Roles of chlorpropamide, alcohol and acetaldehyde in determining the chlorpropamide-alcohol flush.
The value and reproducibility of the chlorpropamide-alcohol flush (CPAF) have been questioned, and objective measures of the test are required. Recording of facial skin temperature, measurement of chlorpropamide, ethanol and acetaldehyde concentrations have been proposed for this purpose. The present study was designed to evaluate the relative contributions of these variables in determining CPAF. Twenty-one Type 2 (non-insulin-dependent) diabetic patients (11 CPAF-positive and 10 CPAF-negative according to previous tests with standard amounts of alcohol and chlorpropamide) were investigated in a random fashion with either chlorpropamide or placebo given on three subsequent evenings before a two-step alcohol challenge with increasing body-weight-matched amounts of alcohol. Higher rises in facial skin temperature and heart rate, higher flush-score and higher acetaldehyde levels resulted from chlorpropamide therapy than followed placebo. After smaller alcohol challenges (with chlorpropamide pretreatment) there were positive intercorrelations between flush-score, rise in facial skin temperature, and plasma concentrations of chlorpropamide and blood acetaldehyde. The increased alcohol dose abolished most of these correlations and a minimum temperature rise of 1.8 degrees C appeared in all but two subjects regardless of previous CPAF classification. During the current experimental conditions, the previously-classified CPAF-positive and CPAF-negative patients did not differ with respect to flush-score, rise in skin temperature, heart rate, blood acetaldehyde or ethanol concentrations, whereas they differed with respect to chlorpropamide concentrations. The present results support the view that CPAF is associated with elevated blood acetaldehyde levels due to inhibition of aldehyde dehydrogenase by chlorpropamide.(ABSTRACT TRUNCATED AT 250 WORDS)
D000079:Acetaldehyde / Q000097:blood*; D000328:Adult; D000428:Alcohol Drinking; D002747:Chlorpropamide / Q000009:adverse effects* / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood*; D005260:Female; D005483:Flushing / Q000097:blood / Q000139:chemically induced* / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos
D010919:Placebos; D000431:Ethanol; D000079:Acetaldehyde; D002747:Chlorpropamide