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At least 199 records · Page 11Linked to original sources
PubMed1980

Blockade of chlorpropamide alcohol flush by aspirin.

The blocking effects of aspirin, chlorpheniramine, and cimetidine were tested against the flush provoked by alcohol in twenty-four chlorpropamide-treated patients with non-insulin-dependent diabetes mellitus. Active preparations were compared in a double-blind manner with an indistinguishable placebo. Aspirin significantly decreased the number of patients who flushed. Five patients studied in detail all showed suppression of chlorpropamide/alcohol flush by aspirin, with a mean facial temperature increase during the flush of 2.4 degrees C after pretreatment with placebo and an increase of 0.4 degrees C after pretreatment with aspirin.

Aspirin↗
PubMed1980

Reversible mild diabetes in children after treatment with chlorpropamide.

In 9 patients with juvenile-onset chemical diabetes treated with oral chlorpropamide, oral or intravenous assessments of carbohydrate tolerance were made regularly three weeks after withdrawal of therapy. 6 patients with sequential intravenous tests achieved statistically significant reversal of their carbohydrate intolerance and have remained normal for an average of 5.6 years (range 1-11 years). 2 patients who subsequently required insulin therapy were maintained in remission for 3.5 years and 5 years, respectively. There appears to be a group of young patients with chemical diabetes who achieve significant remission with sulphonylurea therapy.

Administration, Oral↗
PubMed1987

Chlorpropamide overdose in renal failure: management with charcoal hemoperfusion.

A potentially lethal chlorpropamide overdose in a patient with chronic renal failure on long-term hemodialysis was treated by two courses of charcoal hemoperfusion. Hemoperfusion shortened the half-life clearance of the drug from a mean value of 93.6 to 3.4 hours. Calculation of the fractional extraction indicated that hemoperfusion reduced the body burden of the drug by 24% and 19% (mean values) during the first and second hours of treatment, respectively. We conclude that charcoal hemoperfusion should be considered a definitive therapeutic option in such cases.

Adult↗
PubMed1998

Screening of chlorpropamide in horse plasma by high-performance liquid chromatography with ultraviolet absorbance detection, and confirmation by gas chromatography-mass spectrometry.

A chromatographic method was developed to detect and confirm the presence of chlorpropamide (I) in horse plasma samples, for antidoping control. The plasma sample (1 ml) was extracted with dichloromethane and screened by high-performance liquid chromatography, and confirmation of the drug's presence was accomplished by using gas chromatography-mass spectrometry (GC-MS). The limit of detection was found to be 3.5 ng/ml at a signal-to-noise ratio of three. Derivatization of I with N,O-bis-(trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane allowed for highly stable, accurate and sensitive GC-MS analysis. Plasma samples collected after the administration of diabinese were positive for I (one-five days) in all samples analysed.

Animals↗
PubMed1989

N1-alkyl-substituted derivatives of chlorpropamide as inhibitors of aldehyde dehydrogenase.

On the basis of an earlier observation that the N1-ethyl derivative of the hypoglycemic agent chlorpropamide (CP) inhibited aldehyde dehydrogenase (AlDH) in rats without producing hypoglycemia, we undertook a structure-activity study to assess the effect of altering the alkyl substituents at N1 and N3, as well as substituting O for N at the latter position, and evaluated these analogues for their effect on AlDH in vivo and in vitro. Our results suggest that only those CP analogues that can release alkyl isocyanates nonenzymatically inhibited AlDH. Increasing the steric bulk of the N1-alkyl substituent enhanced isocyanate formation and AlDH inhibition. CP analogues that lacked the NH group at N3 or were otherwise incapable of alkyl isocyanate release were inactive.

Acetaldehyde↗
PubMed1986

Effects of chlorpropamide on loop of Henle function and plasma renin.

We have suggested that inhibition of renin release by sodium chloride is related to increased absorptive solute transport in the loop of Henle. In the rat, we have shown that reduced chloride transport in the loop is associated with increased renin release. Based on indirect evidence, it has been suggested that chlorpropamide (CPMD) increases loop solute transport. This study directly evaluates the effect of CPMD on loop chloride transport and plasma renin activity (PRA) in the male Sprague-Dawley rat. Loop of Henle chloride reabsorption (measured by recollection micropuncture) and PRA were determined before and after acute infusion of CPMD (N = 8) or vehicle (N = 8). Although delivery to the loop was not significantly changed, CPMD increased (P less than 0.05) absolute loop chloride reabsorption from 1798 pEq/min +/- 200 SE to 2453 pEq/min +/- 206 SE. PRA was decreased (P less than 0.01) from 9.2 ng/ml/hr +/- 1.0 SE to 5.6 ng/ml/hr +/- 0.8 SE following CPMD infusion. Comparable vehicle infusion did not alter loop chloride reabsorption or PRA. Arterial pressure, and whole kidney and single nephron glomerular filtration rates were unchanged following infusion of CPMD or vehicle. These results demonstrate that an increase in loop chloride reabsorption is associated with a decrease in renin release. This observation is consistent with the hypothesis that renin release is inversely related to the magnitude of chloride transport in the thick ascending limb of the loop of Henle.

Animals↗
PubMed1991

Effect of chlorpropamide on water and urea transport in the inner medullary collecting duct.

The present in vitro microperfusion study examined whether chlorpropamide (CPM) has a direct effect on hydraulic conductivity (Lp x 10(-6) cm/atm.sec) and 14C-urea permeability (Pu x 10(-5) cm/sec) in the middle and distal inner medullary collecting duct (IMCD) obtained from acutely water-loaded Wistar rats and rats homozygous for diabetes insipidus (DI). CPM (10(-4) M) added to the bath fluid increased the Lp in the water-loaded Wistar rats from -0.05 +/- 0.13 to 6.25 +/- 0.74 (p less than 0.01) and in the DI rats from 0.05 +/- 0.01 to 5.95 +/- 0.84 (p less than 0.01), but had no effect when it was added to the perfusate. CPM stimulated Lp in a dose-dependent manner with the threshold effect at 10(-6) M. However, the addition of CPM (10(-4) M) to submaximal concentration of VP in the bath fluid did not increase the Lp. Furthermore, CPM was unable to block the inhibitory action of PGE2 on the vasopressin (VP)-stimulated Lp. On the contrary, PGE2 blocked the CPM-stimulated Lp. CPM (10(-4) M) in the peritubular fluid was able to cause a significant rise of the Pu from 13.5 +/- 0.8 to 17.3 +/- 1.0 reversibly, which represented 16% of maximum stimulated effect produced by 50 microU/ml of VP. Thus, pharmacological doses of CPM added to the peritubular side have a direct effect on terminal IMCD increasing water and urea permeability in the absence of VP, but this drug does not potentiate the VP-stimulated water transport in the IMCD. Our results were unable to confirm the hypothesis that CPM potentiates the VP-antidiuresis by the inhibition of PGE2 action in the rat IMCD.

Animals↗
PubMed2007

Kinetic analysis of chlorpropamide dissolution from solid dispersions.

Solid dispersions (SDs) of chlorpropamide were prepared by the solvent deposition technique using two grades of microcrystalline cellulose as carrier materials with different ratios of drug to carrier. The dissolution rate of chlorpropmide from the SDs was carried out at two physiological pH values of 1.1 and 7.25 simulating gastric and intestinal environments. The dissolution was dependent on the grade, the ratio of drug to carrier and pH. The higher dissolution was observed for more hydrophilic grade of the carrier as well as the higher ratio of carrier to drug. At the higher pH the drug dissolved much faster than the lower pH. X-ray diffraction showed some reduced drug crystallinity in SDs whereas infrared spectroscopy revealed no drug interactions with solvent and the carriers. The enhanced dissolution was attributed to the reduced drug crystallinity, decreased particle size, increased wettability and reduced aggregation of the hydrophobic drug particles. A novel model denoted as reciprocal powered time model with its theoretical justification was employed to analyze the dissolution data and proved to be superior to commonly used models for the analysis of the data. There was a quantitative relation between the model parameter and the ratio of carrier to drug which could be of value in dissolution rate prediction.

Chlorpropamide↗
PubMed2000

Inhibition of CFU-E/BFU-E by 3'-azido-3'-deoxythymidine, chlorpropamide, and protoporphirin IX zinc (II): a comparison between direct exposure of progenitor cells and long-term exposure of bone marrow cultures.

Erythropoiesis occurs in two stages: proliferation amplifies cell number, and differentiation stimulates the acquisition of the functional properties of red blood cells. The erythroid colony-forming unit (CFU-E) amplifies the differentiation process in response to erythropoietic stress in vitro, whereas the burst-forming unit (BFU-E), which is not particularly sensitive to erythropoietin stimulation, gives rise to the CFU-E and, when stimulated, produces morphologically-identifiable erythroid colonies. The aim of this work was to evaluate the toxic effects of the antiviral agent, 3'-azido-3'-deoxythymidine (AZT), the antidiabetic drug, chlorpropamide (CLP), and the heme-analogous compound, protophorphirin IX zinc (II) (ZnPP), on the proliferation of erythroblastic progenitors by using human umbilical-cord blood cells and murine progenitors from long-term bone marrow cultures. All these agents may interfere with the hemopoietic process, causing myelotoxicity as an adverse effect via different mechanisms. Our results showed selective toxicity of the three drugs on the erythroid progenitors (IC(50): AZT 0.35 +/- 0.13 microM, ZnPP 23.34 +/- 1.16 microM, CLP 1.07 +/- 0.27 mM), with respect to the myeloid progenitors (IC(50): AZT 0.8 microM, ZnPP 103.9 +/- 3.9 microM and CLP > 2800 microM). The IC(50) values were well correlated with peak plasma levels reached in vivo by the drugs. There was a marked similarity between the drug sensitivities of the human and murine progenitors but differences in toxicity exerted by the drugs on the basis of the time of exposure. Drug treatment of long-term cultures, followed by the clonogenic assay of progenitors collected from them in the absence of the drugs, generally resulted in a lower hematotoxicity.

Animals↗
PubMed1985

The 24-hour effects of glyburide and chlorpropamide after chronic treatment of type II diabetic patients.

A single-blind, randomized, comparative evaluation of glyburide (GL) and chlorpropamide (CP) therapy was performed in twenty previously untreated patients with non-insulin dependent diabetes mellitus (NIDDM) of about two years duration. Only newly diagnosed patients who were never treated and whose fasting blood glucose (FBS) levels were greater than 140 mg/dl after a six to eight week trial of dietary restriction were evaluated. Metabolic studies were performed before and after four months of therapy. GL and CP produced essentially the same effects on serum levels of glucose, insulin, glucagon (IRG), growth hormone (GH), cholesterol, and triglyceride. The mean 24-hour glucose levels for both the GL and CP groups were significantly lower than the pretherapy values (p less than 0.001). The mean 24-hour insulin levels did not change significantly during therapy (p greater than 0.05). Excellent control of plasma glucose was possible during the entire day without producing nocturnal hypoglycemia. Neither GL nor CP therapy influenced the mean 24-hour levels of IRG, GH, or cholesterol. However, mean 24-hour levels of triglyceride were lower in both groups. IRG levels were elevated and the pattern of change in the insulin and IRG levels paralleled each other, which suggested that glucagon may play a role in the resistance of insulin action in NIDDM. GH levels were normal and remained unchanged during therapy. It was concluded that detailed 24-hour studies are important for better understanding the spectrum of abnormalities in newly diagnosed patients with NIDDM who were never treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1978

Management of chlorpropamide-induced hypoglycemia with diazoxide.

Diazoxide, as demonstrated by the case we present, may be of substantial value in abolishing hypoglycemia and in preventing its recurrence. The mainstay of treatment for the patient with chlorpropamide toxicity is the constant close monitoring of clinical and laboratory parameters and the correction of hypoglycemia by administration of exogenous glucose when necessary. However, the need for exogenous glucose is reduced with the concomitant use of diazoxide. We therefore suggest that diazoxide should be considered as a part of the routine treatment of sulfonylurea-induced hypoglycemia.

Aged↗
PubMed1984

Characterization of patients with chlorpropamide-alcohol flush.

One hundred and sixty patients with onset of non-ketotic diabetes at the ages of 35-70 were investigated for chlorpropamide-alcohol flush (CPAF), beta-cell function, insulin sensitivity, human leucocyte antigens (HLA), organ specific antibodies and diabetic complications. A positive flush reaction was defined as an increase in facial skin temperature by at least 1.5 degrees C, which was associated with a visible flush reaction in all patients. In accordance with these criteria, 38% of the patients were considered CPAF-positive with a mean rise in facial skin temperature of 2.3 +/- 0.1 degrees C compared with 0.6 +/- 0.1 degrees C in the CPAF-negative patients (p less than 0.001). The CPAF-positive patients could be distinguished from the CPAF-negative with respect to: 1) higher frequency of first degree family history of diabetes (p less than 0.05), 2) lower basal and glucagon-stimulated C-peptide concentrations (p less than 0.02 and p less than 0.001), 3) increased frequency of HLA-A2 (p less than 0.01) and decreased frequency of HLA-B7 (p less than 0.01). The findings thus support the genetically determined nature of CPAF. Considering the criteria for maturity onset diabetes in the young, it is unlikely that CPAF acts as a genetic marker for this particular form of genetic diabetes.

Adult↗
PubMed1985

Facial skin temperature in chlorpropamide alcohol flush.

Objective methods to study the chlorpropamide alcohol flush (CPAF) have been inadequate. Determination of blood acetaldehyde has proved to be a promising method, but the analysis is difficult and time-consuming. To measure the facial skin temperature is more handy. The results of these measurements can be presented as delta T (skin temperature increase), %T (per cent of maximum possible temperature rise) or delta MTCI (malar thermal circulation index) after calculations. The baseline skin temperature is accounted for in %T and delta MTCI. Blood acetaldehyde determinations and placebo-alcohol tests can be used to separate the CPAF reaction from alcohol flushing. Single dose CPAF tests including facial skin temperature measurements were performed in 133 type 2 (non-insulin dependent) diabetics. Facial flush was observed in 42.9%. The specificity and sensitivity of all three skin temperature methods were high: 88.2, 85.5, 96.1%, and 89.5, 86.0, 86.0%, respectively. Skin temperature measurement, whether expressed as delta T, %T or delta MTCI, provides a method to study CPAF with high accuracy.

Adolescent↗
PubMed1981

Circulating prostanoid levels, both basal and during the chlorpropamide alcohol flush, in non-insulin dependent diabetes.

Circulating basal levels of prostanoids were measured in non-insulin dependent diabetics (NIDDs) who showed chlorpropamide alcohol flushing (CPAF), with and without diabetic complications, and in non-diabetic controls. Prostanoids were also measured during CPAF in those diabetics in whom CPAF is or is not blocked by indomethacin and also in CPAF-negative patients. There was no significant difference in circulating prostanoids between diabetics with and without severe vascular disease. The level of prostaglandin F, however, was significantly higher in the diabetic than in the non-diabetic subjects (mean +/- SEM PGFM 521 +/- 23 v. 414 +/- 18 pmol/l respectively P less than 0.01). In the group in whom CPAF could be blocked by indomethacin there was a significant rise in thromboxane during CPAF when compared with basal values (mean +/- SEM 905 +/- 48 v. 688 +/- 46 pmol/l respectively P less than 0.01) which was abolished by prior administration of indomethacin. There was no significant rise in prostacyclin or PGF. The group in which CPAF could not be blocked by indomethacin and the CPAF negative group showed no rise in any of the prostanoids measured. These findings support the concept of at least two different groups of CPAF positive NIDDs, one in which prostanoids are involved in CPAF and one in which they are not. It is the group in which prostanoids are involved in CPAF who seem to be highly protected against vascular disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Chlorpropamide-alcohol flushing is not useful for individual genetic counseling of diabetic patients.

The presence or absence of chlorpropamide-alcohol flushing (CPAF) was not correlated with the classification of diabetes. Five out of twelve patients with juvenile-onset diabetes (JOD) flushed and three out of four patients with maturity-onset diabetes in young people (MODY) did not flush. Consequently, CPAF cannot be used for individual genetic counseling in diabetes mellitus.

Adolescent↗
PubMed1988

A nonhypoglycemic chlorpropamide analog that inhibits aldehyde dehydrogenase.

Chlorpropamide (CP), a sulfonylurea-type oral hypoglycemic agent, is known to provoke a flushing reaction reminiscent of the disulfiram-ethanol reaction in certain individuals. This is manifested in rodents by an increase in blood acetaldehyde levels after ethanol administration. When the sulfonamide N1-nitrogen of CP was substituted with an ethyl group, the product, N1-ethylchlorpropamide, was found to be three times as active as CP in raising ethanol-derived blood acetaldehyde. However, whereas CP lowered fasting blood glucose in rats measured over 6 h, N1-ethylchlorpropamide was devoid of hypoglycemic activity, suggesting that the latter might be potentially useful as an alcohol deterrent agent.

Acetaldehyde↗
PubMed1989

Effects of the mechanical energy of multi-tableting compression on the polymorphic transformations of chlorpropamide.

The effects of the mechanical energy of tableting compression on the polymorphic transformation of chlorpropamide have been examined. A single-punch eccentric tableting machine with a load cell and a non-contact displacement transducer were used to measure compression stress, distance and energy. An amount of 100 mg of the stable form A or the meta-stable form C of the drug was loaded into the press and the sample compressed with a compression stress of 196 MPa at room temperature (20 degrees C). The compression cycle was repeated from 1 to 30 times. The powder X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The results on forms A and C suggested that both forms were transformed into each other in the solid state by mechanical energy during tableting. The contents of forms A and C reached equilibrium at a constant value above 100 J g-1 of compression energy after more than 10 cycles. After 30 tableting cycles of forms A and C, the contents of A, C and the non-crystalline solid were almost constant at about 45, 25 and 30%, respectively. The compression energies were estimated to be about 500-600 J g-1. From the results it seems that the transformation mechanism of forms A and C during tableting were as follows. The crystal form of A or C was converted to a non-crystalline solid by the mechanical energy, and the solid was then transformed into form A or C.

Chemical Phenomena↗