The Chlorpropamide Alcohol Flush CPAF

The CPAF is one of the earliest recognized examples of pharmacogenetics in the management of DM. Many diabetics who take the sulfonylurea, chlorpropamide, experience facial flushing after drinking even small amounts of alcohol. Sulfonylurea-induced alcohol intolerance is seen mainly, but not exclusively, with chlorpropamide and is similar to the interaction between alcohol and disulfiram. The mechanism of the reaction, however, is unclear. The main symptom is facial flushing that occurs more commonly in diabetic than in nondiabetic subjects. It has therefore been proposed that this symptom could be used as a diagnostic test for a certain subset of patients with type 2 DM (37,38). Interestingly, patients who demonstrate CPAF have a noticeably lower prevalence of late complications of diabetes (microangiopathy, macroangiopathy, and neuropathy) than nonflushers. The flush reaction is accompanied by an increase in blood acetaldehyde concentrations, suggesting an inhibition of aldehyde dehydrogenase activity (39,40).

Different prevalences of CPAF have been reported by different authors in type 1 DM, type 2 DM, or healthy subjects. This could be due to different methodological approaches or the different criteria for evaluating CPAF. Bonisolli et al. (41) investigated the association between CPAF and the fast acetylator phenotype (AP) in type 1 and type 2 diabetic patients. An association between fast AP and CPAF was found in type 2 but not in type 1 DM. In addition, a linear relationship was found between the rate of acetylation and the speed of ascent of facial skin temperature after chlorpropamide and alcohol in type 2 diabetics but not in type 1 diabetics. However, many authors do not consider the CPAF test to be sufficiently sensitive and specific, and despite a great deal having been published on the test, its value remains poorly defined (42-45).

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