Acetaldehyde syndrome

Cyanamide is not expected to release cyanide as part of its mechanism of toxicity. The principal toxicological mechanism of cyanamide is inhibition of aldehyde dehydrogenase. Cyanamide can produce acetaldehyde syndrome with concurrent exposure to alcohol, resulting in symptoms that include vomiting, parasympathetic hyperactivity, difficulty in breathing, and confusion. 

Some experienced clinicians belittle the incidence and severity of side effects from dlsulflram23,24. Perhaps administration of lower doses than those Initially recommended accounts for this conviction, since a substantial, well revlewed S literature attests to the occurrence of such undeslred effects. Dlsulflram Itself, especially when given chronically, can elicit aberrant behavioral (even psychotlc26) and cardiovascular reactions, and the acetaldehyde syndrome which follows co-administration of dlsulflram and alcohol (pronotxiced hypotension, headache. 

One ml t assume In any case that the question of whether metronidazole plus alcohol leads to acetaldehyde accumulation and the acetaldehyde syndrome could be confirmed unequivocally. But even this remains unresolved. Although several clinicians report clinical evidence of acetaldehyde accumulation, others are as emphatic In denying that It occurs. Disparate evidence on the effect of metronidazole on alccdiol levels in man also exists Rowe and Atklnson saw no effect on the rate of blood alcohol disappearance using themselves as sidijects, while Montaninl et reported decreased disappearance of blood alcohol... 

It is not known whether acetaldehyde, the primary metabolite of ethanol, is involved in the etiology of the human fetal alcohol syndrome (lARC, 1985). 

It can be speculated that protonation of 50 will afford the carbinolamine 51 besides L-tryptophan. Carbinolamine 51 is a masked acetaldehyde, and it will transfer this moiety to the more basic amino group on L-tryptophan to afford the protonated Schiff base 52, already encountered as an intermediate in the Pictet-Spengler cyclization to TBCs (Fig. 4). Spiroannelation of 52 will ultimately lead to TBCs 21a and 21b which both were found to be present in the products obtained in the acid hydrolysis of 50 (127). It is questionable whether TBCs 21a and/or 21b could account for the eosinophilia syndrome, since both compounds prepared by total synthesis were well tolerated in mice at doses up to 100 mg/kg (23). 

Fetal injury can occur in early pregnancy (fetal alcohol syndrome). It may be due to the metabolite, acetaldehyde, and so acute (binge) consumption is more hazardous than similar total intake on a daily basis. The vulnerable period of pregnancy is at 4-10 weeks. Because of this, prevention cannot be reliably achieved after diagnosis of pregnancy (usually 3-8 weeks). 

Cyanamide also acts as a potent inhibitor of the enzyme aldehyde dehydrogenase, which results in a disulfiram-like reaction in individuals concomitantly exposed to alcohol. Potentiated by the ingestion of alcohol, the accumulation of acetaldehyde in the body presents as a syndrome of vasodilation characterized by facial flushing, headache, nausea, vomiting, difficulty in breathing, sweating, chest pain, hypotension, weakness, blurred vision, and confusion. Calcium cyanamide has been used in aversion therapy for alcoholism. 

The combined effect of carbon disulfide exposure and ethyl alcohol has been examined to determine if carbon disulfide exposure results in the Antabuse syndrome, an intolerance to alcohol. The metabolism of Antabuse, disulfuram, or tetraethylthiuram disulfide (TETD) produces carbon disulfide and diethylamine. The metabolites of Antabuse inhibit the enzymes necessary to metabolize ethyl alcohol (aldehyde dehydrogenase and catalase), which results in the Antabuse syndrome due to a buildup of aldehyde. Symptoms include a sensation of heat, a fall in blood pressure, nausea, and in extreme cases circulatory collapse (Djuric 1971). Research by Freundt et al. (1976) on rats and humans of the combined effects of carbon disulfide exposure and ethanol ingestion indicate that, at low (20 ppm) and medium (400 ppm) levels of carbon disulfide exposure and blood alcohol levels of approximately 0.75%, there is a carbon disulfide inhibition of aldehyde dehydrogenase with an increase in acetaldehyde concentrations in the blood. However, these increased acetaldehyde concentrations were not considered great enough to indicate the Antabuse syndrome. The study authors asserted that the Antabuse syndrome is not likely to occur in subjects who have blood alcohol levels of up to 0.8% and are exposed to 10 ppm carbon disulfide. 

The variety of injuries to a fetus caused by maternal consumption of ethanol is called fetal alcohol syndrome. In catabolism of ethanol by the body, the first step is conversion to acetaldehyde-... 

Karl, P. I., B. H. J. Gordon, C. S. Lieber, and S. E. Fisher. Acetaldehyde Production and Transfer by the Perfused Human Placental Cotyledon. Science 242, 27S-275 (1988). [A report describing some of the processes involved in fetal alcohol syndrome.]... 

D. Enhanced elimination. Hemodialysis is not indicated for disulfiram overdose, but it may remove ethanol and acetaldehyde and has been reported to be effective in treating the acute disulfiram-ethanol interaction. This is not iikeiy to be necessary in patients receiving adequate fluid and pressor support. There are no data to support the use of repeat-dose activated charcoal for any of the disulfiram syndromes. 

Both RALDHl and RALDH2 inefficiently catalyze acetaldehyde metabolism in vitro. Nevertheless, one wonders whether the acetaldehyde produced during chronic alcohol intake competes with retinal metabolism, perhaps contributing to fetal alcohol syndrome. This simple postulate, however, has complex caveats. Not the least of which includes the imprudence of ascribing a specific mechanism to a highly reactive non-specific agent. 

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