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)

The so-called Oriental flushing reaction associated with ingestion of small amounts of alcohol was antagonized by combined antihistamine administration. In stage one of the study, the flushing reaction to low doses of alcohol was produced in Orientals. Most subjects experienced a cutaneous flush, an increase in skin temperature, a decrease in blood pressure, an increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness and nausea. Before the administration of alcohol, one-half of the subjects were given 50 mg of diphenhydramine (H1 receptor antagonist) and 300 mg of cimetidine (H2 receptor antagonist). The second half received placebo tablets. The clearest difference between the antihistamine group and placebo group was in the skin flushing reaction. The antihistamine group showed a significant reduction in the skin flush. The antihistamine also neutralized the systolic hypotension induced by the administration of alcohol. The possible importance of histamine in the expression of sensitivity to alcohol is considered. The relevance to genetic susceptibility for development of alcoholism is discussed.
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PMID:Antihistamine blockade of alcohol-induced flushing in orientals. 334 71

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

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

Abuse of alcohol (ethanol) and abuse of an increasing number of drugs (e.g. analgesics and sedatives) are among the outstanding social and medical problems of many industrialized countries including Switzerland. Since alcohol consumption has profound effects on both the pharmacokinetic and pharmacodynamic actions of a variety of drugs, the rational use of drugs in alcoholics is an increasingly difficult task and requires a thorough understanding of the physiologic, biochemical, pharmacologic and toxic actions of alcohol. Clinically the most important targets of alcohol action are the liver and the central nervous system (CNS), both of which are frequently involved in the mediation of potentially fatal interactions between drugs and alcohol. In practice the most important of these interactions include (a) inhibition of hepatic (cytochrome P450 dependent) drug oxidation by acute alcohol ingestion resulting in increased bioavailability of drugs that are predominantly excreted by hepatic metabolism, (b) inhibition of acetaldehydedehydrogenase by some drugs with production of an acute flushing reaction to alcohol, (c) increased sensitivity of the CNS to a variety of sedative drugs following acute alcohol ingestion leading to enhanced CNS toxicity of most psychoactive drugs, (d) stimulation of hepatic drug oxidation and decreased CNS sensitivity to sedatives after chronic alcohol abuse, thus explaining the "metabolic" and pharmacodynamic tolerance of these patients towards psychoactive agents, and (e) depressed drug metabolism and increased CNS sensitivity to sedative and hypnotic drugs in patients with cirrhosis of the liver. The mechanisms and practical consequences of the clinically most important influences of acute and chronic alcohol ingestion on the pharmacokinetics and the pharmacodynamic actions of drugs are outlined.
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PMID:[Alcohol, alcoholism and drugs]. 391 83

Research that deals with the causes of alcoholism has been hampered by the absence of factor analyses that deal specifically with ethanol's aftereffects. We factor analyzed 100 alcoholics' reports of the effects that they experience after alcohol consumption. Five factors emerged--Hangover, Euphoria, Flushing, Seizures, and Sleepiness. They are described and discussed. Future investigators may find them helpful in assessing theories on the etiology of alcoholism and in studies of ethanol's effects on subsets of alcohol abusers.
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PMID:Factor analysis of the aftereffects of drinking in alcoholics. 397 32

The mechanisms of flushing reactions are pharmacologically and physiologically heterogeneous. Flushing may result from agents acting directly on the vascular smooth muscle or may be mediated by vasomotor nerves. Vasomotor nerves may lead to flushing as a result of events at both peripheral and central sites. In susceptible persons, frequent, intense flushing leads to a cluster of physical signs (rosacea). Flushing provoked by alcohol has been associated with ethnic sensitivity, a possible predisposition to alcoholism, various disulfiramlike agents, one type of diabetes mellitus, and the carcinoid syndrome and other types of neoplasia. Flushing reactions also occur during the menopause, after glutamate ingestion, and in response to oral thermal challenges.
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PMID:Flushing reactions: consequences and mechanisms. 616

New reliable methods for the determination of acetaldehyde in human blood, either from separated plasma or from acid-precipitated whole blood, demonstrate that the blood of healthy Caucasians contains at most only extremely small amounts of acetaldehyde (less than 1 microM) after moderate alcohol intoxication. On the other hand, among about 50% of the Japanese population ethanol ingestion results in elevated blood acetaldehyde levels (10-50 microM) with consequent unpleasant cardiovascular responses such as facial flushing and tachycardia, apparently because of a lack of one of the acetaldehyde-oxidizing aldehyde dehydrogenase isozymes. Elevated acetaldehyde levels may eventually occur also among intoxicated Caucasian alcoholics, primarily as a consequence of abuse-induced loss of hepatic aldehyde dehydrogenase activity, but accentuated by an accelerated ethanol oxidation rate. The elevation is probably reversible, since no acetaldehyde is seen in alcoholics after abstinence and hospital treatment. There is thus little evidence that an elevation of acetaldehyde could serve as a marker for predisposition for alcoholism.
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PMID:Human blood acetaldehyde levels: with improved methods, a clearer picture emerges. 634 52

Ethanol-induced facial flushing was measured in 30 men, aged 21 to 25, who had family histories of alcoholism and in 30 matched controls. The drug was administered as 0.75 ml of 95% ethanol per kilogram of body weight, mixed with a sugar-free soft drink and consumed over 5 minutes. Facial flushing was assessed over 90 minutes using both observational ratings and a plethysmograph. Family history positive (FHP) subjects demonstrated significantly higher levels of flushing than family history negative (FHN) controls on objective measures. Correlations with the flushing response were .83 for blood acetaldehyde, and at least .60 for heart rate and skin temperature. This is the first known demonstration in Caucasians of a possible association between flushing and blood acetaldehyde levels in individuals hypothesized to be at risk for the development of alcoholism.
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PMID:Alcohol-related flushing and the risk for alcoholism in sons of alcoholics. 711 36

Healthy volunteers taking ethanol after pretreatment with calcium carbimide, a drug commonly used in treatment of alcoholism, were studied by echocardiography. Marked facial flushing and accumulation of acetaldehyde after ethanol were accompanied by circulatory acceleration corresponding in magnitude to at least moderate physical exercise. The heart rate (+/- SD) rose from 58 +/- 6 to 107 +/- 11 beats/min (p less than .001) the cardiac output from 4.1 +/- 0.6 to 9.4 +/- 1.1 L/min (p less than .001), and the ejection fraction from 70 +/- 3 to 89 +/- 2% (p less than .001). The systolic blood pressure rose initially from 121 +/- 6 to 143 +/- 5 mmHg (p less than .001). The diastolic blood pressure declined from 80 +/- 0 to 51 +/- 13 mmHg (p less than .01), and the estimated peripheral resistance to one-third of its preethanol level (p less than .001). These marked cardiovascular changes suggest that the ethanol-calcium carbimide interaction can be hazardous to alcoholics with ischaemic or other forms of myocardial diseases.
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PMID:Possible cardiovascular hazards of the alcohol-calcium carbimide interaction. 715 43


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