Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.
Alcohol Alcohol Suppl 1987
PMID:Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects. 342 38

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

The effect of diphenhydramine on the cyanamide-ethanol reaction was evaluated in a double-blind, controlled clinical study. Seven healthy subjects ingested 50 mg calcium carbimide at 4 hours and 100 mg diphenhydramine or placebo at 2 hours before a 0.2 gm/kg iv infusion of ethanol. Blood acetaldehyde and blood ethanol analyses were performed together with recordings of blood pressure, pulse rate, and flushing intensity during the hour after ethanol infusion. Diphenhydramine increased the mean ethanol AUC but did not influence blood acetaldehyde levels. Antihistamine reduced the flushing response by 40% and decreased the pulse rate from 40 minutes onward after ethanol infusion subsequent to calcium carbamide dosing. Blood pressure was not significantly influenced by ethanol at the calcium carbimide dose we used.
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PMID:Diphenhydramine and the calcium carbimide-ethanol reaction: a placebo-controlled clinical study. 351 10

Biotransformations of drugs are controlled or strongly affected by genetic factors. During the past few years several genetic deficiencies of drug-metabolizing reactions catalyzed by members of the family of cytochrome P-450 were observed. Choice of the appropriate drug to study and attention to urinary metabolites have been the essential ingredients for the recent discovery of genetic deficiencies of drug metabolism in man which include recessive deficiency of debrisoquine/sparteine metabolism and of mephenytoin metabolism. The clinical significance of these defects is discussed. Ethanol after metabolism to acetaldehyde is further metabolized to acetic acid by aldehyde dehydrogenase. Numerous isozymes of aldehyde dehydrogenase exist, one of which possesses a high affinity for acetaldehyde. Approximately 40% of the Oriental population lack this high affinity isozyme so that in these individuals who may have symptoms of flushing and other unpleasant effects the acetaldehyde formed is destroyed only at high plasma concentrations.
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PMID:Genetics of drug transformation. 351 92

The industrial use of certain acetamides and formamides (particularly DMAC and DMF) for their solvent properties has resulted in rather extensive examination of their biological properties. Both DMAC and DMF are rapidly absorbed through biological membranes and are metabolized by demethylation first to monomethyl derivatives and then to the parent acetamide or formamide. Relatively high single doses to various species following oral, dermal, i.p., i.v., or inhalation exposures generally are required to produce mortality. The liver is the primary target following acute high level exposure, but massive doses can also produce damage to other organs and tissues. Repeated sublethal treatment by various routes also shows the liver to be the target organ with the degree of damage being proportional to the amount absorbed. With MMF, the potential usefulness as a cancer chemotherapeutic agent needs to be measured against the hepatotoxic effects produced in man. Acetamides and formamides are generally inactive in mutagenicity tests. Mammalian test systems do not appear to be genetically sensitive and DMF has been recommended for use as the vehicle in microbial assays designed to test for genetic activity of hard-to-dissolve chemicals. Embryotoxicity can be demonstrated at high doses; doses which generally show toxicity to the maternal animals. Structural abnormalities in sensitive species such as the rabbit are produced following exposure at near-lethal levels. The spectrum of abnormalities seen is broad and fails to show any time or site specificity in terms of developing organs/organ systems. Inhalation exposures to DMAC and DMF at levels producing some maternal toxicity in rats have produced no teratogenic response and only slight evidence of embryotoxicity. Long-term feeding of relatively high levels of acetamide produces liver cancer in rats. DMAC and DMF appear to be noncarcinogenic. The environmental toxicity of these chemicals is low. Liver damage can be produced by overexposure to these chemicals in man. Airborne concentrations need to be controlled and care should be taken to avoid excessive liquid contact as the chemicals are absorbed through the skin. A relationship exists between the amount of DMAC or DMF absorbed and the amount of MMAC or MMF excreted in the urine so that biomonitoring of the urinary metabolites can indicate situations in which total exposures, both dermal and inhalation, are excessive. An interaction between DMF and ethanol occurs such that signs, including severe facial flushing, appear when DMF-exposed individuals consume alcoholic beverages.
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PMID:Biological effects of acetamide, formamide, and their monomethyl and dimethyl derivatives. 353 Jun 39

The relationship between chlorpropamide alcohol flushing and non-insulin dependent diabetes remains uncertain. It is known, however, that the frequency of facial flushing with alcohol and the temperature response depend upon both the plasma level of chlorpropamide and the starting facial temperature [10]. We tested 23 young adult non-diabetic subjects with 8 g of ethanol after a dose of chlorpropamide 250 mg twice daily for 2 days or a placebo, in a double blind, cross-over manner. Previously, nine other subjects had participated in a pilot study to assess the safety of the chlorpropamide dose and to ensure that adequate plasma chlorpropamide levels were achieved. No subject was negative for chlorpropamide alcohol flushing, as defined by the following criteria: facial temperature rise of 35% or more of maximum possible rise, observer assessment or subject assessment. In 26 of the total 32 subjects, all three criteria were fulfilled. Thus, among young, healthy non-diabetic adults chlorpropamide alcohol flushing would appear to be a normal phenomenon.
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PMID:Chlorpropamide alcohol flushing: a normal response? 360 79

The metabolism of acetaldehyde has received considerable attention in the past owing to its acute and chronic toxic effects in humans. Two major hepatic ALDH isozymes, ALDH I and ALDH II, differing in their structural and functional properties, have been characterized in humans. ALDH I has a low Km for acetaldehyde and is primarily a mitochondrial enzyme, while ALDH II has a higher Km and is of cytosolic origin. An inherited deficiency of ALDH I isozyme found only among Oriental populations is primarily responsible for producing acute alcohol sensitivity symptoms (flushing response) after consumption of small doses of alcohol. Biochemical, immunochemical, and molecular genetics data indicate a structural mutation in the ALDH I isozyme gene responsible for the loss in catalytic activity. Population genetic studies have revealed the prevalence of ALDH polymorphism among individuals of the Mongoloid race. Flushing response to alcohol is a familial trait, and preliminary family data from Japan, China, and Korea suggest an autosomal codominant inheritance for ALDH I isozyme deficiency. The ALDH polymorphism is apparently responsible for the low incidence of alcoholism in Japanese, Chinese, and Koreans. Alcohol sensitivity due to ALDH I isozyme deficiency may inhibit excessive alcohol drinking.
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PMID:Human aldehyde dehydrogenase isozymes and alcohol sensitivity. 361 May 92

The Oriental flushing reaction is an adverse response to alcohol that appears to be genetically determined. In this study, the Oriental flushing reaction that was produced with ingestion of small amounts of alcohol was antagonized by antihistamine administration. A group of 17 subjects was tested. Each subject received placebo, diphenhydramine 50 mg (H-1 receptor antagonist), and cimetidine 300 mg (H-2 receptor antagonist) singularly and in combination. Alcohol was then administered orally. Most subjects given placebo experienced the typical flushing reaction that included a cutaneous flush, increase in skin temperature, decrease in blood pressure, increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness, and nausea. The flush, temperature and systolic hypotension were significantly blocked by the combined antihistamine administration. Cimetidine given alone blocked the flush, temperature increase, and systolic hypotension significantly more than diphenhydramine but less than the combined antihistamines. Diphenhydramine was similar to placebo in its effect on the flushing reaction. The role of histamine in the expression of tolerance to alcohol is not known. Antihistamine antagonism of the adverse flushing reaction suggests that histamine receptors may participate in the intolerance to ethanol in Orientals. Histamine may be an important protective factor in the low prevalence of alcoholism in Orientals.
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PMID:Histamine receptor antagonism of intolerance to alcohol in the Oriental population. 368 Dec 77

Human volunteers were given a small dose of ethanol (0.25 g/kg body weight) after pretreatment with either calcium carbimide (50 mg) or a placebo according to a crossover design. Calcium carbimide, an inhibitor of aldehyde dehydrogenase, caused intense facial flushing and a pronounced rise in the concentration of acetaldehyde in breath. At 15-min intervals throughout the experiment, breath-ethanol concentrations were determined both by gas chromatography (GC) (specific method) and by infrared (IR) spectrometry with an Intoxilyzer model 4011 breath-alcohol analyzer. The results with these two independent methods of analysis were compared in experiments with and without calcium carbimide pretreatment. The regression equations relating breath-ethanol determinations by GC and IR methods in the two test situations were not significantly different. The elevated breath concentrations of acetaldehyde associated with a drug-alcohol flush reaction do not invalidate the use of infrared breath-alcohol devices for evidential purposes.
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PMID:Drug-alcohol flush reaction and breath acetaldehyde concentration: no interference with an infrared breath alcohol analyzer. 372 77

It is known that aldehyde dehydrogenase (ALDH) responsible for metabolism of acetaldehyde deriving from ethanol has two distinct forms of isozymes: ALDH-I (low Km ALDH) and ALDH-II (high Km ALDH), and that many Orientals lack ALDH-I isozyme genetically. In the present study, the role of ALDH isozyme variance in the alcohol sensitivity, drinking habits formation and the development of alcoholism was investigated in Japan, Taiwan and the Phillipines. Isozyme analysis using isoelectric focusing of hair roots specimens from normal volunteers or schizophrenics revealed that about 42% of Japanese, 35% of Taiwanese and 12% of Phillipines were ALDH-I deficient. Questionnaire study of Japanese volunteers indicated that ALDH-I deficient individuals showed flushing, palpitation and other uncomfortable somatic signs, due to reduced metabolism of acetaldehyde, much more frequently than ALDH-I positive ones. Consequently, it occurred that only 19% (8/42) of ALDH-I deficient persons, in contrast to 49% (29/59) of ALDH-I positive ones, were drinking habitually. Patients with alcoholism showed much smaller percentages of ALDH-I deficiency: 4% (5/113) in Japan and 10% (3/29) in Taiwan, than those of control subjects. Summarizing these data, a hypothesis can be presented that genetically derived difference of ALDH activities is one of the determining factors in the sensitivity to alcohol, formation of drinking habits, and finally in the development of alcoholism, at least among Oriental peoples.
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PMID:The role of aldehyde dehydrogenase isozyme variance in alcohol sensitivity, drinking habits formation and the development of alcoholism in Japan, Taiwan and the Philippines. 374 13


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