Pharmaceutical Agents Known to Produce Disulfiram-Like Reaction: Effects on Hepatic Ethanol Metabolism and Brain Monoamines

@article{Karamanakos2007PharmaceuticalAK,
  title={Pharmaceutical Agents Known to Produce Disulfiram-Like Reaction: Effects on Hepatic Ethanol Metabolism and Brain Monoamines},
  author={Petros N. Karamanakos and Periklis Pappas and Vassiliki A. Boumba and Christoforos Thomas and Michalis Malamas and Theodore Vougiouklakis and Marios Marselos},
  journal={International Journal of Toxicology},
  year={2007},
  volume={26},
  pages={423 - 432}
}
Several pharmaceutical agents produce ethanol intolerance, which is often depicted as disulfiram-like reaction. As in the case with disulfiram, the underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the hepatic aldehyde dehydrogenases. In the present study, chloramphenicol, furazolidone, metronidazole, and quinacrine, which are reported to produce a disulfiram-like reaction, as well as disulfiram, were administered to Wistar rats and the… 

Figures and Tables from this paper

Increased Brain Serotonin Rather Than Increased Blood Acetaldehyde as a Common Denominator Behind Alleged Disulfiram-Like Reactions

The ethanol intolerance produced by these agents, whether blood acetaldehyde concentration is elevated or not, could be the result of a “toxic serotonin syndrome,” as in the case of the concomitant use of serotonin-active medications that provoke clinical manifestations similar to those of a disulfiram reaction.

The Alcohol Intolerance Produced by Isoniazid Is Not Due to a Disulfiram-Like Reaction Despite Aldehyde Dehydrogenase Inhibition

Despite inhibition of the hepatic ALDH, ISO did not result in elevated blood acetaldehyde levels after ETH administration, probably due to the induction of cytochrome P450 2E1 which theoretically leads to an increased elimination rate of acetaldehyde preventing its accumulation.

Alcohol-Medication Interactions: The Acetaldehyde Syndrome

Patients should be instructed to avoid medicines and other products containing alcohol, such as syrups, fermented vinegar, sauces and lotions, and doctors, nurses and pharmacists instruct patients to avoid alcohol during treatment with aversive drugs and disulfiram-like reactions inducers.

Effects of the aldehyde dehydrogenase inhibitor disulfiram on the plasma pharmacokinetics, metabolism, and toxicity of benzaldehyde dimethane sulfonate (NSC281612, DMS612, BEN) in mice

BEN plasma concentrations increased after administration of disulfiram, suggesting that ALDH mediates the rapid metabolism of BEN in vivo, which may explain the increased toxicity seen with BEN after administration.

Strategies for Avoiding Benzopyrone Hepatotoxicity in Lymphedema Management-The Role of Pharmacogenetics, Metabolic Enzyme Gene Identification, and Patient Selection.

Although screening techniques are becoming increasingly clinically feasible, uncertainty remains on the link between the genotype, metabolic phenotype, and the exact gene products involved in the hepatometabolism of coumarin, and a targeted pharmacogenomic approach is fully viable.

An update on derivatisation and repurposing of clinical nitrofuran drugs.

  • Nonkululeko H. ZumaJ. AucampD. N'Da
  • Biology, Chemistry
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2019

In vitro metabolic profile and drug‐drug interaction assessment of secnidazole, a high‐dose 5‐nitroimidazole antibiotic for the treatment of bacterial vaginosis

These results are the first reported observation of the metabolism and drug‐drug interaction profile for secnidazole and demonstrate that the agent has minimal to no potential drug interactions of concern.

Salsolinol-like compounds as biomarkers of human alcohol consumption, disease and toxicity

A combined method for detection of catecholamines and tetrahydroisoquinolines by LC-MS/MS is developed, which achieves linearity to four orders of magnitude and is used clinically for diagnosing rare tumors called pheochromocytomas and paragangliomas.

References

SHOWING 1-10 OF 60 REFERENCES

Lack of Disulfiram-Like Reaction with Metronidazole and Ethanol

This study shows that metronidazole does not have an effect on blood acetaldehyde concentrations when ingested with ethanol and does not has any objective or subjective disulfiram-like properties, and it is possible that disulfIRam- like reaction can occur in some subgroups and by other mechanisms than the inhibition of hepatic ALDH.

The mechanism of alcohol intolerance produced by various therapeutic agents.

The results suggest that the so-called "disulfiram-reaction" is mediated mainly, but not exclusively, by inhibition of the low-Km ALDH.

Metabolic and pharmacologic interaction of ethanol and metronidazole in the rat.

Concentration curves of ethanol and acetaldehyde in the blood after an oral dose of ethanol were not altered by pretreatment with metronidazole; in contrast, disulfiram caused marked elevation of acetaldehyde levels.

Mechanism of the inhibition of aldehyde dehydrogenase in vivo by disulfiram and diethyldithiocarbamate.

Results indicate that disulfiram is an irreversible inhibitor of aldehyde dehydrogenase in vivo and can be blocked by cycloheximide.

Metronidazole increases intracolonic but not peripheral blood acetaldehyde in chronic ethanol-treated rats.

The findings suggested that the mechanism behind metronidazole related disulfiram-like reaction might be located in the gut flora instead of the liver, and probably due to the replacement of intestinal anaerobes by ADH-containing aerobes.

Disulfiram-like reaction to certain cephalosporins.

Patients experiencing these often frightening disulfiram-type reactions seldom need specific treatment; however, it is mandatory to strongly caution patients not to consume alcoholic beverages for a few days after treatment with these cephalosporins.

The effect of disulfiram on catecholamine levels in the brain.

In animals pretreated with the monoamine oxidase inhibitor pheniprazine, there was a closer correlation between the decrease in the norepinephrine content and the increase in the dopamine content in the hypothalamus and brainstem.

Inhibition of monoamine oxidase by metronidazole

The mechanism responsible for the neurotoxic effects of MTZ, including dizziness, vertigo, headache and, very rarely, convulsions, incoordination and ataxia, is still unknown and it is speculated that they could be caused by MAO inhibition, as suggested by the partly similar neurotoxic profile of MAO inhibitors.
...