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At least 19 recordsLinked to original sources
PubMed1983

Chlorpropamide-alcohol flushing and plasma chlorpropamide concentrations in diabetic patients on maintenance chlorpropamide therapy.

Forty-three diabetic patients on maintenance chlorpropamide (100-750 mg daily) drank 0.2 ml/kg 90% ethanol after equilibration in a room controlled at 20 degrees C. Twenty-five patients had already noted marked alcohol flushing since starting chlorpropamide therapy (group A), while 13 had not observed this (group B). The remainder were teetotal or unsure of their reaction. Cheek temperature rise correlated with plasma chlorpropamide concentration (r = 0.6, p less than 0.001) in all patients and was inversely related to basal cheek temperature (r = -0.35, p less than 0.02). Plasma chlorpropamide correlated with daily chlorpropamide dose (r = 0.8, p less than 0.001) but not with basal cheek temperature. The correlation between chlorpropamide level and cheek temperature rise was strengthened on analysis of group A alone (r = 0.7, p less than 0.001) and absent in group B (r = 0.2, p greater than 0.3) who tended to have lower chlorpropamide levels and cheek temperature rise than group A.

Body Temperature↗
PubMed1987

Pharmacokinetics of chlorpropamide in epileptic patients: effects of enzyme induction and urine pH on chlorpropamide elimination.

The effects of liver enzyme induction and of urine pH on the pharmacokinetics of chlorpropamide have been studied. A single oral dose of chlorpropamide 250 mg was administered to 8 patients on antiepileptic drugs (phenytoin, carbamazepine) and to 8 healthy volunteers. The half-life of chlorpropamide was significantly shorter in the patients (34.4 h) than in the healthy volunteers (50.2 h), but the difference between the groups in the half-life of antipyrine was even more pronounced (5.1 vs 11.4 h). The clearance and volume of distribution of total chlorpropamide were significantly higher in the patients (2.99 ml X h-1 X kg-1 and 126 ml X kg-1) than in the healthy volunteers (1.60 ml X h-1 X kg-1 and 106 ml X kg-1). The unbound fraction of chlorpropamide in serum was also higher in the patients (5.7%) than in the healthy subjects (4.4%). Neither the volume of distribution nor the clearance of the free fraction of chlorpropamide differed significantly between the groups. There was a significant correlation between the half-lives of chlorpropamide and antipyrine, and the half-life of chlorpropamide also had at least as good an inverse correlation with the urinary excretion of unchanged chlorpropamide. The renal clearance of chlorpropamide correlated well with urine pH and was almost 100-fold higher at pH 7 than at pH 5. Both the metabolic and renal clearances of chlorpropamide are important in its elimination. At urine pH higher than 6.5-7, the renal clearance of chlorpropamide represents more than half its total clearance regardless the degree of induction of liver enzymes.

Adult↗
PubMed1978

[Hyponatremia and hypoglycemia after treatment with chlorpropamide. Case histories with review of the literature on 18 cases of chlorpropamide induced hyponatremia].

A case of chlorpropamide-induced, symptomatic hyponatremia in a diabetic patient is reported. The hyponatremia was associated with loss of appetite, nausea, and vomiting. These symptoms caused reduced food intake which provoked severe hypoglycemia with disturbed consciousness. The hyponatremia developed when the chlorpropamide doses were increased from 400 to 600 mg/day. Withdrawal of chlorpropamide was followed by remission of hyponatremia. Chlorpropamide-induced hyponatremia is a rare complication and is due to an antidiuretic effect of chlorpropamide caused by increased secretion of adiuretin and potentiation of the effect of chlorpropamide caused by increased secretion of adiuretin and potentiation of the effect of adiuretin in the tubuli of the kidney. This case report and the analysis of 18 published cases in the literature show the following characteristics for chlorpropamide-induced hyponatremia: (1) Hyponatremia is a rare complication in the treatment of diabetics with chlorpropamide. The patients typically are female and over sixty. The dosage of chlorpropamide usually was 500 mg daily or even more. (2) Hyponatremia is often unrecognized for a long time because the symptoms are not specific. The characteristic symptoms include loss of appetite, nausea, vomiting, abdominal pain, confusional state and, rarely, convulsions and coma. Recovery occurs spontaneously after withdrawal of the drug. (3) The incidence of this type of hyponatremia is increased in cases of preexisting tendency to water retention such as heart failure and renal failure, and in cases of diuretic therapy. In the light of these findings, the authors believe that chlorpropamide is no longer a drug of choice in the treatment of diabetic women, especially in cases of preexisting tendency to water retention and in diuretic therapy. In such cases, a sulfonylurea without antidiuretic effect is to be preferred.

Adult↗
PubMed1984

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)

Acetaldehyde↗
PubMed1983

Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush.

The chlorpropamide-alcohol flush (CPAF) phenomenon was quantitatively related to blood levels of acetaldehyde and chlorpropamide in 105 Type II diabetics, of whom 74 had not previously taken the drug and 31 were on chronic treatment. Standardized skin temperature recordings were made with a sensitive probe. Plasma ethanol and acetaldehyde concentrations were determined by gas chromatography, and those of chlorpropamide by high-pressure liquid chromatography. There were significant positive correlations between plasma acetaldehyde and the skin temperature increase, between plasma chlorpropamide and plasma acetaldehyde, and between plasma chlorpropamide and the skin temperature increase. CPAF-positive patients became CPAF-negative and vice versa following reduction and increase, respectively, in the dose of chlorpropamide. Thus, the CPAF reaction is a consequence of chlorpropamide inhibition of the oxidation of ethanol-generated acetaldehyde, and it appears that the plasma concentration of chlorpropamide is critical. It remains an open question whether the CPAF test has any prognostic value.

Acetaldehyde↗
PubMed1984

Chlorpropamide-alcohol flush: significance of body weight, sex and serum chlorpropamide level.

Chlorpropamide-alcohol flush (CPAF) tests were carried out in 15 male and 15 female Type 2 diabetics. Twelve subjects were CPAF-positive and 18 were -negative. The two groups did not differ in age or duration of diabetes, but the CPAF-positive subjects weighed less (mean difference 13 kg) and had higher plasma chlorpropamide levels. There was a negative correlation between plasma chlorpropamide and body weight, and a positive correlation between plasma chlorpropamide and the increase in facial skin temperature. Females had higher plasma chlorpropamide, a greater skin temperature increase and lower body weight than males; there were 11 females and only 1 male amongst the 12 CPAF-positive subjects. The findings confirm that plasma chlorpropamide is a major determinant of the CPAF reaction and also show that body weight strongly influences the chlorpropamide level and, consequently, the outcome of the CPAF test. The sex difference in body weight probably accounts for most, if not all, of the sex difference in the incidence of the CPAF.

Body Weight↗
PubMed1987

Erythrocyte aldehyde dehydrogenase, plasma chlorpropamide concentrations and the chlorpropamide alcohol flush.

Erythrocyte aldehyde dehydrogenase activity (EALDH) was measured in 21 diabetics on long-term chlorpropamide therapy. Median EALDH was 0.362 units, range 0.108 to 0.750 units and correlated neither with previously assessed chlorpropamide alcohol flushing nor with coincident plasma or erythrocyte chlorpropamide concentration. The hypothesis that genetic or permanently acquired reduction in EALDH correlates with CPAF status was not supported. There was no concentration-related inhibition of the enzyme by prevailing plasma or erythrocyte chlorpropamide.

Alcohol Drinking↗
PubMed1984

On plasma chlorpropamide, body weight and sex difference in chlorpropamide alcohol flush (CPAF).

There is evidence that the plasma chlorpropamide (CP) concentration is an important determinant of the chlorpropamide alcohol flush (CPAF). In 74 type 2 diabetics a highly significant correlation (r = 0.51, p less than 0.001) was present between the levels of plasma CP and the appearance of CPAF, measured as an index (the sum of the increase of the skin temperature and one-fourth of plasma acetaldehyde increase). Lower or no correlations were found when different threshold levels were considered. Body weight was significantly (p less than 0.001) inversely correlated to plasma chlorpropamide levels, which resulted in higher CP levels in females (mean body weight 68.6 kg, CP concentration 34.4 mg/l) than in males (83.4 kg, 26.0 mg/l), which explains the female preponderance among flushers.

Adolescent↗
PubMed1985

Prevalence of chlorpropamide alcohol flush in Jewish Israeli diabetics. The role of serum chlorpropamide concentrations.

Among 53 patients with noninsulin-dependent diabetes (NIDD), chlorpropamide alcohol flushing (CPAF) was more prevalent than among 18 patients with insulin-dependent diabetes (64 vs. 28%, respectively). Among the former, chronic users of chlorpropamide (CP) had a higher prevalence of CPAF than those challenged once with the drug (86 vs. 56%, respectively). Serum CP concentrations were much higher in CP-treated patients, but levels were not different in CPAF-positive compared with CPAF-negative subjects, regardless of the length of their exposure to the drug. Our data confirm the association between CPAF and NIDD in a Jewish Israeli diabetic population and the effect of serum CP levels on the prevalence of this phenomenon.

Adult↗
PubMed1983

Epidemiological study of prevalence of chlorpropamide alcohol flushing in insulin dependent diabetics, non-insulin dependent diabetics, and non-diabetics.

An epidemiological study was carried out to compare the prevalence of facial flushing in non-diabetics, patients with insulin dependent diabetes, and patients with non-insulin dependent diabetes in response to 40 ml sherry taken 12 hours after 250 mg chlorpropamide or placebo, administered double blind in randomised order. A flush after chlorpropamide but not placebo was reported by 6.2% of non-diabetics (17/273), 9.7% of insulin-dependent diabetics (14/145), and 10.5% of non-insulin dependent diabetics (25/239), excluding those receiving long term chlorpropamide treatment. The differences were not significant. This response was unrelated to age, sex, body mass index, and family history of diabetes in all three groups. Patients taking long term chlorpropamide, however, showed a significantly (p less than 0.01) higher prevalence of flushing after both chlorpropamide and placebo (56.3%; 9/16) compared with the rest of the non-insulin dependent diabetics (16.7%; 40/239), the insulin dependent diabetics (6.9%; 10/145), and the non-diabetics (5.9%; 16/273). Patients receiving long term chlorpropamide would be expected to flush with sherry after a placebo tablet because of therapeutic plasma concentrations of the drug. It is concluded that there is no evidence of an increased prevalence of chlorpropamide alcohol flushing in response to the single challenge test in non-insulin dependent diabetics compared with insulin dependent diabetics and non-diabetics except in selected patients taking chlorpropamide long term. This study does not support the hypothesis that the chlorpropamide alcohol flush is a specific marker for a subtype of non-insulin dependent diabetes.

Adult↗
PubMed1985

Comparison of acute and prolonged effects of glibenclamide and chlorpropamide in patients with non-insulin-dependent diabetes.

The effects of single oral dose of glibenclamide (Gilemid 5 mg) and chlorpropamide (250 mg) on serum insulin and glucose levels and electrolyte (sodium, potassium) balance were studied, in a cross-over double-blind manner, in 11 patients with non-insulin-dependent diabetes. Both drugs increased serum insulin for more than 8 h but less than 24 h. The effect of glibenclamide was slightly stronger than that of chlorpropamide. Serum glucose concentration was significantly decreased by glibenclamide only. Glucose excretion in urine was declined for a longer time by glibenclamide than by chlorpropamide. Neither of the drugs essentially effected on sodium and potassium excretion. After the acute study, all the above patients and 5 additional ones were treated in open care with glibenclamide (2.5-10 mg daily) and chlorpropamide (125-500 mg daily) for 8 weeks in a cross-over manner. Both drugs showed practically similar efficacy; 5 mg of glibenclamide corresponded to 250 mg of chlorpropamide. One patient under chlorpropamide treatment exhibited hyponatraemia. Eight weeks after the commencement of therapy, serum potassium concentration was lower under chlorpropamide than under glibenclamide treatment. The results suggest that, in non-insulin-dependent diabetes, a single oral dose of glibenclamide acts as long as that of chlorpropamide, and that in long-term therapy 5 mg of glibenclamide is equipotent with 250 mg of chlorpropamide.

Adult↗
PubMed1983

Effects of charcoal, sodium bicarbonate, and ammonium chloride on chlorpropamide kinetics.

The effects of activated charcoal, sodium bicarbonate, and ammonium chloride by mouth on chlorpropamide kinetics was studied in six healthy subjects. Activated charcoal, 50 gm, given immediately after 250 mg chlorpropamide reduced its absorption by 90%, but when given in repeated doses from 6 hr on (50 gm followed by 12.5 gm at 6-hr intervals) it did not shorten the chlorpropamide half-life (t 1/2). The t 1/2 of chlorpropamide was shortened from 49.7 +/- 7.4 to 12.8 +/- 1.1 hr by sodium bicarbonate and prolonged to 68.5 +/- 10.5 hr by ammonium chloride. The 72-hr urinary excretion of chlorpropamide was increased fourfold by alkalinization and decreased to 1/20 of baseline by acidification of the urine. The renal clearance of chlorpropamide correlated with urinary pH, ranging from 1 to 1000 ml/hr at the pH from 5 to 8. Urinary pH is likely to explain at least a part of great interindividual differences in the serum chlorpropamide concentrations during steady-state and variations in amount of urinary metabolites. In chlorpropamide intoxications activated charcoal can reduce absorption and alkalinization of the urine accelerates its elimination.

Adult↗