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)

Many diabetics who take chlorpropamide (a sulphonylurea compound) experience facial flushing after drinking even small amounts of alcohol. These flushers have a noticeably lower prevalence of late complications of diabetes (microangiopathy, macroangiopathy, and neuropathy) than non-flushers. This flush reaction is accompanied by increased blood acetaldehyde concentrations, suggesting an inhibition of aldehyde dehydrogenase activity. In the present study the activity of this enzyme in erythrocytes was assessed in the absence of chlorpropamide. Erythrocyte homogenates obtained from flushers and non-flushers were incubated with acetaldehyde and the rate of metabolism studies. Flushers eliminated acetaldehyde more slowly at a low range of concentrations (0--30 mumol/l), suggesting a difference in aldehyde dehydrogenase activity. Further studies are needed to clarify the role of this enzyme in the pathogenesis of diabetic complications.
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PMID:Chlorpropamide-alcohol flushing, aldehyde dehydrogenase activity, and diabetic complications. 681 Oct 34

Sixty three male Japanese, aged 20-40 yr were evaluated as to the degree of facial flushing following a controlled dose of ethanol either as Japanese rice wine or ethanol 0.4 g kg body weight. Thirty four subjects responded with overt facial flushing. The acetaldehyde levels in blood and expired air were significantly higher in the flushing group without a change in ethanol elimination rate. Urinary excretion of Vanilmandelic acid (VMA) and 3 methyoxy-4-Hydroxyphenylglycol (MHPG) are reported.
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PMID:Individual differences in blood and breath acetaldehyde levels and urinary excretion of catecholamines after alcohol intake. 700 32

4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, rapidly abolished the accumulation of acetaldehyde following alcohol ingestion both in volunteers pretreated with the Antabuse analog calcium carbimide and in an antabuse-treated alcoholic. 4-MP also attenuated other typical symptoms, including facial flushing and tachycardia, thus suggesting its usefulness in the acute treatment of severe disulfiram-alcohol reactions.
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PMID:The disulfiram (Antabuse)-Alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. 703 Jan 8

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

Chlorpropamide alcohol flushing (CPAF) in non-insulin-dependent diabetics (NIDDs) has been reported to be associated with a lower tendency to develop late complications. The flush was thought to be mediated by enkephalins and prostaglandins. Early studies could not correlate CPAF to increased levels of acetaldehyde in blood and the flush was not regarded as an antabuse-like reaction. In this study, the increase of plasma acetaldehyde during the flush in 13 CPAF positive diabetics was significantly (P less than 0.005) higher than in the 13 CPAF negative diabetics during a CPAF challenge test. The increase of plasma acetaldehyde was reduced to the level of CPAF negative diabetics in three CPAF positive diabetics when they were exposed to alcohol without premedication with chlorpropamide and they did not flush. The normal breakdown of ethanol to acetic acid via acetaldehyde appears to be inhibited by chlorpropamide in the flushers. Acetaldehyde measurement is an objective method to study the chlorpropamide alcohol flush and it appears superior to the measurement of skin temperature.
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PMID:Increase of plasma acetaldehyde. An objective indicator of the chlorpropamide alcohol flush. 726 73

Young healthy Japanese men were given 0.48 g ethanol/kg body weight orally. Those responding with a marked increase in heart rate after alcohol also exhibited facial flushing and had higher acetaldehyde levels than those not responding, in spite of similar blood alcohol levels. The activity of aldehyde dehydrogenase in erythrocytes was found to correlate significantly (r=-0.73, p < 0.01) with the increase in heart rate after alcohol drinking. It is suggested that erythrocyte aldehyde dehydrogenase activity affects or reflects blood acetaldehyde levels and physiological response to alcohol, and may prove useful as a marker for alcohol sensitivity in Orientals.
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PMID:Correlation between human erythrocyte aldehyde dehydrogenase activity and sensitivity to alcohol. 741

A sensitive method for determination of human blood acetaldehyde (AcH), which avoids artefactual ethanol-derived Ach formation, was developed. AcH was trapped by collecting blood directly into isotonic semicarbazide, the plasma separated, AcH liberated by perchloric acid and analyzed by gas chromatography. Breath AcH was also trapped in semicarbazide and analyzed similarly. Using an experimentally determined blood:breath partition ratio of 190, calculated pulmonary blood and measured antecubital blood AcH were very similar at various concentrations. Blood AcH was found generally to be very low (< 10 microM) at moderate ethanol levels. Calcium carbimide (0.25 mg/kg) caused moderate flushing reactions and elevated AcH to 25-188 microM. 4-Methylpyrazole (5 mg/kg i.v.) rapidly attenuated AcH levels and symptoms, indicating its potential use in the treatment of disulfiram-ethanol reactions. AcH in the cerebrospinal fluid of 5 highly intoxicated patients was almost absent (0-5 microM). Blood AcH in occasional or chronic alcohol abusers were generally low (< 10 microM), elevated AcH levels being observed only in association with clinical abnormalities. The results indicate that in general, previously reported human blood AcH levels are erroneously high and that breath levels reflect blood levels. Blood AcH may play a lesser role in the actions of ethanol in humans than is often assumed.
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PMID:Low acetaldehyde levels in blood, breath and cerebrospinal fluid of intoxicated humans as assayed by improved methods. 742 34

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

The prevalence of the alcohol-flushing reaction was assessed in a group of healthy Caucasian medical students (200) by self-reporting and was found to occur in approximately 50% of female and 8% of male subjects. In most of the alcohol flushers there were other family members similarly affected. The presence of this side-effect after a small quantity of alcohol did not necessarily decrease the amount of alcohol consumed. A test dose of ethanol (0.4 g/kg body weight) confirmed the presence of the alcohol-induced flushing, which was of much shorter duration and intensity than that of the Oriental alcohol-induced flusher, as measured by laser Doppler velocimetry, and was not associated with high circulating concentrations of acetaldehyde. Topical administration of 5 M acetaldehyde showed an enhanced erythema in Caucasian flushers compared to non-flushing controls. This effect was not observed with topical ethanol. Low erythrocyte ALDH1 activity was found in all Caucasians (n = 30) who showed the alcohol-induced flushing reaction.
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PMID:Identification and characterisation of alcohol-induced flushing in Caucasian subjects. 798 81


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