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)

Individual differences in response to alcohol have been observed in various ethnic and racial groups. A positive correlation between alcohol sensitivity and elevated blood acetaldehyde level in conjunction with deficiency of an isozyme of aldehyde dehydrogenase (ALDH I) was noted in Japanese subjects given an acute dose of alcohol. Invariably, significantly higher blood acetaldehyde levels were measured in ALDH I-deficient subjects after ethanol loading. The initial flushing in Orientals after alcohol ingestion might be due to their inability to metabolize acetaldehyde quickly and effectively in the absence of the low Km ALDH I isozyme. While Oriental populations of Mongoloid origin showed varying degree of isozyme deficiency, none of the Caucasian or Negroid populations have this isozyme abnormality.
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PMID:Aldehyde dehydrogenase polymorphism: molecular basis and phenotypic relationship to alcohol sensitivity. 342 17

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.
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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 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

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

In the course of celiac plexus alcohol block, facial flushing, palpitations, and hypotension are occasionally incurred in some patients. We hypothesized that the phenomenon represents acetaldehyde syndrome, not response to increased blood levels of ethanol as might be supposed. In order to prove our hypothesis, we selected five patients scheduled to undergo celiac plexus alcohol block, and, with their consent, we measured blood concentration of ethanol and acetaldehyde before and for 6 hr after the block. We also determined the phenotypes of aldehyde dehydrogenase (ALDH) in their hair roots. We found that "flushers" are found exclusively among subjects without ALDH I, and that their blood levels of acetaldehyde were significantly higher than those of "non-flushers" within 10 min after the block. The flushers also gave histories of facial flushing after ingestion of small amounts of ethanol. On the basis of such histories one can anticipate whether acetaldehyde syndrome is likely or unlikely to accompany the block.
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PMID:Acetaldehyde syndrome after celiac plexus alcohol block. 377 61

A rise in blood acetaldehyde concentrations following alcohol ingestion was significantly inhibited when healthy nonflushing subjects were administered a clinical dose of pantethine orally. However, similar findings were not observed in flushing (alcohol-sensitive) subjects lacking hepatic low Km aldehyde dehydrogenase (ALDH). The blood ethanol concentrations were not altered by this treatment in either flushing or nonflushing subjects. Acetaldehyde (45 microM) added in vitro to whole blood and plasma obtained 1 hr after pantethine administration disappeared as the incubation continued similarly as with blood and plasma obtained prior to pantethine treatment. Pantethine-related metabolites, such as taurine, pantetheine, coenzyme A, and pantothenate, activated ALDH in vitro. Hepatic acetaldehyde levels following ethanol loading of rats treated with pantethine were much lower than in untreated rats. The pantethine action observed only in nonflushing subjects might be due to an accelerated oxidation of acetaldehyde by the activation of low Km ALDH by pantethine-related metabolites formed in the liver.
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PMID:Lowering of blood acetaldehyde but not ethanol concentrations by pantethine following alcohol ingestion: different effects in flushing and nonflushing subjects. 389 99


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