Colchicine: Its mechanism of action and efficacy in crystal-induced inflammation

被引：46

作者：

Nuki G. ^{[1
]}

机构：

[1] University of Edinburgh, Osteoarticular Research Group, The Queen's Medical Research Institute, Edinburgh EH16 4TJ

来源：

Current Rheumatology Reports | 2008年 / 10卷 / 3期

关键词：

Colchicine; Gout; Gouty Arthritis; CPPD; Acute Gout;

D O I：

10.1007/s11926-008-0036-3

中图分类号：

学科分类号：

摘要：

New light has been shed on the mechanisms of action of colchicine in crystal-associated arthropathies. Colchicine, long used to treat gout, arrests microtubule assembly and inhibits many cellular functions. At micromolar concentrations, it suppresses monosodium urate crystal-induced NACHT-LRR-PYD-containing protein-3 (NALP3) inflammasome-driven caspase-1 activation, IL-1β processing and release, and L-selectin expression on neutrophils. At nanomolar concentrations, colchicine blocks the release of a crystal-derived chemotactic factor from neutrophil lysosomes, blocks neutrophil adhesion to endothelium by modulating the distribution of adhesion molecules on the endothelial cells, and inhibits monosodium urate crystal-induced production of superoxide anions from neutrophils. Cytochrome P450 3A4, the multidrug transporter P-glycoprotein, and the drugs that bind these proteins influence its pharmacokinetics and pharmacodynamics. Trial evidence supports its efficacy in acute gout and in preventing gout flares, but it has narrow therapeutic index, and overdosage is associated with gastrointestinal, hepatic, renal, neuromuscular, and cerebral toxicity; bone marrow damage; and high mortality. Copyright © 2008 by Current Medicine Group LLC.

引用

页码：218 / 227

页数：9

共 100 条

[1]

Nuki G., Treatment of crystal arthropathy - history and advances, Rheum Dis Clin N Am, 32, pp. 333-357, (2006)

[2]

Jordan K.L., Cameron S., Snaith M., Et al., British Society for Rheumatology and British Health Professionals in Rheumatology Guidelines for the Management of Gout, Rheumatology, 46, pp. 1372-1374, (2007)

[3]

Abramson S.B., Treatment of gout and crystal arthropathies and uses and mechanisms of action of nonsteroidal antiinflammatory drugs, Curr Opin Rheumatol, 4, pp. 295-300, (1992)

[4]

Yu T., The efficacy of colchicine prophylaxis in articular gout. A reappraisal after 20 years, Semin Arthritis Rheum, 12, pp. 256-264, (1982)

[5]

Kunei R.W., Duncan G.J., Watson D., Et al., Colchicine myopathy and neuropathy, N Engl J Med, 316, pp. 1562-1568, (1987)

[6]

Wallace S.L., Singer J.Z., Duncan G.J., Et al., Renal function predicts colchicine toxicity: Guidelines for the prophylactic use of colchicine in gout, J Rheumatol, 18, pp. 264-269, (1991)

[7]

Cohen A., Gout, Am J Med Sci, 192, pp. 448-493, (1936)

[8]

Borstad G.C., Bryant L.R., Abel M.P., Et al., Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis, J Rheumatol, 31, pp. 2429-2432, (2004)

[9]

Paulus H.E., Schlosstein L.H., Godfrey R.G., Et al., Prophylactic colchicine therapy in intercritical gout. A placebo-controlled study of probenecid-treated patients, Arthritis Rheum, 17, pp. 609-614, (1974)

[10]

Dalbeth N., Haskard D.O., Mechanisms of inflammation in gout, Rheumatology, 44, pp. 1090-1096, (2005)

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