Clinical Responses in Relation to Blood Acetaldehyde Levels

Abstract

A study was undertaken to examine the relationship between blood acetaldehyde levels and clinical responses in volunteers receiving the anti-alcohol drugs disulfiram and calcium cyanamide. In the first part of this study volunteers received different doses of disulfiram (125 mg and 500 + 250 mg), of calcium cyanamide (25 mg, 50 mg and 100 mg) and of ethanol (0.2 g/kg orally and 0.5 g/kg intravenously). The ensuing interactions ranged from no reaction at all to an intense hypotensive cyanamide-ethanol reaction (CER). A blood acetaldehyde concentration-effect relationship was suggested. In the second part of this study seven subjects received 50 mg of calcium cyanamide 4 hr prior to an intravenous ethanol dose of 0.2 g/kg. The maximum blood level of acetaldehyde ranged from 16 to 241 microM. Aversive interactions started to occur at acetaldehyde levels around 40-60 microM. Changes in flushing reaction and diastolic blood pressure appeared best to reflect changing blood acetaldehyde levels. As a rule, however, the expected cyanamide-ethanol and disulfiram-ethanol reactions are more clearly registered as an increase in acetaldehyde levels than as the ensuing physiological responses.

Polymorphism of Alcohol‐Metabolizing Genes Affects Drinking Behavior and Alcoholic Liver Disease in Japanese Men

“…'-' Thus, subjects with ADH2*2/*2 might not drink a large amount of alcohol, because aversive reactions to acetaldehyde generally appear when blood concentration reaches -40 to 60 pM. 38 Current results are consistent with reports that alcoholavoiding rats showed lower ALDH activity and higher ADH activity in comparison with alcohol-preferring rats.3994" It could also be possible that the rate of ethanol elimination and, in turn, the level of hepatic ADH activity modulate alcohol consumption with higher ADH activity, thus resulting in a more rapid clearance of ethanol and a higher concentration of acetaldehyde. This hypothesis was confirmed by a previous alcohol intake study in rodents that showed consumption was inversely related to alcohol dehydrogenase activity, indicating that the animals were willing to drink more as alcohol was metabolized more slowly (lower ADH activity)!l Among humans, ALDHZdeficient individuals (heterozygous for ALDH2*1/*2 and homozygous for ALDH2*2/*2) have a lower acetaldehyde elimination rate than individuals homozygous for ALDH2* 1/* 1 and show higher blood acetaldehyde levels.25 In addition, Thomasson et al" have found that individuals homozygous for ALDH2*1/*1 and ADH2*2/*2 tend to have a higher ethanol elimination rate than those heterozygous for ADH2* 1/ *2.…”

Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

“…[162][163][164] After alcohol consumption, both drugs lead to high blood acetaldehyde levels that result in a range of unpleasant effects. 165,166 Although some studies have reported that treatments with ALDH inhibitors effectively reduce alcohol relapse in withdrawn alcoholics, 162 it remains unclear whether their protective effects against alcohol relapse are actually based on the adverse effects induced by acetaldehyde. Instead, the reduction of alcohol consumption in ALDH inhibitors-treated alcoholics might be due to their belief that a harmful and potentially fatal reaction could occur after alcohol drinking.…”

Reduction in the anxiolytic effects of ethanol by centrally formed acetaldehyde: the role of catalase inhibitors and acetaldehyde-sequestering agents

“…First of all, it appears from the literature that peripheral acetaldehyde is not anxiolytic and, if anything, would actually produce anxiogenic effects as seen in the reports from human studies (Chao 1995;Johnsen et al 1992). In those studies, subjects who had consumed alcohol and had high levels of blood acetaldehyde due to a mutation in ALDH or because of pharmacological inhibition of ALDH as a treatment to prevent alcohol consumption had an aversive reaction that shares some of the sympathetic characteristics of an acute anxiety episode: increases in heart and pulse rates, dizziness, nausea, etc.…”