秋水仙碱中毒:古代药物的阴暗面。
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芬克尔斯坦Y,部,Hutson JR Juurlink DN,阮P, Dubnov-Raz G, Pollak U,科伦克,林杰宏Y
秋水仙碱中毒:古代药物的阴暗面。
中国Toxicol(费拉)。2010年6月,48(5):407 - 14所示。doi: 10.3109 / 15563650.2010.495348。
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20586571 (在PubMed]
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作品简介:秋水仙碱主要用于治疗和预防痛风和家族性地中海热(FMF)。它有一个狭窄的治疗指数,由于没有明确的区分无毒,有毒的,和致命剂量,引起临床医生的大混乱。虽然秋水仙碱中毒有时会有意的,无意的毒性是普遍的,往往也是与一个贫穷的结果。方法:我们进行了一个系统回顾通过搜索奥维德MEDLINE在1966年和2010年1月。必威国际app搜索策略必威国际app包括“秋水仙碱”和“中毒”或“过量”或“毒性”或“中毒”。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 (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available. CONCLUSION: Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.