口服降糖药诱发的“双硫仑样”反应的生化方面研究。

Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics.

作者信息

Asaad M M, Clarke D E

出版信息

Eur J Pharmacol. 1976 Feb;35(2):301-7. doi: 10.1016/0014-2999(76)90232-6.

Abstract

In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.

摘要

采用大鼠肝脏匀浆进行的体外实验，旨在检验口服降糖药与单胺及乙醇代谢相互作用的某些拟议酶促机制。通过测量吲哚乙酸（IAA）生成量来研究色胺的氧化降解，并就单胺氧化酶、醛脱氢酶和乙醇脱氢酶的活性得出结论。醋磺己脲、羟磺己脲、甲苯磺丁脲、甲磺丁脲和氯磺丙脲均未显示对这三种酶有任何特异性抑制作用。乙醇（0.2% w/v）和双硫仑可减少IAA生成，缺乏醛脱氢酶和烟酰胺腺嘌呤二核苷酸（NAD）时也会如此，但降糖药不会增强这些减少作用。结果表明，某些患者在服用口服降糖药时饮用乙醇会出现“双硫仑样”反应，这取决于对单胺和/或乙醇代谢的特异性干扰之外的某些因素或附加因素。