Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver alcohol dehydrogenase (ADH) represents the main enzyme of normal alcohol metabolism. Total activity of this enzyme varies largely due to the occurrence of isoenzymes and of genetic polymorphisms. One genetic variant, called "atypical", is characterized by a higher specific activity. In carriers of this variant enzyme an initially faster rate of ethanol metabolism leads to higher blood acetaldehyde levels. Acetaldehyde, as a toxic intermediary metabolite, causes tachycardia, nausea and flushing of the face. A high frequency for "atypical" ADH is observed in mongolid races and consequently a hypersensitivity to alcohol is often observed in Orientals. Hence, certain genetically determined enzyme patterns may represent an aversive factor with regard to alcohol consumption. In Caucasians the phenotypes with "atypical" ADH are less frequent. However, in individuals with the "atypical" variant regular intake of alcohol may lead to an increased organotoxicity due to acetaldehyde.
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PMID:[Pathobiochemistry of alcoholism]. 45 82

A cutaneous test has been applied in examination of the flushing response to ethanol and acetaldehyde in 402 Chinese of Han ethnicity. Using this noninvasive method, five response subtypes have been observed: (A) fast flushing to both ethanol and acetaldehyde; (B) fast flushing only to ethanol but not to acetaldehyde; (C) slow flushing to ethanol only; (D) no response either to ethanol or to acetaldehyde; (E) vasoconstriction to ethanol, or to both ethanol and acetaldehyde. A total of 94% in subtype (A) are reported to be flushers, while only 25% was reported in subtype (D). Other physiological responses, such as tachycardia, dizziness, headache, drowsiness, and nausea are less frequent after alcohol ingestion. The recent history of consumption of alcohol of the subjects in different subtypes was also obtained. Although alcohol-induced flushing is thought to be a deterrent factor to heavy consumption of alcohol, the frequency of drinking of alcoholic beverages was not found to be different between flushers and nonflushers.
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PMID:Cutaneous vasomotor sensitivity to ethanol and acetaldehyde: subtypes of alcohol-flushing response among Chinese. 208 31

We have studied the interaction of viqualine, a 5-hydroxytryptamine (5-HT) uptake inhibitor, with ethanol in 16 healthy men aged 20 to 34 years. The subjects were randomly assigned to receive ethanol dosed to maintain blood alcohol concentrations of 17-22 mmol.l-1 (n = 8) or orange juice (n = 8) on each of two test days one week apart and preceded, in random order, by 3 days of viqualine 75 mg bd or placebo. Ethanol had no effect on steady-state viqualine concentrations or the inhibition of 5-HT uptake. Viqualine did not affect acetaldehyde concentrations or cause an aversive alcohol-sensitizing reaction. The deleterious effects of ethanol on word recall, manual tracking, body sway, and self-ratings of intoxication, sedation, and performance were not modified by the presence of viqualine. Within each beverage group performances and self-ratings on viqualine and placebo days were not different. The first dose of viqualine was associated with transient nausea. Viqualine and ethanol do not interact kinetically or dynamically on the variables examined in this study.
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PMID:Kinetic and dynamic interactions of oral viqualine and ethanol in man. 291 97

Differences in the pharmacokinetics of alcohol absorption and elimination are, in part, genetically determined. There are polymorphic variants of the two main enzymes responsible for ethanol oxidation in liver, alcohol dehydrogenase and aldehyde dehydrogenase. The frequency of occurrence of these variants, which have been shown to display strikingly different catalytic properties, differs among different racial populations. Since the activity of alcohol dehydrogenase in liver is a rate-limiting factor for ethanol metabolism in experimental animals, it is likely that the type and content of the polymorphic isoenzyme subunit encoded at ADH2, beta-subunit, and at ADH3, the gamma-subunit, are contributing factors to the genetic variability in ethanol elimination rate. The recent development of methods for genotyping individuals at these loci using white cell DNA will allow us to test this hypothesis as well as any relationship between ADH genotype and the susceptibility to alcoholism or alcohol-related pathology. A polymorphic variant of human liver mitochondrial aldehyde dehydrogenase, ADLH2, which has little or no acetaldehyde oxidizing activity has been identified. Individuals with the deficient ALDH2 phenotype do not have altered ethanol elimination rates but they do exhibit high blood acetaldehyde levels and dysphoric symptoms such as facial flushing, nausea and tachycardia, after drinking alcohol. Because acetaldehyde is so reactive, it binds to free amino groups of proteins including a 37 kilodalton hepatic protein-acetaldehyde adduct and may elicit an antibody response. We would predict that individuals who have low ALDH2 activity because of liver disease or because they have the inactive ALDH2 variant isoenzyme might form more protein-acetaldehyde adducts and elicit a greater immune response. These adducts may represent good biological markers of alcohol abuse and may also play a role in liver injury due to chronic alcohol consumption.
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PMID:Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. 306 25

Hyperacetataemia during acetate haemodialysis has been associated with the development of a variety of unpleasant symptoms, although a direct toxic effect of acetate is hard to prove. Acetaldehyde, which is produced during the metabolism of ethanol to acetate, has various toxic effects including some of those reported during acetate dialysis such as nausea, headache and palpitations. Using a novel, recently developed method we studied blood acetaldehyde concentrations during acetate dialysis in 15 patients and found significant increases in five, with a mean peak value in these patients of 1.36 mumol/l (normal less than 0.4 mumol/l). These five patients also developed high blood acetate concentrations during a subsequent acetate dialysis and showed a significant correlation between blood acetaldehyde and acetate concentrations (r = 0.55, P less than 0.05). Blood acetaldehyde did not change during bicarbonate dialysis in these patients. Our results suggest that significant accumulation of acetaldehyde may occur during acetate dialysis, especially in those patients whose metabolic capacity for acetate is somehow impaired, and that acetaldehyde may contribute to some of the symptoms previously ascribed to 'acetate' intolerance.
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PMID:Changes in blood acetaldehyde concentrations during acetate haemodialysis. 314 21

A double-blind, placebo-controlled study in eight healthy male volunteers was conducted to study possible disulfiram-type reactions and hypoprothrombinemia associated with cefotetan administration. Three doses of cefotetan (2 g) or of placebo were administered at 12-h intervals. Ethanol (0.5 g/kg of total body weight) was ingested 1 h after the third dose. Blood ethanol, serum acetaldehyde, and prothrombin times were measured throughout the study. Heart rate, blood pressure, and clinical signs as well as symptoms suggestive of a disulfiram-type reaction were also noted. Five of eight volunteers that received cefotetan showed significant flushing. A significant increase in heart rate also was noted. No change in mean arterial pressure was observed during the cefotetan phase, and no one experienced nausea or vomiting. No statistical differences were observed between phases with respect to ethanol area under the time-concentration curve, elimination rate, or serum acetaldehyde concentrations. A slight but statistically significant increase in prothrombin time also was observed with cefotetan. This study suggests that patients receiving cefotetan might be at risk to develop disulfiram-type reactions and hypoprothrombinemia.
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PMID:Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia. 347 45

Ingestion of a moderate dose of ethanol (0.8 g/kg) by volunteers prior to 4-h inhalation exposure to m-xylene (6.0 or 11.5 mmol/m3) caused marked alterations in xylene kinetics. After ethanol intake the blood xylene level rose about 1.5-2.0-fold and urinary methylhippuric acid excretion declined by about 50% suggesting that ethanol decreased the metabolic clearance of xylene by about one half during xylene inhalation. This effect was noticeable up until a few hours after completed xylene exposure. Urinary excretion of 2,4-xylenol, the minor m-xylene metabolite, was generally not decreased by ethanol and sometimes the reverse seemed to be the case. The disturbance of xylene kinetics can be hypothesized to be caused mainly by ethanol-mediated inhibition of microsomal metabolism. When four volunteers who ingested ethanol prior to m-xylene inhalation at the higher concentration were monitored for blood acetaldehyde, transiently raised levels were found without notable effects on ethanol elimination. This observation may explain why some individuals experienced dizziness and nausea during the combined ethanol-xylene exposure.
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PMID:Metabolic interaction between m-xylene and ethanol. 709 64

Acute ethanol ingestion inhibits the metabolism of the common industrial solvents trichloroethylene and dimethylformamide. The solvents in turn may interact with ethanol metabolism as shown by an accumulation of acetaldehyde and occasional symptoms of alcohol intolerance. It was recently found that mutual metabolic interaction occurs even in the context of ethanol ingestion (0.8 g/kg in single dose) combined with subsequent inhalation exposure to m-xylene (6.0 & 11.5 mmol/m3 (140 & 280 ppm), over 4 h). Ethanol impaired the metabolic clearance of m-xylene, raised the blood xylene concentration, and decreased the urinary excretion of methylhippuric acid. Thus, ingestion of ethanol is a noticeable source of error in the biological monitoring of xylene uptake. Some people appear to be susceptible to combined ethanol-xylene exposure and may develop nausea and dermal flush.
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PMID:Acute solvent-ethanol interactions with special reference to xylene. 713 27

Despite standardization, marked interindividual variation in the severity of the disulfiram-alcohol reaction (DAR) has been observed. We studied the DAR in 51 consecutive alcoholics with (n = 16) and without (n = 35) significant alcoholic liver disease. Clinical signs of the DAR were much weaker in the patients with compared with those patients without liver disease. Because acetaldehyde is thought to be the main cause of the DAR, we studied ethanol and acetaldehyde kinetics in 13 patients (6 females, 7 males) with alcoholic liver disease (documented by biopsy, clinical and/or radiological findings, and by quantitative liver function) [galactose elimination capacity (GEC) 4.2 +/- SD 1.0 mg/min/kg; aminopyrine breath test (ABT) 0.14 +/- 0.10% dose x kg/mmol CO2] and 13 age- and sex-matched controls (alcoholics without significant liver disease, GEC 7.1 +/- 0.7; ABT 0.81 +/- 0.35). Clinical signs of acetaldehyde toxicity during the DAR (flush, nausea, tachycardia, and blood pressure drop) were absent in alcoholic liver disease, but clearly evident in controls. Blood ethanol kinetics were similar in both groups, Cmax and area under the concentration-time curve (AUC) being 6.27 +/- 1.82 and 368.9 +/- 72.9 mmol x min/liter in alcoholic liver disease, and 6.62 +/- 1.71 and 377.6 +/- 124.5 in controls, respectively. In contrast, there was a strong (p < 0.001) difference in Cmax and AUC of acetaldehyde, respective values being 33.46 +/- 21.52 and 1463.8 +/- 762.5 mumol x min/liter in alcoholic liver disease, and 110.87 +/- 56.00 and 4162.0 +/- 2424.6 in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Divergence of ethanol and acetaldehyde kinetics and of the disulfiram-alcohol reaction between subjects with and without alcoholic liver disease. 762 69

Sulfiram, a drug applied topically to treat scabies, produces effects similar to those of disulfiram after subsequent ingestion of ethanol. Disulfiram, used in aversion therapy in the treatment of alcoholism, inhibits hepatic aldehyde dehydrogenase (ALDH) causing an accumulation of acetaldehyde after ethanol ingestion. The increased tissue levels of acetaldehyde cause a spectrum of undesirable side-effects including flushing, nausea, vomiting, and tachycardia, which are referred to as the disulfiram reaction. Previous studies have shown that in vitro sulfiram is a very weak inhibitor of ALDH, but solutions of sulfiram markedly increase in potency with time. In the present study, fresh solutions of sulfiram were exposed to fluorescent room light under ambient conditions and analyzed at timed intervals by HPLC. At least eight products, including disulfiram, were formed in the light-exposed sulfiram solutions, but not in solutions kept in the dark. Structural characterization of two of the photolysis products was obtained by on-line microbore HPLC-mass spectrometry (mu LC-MS) and on-line microbore HPLC-tandem mass spectrometry (mu LC-MS/MS) using continuous flow-liquid secondary ion mass spectrometry (CF-LSIMS) as the primary ionization method. Sulfiram was converted to disulfiram at an initial rate of 0.7%/hr, and the formation of disulfiram correlated with the increase in ALDH inhibition in vitro. The results of this investigation show that while sulfiram is a weak inhibitor of ALDH in vitro, it is readily photoconverted to disulfiram, a very potent inhibitor of ALDH, which may explain the adverse reaction to ethanol after sulfiram therapy.
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PMID:Photolysis of sulfiram: a mechanism for its disulfiram-like reaction. 798 3


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