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At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Chlorpropamide-induced cholestatic liver failure resulting in death.

OBJECTIVE: To describe the first reported case of a death that occurred as a result of chlorpropamide-induced cholestatic liver disease. METHODS: We review the clinical and laboratory details of an 81-year-old man with type II diabetes mellitus, who was hospitalized because of nausea, vomiting, and jaundice. RESULTS: The patient had been taking a sulfonylurea (chlorpropamide, 250 mg orally three times a day) for 2 months. On initial assessment, the patient was noted to have cutaneous and scleral icterus and an erythematous maculopapular rash on the torso. The alkaline phosphatase level was substantially increased, and the transaminases were mildly increased. Use of all medications was discontinued. In the hospital, the patient's status rapidly deteriorated, and death ensued after cardiopulmonary arrest on day 6. CONCLUSION: The findings were consistent with a hypersensitivity reaction to chlorpropamide that ultimately resulted in fulminant cholestatic liver disease and death.

Journal Article↗
PubMedDate not supplied

[The effect of chlorpropamide on the course of latent insular insufficiency in rats under conditions favorable for its transition to patent diabetes].

Experiments were conducted on 162 female rats which had sustained alloxan diabetes during the period of sexual immaturity and had latent insular insufficiency (prediabetes and latent diabetes). Possibilities of chlorpropamide under conditions promoting decompensation development were studied. The animals were given propamide in daily doses of 100 mg per 1 kg of weight for one month, including the period of sexual maturation. Observation period--up to 5 months. A favourable effect of chlorpropamide was noted by the end of puberty and persisted in the course of further observation; the difference from control animals by the frequency of latent and manifest diabetes was intensified under the effect of glucose overfeeding during the perinatal period. Chlorpropamide improved the course of latent insular insufficiency in the rats and was capable of preventing its change into manifest diabetes.

Animals↗
PubMed1978

Bioassay of chlorpropamide for possible carcinogenicity.

A bioassay of chlorpropamide for possible carcinogenicity was conducted by administering the test material in feed to Fischer 344 rats and B6C3F1 mice. Groups of 35 rats and 35 mice of each sex were administered chlorpropamide as follows: rats 5 days per week for 103 to 105 weeks at 3,000 or 6,000 ppm, and mice 5 days per week for 34 weeks at 5,000 or 10,000 ppm, followed by 70 weeks at 2,500 or 5,000 ppm. The time-weighted average doses for mice were 3,317 ppm for low-dose males and females, and 6,635 ppm for high-dose males and females. Matched controls consisted of groups of 15 untreated rats and 15 untreated mice of each sex. All surviving rats and mice were killed at 103 to 105 weeks. Mean body weights of both low- and high-dose rats were lower than those of the matched controls throughout the study. In mice, doses were reduced at week 34, due to early deaths in the high-dose groups; following this adjustment the treated mice gained weight, but the weights never reached those of the controls. Survival of the treated rats and the low-dose mice was adequate for meaningful statistical analyses of the incidences of tumors. In both rats and mice, the incidences of tumors among the treated groups were not significantly increased in comparison with matched controls. It is concluded that under the conditions of this bioassay, chlorpropamide was not carcinogenic for Fischer 344 rats or B6C3F1 mice.

Journal Article↗
PubMed1988

Evaluation of antidiabetic effects of chlorpropamids in the presence of aspirin.

The present work has been done in an attempt to evaluate the hypoglycemic effect of Chlorpropamide in the presence of aspirin. Diabetiogenic effect of Alloxan was utilized which produced an Insulin-Dependent Diabetic State in the animals. Diabetic animals were given oral Chlorpropamide (100 mg/kg body weight) and it was seen that the drug reduced the blood sugar values although not to a significant level. Later the animals were given aspirin (30 mg/kg body weight) alongwith the daily dose of Chlorpropamide and a more significant reduction of blood sugar level took place.

Journal Article↗
PubMed1979

Transient neonatal diabetes mellitus. Treatment with chlorpropamide.

Nonketotic diabetes mellitus developed in a "small-for-dates" baby at the age of 6 days. The disease was controlled initially with insulin but beginning at the age of 40 days, chlorpropamide was substituted gradually for insulin over a 24-day period. Treatment was stopped at the age of 13 weeks and the baby remained well thereafter. It is suggested that chlorpropamide might be useful in the treatment of transient neonatal diabetes.

Chlorpropamide↗
PubMed1976

Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow.

Anicteric hepatitis, associated with fever and exfoliative dermatitis, developed in a diabetic patient two weeks after intake of a long-acting sulfonylurea, chlorpropamide (Diabinese). Granulomas showing heavy infiltration with eosinophils were found in the liver and bone marrow. These were interpreted as manifestations of an allergic reaction. The clinical signs, abnormal laboratory findings, and hepatic lesions subsided spontaneously on withdrawal of the drug. Bone marrow changes, however, persisted seven months after cessation of the drug. To our knowledge, this is the first report of a patient with liver and bone marrow inflammation characterized by granulomas with eosinophilic infiltration following intake of chlorpropamide.

Biopsy↗
PubMedDate not supplied

Effect of sucralfate on the absorption and pharmacokinetics of chlorpropamide.

This study compared the pharmacokinetics of chlorpropamide (C) when administered alone, or in combination with sucralfate (S) to evaluate whether a drug-drug interaction exists between these two agents in vivo. A two-way, randomized, cross-over study was performed in 12 healthy male volunteers who received 250 mg C alone or were pretreated with S qid for two days and then received a single 250-mg dose of C with S on day 3 and continued to take sucralfate throughout the day while serial blood samples were drawn. High-performance liquid chromatography determination of plasma concentrations found there to be no statistically significant differences in maximum concentration, time to maximum concentration, elimination rate constant, or area under the concentration-time curve from 0 to 96 hours. However, there was a statistically significant difference in the area under the curve from 0 to infinity data (P less than .05). The authors conclude that there appears to be no drug interaction between sucralfate and chlorpropamide when given concurrently; however, a trend towards less drug availability was seen that may warrant a future multiple-dose study to further evaluate the significance of this finding.

Adult↗
PubMedDate not supplied

Chlorpropamide-alcohol flushing in non insulin-dependent diabetes: prevalence of small and large vessel disease and or risk factors for angiopathy.

One hundred and eight non insulin-dependent diabetics were tested for alcohol flushing after chlorpropamide administration (CPAF test). The overall prevalence of patients who flushed at the first challenge was 32%. However, nearly half of them still flushed after alcohol administration, when placebo was given instead of chlorpropamide, so that the prevalence of 'true' flushers was only 17%. Even though the distribution of retinal lesions was similar in 'true' flushers and in non flushers, severe loss of visual acuity was confined to the non flushers and aspecific flushers. The frequency of pathological ECG findings and of peripheral pulse reduction or abolition was significantly higher in the non flushers and aspecific flushers. Blood pressure, serum lipids and hemostatic parameters were similar in the two groups, and therefore do not explain the differences in prevalence of lesions. This study confirms the previous findings of a lower prevalence of large vessel lesions in flushers; however, the prevalence of 'true' CPAF phenomenon in our out-patient population appears to be much lower than previously reported.

Adult↗
PubMedDate not supplied

Favorable effects of glibenclamide in a patient exhibiting idiosyncratic hepatotoxic reactions to both chlorpropamide and tolbutamide.

A middle-aged diabetic woman after four weeks of chlorpropamide treatment developed cholestatic hepatitis with systemic manifestations of idiosyncratic reaction. After recovery, unintended rechallenge with the same drug induced a brisk exacerbation of the symptoms and signs that reversed completely following chlorpropamide withdrawal. Tolbutamide medication was subsequently well tolerated for several weeks, followed by another flare of cholestatic liver lesion and cutaneous eruption with eosinophilia (after each reaction the patient was treated with insulin). Eventually glibenclamide (glyburide) was instituted resulting in very satisfactory control of diabetes, with no untoward reaction.

Adult↗
PubMed1990

The relationship between debrisoquine oxidation phenotype and the pharmacokinetics of chlorpropamide.

The pharmacokinetics and urinary metabolite pattern of a single oral dose of chlorpropamide 250 mg have been studied in 6 extensive and 5 poor metabolizers of debrisoquine. Ammonium chloride was given orally to acidify the urine in order to make elimination of the parent drug dependent on metabolism alone. The concentration profile in serum and the pharmacokinetic parameters of the parent drug were similar in both groups. However, the ratio in urine of unchanged chlorpropamide to its hydroxylated metabolites was higher in poor than in extensive metabolizers.

Adult↗
PubMed1990

Studies on induction of delta-aminolevulinic acid synthase, ferrochelatase, cytochrome P-450 and cyclic AMP by phenformin. Chlorpropamide, allylisopropylacetamide and lead in hepatocytes from normal and experimental diabetic rats.

The present work demonstrates that phenformin exerted an inducing effect on delta-aminolevulinic acid synthase (ALA-S) and ferrochelatase activities and on cytochrome P-450 content in isolated hepatocytes from rats with experimental diabetes. Similar results were obtained with respect to ALA-S activity and cytochrome P-450 content when chlorpropamide was used. The inducing effect exerted by allylisopropylacetamide (AIA) on ALA-S and ferrochelatase activities in diabetic hepatic cells was markedly greater than that observed in normal hepatocytes. This stimulatory response was not enhanced by adding dibutyryl cyclic AMP (cAMP). When phenformin was added to isolated rat hepatocytes of normal rats, induction of ALA-S and ferrochelatase activities and cytochrome P-450 content was observed only in the presence of added dibutyryl cAMP. Addition of chlorpropamide to this in vitro system did not exert an inducing effect on the same enzymes even in the presence of dibutyryl cAMP. The present results add more experimental evidence about the lability of the heme pathway of diabetic hepatocytes.

5-Aminolevulinate Synthetase↗
PubMed2006

Effect of pressure up to 5.5GPa on dry powder samples of chlorpropamide form-A.

The effect of pressure up to 5.5GPa on a dry powder sample of chlorpropamide (4-chloro-N-((propylamino)-carbonyl)-benzenesulfonamide), form-A (sp. gr. P2(1)2(1)2(1), a=9.066A, b=5.218A, c=26.604A), was studied in situ in a Merrill-Bassett diamond anvil cell using high-resolution X-ray powder diffraction (a synchrotron radiation source at SNBL ESRF, Grenoble). No evidence of the polymorphic transformation of chlorpropamide form-A to form-C was observed. The A-C polymorphic transition on tabletting previously reported by is therefore likely to be due to local heating effects. Similarly, the phase transitions of form-A reported by to be induced by pressure applied to a sample in its saturated ethanol solution (at 0.9 and at 2.0GPa) would appear to be solvent-mediated. In the dry sample, a phase transition may be supposed to occur at pressures above 4GPa, but this requires further studies.

Chlorpropamide↗
PubMed1979

Chlorpropamide alcohol flushing and diabetic retinopathy.

"Mason-type" diabetics (mild diabetes which is dominantly inherited) are relatively free of retinopathy. Alcohol almost invariably causes facial flushing in these patients when they are given chlorpropamide (chlorpropamide alcohol flush, C.P.A.F.). 291 non-insulin-dependent diabetics were examined to see whether there was a difference in frequency of retinopathy between C.P.A.F. positive and negative cases who were of comparable age and duration of diabetes. Retinopathy was commoner and often severe in CPAF negative patients. Blindness from retinopathy was almost confined to C.P.A.F.-negative cases. Lens opacities, on the other hand, were equally common in both groups. Since C.P.A.F. is an inherited trait, retinopathy in non-insulin-dependent diabetics is to a considerable extent, although not entirely, determined by genetic factors.

Cataract↗
PubMed1984

[Facial vasomotor flushing due to alcohol-chlorpropamide. Prevalence in diabetic and non-diabetic patients].

Using a standard test (sherry 40 ml 12 hours and 36 hours after 250 mg chlorpropamide), chlorpropamide-alcohol flush (CPAF) prevalence was 34 p. 100 (19/56) in non insulin-dependent diabetics (NIDD), 10 p. 100 (3/30) in insulin-dependent diabetics and 7 p. 100 (2/27) in controls. Family history of diabetes was not associated with CPAF trait. Conflicting results in the literature might be explained by bias in patients selection or methodology.

Adult↗
PubMed1992

N1-hydroxylated derivatives of chlorpropamide and its analogs as inhibitors of aldehyde dehydrogenase in vivo.

Certain (arylsulfonyl)urea hypoglycemic drugs exemplified by chlorpropamide (CP) are known to interact pharmacologically with alcohol (ethanol) to elicit a chlorpropamide-alcohol flushing (CPAF) reaction that is reminiscent of the disulfiram-ethanol reaction (DER). In the present structure-activity study, designed to elucidate the mechanism of inhibition of aldehyde dehydrogenase (AlDH) by CP, we discovered that the N1-methoxy derivative of CP 2a was a potent inhibitor of AlDH in vivo similar in activity to that of the N1-ethyl derivative 2b. Both 2a and 2b can release n-propyl isocyanate, a known inhibitor of AlDH, nonenzymatically. However, (arylsulfonyl)carbamates that are structurally analogous to 2a were also active inhibitors of AlDH, whereas the corresponding (arylsulfonyl)carbamate analogs of 2b were uniformly without activity. We propose a mechanism of bioactivation of 2a and its analogs that involves initial O-demethylation followed by disproportionation and solvolysis of the intermediate formed to release nitroxyl, the putative inhibitor of AlDH.

Aldehyde Dehydrogenase↗
PubMed1993

The qualitative and quantitative analysis of chlorpropamide polymorphic mixtures by near-infrared Fourier transform Raman spectroscopy.

We analyzed binary mixtures of polymorphs A and B of chlorpropamide ((1-[4-chlorobenzenesulphonyl]-3-propyl urea)) by near-infrared Fourier transform Raman spectroscopy (FTRS). The individual polymorphs were prepared and characterized by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) microscopy, and physical appearance. The FTR spectra of the two polymorphs showed distinct differences which result from "crystal splitting" effects. A series of 13 different mixtures of polymorph A and B was prepared by geometric mixing and their FTR spectra statistically analysed by factor analysis programming. Predictions of the A/B polymorphic composition of mixtures were made and compared with the theoretical values. The results demonstrate that FTRS combined with factor analysis programming may be successfully applied to the in situ monitoring of the A/B polymorphic nature of a chlorpropamide sample.

Calorimetry, Differential Scanning↗
PubMed1987

Effect of short- and long-term chlorpropamide therapy on oral glucose tolerance and erythrocyte insulin receptors in non-obese non-insulin dependent diabetes mellitus.

Erythrocyte (RBC) insulin receptors and the insulin response to glucose load (oGTT) were evaluated in ten male, non-obese, non-insulin dependent diabetic patients (NIDDM) before and after 14 and 90 days of 250 mg/day of chlorpropamide administration. In addition, as a control group, twelve healthy non-obese subjects were studied. Diabetic patients with fasting plasma glucose level higher than 14 mmol/l (group A), presented a significant improvement in the incremental glucose area only after 90 days of therapy. There was an evident reduction in insulin secretion, in comparison to normals, which however increased progressively during drug administration. No alterations in insulin binding to RBC receptors were observed either before or after the use of chlorpropamide, but the normalization of the initially low number of receptors per cell (N) and an increased high affinity constant (Ke) were achieved. In group B with fasting glucose less than 14 mmol/l there was a significant reduction in plasma glucose levels during oGTT without changes in glucose areas and a significant improvement of the insulin secretion was noted only in the early samples. Except for transient alterations in N and Ke no significant changes were observed in insulin-RBC binding parameters. We conclude that the improvement in the glucose tolerance in NIDDM is associated both to a greater insulin secretion and to the correction of the alterations in receptor parameters which could be related, at least partially, to proportionate changes in reticulocyte count.

Administration, Oral↗