McMartin Kenneth, Jacobsen Dag, Hovda Knut Erik
Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center - Shreveport, 1501 Kings Highway, Shreveport, Louisiana, 71130-3932, USA.
Department of Acute Medicine, Division of Medicine, Oslo University Hospital, NO-0424, Oslo, Norway.
Br J Clin Pharmacol. 2016 Mar;81(3):505-15. doi: 10.1111/bcp.12824. Epub 2016 Jan 4.
The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic 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 poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols 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 effective in these poisonings, there are substantial practical problems with its use and so 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.
甲醇、乙二醇和二甘醇等醇类物质有许多共同特征,其中最重要的是这些化合物本身相对无毒,但会首先通过乙醇脱氢酶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,这两种情况都导致了大多数中毒病例,无论是无意还是有意摄入。尽管代谢性有毒醇类中毒在总体发生率上相对较低,但不幸的是,此类中毒会以群体发作的形式出现,并可能导致严重的发病率和死亡率。传统上,这些中毒情况用乙醇治疗,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。尽管乙醇在这些中毒情况中可能有效,但其使用存在诸多实际问题,因此,作为乙醇脱氢酶的强效竞争性抑制剂,甲吡唑被开发出来,有望为代谢性有毒醇类中毒提供更好的治疗方法。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醇类的解毒剂。然而,乙醇仍然是一种重要的替代选择,因为获取甲吡唑可能受到限制、成本可能过高,或者医生由于经验原因可能更倾向于使用乙醇。