Lab Clin Med. 2002;139(6):364–371. [PubMed] [Google Scholar]
Is colchicine a treatment alternative in the management of cutaneous conditions?
(1) Background: Colchicine is a natural alkaloid with anti-inflammatory properties used to treat various disorders, including some skin diseases. This paper aims to incorporate all the available studies proposing colchicine as a treatment alternative in the management of cutaneous conditions.
How does colchicine affect antigen presentation in mice?
3.1.5 Stimulation of antigen presentation At relatively low concentrations (3µg/ml), mice colchicine promotes maturation of dendritic cells, generation of cytokines and the presentation of antigen to allogenic naive CD4+ lymphocytes [33].
What should I know about colchicine before taking it?
Colchicine should not be used to treat pain that occurs as a result of other conditions. Colchicine is a substrate for the P-glycoprotein transporter and the CYP3A4 metabolizing enzyme.
What is colchicine used for?
Hence, treatment of animals with colchicine is commonly used to promote the accumulation of secretory proteins in the cytoplasm. 1. Deeply anesthetize rat with sodium pentobarbital (40 mg/kg, ...
How much colchicine should I take for FMF?
The average daily dose is 1–1.5 mg.
Why is ginger high sterility?
In Vitro Polyploidy. Ginger displays high sterility as a result of chromosome aberrations such as translocations and inversions. Hence, other breeding methods such as mutation and polyploidy breeding are required to obtain genetically improved plants.
Is colchicine toxic to humans?
Acute intoxication with colchicine occurs relatively often, because the therapeutic dose is close to the toxic dose. Gastrointestinal, hematological, and neurological reactions are the most frequent effects [ 31 ]. An accidental overdose of colchicine by nasal insufflation has been reported in a young male drug abuser who had mistaken it for metamfetamine. The effects included gastrointestinal distress, myalgia, thrombocytopenia, hypocalcemia, and hypophosphatemia [ 32 ]. Electrolyte disturbances can occur [ 7–9 ]. Deaths have been reported [ 8 ].
Is colchicine more toxic than oral?
Intravenous administration is potentially much more toxic than oral administration ; because of its unfavorable benefit to harm, balance and the availability of less dangerous treatments, colchicine should not be given intravenously [ 29, 30 ].
Is colchicine better tolerated for gout?
It has been suggested that the dosages of colchicine recommended by the British National Formulary in patients with gout should be revised; lower doses are probably better tolerated and equally efficacious [ 28 ].
Does galanin help the hippocampal?
Higher levels of galanin promoted the survival of hippocampal neurons after kainic acid lesions, possibly through the inhibition of glutamate release. Long-term neuroprotective actions of endogenously administered galanin in the adult central nervous system remain controversial. View chapter Purchase book.
What is the primary mechanism of action of colchicine?
The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, ...
What is the substrate for cytochrome P450?
Colchicine is a substrate for intestinal and hepatic cytochrome P450 3A4 (CYP3A4), and also a substrate for P-glycoprotein 1 (P-gp) reflux transporter. Colchicine is primarily eliminated by hepatobiliary excretion. Renal excretion accounts for 10–20% of colchicine elimination in patients with normal renal function.
Does colchicine help with febrile attacks?
Although colchicine does not totally prevent febrile attacks, its long term use can arrest the progression of AA amyloidosis.
Does colchicine help with gout?
The high dose treatment arm had more associated gastrointestinal side effects. The general consensus for the treatment of acute gout is to use low doses of colchicine. In view of its potential side effects, including renal, hepatic and gastrointestinal side effects, dosage adjustments also need to be considered.
Does colchicine inhibit neutrophil chemotaxis?
Colchicine concentrates intensively in leukocytes. In vitro, colchicine at concentrations as low as 0.1nM inhibi ts neutro phil chemotaxis and the release of a glycopeptide crystal-derived chemotactic factor (CCF) from neutrophil lysosomes after phagocytosis of monosodium urate crystals (MSU) [9].
Abstract
Although colchicine has been used for centuries, its neuromuscular toxicity in humans is largely unrecognized. In this report we describe a characteristic syndrome of myopathy and neuropathy and present 12 new cases of the condition.
Patient 1
A 59-year-old man presented with a six-month history of intermittent weakness in the muscles of his arms and legs. Because of recurrent gouty arthritis, he had taken colchicine, 0.6 mg twice daily, for two years.
Patient 2
An 86-year-old man with gout had taken 0.6 mg of colchicine twice daily for three years. He became progressively weaker over three months and had difficulty in rising from chairs and lifting objects. During the three weeks preceding evaluation, he could no longer walk without support and he noticed a slight numbness in his hands and toes.
Patient 3
A 60-year-old man undergoing dialysis was seen in consultation before corticosteroid therapy was given because of a presumptive diagnosis of polymyositis. The diagnosis was based on the presence of weakness, a greatly elevated serum creatine kinase level, and an electromyogram typical of myositis.
Patient 4
An 85-year-old man with gout, chronic renal insufficiency, and progressive weakness for two months was admitted because of dehydration and failure to thrive. He had taken colchicine, 0.6 mg twice daily, for several years.
Methods
We acquired cases both prospectively and retrospectively from 1984 to 1986 in the following ways. (1) We saw seven of the patients when they were referred for neuromuscular consultation at our hospital.
Electrodiagnosis
In three of the four patients studied while symptomatic, concentric needle electromyography of proximal muscles showed prominent fibrillations and positive sharp waves; motor-unit potentials were excessively polyphasic, brief in duration, and small in amplitude. Such findings are typical of polymyositis and other necrotizing myopathies.
What is colchicine used for?
Colchicine, nowadays, has really shaped the way pericardiologists manage and treat patients with acute , recurrent and constrictive pericarditis. 1 It was first extracted, as an alkaloid derivative, by French chemists P.S. Pelletier and J.B. Caventou in the early 1800s. The first reported use of colchicine in pericardial diseases was in 1987 by Rodriguez de la Serna A et al, for the treatment of three patients with suspected recurrent pericarditis despite the use of corticosteroids. In the modern era of medicine, it is primarily used for the treatment of Familial Mediterranean Fever (FMF), an auto-inflammatory disorder that affects the pericardium and pleura as well as episodes of gout. Colchicine has since been the focus of many observational and randomized studies for pericardial diseases. In fact, it is now a class IA medication to treat acute and recurrent pericarditis. 2 Despite the gastrointestinal possible side-effects, colchicine is considered a safe anti-inflammatory drug. The focus of this expert review is to:
What is colchicine metabolized by?
Colchicine is a lipid-soluble medication that is absorbed in the jejunum and ileum. 3 It has 44% bioavailability 4 and it is metabolized by CYP3A4. Colchicine is predominantly excreted by the liver with 10-20% being excreted by the kidneys. 5 The anti-inflammatory effect of colchicine differs from conventional non-steroidal anti-inflammatory drugs (NSAIDs) and steroids in that it does not act on the arachidonic acid pathway. Rather, it targets white blood cells (WBCs) and causes microtubule depolymerization (Figure 1 and 2), which in turn inhibits motility, phagocytosis and degranulation of the WBCs. 2,6 It also inhibits interleukin-1beta (IL-1β) and interleukin-18 (IL-18) by interfering with NLRP3 inflammasome protein complex, 6-8 which is increasingly recognized as playing a role in acute coronary syndrome, crystal-induced gout and more importantly recurrent idiopathic pericarditis (Figure 3).
Is colchicine safe for pericardial effusion?
Post cardiac injury syndrome is increasing in frequency, and though colchicine has been proven efficacious in this arena, its utilization is underwhelming. Currently, there is no strong evidence for the use of colchicine for pericardial effusions and constrictive pericarditis, however, evidence of pericardial inflammation should prompt the clinician to attempt a trial given the experience with colchicine in pericardial inflammatory conditions. Nevertheless, this would be an interesting area of future research.
Is colchicine a class IA?
Colchicine has since been the focus of many observational and randomized studies for pericardial diseases. In fact, it is now a class IA medication to treat acute and recurrent pericarditis. 2 Despite the gastrointestinal possible side-effects, colchicine is considered a safe anti-inflammatory drug.
Is colchicine used for gout?
In the modern era of medicine, it is primarily used for the treatment of Familial Mediterranean Fever (FMF), an auto-inflammatory disorder that affects the pericardium and pleura as well as episodes of gout. Colchicine has since been the focus of many observational and randomized studies for pericardial diseases.
Does colchicine help with pericardial inflammation?
Clinicians are also trying to avoid an evolution towards constrictive physiology that is often associated with debilitating right heart failure. While there is no clear role for anti-inflammatories like colchicine in the chronic calcific stages of constriction, there is a role in trans ient constrictive pericarditis. Acute pericarditis could be associated, transiently, with constriction physiology that could resolve with medical therapy. This constellation of findings is commonly referred to as transient constriction. The use of colchicine has been described in conjunction with NSAIDs and/or steroids, however, the evidence is not robust and should be the focus of future studies. Colchicine should be encouraged if there is evidence of ongoing pericardial inflammation as evidenced by whether a high CRP and/or in the presence of thick pericardium (>3 mm) with late gadolinium enhancement (LGE) of the pericardium on CMR. 19,20
How long does it take for a tea color to appear in urine?
Darkening of the urine to a tea-colored hue also sometimes accompanied the physical symptoms. The onset of the symptoms usually occurred after 2 to 3 weeks of combined therapy, but in some cases, the patient noticed changes after about a week. Occasionally, there was a latent period of 2 to 3 months or more.
Can you stand up on statins with myopathy?
In some cases, the weakness was so severe that the patient could not even stand up. In about one-third of the cases, muscle weakness was accompanied by muscle pain.
Can statin cause myopathy?
Statin-induced myopathy often occurs and is the result of increased statin plasma concentrations caused by interacting drugs, usually inhibitors of CYP3A4. For some statin drug interactions, other mechanisms may also be involved. Colchicine can also produce myopathy, and rhabdomyolysis has been reported in severe cases.
Can myopathy cause brown urine?
The patient should be advised to immediately report any muscle pain or weakness as well as brownish or darkened urine. The patient is likely to fare better if the myopathy is diagnosed quickly and the drugs are discontinued.
Is colchicine a statin?
A study of statin-induced myopathy found that 40% of the patients received a drug that may have predisposed them to the muscle damage, and colchicine was the second-most-common interacting drug. 15 A more recent report focusing only on simvastatin drug—drug interactions (DDIs) reported that the combination with colchicine was the second-most-common DDI exposure, after gemfibrozil.
What is colchicine used for?
Today, colchicine is widely used for treatment of acute gout flares, prophylaxis against gout flares and treatment of other crystal diseases and FMF.
Does colchicine help with cardiac disease?
Colchicine and cardiac conditions. The past decade has seen a rapid increase in both the study and use of colchicine in a range of cardiac diseases, consistent with the burgeoning understanding that inflammation plays a key role in the development and propagation of many such conditions.
Does colchicine inhibit inflammatory cells?
The mechanisms through which colchicine exerts its anti-inflammatory properties are multiple. Perhaps the best appreciated of these mechanisms is the ability of colchicine to bind to free tubulin dimers which, when incorporated into microtubules, block subsequent microtubule polymerization [ 2 ]. This dose-dependent mechanism appears to be directly responsible, at least in vitro, for the effects of colchicine on cell migration, cytokine release and intracellular trafficking, and plays an important role in the disruption of inflammatory cell activities by colchicine [ 3 ]. The extent to which this mechanism contributes to the effects of colchicine at clinically therapeutic doses is less well established. Colchicine inhibits neutrophil adhesion, extravasation and recruitment by altering neutrophil L-selectin expression and endothelial cell E-selectin distribution, and suppressing the release of the chemotactic agent leukotriene B 4 [ 4 ], as well as altering neutrophil deformability [ 5 ]. Colchicine also modulates leucocyte-mediated inflammatory activities, including inhibiting leucocyte production of superoxides and release of various cytokines and pyrogens [ 6, 7 ]. Whether all of these effects are secondary to the impact of colchicine on microtubules remains to be determined.
Is colchicine good for rheumatic disease?
In rheumatic disease, colchicine is most useful for conditions driven by macrophages and neutrophils. Colchicine’s anti-inflammatory effects hold promise for prevention/management of cardiovascular conditions, including acute coronary syndromes.
Is colchicine safe for gout?
Colchicine is an ancient medication that is currently approved for the treatment of gout and FMF. However, colchicine has a wide range of anti- inflammatory activities, and studies indicate that it may be beneficial in a variety of other conditions. This paper reviews the evidence for the well-established use of colchicine in gout, as well as several other rheumatic diseases. In addition, we highlight the potential benefit of colchicine in cardiac disease, including coronary artery disease in patients both with and without gout.
Does colchicine help with CAD?
Studies have found that many of the inflammatory mechanisms that are targeted by colchicine play a role in the pathogenesis of coronary artery disease (CAD). NLRP3 inflammasome activation has been noted in cardiac fibroblasts after a myocardial infarction (MI), and is thought to mediate myocardial ischaemia–reperfusion injury [ 72, 73 ]. Colchicine may also improve cardiac survival and left ventricular remodelling by inhibiting granulocyte accumulation within infarcts, and possibly by upregulating anti-inflammatory M2 macrophages while suppressing pro-inflammatory M1 macrophages [ 74 ]. A study by Shah et al. [ 75] found that both in vitro and in vivo, therapeutic levels of colchicine had no effect on pure platelet aggregation, but were associated with decreased neutrophil–platelet and monocyte–platelet aggregation [ 75 ]. These data suggest that colchicine may have the potential to reduce the size or propagation of clots that occur in the setting of inflammation, such as during MI, without impairing the ability of platelets to perform their clotting function in the setting of non-inflammatory lesions, such as acute skin breaks.
What is colchicine used for?
Medically reviewed by Carmen Fookes, BPharm. Last updated on Oct 5, 2020. 1. How it works. Colchicine is a medicine that is used to relieve the symptoms of gout. It is thought to work by blocking how our immune system responds to the presence of urate crystals in synovial fluid (the fluid between our joints).
How long does colchicine take to reach peak concentration?
6. Response and effectiveness. Peak concentrations of colchicine are reached within 0.7 to 2.5 hours after oral administration. Food does not affect the absorption of colchicine.
What medications interact with colchicine?
Common medications that may interact with colchicine include: aprepitant. antifungals such as itraconazole, fluconazole, and ketoconazole. cyclosporine. digoxin. HIV medications, such as amprenavir , atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, and saquinavir.
Is Colcrys a generic?
Colcrys is a brand name of colchicine. Colchicine is available as a cost-saving generic. 3. Downsides. If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:
Does colchicine cause nausea?
Regular blood tests may be needed if you take colchicine long-term. If you experience any gastrointestinal side effects from colchicine such as abdominal pain, diarrhea, nausea, or vomiting, contact your doctor to discuss.
Can colchicine cause hair loss?
These may be an initial sign of toxicity and the dosage of colchicine may need to be reduced or stopped. Contact your doctor for further advice. Other side effects include muscle pain or weakness, hair loss, rash, changes in the numbers of blood cells or liver enzymes, and low sperm counts.
Can you take colchicine with grapefruit?
Do not take colchicine with grapefruit or grapefruit products. If you develop any symptoms of muscle pain or weakness or numbness in the fingers or toes, contact your doctor immediately and discontinue colchicine. Also, contact your doctor if you experience any unusual bleeding or bruising or skin discoloration. 6.