Jacobsen D, McMartin K E
Med Toxicol. 1986 Sep-Oct;1(5):309-34. doi: 10.1007/BF03259846.
Methanol and ethylene glycol poisonings share many characteristics both clinically and biochemically. Both alcohols are metabolised via alcohol dehydrogenase to their toxic metabolites. Methanol is slowly metabolised to formaldehyde which is rapidly metabolised to formate, the metabolite mainly responsible for methanol toxicity. Formate metabolism depends upon the folate pool which is small in primates compared with other animals. Therefore, formate accumulates in primates during methanol intoxication and is mainly responsible for the metabolic acidosis in the early stage of intoxication. In late stages lactate may also accumulate, mainly due to formate inhibition of the respiratory chain. This tissue hypoxia caused by formate may explain the ocular as well as the general toxicity. Ethylene glycol is metabolised more rapidly than methanol, via alcohol dehydrogenase to glycolaldehyde which is rapidly metabolised to glycolate, the metabolite mainly responsible for the metabolic acidosis in ethylene glycol poisoning. Glycolate is metabolised by various pathways, including one to oxalate which rapidly precipitates with calcium in various tissues and in the urine. Ethylene glycol toxicity is complex and not fully understood, but is mainly due to the severe metabolic acidosis caused by glycolate and to the calcium oxalate precipitation. The clinical course in both poisonings is initially characterised by the development of metabolic acidosis following a latent period, which is more pronounced in methanol poisoning and is the time taken for both alcohols to be metabolised to their toxic metabolites. In methanol poisoning there are usually visual symptoms progressing to visual impairment, whereas ethylene glycol victims develop renal and cardiopulmonary failure. Prognosis is excellent in both poisonings provided that there is early treatment with alkali to combat acidosis, ethanol as an antimetabolite, and haemodialysis to remove the alcohols and their toxic metabolites. Ethanol is also metabolised by alcohol dehydrogenase, but has a much higher affinity for this enzyme than methanol and ethylene glycol. Presence of ethanol will therefore inhibit formation of toxic metabolites from methanol and ethylene glycol. Due to competition for the enzyme, the therapeutic ethanol concentration depends on the concentration of the other two alcohols, but a therapeutic ethanol concentration around 22 mmol/L (100 mg/dl) is generally recommended. Most patients are, however, admitted at a late stage to hospitals not capable of performing analyses of these alcohols or their specific metabolites on a 24-hour basis.(ABSTRACT TRUNCATED AT 400 WORDS)
甲醇中毒和乙二醇中毒在临床和生化方面有许多共同特征。两种醇类都通过乙醇脱氢酶代谢为其有毒代谢产物。甲醇缓慢代谢为甲醛，甲醛迅速代谢为甲酸，甲酸是导致甲醇毒性的主要代谢产物。甲酸的代谢依赖于叶酸池，与其他动物相比，灵长类动物的叶酸池较小。因此，在甲醇中毒期间，甲酸在灵长类动物体内蓄积，是中毒早期代谢性酸中毒的主要原因。在后期，乳酸也可能蓄积，主要是由于甲酸对呼吸链的抑制作用。甲酸引起的组织缺氧可能解释了眼部毒性以及全身毒性。乙二醇的代谢速度比甲醇快，通过乙醇脱氢酶代谢为乙醇醛，乙醇醛迅速代谢为乙醇酸，乙醇酸是乙二醇中毒时代谢性酸中毒的主要原因。乙醇酸通过多种途径代谢，包括一条途径生成草酸盐，草酸盐会在各种组织和尿液中迅速与钙结合沉淀。乙二醇中毒的情况较为复杂，尚未完全了解，但主要是由于乙醇酸引起的严重代谢性酸中毒以及草酸钙沉淀。两种中毒的临床病程最初都表现为在潜伏期后出现代谢性酸中毒，这在甲醇中毒中更为明显，潜伏期是两种醇类代谢为其有毒代谢产物所需的时间。在甲醇中毒中，通常会出现视觉症状并发展为视力损害，而乙二醇中毒患者会出现肾衰竭和心肺功能衰竭。如果早期用碱治疗以对抗酸中毒、用乙醇作为抗代谢物以及进行血液透析以清除醇类及其有毒代谢产物，两种中毒的预后都很好。乙醇也通过乙醇脱氢酶代谢，但对该酶的亲和力比甲醇和乙二醇高得多。因此，乙醇的存在会抑制甲醇和乙二醇生成有毒代谢产物。由于对该酶的竞争，治疗性乙醇浓度取决于另外两种醇类的浓度，但一般建议治疗性乙醇浓度约为22 mmol/L（100 mg/dl）。然而，大多数患者在晚期才被送往无法24小时进行这些醇类或其特定代谢产物分析的医院。（摘要截选至400字）
