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At least 973 records · Page 54Linked to original sources
PubMed1984

Alterations of plasma opioid activity in human diabetics.

Plasma opioid levels were determined in 9 obese non-diabetic subjects, their 8 age matched controls, and in 29 diabetic patients; 10 maintained on diet alone, 6 on an oral hypoglycemic agent (chlorpropamide) and 13 treated with insulin. Five age matched controls for the diabetic groups were also studied for comparison. beta-endorphin and met-enkephalin levels were measured by radioimmunoassay. Enkephalin-like activity was measured by a receptor assay. Among the study groups, diabetic patients receiving insulin showed a 64% elevation of plasma beta-endorphins and diabetic patients on chlorpropamide showed a 121% increase in enkephalin-like activity. There were no statistically significant differences in the plasma met-enkephalin values in the treatment groups though levels were decreased (p less than 0.05) in diabetics vs non-diabetics. The pathophysiological importance of these alterations remains to be elucidated.

Chlorpropamide↗
PubMed1982

Glycosylated hemoglobin and its temporal relationship to plasma glucose in non-insulin dependent (type 2) diabetes mellitus.

Total glycosylated hemoglobin (HbAI) and random plasma glucose were measured at monthly intervals for 6 mo in 33 non-insulin dependent (type 2) diabetics. The mean HbAI and mean plasma glucose in individual patients over the 6 mo showed a close correlation (p less than 0.001). A significantly higher HbAI (p less than 0.001) for a given plasma glucose was seen in those patients receiving combined chlorpropamide and metformin therapy (n = 14) than in those receiving chlorpropamide alone (n = 19). For each patient correlation coefficients were calculated between plasma glucose and HbAI with time lags of 0.1 and 2 mo. The coefficients with no time lag showed a significant tendency to be positive (p less than 0.01) whereas those with time lags of 1 or 2 mo were not significant. A constant proportional variability of both HbAI and plasma glucose over time was demonstrated, the mean coefficient of variation for HbAI being 8.4 +/- 2.7% and for plasma glucose 22.3 +/- 9.7%. We conclude that HbAI provides an index of plasma glucose control, not during the preceding few months as was previously thought but, during the previous few weeks. In terms of variability from month to month a single HbAI determination was equivalent to approximately the mean of 3 single plasma glucose values.

Blood Glucose↗
PubMed1991

Hypoglycemia associated hospitalizations in a population with a high prevalence of non-insulin-dependent diabetes mellitus.

In order to evaluate the rates, causes, and clinical features of hospitalizations associated with hypoglycemia in a population with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM), a retrospective analysis of medical records was conducted in a multi-hospital primary care system on the Navajo Indian Reservation. During an estimated 26,125 person-years of observation among diabetic patients, there were 126 hypoglycemia-associated admissions related to diabetes among 109 diabetic patients, yielding a hospitalization rate of 4.7 per 1000 person-years (95% CI 4.1-5.7). Using estimates of drug utilization based on a defined daily dose, hospitalization rates were 5.8 per 1000 PY (95% CI 4.4-7.6) for chlorpropamide, 16.0 per 1000 PY (95% CI 9.5-26.9) for glyburide, and 9.1 per 1000 PY (95% CI 6.9-11.9) for insulin. After stratification by age, the relative risk for hypoglycemia-associated hospitalization among patients prescribed glyburide compared to those prescribed chlorpropamide was 2.8 (95% CI 1.6-4.9). Hypoglycemia-associated hospitalizations were relatively common among patients with NIDDM, particularly among those treated with glyburide.

Arizona↗
PubMedDate not supplied

Structure vs. activity in the sulfonylurea-mediated disulfiram-ethanol reaction.

The oral hypoglycemic agents, chlorpropamide (CP) and tolbutamide (TB) are known to elicit a clinical disulfiram-ethanol reaction (DER) when consumed with alcohol. In rats, this DER is manifested in vivo by the elevation of blood acetaldehyde (AcH) levels, a consequence of the inhibition of hepatic aldehyde dehydrogenase (AIDH). Administration of CP or TB to rats (1.0 mmol/kg, IP), followed by ethanol one hour before sacrifice, raised blood AcH levels 12- and 2-times that of control animals, respectively for CP and TB when measured at 3 hours, and 20-fold and 8-fold at 16 hours post drug administration. CP and TB had no effect on AIDH activity when incubated with either intact or osmotically disrupted rat liver mitochondria, indicating that a metabolite of CP or TB is responsible for the inhibition of AIDH in vivo. Hydrolysis products of CP, the 2'-hydroxylated products of CP, tolpropamide and tolethamide, or the 3'-hydroxylated analogs of CP and tolpropamide, were uniformly inactive in elevating ethanol-derived blood AcH. Pretreatment of rats with 3-amino-1,2,4-triazole or SKF-525A had no effect on the elevation of blood AcH mediated by CP or TB, while phenobarbital pretreatment decreased blood AcH by 69%. Although our results clearly indicated that side chain hydroxylation and subsequent oxidation do not play a role in AIDH inhibition by CP or TB, the nature of the side chain attached to the sulfonylurea moiety appears to influence this inhibitory activity in vivo. Thus, the order of activity in the homologous series was, chlorpropamide greater than chlorbutamide greater than chlorethamide much greater than chlormethamide, chlorisopropamide = 0.

Aldehyde Dehydrogenase↗
PubMed2005

Quantitative determination of polymorphic composition in intact compacts by parallel-beam X-ray powder diffractometry II. Data correction for analysis of phase transformations as a function of pressure.

An analytical, non-destructive method using parallel-beam transmission powder X-ray diffractometry (PXRD) is presented for in situ whole compact detection and quantification of solid-state phase transformations in powder compacts. Accurate quantification of analyte in intact compacts using PXRD requires a mathematical correction prior to interpolation of calibration data to account for sample differences that result as a function of pressure; namely, compact thickness and solid fraction. Chlorpropamide is examined as a model system, selected because of its susceptibility to polymorphic transformations when consolidated using moderately low pressures. The results indicate that quantification of the transformed phase of chlorpropamide without corrections for solid fraction and thickness, underestimates the extent of transformation by 2.4%. Although the magnitude of the correction for this particular system of polymorphs is small, more significant values are expected for other compounds, particularly those with sufficient compactibility to allow the formation of low solid fraction calibration samples.

Chlorpropamide↗
PubMed1985

Once-daily use of glyburide.

Ideally, metabolic control with sulfonylureas should be maintained for 24 hours. To determine an optimal glyburide dosage schedule, the effects of glyburide once (every morning) or twice daily and chlorpropamide once daily (every morning) were compared in 18 men with non-insulin-dependent diabetes mellitus in a randomized, double-blind fashion. After discontinuation of previous hypoglycemic agents for 10 days, patients were admitted to a metabolic ward for two weeks (Study A). Glycemic measurements were performed on Day 14. Subjects were readmitted after 12 weeks of outpatient therapy for another two weeks (Study B), and glycemic determinations were repeated. Weight was kept constant during and between Studies A and B. Effective hypoglycemic action of each drug regimen was demonstrated. When six glycemic parameters were compared, there was no significant difference between groups. Thus, over a 14-week period, both glyburide regimens were similar and as effective as chlorpropamide once daily.

Blood Glucose↗
PubMed2000

Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1.

The interactions of sulfonylureas and a novel anti-diabetic drug, nateglinide, with rat renal organic anion transporter (rOAT1) expressed in Xenopus laevis oocytes were studied. Uptake of p-aminohippurate via rOAT1 was markedly inhibited by glibenclamide and nateglinide, and moderately by chlorpropamide and tolbutamide. The inhibition constant values (K(i)) for chlorpropamide, glibenclamide, tolbutamide and nateglinide were 39.5, 1.6, 55.5 and 9.2 microM, respectively. Kinetic analysis showed that the inhibition of p-aminohippurate uptake by glibenclamide was competitive. Sulfonylureas examined and nateglinide did not show a trans-stimulation effect on [14C]p-aminohippurate efflux from rOAT1-expressing oocytes. There was no stimulation of [3H]glibenclamide uptake via rOAT1. These findings suggested that sulfonylureas and nateglinide interact with rOAT1, but these drugs are not translocated via the transporter.

Animals↗
PubMed1979

Sensitivity to enkephalin as a cause of non-insulin dependent diabetes.

Non-insulin-dependent diabetes is associated with facial flushing after alcohol in patients on chlorpropamide (chlorpropamide alcohol flushing, C.P.A.F.) especially when there is a family history of diabetes. C.P.A.F. in three subjects (two diabetics, one non-diabetic) was blocked by the specific opiate antagonist naloxone. In nine subjects (six diabetics) C.P.A.F. was reproduced by the enkephalin analogue with opiate-like activity [D-Ala2, MePhe4, Met (O)-ol] enkephalin (DAMME). C.P.A.F. thus may be due to increased sensitivity to endogenous opiates. DAMME and other substances with opiate-like activity, such as morphine and beta-endorphin, affect carbohydrate metabolism and insulin secretion. Increased sensitivity to endogenous opiates such as enkephalin may thus give rise to non-insulin-dependent diabetes associated with C.P.A.F.

Alcoholic Beverages↗
PubMed2002

Quantitative determination of polymorphic composition in intact compacts by parallel-beam X-ray powder diffractometry.

This paper details the development of a method using parallel-beam X-ray powder diffractometry as a novel means of determining polymorphic composition in intact compacts. Two polymorphic systems, chlorpropamide and glycine, were selected. The polymorphic components were weighed, mixed, and compressed using a Carver press with 3/8-in. concave tooling. The compacts were then analyzed using parallel-beam X-ray powder diffractometry in transmission geometry. The data were processed using the profile-fitting module in the Shimadzu XRD-6000 software V 4.1 (for NT 4.0/98). The integrated intensity ratio of a selected peak for each crystal form was used for quantitation of each polymorph. Excellent linear correlation was observed for both polymorphic systems. The convex shape of the compact surface had no effect on the XRD patterns. Since parallel-beam X-ray diffractometry is not sensitive to the shape of the sample surface, it provides a simple method for quantifying polymorphs in intact compacts. Further work to extend this to formulated tablets is ongoing. The relatively larger variation in one of the peaks in the chlorpropamide study was found to be consistent with the computational analysis of the slip behavior of the stable polymorph. This method provides the first reported non-invasive X-ray diffraction pattern quantitation of crystal forms in intact compacts.

Chemistry, Pharmaceutical↗
PubMed1984

Sulfonylureas enhance in vivo the effectiveness of insulin in type 1 (insulin dependent) diabetes mellitus.

Indirect evidence suggests that sulfonylureas, in addition to stimulating insulin release, exert additional effects at extrapancreatic levels which are of value in the management of type 2 diabetes. In order to characterize in vivo some of these effects, insulin sensitivity was studied in 9 type 1 diabetics with no residual insulin secretory activity, during treatment with chlorpropamide (250 mg b.i.d. for 8 days) and with glipizide (5 mg t.i.d. for 8 days). Employing the glucose clamp technique with the aid of an artificial pancreas (Biostator), glucose disposal during insulin infusion (0.1 U/kg in 60 min) was calculated by the amount of glucose required to keep the blood glucose at preinfusion levels. Chlorpropamide and glipizide administration was accompanied by a significant increase of the amount of glucose required to clamp blood glucose levels, while serum (free) insulin levels were superimposable during the different clamping studies. In the absence of endogenous insulin release, these data strongly suggest that the two sulfonylureas employed enhance in vivo the peripheral sensitivity to insulin. Further studies are required to indicate a preferential site of action (liver, muscle, adipose tissue) of sulfonylureas.

Adolescent↗
PubMed1983

Residual beta-cell function in type II diabetes and evaluation of the hepatic insulin extraction.

Insulin and C-peptide (free insulin and C-peptide in insulin-treated patients) were measured after glucose stimulation in nine Type II diabetics on chlorpropamide, eleven insulin-treated maturity-onset diabetics and in 8 normal controls. Dissociation between C-peptide and insulin response to glucose was observed in several diabetics. The relation between incremental molar areas under C-peptide and insulin curves, after glucose challenge (delta CPR - delta IRI/delta CPR) were used to evaluate the hepatic insulin extraction in all but the insulin-treated diabetics. The lower insulin requirements and better control of the short-duration insulin-treated maturity-onset diabetics in relation to the long-term ones could not be explained either by the residual insulin secretion or by the level of "insulin antibodies". The chlorpropamide-responsive patients presented higher insulin levels after the glucose challenge and a lower hepatic insulin extraction than the non-responsive ones.

Adult↗
PubMed2003

Hypoglycemic effect of Sclerocarya birrea [(A. Rich.) Hochst.] [Anacardiaceae] stem-bark aqueous extract in rats.

This study was undertaken to evaluate the hypoglycemic effect of Sclerocarya birrea [(A. Rich.) Hochst.] subspecies caffra (Sond.) Kokwaro [family: Anacardiaceae] stem-bark aqueous extract in normal (normoglycemic) and in streptozotocin (STZ)-treated, diabetic Wistar rats. In one set of experiments, graded doses of S. birrea stem-bark aqueous extract (SB, 100-800 mg/kg p.o.) were separately administered to groups of fasted normal and fasted diabetic rats. In another set of experiments, a single dose of the plant aqueous extract (SB, 800 mg/kg p.o.) was used. The hypoglycemic effect of this single dose (SB, 800 mg/kg p.o.) of S. birrea stem-bark aqueous extract was compared with that of chlorpropamide (250 mg/kg p.o.) in both fasted normal and fasted diabetic rats. Following acute treatment, relatively moderate to high doses of S. birrea stem-bark extract (SB, 100-800 mg/kg p.o.) produced dose-dependent, significant reductions (P < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. Chlorpropamide (250 mg/kg p.o.) also produced significant reductions (P < 0.05-0.001) in the blood glucose concentrations of the fasted normal and fasted diabetic rats. Administrations of the single dose of S. birrea stem-bark aqueous extract (SB, 800 mg/kg p.o.) significantly reduced (P 0.01 < 0.001) the blood glucose levels of both fasted normal (normoglycemic) and fasted STZ-treated, diabetic rats. The results of this experimental animal study indicate that aqueous extract of Sclerocarya birrea possesses hypoglycemic activity, and thus lend credence to the suggested folkloric use of the plant in the management and/or control of adult-onset, type-2 diabetes mellitus in some African communities.

Administration, Oral↗
PubMed1980

Tolazamide-induced cholestasis.

The sulfonylurea hypoglycemic agent tolazamide is thought to be a rare cause of jaundice and to exhibit no hepatic cross-sensitivity with other sulfonylurea compounds. We have described a patient who had self-limited cholestatic jaundice after treatment with chlorpropamide. Subsequent treatment with tolazamide resulted in recurrence of jaundice, which disappeared after cessation of treatment. Tolazamide may exhibit hepatic cross-sensitivity with chlorpropamide.

Chlorpropamide↗
PubMed1971

Effects of various drugs on insulin antibodies.

1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the serum was incubated with a known concentration of insulin for 90 min at 37 degrees C and the insulin not bound to antibody was estimated by the rat hemidiaphragm method.3. No significant (P>0.5) development of insulin antibody could be detected in the serum samples collected 1 month after the first and 15 days after the second monthly injections in groups of ten male guinea-pigs and six female guinea-pigs. However, the titre of insulin antibody in the serum of these groups of guinea-pigs 15 days after the third monthly injection of insulin antigen emulsion was significantly (P<0.01) raised. There was no further increase in the titre of insulin antibody in the sera 15 days after the fourth and fifth monthly injections of insulin antigen emulsion. Thus the peak titre was reached 15 days after the third monthly injection of the antigen.4. Two groups of ten male guinea-pigs each received testosterone propionate or diethylstilboestrol daily for 1 week after each monthly injection of insulin antigen emulsion. Two other groups of six female guinea-pigs each received testosterone propionate or diethylstilboestrol in a similar manner. One more group of ten female guinea-pigs received both sex hormones for 1 week after each monthly injection of insulin antigen emulsion. Testosterone facilitated the induction of insulin antibody in the serum of males but did not affect the antibody titre in the female guinea-pigs. Diethylstilboestrol facilitated the induction of insulin antibody in the serum of groups of either sex, the peak titre being attained after the second monthly injection of insulin antigen emulsion. The response of the females which received both sex hormones was similar to that of females which received diethylstilboestrol alone.5. Fifteen days after the third monthly injection of insulin antigen emulsion a group of ten guinea-pigs received hydrocortisone subcutaneously each day for 1 month. The serum antibody titre was estimated at the end of the drug treatment, and was significantly (P<0.01) reduced.6. Fifteen days after the third monthly injection of insulin antigen emulsion three different groups of five-six guinea-pigs each received tolbutamide, chlorpropamide or phenformin orally every day for a month. Antibody titres of the serum were estimated at the end of this period; there was no significant (P>0.05) reduction in groups receiving chlorpropamide or phenformin, but the serum antibody titre of the group receiving tolbutamide was significantly (P<0.01) raised.7. Fifteen days after the third monthly injection of insulin antigen emulsion different groups of five-six guinea-pigs received one of the following: 5-bromouracil, 5-fluorouracil, 6-mercaptopurine, methotrexate, 6-azauridine, busulphan, chlorambucil, cyclophosphamide, actinomycin-D or mytomycin-C intraperitoneally each day for 5 days. The serum antibody titre of all the groups of guinea-pigs was significantly (P<0.01) reduced. On the other hand the serum antibody titre of a control group of six guinea-pigs receiving normal saline intraperitoneally each day for 5 days was not significantly (P>0.5) affected.

Animals↗
PubMed1985

Beneficial effect of moderate weight loss in older patients with non-insulin-dependent diabetes mellitus poorly controlled with insulin.

Fifteen patients with non-insulin-dependent diabetes mellitus, poorly controlled on insulin, were enrolled in a weight loss program. Criteria included a fasting plasma glucose concentration greater than 200 mg/dl, age in excess of 65 years, and the presence of obesity. Twelve of the 15 patients were able to complete the program, and the average weight loss of the group was 9 kg. Prior to initiation of the weight loss program the 12 patients were receiving (mean +/- SEM) 52 +/- 5 units of insulin per day and had a mean (+/- SEM) fasting plasma glucose concentration of 258 +/- 10 mg/dl. Insulin treatment was discontinued in all subjects during the weight loss period, and did not need to be resumed when weight stabilization had occurred. On the other hand, reasonable diabetic control could not be maintained without medication, and all patients were started on chlorpropamide during the period of weight stabilization. With this approach, a mean (+/- SEM) fasting glucose concentration of 137 +/- 4 mg/dl was achieved with a daily chlorpropamide dose of 354 +/- 30 mg. This dramatic clinical change took place despite the fact that no patient achieved ideal body weight. These results document the ability of a moderate amount of weight loss to transform patients with non-insulin-dependent diabetes mellitus, who are overweight and older than 65 years of age, from treatment failures to treatment successes.

Aged↗
PubMed1996

Photohemolytic potency of oral antidiabetic drugs in vitro: effects of antioxidants and a nitrogen atmosphere.

The sulphonamide-derived oral antidiabetic drugs carbutamide, chlorpropamide, glibenclamide, glibornuride, gliclazide, glipizide, gliquidone, glisoxepide, glymidine, tolazamide and tolbutamide were investigated for photohemolytic properties in vitro. Irradiation with a SOL 3 apparatus (solar simulating irradiation) revealed hemolysis in the presence of chlorpropamide, glipizide, gliquidone, glymidine and tolbutamide (all in the concentration 10(-3) mol/l). Except for glymidine, which exerted photohemolysis in the concentration 10(-4) mol/l, no hemolytic effects were seen in the concentration of 10(-4) mol/l or 10(-5) mol/l. Irradiation with TL 12 light bulbs (UVB), a UVASUN 5000 apparatus (UVA) or an experimental lamp (visible light) did not induce phototoxic hemolysis with either of the test substances. Addition of the antioxidants ascorbic acid, alpha-tocopherol or superoxide dismutase significantly inhibited the phototoxic hemolysis. Investigations carried out in a nitrogen-rich atmosphere reduced the hemolysis as well. These findings indicate an involvement of reactive oxygen species in the mechanism of action of the hemolytic process in the presence of oral antidiabetic drugs.

Antioxidants↗
PubMed1980

Asthma induced by enkephalin.

A total of 291 diabetics were studied to see whether an asthmatic reaction was associated with facial flushing induced by chlorpropamide and alcohol. Of these patients, 191 reported facial flushing, of whom 12 reported breathlessness as well. Of these 12, five also described wheezing, and respiratory function tests showed them to have asthma. Three of these five patients underwent further tests, which showed that the asthmatic reaction could be prevented by giving disodium cromoglycate and the specific opiate antagonist naloxone. One patient developed wheezing when given an enkephalin analogue with opiate-like activity. Asthma induced by chlorpropamide and alcohol was concluded to be mediated by endogenous peptides with opiate-like activity such as enkephalin.

Asthma↗
PubMed1977

Drug interactions with oral sulphonylurea hypoglycaemic drugs.

The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

Allopurinol↗