Chlorpropamide Alcohol

Facial dushing after ingestion of alcohol occurs in up to one-third of patients taking chlorpropamide. The mechanism, like that of the disulfiram reaction, probably involves inhibition of the oxidation of acetaldehyde, a metaboUte of ethanol. The plasma concentration of chlorpropamide may be correlated with chlorpropamide—alcohol dushing. 

The chlorpropamide-alcohol flush reaction, although extensively studied, is by no means fully understood. It seems to be related to the di-sulfiram-alcohol reaction, and is accompanied by a rise in blood-acetaldehyde levels (see also Alcohol -i- Disulfiram , p.61). It also appears to be genetically determined and may involve both prostaglandins and endogenous opioids. The decreased hdf-life of tolbutamide in alcoholics is probably due to the inducing effects of alcohol on liver microsomal enzymes. ... 

The chlorpropamide-alcohol interaction (flushing reaction) is very well documented, but of minimal importance. It is a nuisance and possibly socially embarrassing but normally requires no treatment. Patients should be warned. The incidence is said to lie between 13 and 33% > although one study claims that it may be as low as 4%. Since it can be provoked by quite small amounts of alcohol (half a glass of sherry or wine) it is virtually impossible for sensitive patients to avoid it if they drink. Most manufacturers issue warnings about the possibility of this reaction with other sulphonylureas, but it is very rarely seen and can therefore almost always be avoided by replacing chlorpropamide with another sulphonylurea. Alcoholic subjects may need above-average doses of tolbutamide. 

Johnston C, Wiles PG, Pyke DA. Chlorpropamide-alcohol flush the case in favour. Didbet-... 

Leslie RDG, Pyke DA. Chlorpropamide-alcohol flushing a dom inantly inherited trait associated with diabetes. BMJ (1978) 2,1519-21. 

Hillson RM, Hockaday TDR. Chlorpropamide-alcohol flush a critical reappraisal. Diabeto-logia ( 9S4) 26,6-11. 

Waldhausl W. To flush or not to flush Comments on the chlorpropamide-alcohol flush. Di-... 

GroopL, Eriksson CJP,Huupponen YlikarhiR,PelkonenR. Roles of chlorpropamide, alcohol and acetaldehyde in determining the chlorpropamide-alcohol flush. Diabetologia (1984) 26,34-38. 

Johnston C, Wiles PG, Medbak S, Bowcock S, Cooke ED, fyke DA, Rees LH. The role of endogenous opioids in die chlorpropamide alcohol flush. Clin Endocrinol (Ox (1984) 21, 489-97. 

De Silva NE, Tunbridge WMG, Alberti KGMM Low incidence of chlorpropamide-alcohol flushing in diet-treated, non-insulin-dependent diabetics. Lawcef (1981) i, 128-31. 

There are several sulphonylureas hut there is no evidence for any difference in their effectiveness. Only chlorpropamide has appreciably more side effects, mainly because of its prolonged duration of action and the consecjuent hazard of hypoglycaemia (but also as a result of the common and unpleasant chlorpropamide-alcohol flush phenomenon). ... 

Chlorpropamide. Chlorpropamide (l-[(p-chlorophenyl)sulfonyl]-3-propylurea), mol wt 276.75, is a white, crystalline powder, having a slight odor, mp 127—129°C. It is sold as Diabinese, is soluble in water at pH 6 (2.2 mg/mL), and practically insoluble at pH 7.3, soluble in alcohol, and sparingly soluble in chloroform, ether, and benzene. 

Alcohol (acute intoxica- Chlorpropamide Fluconazole Mefenamic acid Quinidine, quinine... 

Chlorpropamide Diabinese) has a relatively slow onset of action, with its maximal hypoglycemic potential often not reached for 1 or 2 weeks. Similarly, several weeks may be required to eliminate the drug after discontinuation of therapy. This drug can cause flushing, particularly when taken with alcohol, and can also cause hyponatremia. This effect has been employed to treat some patients who have partial central diabetes insipidus, an unrelated condition due to a pituitary ADH deficiency. 

Sulfonylureas [NE] Chlorpropamide is most likely to produce a disulfiram-like reaction acute alcohol intake may increase hypoglycemic effect (especially in fasting patients). 

For instance, blurring of vision and diplopia are caused by the use of imipramine, iproniazid, chlorpromazine, thioridazine, and promethazine. Impairment of visual acuity is caused by chlorpropamide, tolbutamide, alcohol, chlorpromazine, phenylbutazone, indomethacin, chloroquine, sulfonamides, ethambutol, chloramphenicol, isonex, clioquinol, quinine, streptomycin, and paraaminosalicylate. Yellow vision (xanthopsia) has been traced to the use of sulfonamides, streptomycin, methaqualone, barbiturates, chlorothiazide,... 

Chlorpropamide, tolbutamide, tolazamide, acetohexamide, metronidazole Alcohol Disulfiram-like reaction... 

Numerous barbiturates and oral hypoglycemic sulfonyl-ureas also have aliphatic side chains that arc su.sceptible to oxidation. Note that the sedative hypnotic amobarbital (Amytal) undergoes extensive to - I oxidation to the corresponding 3 -hydroxylated metabolite.Other barbiturates, such as pentobarbital, thiamylal,and secobarbital," reportedly are metabolized by way of a and to - I oxidation. The ri-propyl side chain attached to the oral hypoglycemic agent chlorpropamide (Diabinc.se) undergoes extensive to -I hydroxylation to yield the secondary alcohol 2 -hydroxy-chlorpropamide as a major urinary metabolite in humans. " ... 

Acetohexamideis metabolized by reduction in the liver of its ketone function to an alcohol, hydroxyhexamide, which is pharmacologically active (79,86). After oral administration, the plasma concentration of the parent compound peaks in 1-2 h, then falls rapidly. The active metabolite has a longer half-life and prolongs the duration of action. Hydroxyhexamide is excreted primarily in the urine with a small amount of the parent and other clinically unimportant metabolites. Chlorpropamide is quite long lived in circulation, with an elimination half-life of about 36 h. It is slowly metabolized by hydroxylation at the 2 or 3 position of the propyl substituent, yielding metabolites that retain some activity and by N-dealkylation to p-chlorobenzenesulfonyl-urea (86, 89). Urinary excretion is the main... 

Other side effects of sulfonylureas include nausea and vomiting, cholestatic jaundice, agranulocytosis, aplastic and hemolytic anemias, generalized hypersensitivity reactions, and rashes. About 10-15% of patients who receive these drugs, particularly chlorpropamide, develop an alcohol-induced flush similar to that caused by disulfiram see Chapter 23). Sulfonylureas, especially chlorpropamide, may induce hyponatremia by potentiating the effects of vasopressin on the renal collecting duct see Chapter 29), and this effect on water retention has been used to therapeutic advantage in patients with mild forms of central diabetes insipidus. 

The documentation of the interactions between antidiabetic drugs and alcohol is surprisingly patchy (with the exception of chlorpropamide and alcohol) but they are of recognised clinical importance. 

Fitzgerald MG, Gaddie R, Malins JM, O Sullivan DJ. Alcohol sensitivity in diabetics receiving chlorpropamide. Diabetes (1962) 11, 40-3. 

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