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PubMed1989

Inadvertent sulfonylurea-induced hypoglycemia. A dangerous, but preventable condition.

Two patients with severe hypoglycemia due to inadvertent use of oral hypoglycemic agents are described. Unintentional substitution of tablets with sulfonylurea drugs was related in both cases to a similarity in shape and color of the pills. In one case glyburide was interchanged with an artificial sweetener, while in the other case chlorpropamide was dispensed by a pharmacist instead of quinidine bisulfate. To our knowledge, 20 similar cases have been reported in the medical literature. Most of them were attributed to sound-alike trade names of drugs. Inadvertent sulfonylurea-induced hypoglycemia has to be included in the differential diagnosis of severe unexplained hypoglycemia. This dangerous condition can be prevented by instructing patients to carefully identify their drugs, introducing typed prescription forms using generic names, and avoiding similar names and appearance of pills.

Aged↗

PubMed1988

Oral lichenoid drug reaction.

This is a case report of an oral lichenoid drug reaction of the buccal sulci in a female diabetic patient who was on an anti-hypertensive drug, alpha-methyldopa (Aldomet) and an oral hypoglycaemic drug, chlorpropamide (Diabinese). The clinical features, histological findings and management are presented.

Chlorpropamide↗

PubMed1987

Effect on rat embryos of in vitro culture in sera from human diabetic patients.

Recently conditions have been established whereby rat embryos can be cultured in vitro in human serum over the period of their major morphogenesis. By standardizing the amount of glucose in sera from diabetic subjects prior to culture, it has been possible to investigate factors other than hyperglycemia which might account for the increased incidence of congenital defects seen in infants of diabetic mothers. The incidence of abnormalities in rat embryos cultured in sera from chlorpropamide-treated diabetics was not significantly different from that using control sera from normal subjects. On the other hand, sera from insulin-dependent diabetics produced more defects in rat embryos than sera from either normal subjects or diabetics on oral agents. The incidence of abnormal rat embryos does not appear to be correlated with patient age, with the original blood glucose concentration or with the concentration of hemoglobin A1 or, in the insulin group, with the total daily insulin dosage.

Animals↗

PubMed1988

Evidence for a large and flexible region of human serum albumin possessing high affinity binding sites for salicylate, warfarin, and other ligands.

The relations between the single high affinity binding sites for azapropazone, phenylbutazone, chlorpropamide, sulfathiazole, and iophenoxate and the binding regions of human serum albumin represented by the marker ligands diazepam, phenol red, salicylate, and warfarin were examined by a series of competition experiments. Binding was determined by equilibrium dialysis at pH 7.0. In order to ensure an accurate analysis of the competition experiment, the number of moles of ligand bound per mole of protein was usually 0.4 or less to minimize ligand binding to weaker sites. Furthermore, binding of both ligands was determined in all experiments (except for iophenozate). None of the test ligands competed with diazepam for a common high affinity binding site, but, surprisingly, they were all able to displace two or three of the other marker ligands according to a competitive scheme. These findings show, first, the existence of a particular serum albumin region for high affinity binding of diazepam. Secondly, they imply that it is not necessary to assume the existence of new drug binding regions beyond those existing for phenol red, salicylate, and warfarin. On the contrary, the relatively many examples of competitive binding indicate that the binding regions represented by the last-mentioned three marker ligands are placed quite close to each other in the albumin molecule in a common region, which is suggested to be located at subdomains 1C and 2A-B. The region must be relatively large, because in some cases independent high affinity binding of pairs of ligands is observed. It is probably also rather flexible, inasmuch as no clear relation could be found between the chemical structure of the test ligands and the two or three marker ligands with which they compete. Correlations between primary association constants and partition coefficients for both marker ligands and test ligands, in the unionized forms, between n-hexane or 1-octanol and aqueous media showed that hydrophobic forces are important for the binding processes. However, the data also showed that other attractive forces must be operative as well.

Apazone↗

PubMed1979

[Hypernatremia and adipsia (author's transl)].

We have studied an infant (female) with a persisting hypernatremia and adipsia, examined for the first time at the age of five months. The funtional test carried out showed an insensibility of the osmoreceptors for very important changes in POsm. carryng with them a lack of response of the ADH. Neuroradiological studies demostrated hydrocephalia secondary to a stenosis of the aqueduct of Silvio. Treatment with chlorpropamide proved effective. The literature is being revised comparing out results with those of other authors.

Chlorpropamide↗

PubMed1972

Non-hormonal drugs for the treatment of diabetes insipidus.

Patients with diabetes insipidus may be successfully controlled with drugs other than vasopressin. These have the advantage of being effective when administered orally. The most important are the diuretics and the hypoglycemic agent chlorpropamide. The mode of action, indications and side effects of these drugs are reviewed. A third potentially useful agent is clofibrate. Recent experience with this drug has been described but more observations are needed before its possible role in the management of diabetes insipidus can be established.

Chlorothiazide↗

PubMed1979

Clinical resistance to vasopressin. Detection of antibody by hemagglutination.

We describe a patient with hypothalamic diabetes insipidus who after 20 years became refractory to the effect of commercial vasopressin injection. Vasopressin antibodies were measured using a sensitive hemagglutination technique. Resistance was associated with a high titer of antibodies that disappeared once vasopressin therapy was withdrawn and the diabetes insipidus was controlled with chlorpropamide. Antibodies were also measured in four additional patients with diabetes insipidus while they were or were not receiving vasopressin. A patient who had received the drug for only two years already had a substantial titer of antibodies to vasopressin, but in this case the response to the hormone was not impaired.

Adolescent↗

PubMed1977

Partial deficiency of antidiuretic hormone in a cat.

Marked polydipsia and polyuria developed subsequent to trauma in a 1 1/2-year-old male Abyssinian cat. Diabetes insipidus was suspected, inasmuch as intramuscualr vasopressin administration resulted in amelioration of polydipsia and polyuria. However, hypertonic (3%) saline solution given intravneously resulted in anuria, an indication of antidiuretic hormone activity. Polyuria and polydipsia were abolished by oral chlorpropamide therapy, which was indirect evidence for partial deficiency of antidiuretic hormone.

Animals↗

PubMedDate not supplied

Effects of DDAVP in cranial diabetes insipidus as compared to other antidiuretic drugs.

Five antidiuretic drugs were administered in each of twenty patients with cranial diabetes insipidus (DI). A daily intranasal dose of 10 microgram DDAVP (Adiuretin) produced longer and stronger antidiuretic effects than the posterior pituitary snuff, containing 100 microgram AVP, and than 12.5 microgram synthetic LVP spray, but a shorter antidiuresis than 12.5 microgram vasopressin tannate in oil, administered intramuscularly, antidiuresis lasting 14, 6, 4 and 36 hs respectively. Chlorpropamide produced an inconstant and less potent antidiuresis. 10microgram DDAVP given per nostril twice a day cancelled completely and without side effects DI in five patients with bronchospastic reaction to-pituitary snuff; the same daily dose was sufficient for the safe treatment of two DI women along pregnancy and lactation periods. It is recommended to use DDAVP as elective drug for the treatment of cranial DI.

Adult↗

PubMed1968

Circadian variation of glucose, insulin, and free fatty acids during long-term use of oral hypoglycaemic agents in diabetes mellitus.

The circadian rhythms of preprandial and postprandial blood glucose, free fatty acids, and insulin levels were measured in groups of normal and of diabetic patients controlled by diet alone or by diet with tolbutamide, chlorpropamide, or metformin. All groups showed a greater insulin release after the first meal of the day than after subsequent meals. Diabetic patients controlled for more than two years on diguanide therapy showed the closest resemblance to non-diabetic control subjects. There was no significant difference between the values for diabetic patients on long-term control with diet alone and those on short- or long-acting sulphonylurea. The circadian rhythms disappeared in obese subjects on total starvation.

Aged↗

PubMed1983

Drug interactions of gliclazide and other sulfonylureas in protein binding in vitro and in hypoglycemic effect in rats.

Possible drug interaction in clinical use of a hypoglycemic sulfonylurea, gliclazide, was examined by two measures: its binding to protein in vitro and its hypoglycemic effect in vitro in the presence of other therapeutic agents. Binding of radiolabeled sulfonylureas to human serum albumin at its physiological concentration was determined by ultrafiltration in the presence of other agents. The concentrations of all agents examined were at their therapeutic (i.e., clinically observable) levels in the blood. Protein binding of [3H]gliclazide and [14C]tolbutamide was modified by salicylic acid and phenylbutazone but not by tolmetin, warfarin and propranolol. Binding of [3H]glibenclamide was not influenced by these agents under conditions employed. Blood glucose lowering effect of sulfonylureas was studied in rats to which other agents were given. The hypoglycemic effect of gliclazide and chlorpropamide was enhanced by concomitant administration of acetylsalicylic acid and phenylbutazone but not by dicumarol and warfarin. The enhancement of hypoglycemic effect is likely to result from the interaction of protein binding between the drugs.

Animals↗

PubMed1984

Diabetes insipidus: occurrence after minor head trauma.

Post-traumatic diabetes insipidus is a rare entity, usually associated with severe head trauma, often with skull fracture and cranial nerve dysfunction. A 24-year-old male presented to a medical clinic 2 weeks after a minor head injury with presenting symptoms of polyuria with nocturia and intense polydipsia. A diagnosis of post-traumatic diabetes insipidus was made. Although other causes of polyuria syndromes must be ruled out, plotting urine versus plasma osmolalities can provide rapid preliminary diagnostic help when considering diabetes insipidus. First-line treatment should include a trial of chlorpropamide and hydrochlorothiazide. Caution should be exercised in not overlooking associated anterior pituitary damage, which may develop several years post-trauma.

Adult↗

PubMed1984

Hypernatremia and adipsia in a dog.

Primary adipsia and defective osmoreceptor function were diagnosed in a 7-month-old female Miniature Schnauzer. Also, the dog was noted to be dehydrated and to have chronic hypernatremia. On multiple occasions the dog's urine osmolality: plasma osmolality was greater than 4. The dog had inappropriate responses to isoosmotic and hypertonic NaCl infusions. Chlorpropamide administration initiated water intake but the volume was insufficient to avoid hypernatremia. The chronic hypernatremia and dehydration were treated successfully by mixing the calculated maintenance fluid volume in canned food. At 25 months of age, the dog died several days after becoming dehydrated and severely hypernatremic. Astrogliosis and neuronal degeneration were noted in both the thalamic and hypothalamic regions, but were believed to be nonspecific degenerative lesions compatible with seizures and severe dehydration.

Animals↗

PubMed1980

Kinetics-effect relations of glipizide and other sulfonylureas.

The kinetics-effect relations of glipizide (Gz), glibenclamide (Gb), tolbutamide (Tb) and chlorpropamide (Cp) were studied in diabetics and healthy volunteers, by gas chromatographic (Tb, Cp), high-pressure liquid chromatographic (Gz), radioimmunologic (Gb, insulin) and enzymatic (glucose) analyses. For each of the four drugs, the steady state concentrations showed very large between-patient variations, not attributable to dosage or weight differences but to individual differences in drug kinetics and to insufficient compliance. Single-dose comparisons in healthy volunteers showed that Gz and Gb are much more potent than Tb and Cp, and suggested that Gz is the most rapid-acting one. Food did not affect the bioavailability of any of the four drugs, but delayed Gz absorption. Both Gz and Gb yielded better blood glucose reductions when given 30 minutes before, than together with, meals. Each drug could evoke glucose reduction without enhancing peripheral insulin levels; this probably reflects extrapancreatic sulfonylurea effects. In conclusion, it appears that a) the dosage of each sulfonylurea must be individualized, b) Gz and Gb are much more potent than Tb and Cp, c) Gz has the most favourable therapeutic profile as it seems to be the most rapid- and short-acting of the four sulfonylureas. d) Gz and Gb should be given before rather than together with, meals, in order to obtain optimal effects.

Blood Glucose↗

PubMed1994

Closet hypoglycemia.

An elderly nondiabetic woman was found stuporous and unresponsive at home. In the emergency department, testing revealed that she had a serum glucose of 40 mg/dL (2.2 mmol/L). No underlying metabolic cause could be determined. An inspection of her medications disclosed a professional medication sample bottle labeled as containing a nonsteroidal anti-inflammatory drug (NSAID) that actually contained chlorpropamide tablets. Drugs, notably sulfonylureas, must be considered as a possible cause of unexplained severe hypoglycemia.

Aged↗

PubMed1977

Treatment of diabetes insipidus with DDAVP.

The treatment of a patient with diabetes insipidus (DI) is described, and the general treatment of the syndrome is reviewed. The patient was a 16-year-old male who had experienced pain, inflammation and tenderness in the left gluteal region owing to an abcess at the site of intramuscular injection of vasopressin tannate in oil (VTO). (He had been diagnosed as having DI at age 8. Since then, he had been maintained on VTO, lypressin and posterior pituitary snuff.) After the abscess healed during hospital treatment, VTO was stopped and the patient's urinary output increased sharply; urine specific gravity and osmolarity decreased correspondingly. Three days after stopping VTO, the investigational drug, 1-deamino-8-D-arginine vasopressin (DDAVP), was begun at 10 microgram every 12 hours. The dose was eventually increased to 20 microgram every 12 hours, and the patient was discharged on this regimen which controlled his urine output, specific gravity and osmolarity. Other treatments reviewed include antidiuretic-hormone-replacement agents (vasopressin, lypressin) and drugs used to potentiate low ADH levels (chlorpropamide, clofibrate and carbamazepine).

Adolescent↗

PubMed1999

Cromakalim: embryonic effects and reduction of tolbutamide-induced dysmorphogenesis in vitro.

Cromakalim is a K(+) channel opener that causes smooth muscle relaxation by activating ATP-sensitive K(+) (K(ATP)) channels and producing membrane hyperpolarization. Cromakalim counteracts sulfonylurea-induced K(ATP) channel inhibition in adult cells, but little is known regarding its embryonic effects, alone or in combination with sulfonylureas. K(ATP) channels have been demonstrated in the embryo, but their role in normal and abnormal development is unknown. Early-somite mouse embryos were exposed for 24 hr in vitro to cromakalim at concentrations of 0 (Cntl), 1, 10, 100, 200, or 500 microM in 0.125% DMSO. Embryos were also exposed for 24 hr in vitro to a dysmorphogenic tolbutamide concentration (110 microg/ml) combined with a subdysmorphogenic concentration of cromakalim (1 microM). Embryos were evaluated for somite number, heart rate, malformations, and embryonic and yolk sac protein content. Embryos exposed to 1 microM cromakalim were similar to controls. Cromakalim exposure increased malformation rates at concentrations >/=200 microM, decreased heart rates at >/=10 microM, and decreased somite and protein values at 500 microM. Defects involved cranial neural tube, optic vesicle, heart, and somites. A malformation rate of 59% in embryos exposed to 110 microg/ml tolbutamide was reduced to 13% by adding 1 microM cromakalim to the culture medium. Heart rate, somite number, and protein values were also improved by combined exposure to cromakalim and tolbutamide compared with exposure to tolbutamide alone. These results support previous findings with diazoxide (K(+) channel opener) and chlorpropamide (sulfonylurea) and further suggest a potential role for K(ATP) channel effects in sulfonylurea-induced dysmorphogenesis.

Abnormalities, Multiple↗

PubMed1998

Characterization of sulfonylurea receptors in isolated human pancreatic islets.

Current information on pancreatic islet sulfonylurea receptors has been obtained with laboratory animal pancreatic beta cells or stable beta-cell lines. In the present study, we evaluated the properties of sulfonylurea receptors of human islets of Langherans, prepared by collagenase digestion and density-gradient purification. The binding characteristics of labeled glibenclamide to pancreatic islet membrane preparations were analyzed, displacement studies with several oral hypoglycemic agents were performed, and these latter compounds were tested as for their insulinotropic action on intact human islets. [3H]glibenclamide saturable binding was shown to be linear at < or =0.25 mg/ml protein; it was both temperature and time dependent. Scatchard analysis of the equilibrium binding data at 25 degrees C indicated the presence of a single class of saturable, high-affinity binding sites with a Kd value of 1.0+/-0.07 nM and a Bmax value of 657+/-48 fmol/mg of proteins. The displacement experiments showed the following rank order of potency of the oral hypoglycemic agents we tested: glibenclamide = glimepiride > tolbutamide > chlorpropamide >> metformin. This binding potency order was parallel with the insulinotropic potency of the evaluated compounds.

ATP-Binding Cassette Transporters↗