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针对形成有毒代谢物的醇类中毒的解毒剂。

Antidotes for poisoning by alcohols that form toxic metabolites.

作者信息

McMartin Kenneth, Jacobsen Dag, Hovda Knut Erik

机构信息

Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.

Department of Acute Medicine, Division of Medicine, Oslo University Hospital, Oslo, Norway.

出版信息

Br J Clin Pharmacol. 2025 Mar;91(3):662-671. doi: 10.1111/bcp.16232. Epub 2024 Sep 5.

Abstract

The alcohols methanol, ethylene glycol and diethylene glycol share many characteristics. The most important is that the compounds themselves are relatively nontoxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisonings, from either unintentional or intentional ingestion. Although relatively infrequent, toxic alcohol poisonings do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be an effective antidote, there are substantial practical problems with its use. Therefore fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive or the physician may prefer ethanol due to experience.

摘要

甲醇、乙二醇和二甘醇有许多共同特性。最重要的是,这些化合物本身相对无毒,但会通过乙醇脱氢酶初步代谢为各种有毒中间体。这些化合物在全球范围内的商业产品以及自制酒精饮料中都很容易获得,无论是无意还是有意摄入,这两者都导致了大多数中毒事件。尽管相对不常见,但有毒酒精中毒不幸地确实会以群体事件的形式发生,并可能导致严重的发病率和死亡率。传统上,这些中毒事件用乙醇治疗,因为它会竞争乙醇脱氢酶的活性位点,减少有毒代谢物的形成。尽管乙醇可能是一种有效的解毒剂,但其使用存在诸多实际问题。因此,开发了一种强效乙醇脱氢酶竞争性抑制剂——甲吡唑,以期更好地治疗代谢性有毒酒精中毒。甲吡唑副作用少,在实际应用中易于使用,并且在一些(但不是所有)患者中可能无需进行血液透析。因此,在许多国家,甲吡唑已在很大程度上取代乙醇成为有毒酒精的解毒剂。然而,乙醇仍然是一种重要的替代选择,因为甲吡唑的获取可能受限、成本可能过高,或者医生由于经验更倾向于使用乙醇。

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