Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CHLORPROPAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1999

Antihyperglycaemic effect of Mangifera indica in rat.

The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats. In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity. This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded.

Animals↗
PubMed2005

Metformin monotherapy for type 2 diabetes mellitus.

BACKGROUND: Metformin is an anti-hyperglycaemic agent used for the treatment of type 2 diabetes mellitus. Type 2 diabetes may present long-term complications: micro- (retinopathy, nephropathy and neuropathy) and macrovascular (stroke, myocardial infarction and peripheral vascular disease). Two meta-analyses have been published before, although only secondary outcomes were assessed. OBJECTIVES: To assess the effects of metformin monotherapy on mortality, morbidity, quality of life, glycaemic control, body weight, lipid levels, blood pressure, insulinaemia, and albuminuria in patients with type 2 diabetes mellitus. SEARCH STRATEGY: Studies were obtained from computerised searches of multiple electronic databases and hand searches of reference lists of relevant trials identified. Date of last search: September 2003. SELECTION CRITERIA: Trials fulfilling the following inclusion criteria: Diabetes mellitus type 2, metformin versus any other oral intervention, assessment of relevant clinical outcome measures, use of random allocation. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data, using a standard data extraction form. Data were summarised under a random effects model. Dichotomous data were expressed as relative risk. We calculated the risk difference (RD), and the Number Needed to Treat, when it was possible. We collected data of mean and standard deviation from changes to baseline. However many trials reported end point data. This limitation lead to the expression of the results as standardised mean differences (SMD) and an overall SMD was calculated. Heterogeneity was tested for using the Z score and the I-squared statistic. Subgroup, sensitivity analysis and meta-regression were used to explore heterogeneity. MAIN RESULTS: We included for analysis 29 trials with 37 arms (5259 participants), comparing metformin (37 arms and 2007 participants) with sulphonylureas (13 and 1167), placebo (12 and 702), diet (three and 493), thiazolidinediones (three and 132), insulin (two and 439), meglitinides (two and 208), and glucosidase inhibitors (two and 111). Nine studies reported data on primary outcomes. Obese patients allocated to intensive blood glucose control with metformin showed a greater benefit than chlorpropamide, glibenclamide, or insulin for any diabetes-related outcomes (P = 0.009), and for all-cause mortality (P = 0.03). Obese participants assigned to intensive blood glucose control with metformin showed a greater benefit than overweight patients on conventional treatment for any diabetes-related outcomes (P = 0.004), diabetes-related death (P = 0.03), all-cause mortality (P = 0.01), and myocardial infarction (P = 0.02). Patients assigned to metformin monotherapy showed a significant benefit for glycaemia control, weight, dyslipidaemia, and diastolic blood pressure. Metformin presents a strong benefit for HbA1c when compared with placebo and diet; and a moderated benefit for: glycaemia control, LDL cholesterol, and BMI or weight when compared with sulphonylureas. AUTHORS' CONCLUSIONS: Metformin may be the first therapeutic option in the diabetes mellitus type 2 with overweight or obesity, as it may prevent some vascular complications, and mortality. Metformin produces beneficial changes in glycaemia control, and moderated in weight, lipids, insulinaemia and diastolic blood pressure. Sulphonylureas, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, insulin, and diet fail to show more benefit for glycaemia control, body weight, or lipids, than metformin.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

All-cause mortality in diabetic patients treated with combinations of sulfonylureas and biguanides.

BACKGROUND AND AIMS: Increased mortality in diabetic patients treated with combinations of high doses of sulfonylureas and metformin was recently reported. This study was aimed at the assessment of mortality in patients treated with low-dose combinations of sulfonylureas and biguanides. METHODS: An observational cohort study was performed on a consecutive series of 927 outpatients with type 2 diabetes mellitus. Of these patients, 376 were treated with combinations of sulfonylureas (mean daily dose +/- SD: 7.3 +/- 3.2 mg for glibenclamide, and 338 +/- 79 mg for chlorpropamide) and biguanides (daily dose: 1.1 +/- 0.3 g for metformin, 60.1 +/- 19.6 mg for phenformin). Mortality was assessed through a search in the City of Florence Registry Office, with an average follow-up of 55.1 months. RESULTS: After adjusting for other potential confounders (including age, duration of diabetes, BMI, hypertension, lipid profile, HbA1c, and insulin treatment), mortality was significantly higher in patients treated with combinations of sulfonylureas and biguanides than in the rest of the sample, (relative risk, RR: 2.08; 95% confidence interval, CI 1.18-3.67, and RR: 1.68; 95%CI 1.01-2.79 among women and men, respectively). CONCLUSIONS: A higher mortality was observed in patients treated with combinations of sulfonylureas and biguanides, even at low doses. Safety of such combinations deserves further investigation.

Aged↗
PubMed2005

Comparison of statistical analysis and Bayesian Networks in the evaluation of dissolution performance of BCS Class II model drugs.

This project compared the effect of formulation variables on the dissolution performance of model Biopharmaceutics Classification System (BCS) Class II drugs from hard gelatin capsules using statistical analysis and Bayesian networks. The drugs chosen for this study were carbamazepine (CAR), chlorpropamide (CHL), diazepam (DIA), ketoprofen (KET), and naproxen (NAP). Formulations contained anhydrous lactose, microcrystalline cellulose, sodium stearyl fumerate, sodium lauryl sulfate, and croscarmellose sodium. A Box-Behnken experimental design was used in the statistical analysis. The weakly acidic drugs were tested using USP apparatus II with capsule sinkers in 0.1M pH 6.8 Potassium Phosphate buffer. The weakly basic drugs were tested using USP apparatus I in 0.1N HCl buffer. Mean dissolution profiles were compared via calculation of the similarity factor. The Box-Behnken experimental design was found to be useful in assessing primary and secondary excipient effects on dissolution. The Bayesian Network developed for the dataset mirrored the key excipient effects on dissolution performance.

Bayes Theorem↗
PubMed1984

Adsorption of sulfonylureas onto activated charcoal in vitro.

Adsorption of carbutamide, chlorpropamide, tolazamide, tolbutamide, glibenclamide (glyburide), and glipizide onto activated charcoal was compared in vitro using different charcoal-to-drug ratios. Maximal binding capacities of different sulfonylureas were 0.45-0.52 g/g of charcoal at pH 7.5. The affinity of the second generation derivatives, glibenclamide and glipizide, was considerably higher than that of the first generation derivatives. The affinity of sulfonylureas to charcoal was higher at pH 4.9 than at pH 7.5. Poor water solubility of sulfonylureas at pH 1 prevents the adequate testing in these conditions. Contrary to what has appeared previously, activated charcoal effectively adsorbs different sulfonylureas and can be used to possibly prevent their gastrointestinal absorption.

Adsorption↗
PubMed1989

Simultaneous determinations of tolbutamide and its hydroxy and carboxy metabolites in serum and urine: application to pharmacokinetic studies of tolbutamide in the rat.

Methods of analysis of tolbutamide (1) and its hydroxylated (2) and carboxylated (3) metabolites in serum and urine based on high-performance liquid chromatography were developed. The separation was performed on a Apex ODS column in the isocratic mode using a mobile phase composed of 22.5% acetonitrile, 77.5% Sorensen phosphate buffer (pH 7.0), and 0.30 mL of tetrabutylammonium phosphate reagent (Pic A). The compounds were detected at 254 mm. The retention times of 3, 2, 1, and the internal standard chlorpropamide were 3.1, 4.1, 14.8, and 10.0 min, respectively. These conditions were suitable for the simultaneous quantitation of 1, 2, and 3 in serum or plasma samples, but not for the determination of metabolites 2 and 3 in urine. For the analysis of 2 and 3 in urine, the mobile phase was modified to 18% acetonitrile, 82% Sorensen phosphate buffer (pH 7.0), and 0.35 mL of Pic A. Under these conditions, the retention times of the carboxy and hydroxylated metabolites and the internal standard salicylic acid were 4.6, 6.7, and 8.1 min, respectively. These methods were applied to study the pharmacokinetics of 1 administered intravenously and intraperitoneally to the rat. Tolbutamide was almost completely recovered as metabolites 2 and 3 in the urine within 24 h.

Animals↗
PubMed2004

Analgesic, antiinflammatory and antidiabetic properties of Harpagophytum procumbens DC (Pedaliaceae) secondary root aqueous extract.

South Africa is blessed with a rich floral biodiversity of medicinally useful plants. One such plant is Harpagophytum procumbens DC (Family: Pedaliaceae). H. procumbens is widely used in South African traditional medicine for the treatment, management and/or control of a variety of human ailments. In the present study, the analgesic effect of H. procumbens secondary root aqueous extract was evaluated in mice, using the 'hot-plate' and 'acetic acid' test methods; while the antiinflammatory and antidiabetic effects of the plant's secondary root extract were investigated in rats. Fresh egg albumin-induced pedal oedema and streptozotocin (STZ)-induced diabetes mellitus were used as experimental test models of inflammation and diabetes Diclofenac (DIC, 100 mg/kg i.p.) was used as a reference analgesic and antiinflammatory agent for comparison. Chlorpropamide (250 mg/kg p.o.) was used as a reference hypoglycaemic agent for comparison. H. procumbens root aqueous extract (HPE, 50-800 mg/kg i.p.) produced significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. H. procumbens root extract (HPE, 50-800 mg/kg i.p.) also produced dose-related, significant reductions (p < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw oedema. Furthermore, the plant extract (HPE, 50-800 mg/kg i.p.) produced dose-dependent, significant reductions (p < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. The results of this experimental animal study indicate that H. procumbens root aqueous extract possesses analgesic, antiinflammatory and hypoglycaemic properties, and lend pharmacological support to the suggested folklore uses of Harpagophytum procumbens root in the management and/or control of painful, arthritic and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.

Acetic Acid↗
PubMed2006

Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats.

The present study was undertaken to investigate the analgesic, antiinflammatory and hypoglycaemic effects of Zingiber officinale dried rhizomes ethanol extract (ZOE) in mice and rats. The analgesic effect of ZOE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while the antiinflammatory and hypoglycaemic effects of the plant extract were investigated in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. ZOE (50-800 mg/kg i.p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The plant extract (ZOE, 50-800 mg/kg p.o.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced acute inflammation, and caused dose-related, significant (p < 0.05-0.001) hypoglycaemia in normal (normoglycaemic) and diabetic rats. The findings of this experimental animal study indicate that Zingiber officinale rhizomes ethanol extract possesses analgesic, antiinflammatory and hypoglycaemic properties; and thus lend pharmacological support to folkloric, ethnomedical uses of ginger in the treatment and/or management of painful, arthritic inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural Africa communities.

Analgesics↗
PubMed2001

Studies on the hypoglycaemic activity of Punica granatum seed in streptozotocin induced diabetic rats.

The hypoglycaemic activity of Punica granatum Linn. (Family Punicaceae) seed extract on rats made diabetic by streptozotocin (STZ) was investigated. The methanol extract of the seed at doses of 300 and 600 mg/kg, and chlorpropamide 200 mg/kg was administered to STZ diabetic rats. The seed extract (150, 300 and 600 mg/kg, orally) caused a significant reduction of blood glucose levels in STZ induced diabetic rats by 47% and 52%, respectively, at the end of 12 h.

Administration, Oral↗
PubMed2001

Evaluation of the antidiabetic action of Mangifera indica in mice.

The leaves of Mangifera indica were assessed for antidiabetic properties using normoglycaemic, glucose-induced hyperglycaemia and streptozotocin (STZ) induced diabetic mice. The aqueous extract produced a reduction of blood glucose level in normoglycaemic and glucose-induced hyperglycaemia, but did not have any effect on streptozotocin-induced diabetic mice. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity.

Animals↗
PubMed1993

Effects of antidiabetic sulphonylureas, cromakalim and their interaction in guinea-pig isolated tracheal smooth muscle.

Glibenclamide, glipizide and glibornuride showed dual effects in guinea-pig isolated trachea. The drugs antagonized the relaxant response to the K+ channel opener cromakalim (order of effectiveness: glibenclamide > glipizide > glibornuride) and at concentrations of 1-1000 microM produced airway smooth muscle relaxation (order of potency: glibenclamide > glipizide = glibornuride). Gliclazide, tolbutamide and chlorpropamide did not antagonize cromakalim nor did the two latter drugs produce tracheal relaxation. The sulphonylureas and cromakalim were compared as airway relaxants against a panel of different spasmogens. The order of tissue responsiveness for the sulphonylureas was: spontaneous tone = LTD4 > PGF2 alpha = histamine = 30 mM K+ > carbachol and for cromakalim: spontaneous tone = LTD4 = PGF2 alpha = histamine > carbachol > 30 mM K+. Glibenclamide, but not cromakalim, relaxed contractions induced by 124 mM K+. Phentolamine and Ba2+, which are reported blockers of ATP-regulated K+ channels, failed to influence sulphonylurea-induced airway smooth muscle relaxation. Glibenclamide reversed tracheal relaxation produced by cromakalim, whereas cromakalim failed to reverse relaxation induced by glibenclamide. The mechanism for the additional property of sulphonylureas to relax airway smooth muscle is unclear, but the results do not support a role for involvement of cromakalim-sensitive K+ channels.

Animals↗
PubMed1978

A micromethod for the isolation of drugs from blood using amberlite XAD-2.

The extraction of drugs from small blood samples (1 ml or less) for subsequent quantitative determination is described. Isolation was carried out by adsorption of the drugs to Amberlite XAD-2 resin utilizing a batch procedure that enabled the simultaneous extraction of up to 200 samples in approx. 5 hours. A new desorption technique yielded extracts of high purity that could be used directly for gas chromatographic or radioimmunological determinations, even if hemolyzed or putrid blood was to be examined. The following 26 substances were quantitated after addition to postmortem blood speciments at concentrations of 1-10 microgram/ml: tilidine, diphenhydramine, dibenzepine, imipramine, chlorpromazine, amphetamine, pentazocine, phenacetin, methaqualone, meprobamate, parathion, diazepam, digoxin, beta-methyldigoxin, carbromal, glutethimide, amobarbital, pentobarbital, cyclobarbital, phenobarbital, diphenylhydantoin, carbutamide, tolbutamide, glycodiazin, tolazamide and chlorpropamide. Thereby recoveries of 60-100% could be achieved. The reproducibility of the procedure was satisfactory as demonstrated by coefficients of variation of 3.7-8%.

Humans↗
PubMed1996

Association of aldehyde dehydrogenase with inheritance of NIDDM.

To investigate the influence of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) genotype on the clinical features of diabetes, 212 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) (154 males and 58 females aged 17-83 years; mean age 58.2 years) were investigated. Genotyping of ALDH2 was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The pattern of inheritance of diabetes and various clinical parameters was compared between active and inactive ALDH2 groups. Of the 212 subjects, 120 had active ALDH2 and 92 had inactive ALDH2. The percentage of patients with a diabetic mother was higher in the inactive ALDH2 group (32.6%) than in the active ALDH2 group (19.2%) (p < 0.05). The prevalence of proliferative retinopathy was lower in the inactive ALDH2 group than in the active ALDH2 group (p < 0.05). However, other clinical parameters showed no difference. We conclude that maternal inheritance of diabetes was common in the inactive ALDH2 group. The finding is suggestive of a relationship between alcohol intolerance and inheritance of diabetes. We speculate that the interaction between mitochondrial DNA and ALDH2 inactivity causes an increase of mitochondrial DNA mutations or deletions, thereby inducing the maternal inheritance of diabetes. The relationship of the ALDH2 genotype with proliferative retinopathy is interesting, because it resembles that of chlorpropamide alcohol flushing with severe diabetic retinopathy. The interaction of aldehyde dehydrogenase isoenzymes might have an aetiological role, since aldehyde dehydrogenase 1 plays an important part in oxidation of retinal to retinoic acid. However, the number of affected patients with proliferative retinopathy was small, hence, our result should be considered as a preliminary finding.

Adolescent↗
PubMed1975

The measurement of drug consumption. Drugs for diabetes in Northern Ireland, Norway and Sweden.

The consumption of insulin and oral antidiabetic drugs was measured at the gross sales level in Sweden and Norway and at the prescription level in Northern Ireland. ""Agreed daily doses'' were used as units of comparison, which defined as follows: insulin 40 I.U., tolbutamide 1 g, acetohexamide 500 mg etc. Consumption was expressed as the number of ""agreed daily doses'' per 1,000 inhabitants per day. This provided a rough estimate of the number of subjects for whom the drug had been prescribed per 1,000 population. The data were collected during the three months April-June 1971. Marked differences in the consumption of antidiabetic drugs were found between the three countries and also between areas within each country. The consumption of insulin was similar in Norway and Northern Ireland (3.5 and 3.9 agreed daily doses per 1,000 inhabitants per day), but almost twice as high in Sweden. In Norway much lower use was found in certain rural areas. The variation in the consumption of oral antidiabetic drugs was even more marked. Surprisingly, consumption was considerably higher in Sweden (15.8) than in the nearby Norway (7.3), and was even lower in Northern Ireland (4.3). The major use was of sulphonylureas, especially chlorpropamide. Within the countries there was marked regional variation in the choice of individual biguanides and sulphonylureas. The data are discussed in relation to such factors as the incidence of diabetes, the sole use of dietary treatment etc. It is concluded that studies in depth, which link the actual use of drugs by patients to diagnosis, diabetic symptoms and clinical outcome of treatment are necessary in order to explore the reasons behind the marked geographical differences and to define a rational drug policy. However, the methods described in the study may be used for early detection of gross national differences in drug utilization, the further investigation of which may reveal to be of great public health interest.

Diabetes Mellitus↗
PubMed1985

[Histiocytosis X. Follow-up for over 20 years in a patient with Hand-Schüller-Christian disease].

Since 1963 we have observed a patient with Hand-Schüller-Christian disease with involvement of the skeleton, skin and hypophysis/hypothalamus with diabetes insipidus. The diabetes insipidus was successfully treated initially with chlorpropamid and later with carbamazepin. Alterations of the lung parenchyma were seen radiologically in 1966, and two years later the patient complained of exertional dyspnea. The lung disease was progressive with the deterioration of lung function despite corticosteroid and D-penicillamine treatment. The patient now has marked dyspnea even at rest. The osteolytic lesions have not changed in recent years.

Adult↗
PubMed1996

Granulomatous hepatitis associated with glyburide.

A wide variety of diseases and injuries can cause granulomatous hepatitis, and drug-induced granulomatous hepatitis is a well-described entity. Sulfonylurea derivatives, which are commonly used oral hypoglycemic agents in the treatment of non-insulin-dependent diabetes mellitus, have been implicated in liver disease. However, glyburide, a second-generation sulfonylurea and a potent hypoglycemic drug, is considered to have less hepatic side effects than chlorpropamide. It has been reportedly associated with cholestatic jaundice and hepatitis and with hypersensitivity angitis. A case of necrotizing granuloma has been reported. We present a second case of granulomatous hepatitis occurring in a patient who had been taking glyburide for approximately three years, and we review the literature for glyburide-associated hepatitis.

Chemical and Drug Induced Liver Injury↗
PubMedDate not supplied

Genetic and metabolic risk factors for the development of late complications in type I (insulin-dependent) diabetes.

The genetic background seems to be involved in the development of type I diabetes and it might also be involved in the development of diabetic complications, but studies carried out so far have yielded conflicting results. The aim of this study was to evaluate the influence of some genetic markers and metabolic factors in the development of late diabetic complications. One hundred and twenty-seven patients (69 males, 58 females) with type I diabetes were evaluated for ABO and Rh blood groups, chlorpropamide alcohol flush (CPAF) and acetylator phenotype (AP) as well as for life-habits (smoking, alcohol use, diet and drug compliance), metabolic indexes (M-value, HbA1, cholesterol and triglyceride levels) and late complications of diabetes [coronary heart disease (CHD), arterial hypertension (AH), retinopathy and nephropathy]. Diabetic patients were more frequently fast acetylators and CPAF positive than controls and CPAF was more frequent among females than among males. None of the genetic markers used in this study appeared as a risk factor for the development of diabetic complications. At multiple logistic analysis different risk factors appeared for each microangiopathic complication. For retinopathy: female sex, duration of disease and triglyceride levels; for nephropathy: male sex, cholesterol levels and hypertension. These risk factors have already been recognized in previous studies, while the genetic markers evaluated in our study do not identify a greater or smaller risk for the development of late complications.

Adult↗
PubMedDate not supplied

Are the 'second generation' oral hypoglycemic agents really different?

The common denominator of the numerous data collected from experimental studies on isolated organs, on healthy subjects and on diabetic patients, is a specific effect of sulfonylureas on insulin release in the presence (or absence) of glucose. However, there are significant differences in the capacity of the various chemical preparations active in that respect. There are biochemical data suggesting that the glyburide- and chlorpropamide-type of preparations are affecting sites of the B-cells that are different from both the glucose and the tolbutamide receptors. Thus, glibenclamide seems to be qualitatively different from the older sulfonylureas, being more a potentiator than a stimulator. Therefore, we called this type the representative of 'the second generation' drugs. The extra-B-cell actions of these drugs, predominantly the stimulation of somatostatin and the inhibition of glucagon, are favorably adding to these antidiabetic actions. In clinical therapy, these specific properties make it possible to diagnose and to treat patients successfully who were regarded before as being non-responsive to sulfonylureas and being insulin-dependent. On the basis of blood glucose decreases and C-peptide increases, a specific glibenclamide-glucose-response-test has been described which is a valuable medium for predicting the outcome of oral antidiabetic therapy.

Administration, Oral↗