The Disulfiram (Antabuse)‐Alcohol Reaction in Male Alcoholics: Its Efficient Management by 4‐Methylpyrazole

Lindros, Kai O.; Stowell, Allan; Pikkarainen, P; Salaspuro, Mikko

doi:10.1111/j.1530-0277.1981.tb05354.x

Cited by 70 publications

(17 citation statements)

References 16 publications

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“…A similar effect was found with 4-MP infusion into ALDH inhibitor-pretreated sub jects followed by ethanol intake (16,17 As to non-flushing Orientals and Cau casians possessing both the low-Km ALDH and another major ALDH isozyme found in every human with a higher Km value for AcH (22, 23), they appear to have a sufficient capacity for AcH oxidation to prevent hepatic AcH output under normal conditions, but there is not such a high capacity to cover the 50% increase in ethanol oxidation observed in Caucasian alcoholics (11 , 12). Therefore, in alcohol aversion therapy, partial inhibition of ALDH activity probably leads to a con dition similar to that of flushing Orientals who show significant accumulation of AcH during ethanol intoxication.…”

Section: Discussionsupporting

confidence: 54%

“…On the contrary, reduction in the ethanol oxidation rate is often highly effective for alleviation of acute AcH toxicity in the subject pretreated with ALDH inhibitor. Partial inhibition of ethanol elimination by infusing a small dose of 4 methylpyrazole (4-MP), a specific inhibitor of alcohol dehydrogenase (13) with low toxicity (14,15), to cyanamide (another ALDH inhibitor)-treated subjects lead to a rapid fall in the level of AcH and associated responses (16,17). During the course of our previous experiment investigating AcH ac cumulation in relation to ethanol and AcH oxidizing capacity, 4-MP was found to be highly effective in reducing AcH levels also in flushing Orientals (18).…”

Section: Abstract-alcohol-sensitivementioning

confidence: 99%

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Suppression of Acetaldehyde Accumulation by 4-Methylpyrazole in Alcohol-Hypersensitive Japanese

Inoue

Kera

Kiriyama

et al. 1985

Japanese Journal of Pharmacology

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Abstract-Alcohol-sensitiveJapanese subjects with facial flushing and an increase in heart rate during ethanol intoxication exhibited marked individual variation in accumulation of acetaldehyde. This variation correlated well with the intensity of the above mentioned physiological responses.Oral pretreatment with 10 mg/kg 4-methylpyrazole, which inhibited the ethanol elimination rate by 15-25%, strongly suppressed both acetaldehyde accumulation and the associated responses. Under this condition, the sensitivity to acetaldehyde appeared to be reduced, and the correlation between the acetaldehyde level and the physiological responses disap peared.The effectiveness of even a low dose of 4-methylpyrazole suggests its clinical usefulness for alleviation of acute acetaldehyde toxicity in alcohol hypersensitive Japanese individuals as well as in disulfiram-treated alcoholics.

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Section: Discussionsupporting

confidence: 54%

Section: Abstract-alcohol-sensitivementioning

confidence: 99%

Suppression of Acetaldehyde Accumulation by 4-Methylpyrazole in Alcohol-Hypersensitive Japanese

Inoue

Kera

Kiriyama

et al. 1985

Japanese Journal of Pharmacology

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“…During alcohol intake, substantial decreases in blood acetaldehyde levels with concomitant amelioration of acetaldehyde-related cardiovascular effects in response to 4-MP are found among white subjects with pharmacological ALDH-inhibition (Kupari et al, 1983;Lindros et al, 1981) and Asian subjects with inherited ALDH deficiency (Inoue et al, 1984). In the present study, the acetaldehyde level obtained during alcohol intoxication was indistinguishable from the acetaldehyde formed in vitro during sample processing; that is, we could find no evidence for the existence of free and loosely bound acetaldehyde in the peripheral venous blood during alcohol intoxication in white subjects.…”

Section: Discussionmentioning

confidence: 99%

Ethanol, Acetaldehyde, Acetate, and Lactate Levels After Alcohol Intake in White Men and Women: Effect of 4‐Methylpyrazole

Sarkola

Iles

Kohlenberg-Mueller

et al. 2002

Alcoholism Clin & Exp Res

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The alcohol-induced elevation in blood acetate level is caused, in part, by ADH-mediated ethanol oxidation. Although no evidence was found for measurable acetaldehyde levels in the peripheral venous blood during alcohol intoxication, the effect of 4-MP on breath acetaldehyde in women supports the view that ADH-mediated acetaldehyde elevations reflected in the airways, but too low to be detected in the peripheral venous blood, may occur in women during alcohol intoxication in the present experimental conditions.

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“…They are most active against P450 2D6, where they have relative potency of paroxetine > flouxetine > sertraline, fluvoxamine > citalopram > venalafaxine, nefazodone, with K i s ranging from 0.07 to 33 M (Fig. 2.15a) [247][248][249][250]. Their inhibitory action, however, is not limited to P450 2D6.…”

Section: Interactions With Serotonin Selective Reuptake Inhibitorsmentioning

confidence: 99%

Handbook of Drug Interactions

Karalliedde¹,

Henry²

2012

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PrefaceAdverse drug reactions and drug interactions remain a major issue in 2011. During the second edition of our book, FDA reported greater than 370,000 serious adverse events in 2009 and more than 100,000 for the first quarter of 2010. The Adverse Event Reporting System is a database that gives computerized statistics used to support FDA's post-marketing safety surveillance for all approved drugs. A serious event is defined as requiring hospitalization, being life-threatening, causing disability or congenital anomalies, for example. Importantly, more than 63,000 deaths were recorded in 2009, and more than 20,000 occured during the first quarter of 2010.The second edition of Handbook of Drug Interactions: A Clinical and Forensic Guide has been updated to reflect new information and also includes new chapters of interest. In this respect, it is a continuation of the first edition and part of the ongoing story of drug-drug interactions.Pharmacogenomics is a rapidly growing field covering the genetic basis for individual variability in drug responses. This new section allows the reader to review important polymorphisms in drug metabolizing enzymes and applies the findings to forensic interpretation through interesting cases involving opiates.Although the section relating to central nervous system drugs encompasses a number of potential drugs with illicit use such as benzodiazepines and opiates, a chapter dealing exclusively with drugs of abuse has been added to the second edition. Cocaine, amphetamines, cannabis, flunitrazepam and GHB are now discussed. Alcohol and nicotine are still covered in the section related to environmental and social pharmacology.The existing chapters from the first edition have, in most cases, been updated and edited to reflect new data or bring out better tables and diagrams. More recent drugs and formulations are included. Recent references have been added for completeness. This volume emphasizes explanations when possible and covers both pharmacokinetic and pharmacodynamic drug interactions. The result, we hope, will continue to prove useful to health and forensic professionals as well as students.

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The Disulfiram (Antabuse)‐Alcohol Reaction in Male Alcoholics: Its Efficient Management by 4‐Methylpyrazole

Cited by 70 publications

References 16 publications

Suppression of Acetaldehyde Accumulation by 4-Methylpyrazole in Alcohol-Hypersensitive Japanese

Suppression of Acetaldehyde Accumulation by 4-Methylpyrazole in Alcohol-Hypersensitive Japanese

Ethanol, Acetaldehyde, Acetate, and Lactate Levels After Alcohol Intake in White Men and Women: Effect of 4‐Methylpyrazole

Handbook of Drug Interactions

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