Roles of chlorpropamide, alcohol and acetaldehyde in determining the chlorpropamide-alcohol flush

Groop, L.; Eriksson, C. J. Peter; Huupponen, Risto; Ylikahri, Reino; Pelkonen, Risto

doi:10.1007/bf00252260

Cited by 23 publications

(8 citation statements)

References 17 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CPAF results from the inhibition of aldehyde dehydrogenase by chlorpropamide resulting in increased plasma acetaldehyde concentrations. 6 In some patients, administration of indomethacin, aspirin, or naloxone inhibited CPAF.9-' ' These data suggested that endogenous opiates or prostaglandins were the actual mediators of flushing.…”

Section: Discussionmentioning

confidence: 99%

Opiate Antagonist Nalmefene Inhibits Ethanol‐induced Flushing in Asians: A Preliminary Study

DeMaster

Shafer

et al. 1988

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

Ethanol-induced flushing (EIF) occurs in up to 80% of Asians and is characterized by facial flushing, tachycardia, and increased cardiac output. Since endogenous opiates and prostaglandins may be mediators of flushing syndromes, we attempted to block EIF in four Asian flushers with single doses of either the opiate antagonist nalmefene, or the prostaglandin synthesis inhibitor indomethacin. Nonflushers (2 Caucasian, 2 Asian) and four Asian flushers were given on separate days water, ethanol (0.4 g/kg p.o.), ethanol plus nalmefene (2 mg i.v.), or ethanol plus indomethacin (50 mg p.o.). Ethanol concentrations of flushers and nonflushers were similar. Mean (+/- SEM) plasma acetaldehyde concentrations of flushers (28.2 +/- 11.8 microM) were significantly greater than nonflushers (1.4 +/- 0.5 microM) following ethanol ingestion (p less than 0.001). Ethanol alone always induced a significant rise in facial skin temperature [mean area under the curve (AUC) = 5142 +/- 648 % delta T x min, p less than 0.01] and of pulse (mean AUC = 1622 +/- 120 bpm x min, p less than 0.001) in flushers compared to water ingestion. A single dose of nalmefene (2 mg i.v.) but not indomethacin (50 mg p.o.), reduced the mean (+/- SEM) ethanol-induced rise in facial skin temperature of flushers by 58 +/- 14% (p less than 0.05) without changing plasma acetaldehyde concentrations. These data are preliminary evidence that the opiate antagonist, nalmefene, blocks some of the vascular manifestations of EIF without altering the elevated plasma concentrations of acetaldehyde.

show abstract

Section: Discussionmentioning

confidence: 99%

Opiate Antagonist Nalmefene Inhibits Ethanol‐induced Flushing in Asians: A Preliminary Study

DeMaster

Shafer

et al. 1988

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

show abstract

“…The fact that patients on long term chlorpropamide treatment flush more often than those who received a single dose shows that chlorpropamide concentration may be important (Jerntorp et al 1981b). Indeed, Groop et al (1984) showed positive correlations between the flush score and plasma chlorpropamide or blood acetaldehyde concentrations.…”

Section: Chlorpropamide-alcohol Flushmentioning

confidence: 98%

Adverse Cardiovascular Effects of Sulphonylurea Drugs

Huupponen

1987

Medical Toxicology

View full text Add to dashboard Cite

Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.

show abstract

“…Acetaldehyde, a natural aldehyde metabolite, can react with proteins. It is present in low concentration in normal plasma but in higher concentration after ethanol consumption or with antibuse or chlorpropamide therapy (Groop et al, 1984). Finally, there has been considerable interest in recent years in the nonenzymatic glycosylation of proteins (Kennedy and Baynes, 1984).…”

mentioning

confidence: 99%

The Presence of Aldehyde‐Reacted Proteins in Normal and Multiple Sclerosis White Matter

Epand¹,

Dell²,

Tonogai³

et al. 1985

Journal of Neurochemistry

View full text Add to dashboard Cite

The incorporation of tritium from NaB3H4 into the major protein components of myelin and the presence of weak fluorescence emission bands at wavelengths of approximately 440 and 500 nm from sodium dodecyl sulfate-solubilized, delipidated white matter are indicative of the presence of the products of aldehyde reactions with proteins. The incorporation of tritium from NaB3H4 into myelin proteins was confirmed by reaction with purified components of myelin basic protein or with lipophilin, a purified fraction of proteolipid protein. From the extent of tritium incorporation into the purified proteins, it is estimated that approximately 0.2 mol of tritium is incorporated/mol of myelin basic protein and approximately 0.4 mol of tritium/mol of proteolipid protein. There is approximately 50% greater incorporation of tritium into a more degraded, less positively charged form of the basic protein. The incorporation of tritium into normal and multiple sclerosis white matter was compared. There is a small but statistically significant difference in the percentage of the total counts incorporated into the major protein fractions for the two groups, with the multiple sclerosis samples showing a higher percentage of the counts in the Wolfgram protein and a lower percentage in the myelin basic protein compared with the normal samples.

show abstract

Roles of chlorpropamide, alcohol and acetaldehyde in determining the chlorpropamide-alcohol flush

Cited by 23 publications

References 17 publications

Opiate Antagonist Nalmefene Inhibits Ethanol‐induced Flushing in Asians: A Preliminary Study

Opiate Antagonist Nalmefene Inhibits Ethanol‐induced Flushing in Asians: A Preliminary Study

Adverse Cardiovascular Effects of Sulphonylurea Drugs

The Presence of Aldehyde‐Reacted Proteins in Normal and Multiple Sclerosis White Matter

Contact Info

Product

Resources

About