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[Treatment of diabetes insipidus].

Although water alone taken in sufficient amount should correct any metabolic abnormality, a proper therapy is available to reduce the symptoms of the diabetes insipidus. In patients with reduced circulating levels of vasopressin, chlorpropamide, clofibrate, idroclorotiazide etc., enhance the effect of vasopressin on the renal tubule or induce a release of vasopressin, thus reducing the diuresis. On the contrary patients with complete diabetes insipidus require replacement therapy. Different forms of extractive vasopressin unfortunately are available: "aqueous vasopressin", "tannate vasopressin" in a suspension of peanut oil etc., are provided of many side-effects because of the impurities in their preparation. DDAVP is a synthetic analogous of natural vasopressin more specific for antidiuresis and with a long-activity. This compound available in a buffered aqueous solution is administrated by blowing into the nose. In our experience, 23 patients with different forms of central diabetes insipidus have successfully treated with 2-3 daily administrations of this drug without any side effect. The recent demonstration that DDAVP given orally exerts an antidiuretic activity in patients with diabetes insipidus is of therapeutic interest. It is conceivable that DDAVP in a properly formulated tablet will become a therapeutic option for the future treatment of patients with central diabetes insipidus.

Deamino Arginine Vasopressin↗

Generalised lipodystrophy.

We report a Malay girl suffering from generalised lipodystrophy, with clinical features of absence of body adipose tissue, hepatomegaly, hyperpigmentation and muscular hypertrophy. She also had hyperlipaemia, hypercholesterolemia and non-ketotic insulin-resistant diabetes mellitus. The possibility of malnutrition-related diabetes mellitus was excluded because of (a) no personal or family history of malnutrition (b) no pancreatic calcification (c) total loss of subcutaneous fat and (d) her requirement for insulin was more than 21.2 units/kg body weight which would be too high even for malnutrition-related diabetes mellitus. Attempts were made to control her diabetes initially with subcutaneous boluses insulin, then continuous intravenous insulin infusion (CIVII) and finally orally with fenfluramine and chlorpropamide.

Child↗

[The forensic chemical determination of antidiabetic agents].

Method of detection, purification and determination of some antidiabetic agents (ADA)--bucarban, butamid, glybenclamid, glybutide, methformine, prediane, chlorpropamide, chlocyclamide, cyclamide in biological material was developed. Microcrystalline reaction with 10% alcoholic potassium iodide, colour reactions and investigation by TLC method both native substances and nitration products were developed to identify ADA. The assay is performed by spectrophotometry. Detection limit is 2-5 mg of each substance in 50 g of the material.

Chromatography, Thin Layer↗

Distinguishing features of idiopathic flushing and carcinoid syndrome.

We compared the clinical and biochemical profiles of 11 patients with idiopathic flushing (IF) with those of eight patients with carcinoid syndrome (CS). Patients with IF were more often women, had a longer duration of symptoms, and were younger. Palpitations, syncope, and hypotension occurred only in patients with IF, while wheezing and abdominal pain occurred only with CS; diarrhea occurred in both types of patients. Elevated blood serotonin levels were present primarily in CS. Increased levels of urine 5-hydroxyindoleacetic acid was specific for CS but unsufficiently sensitive to detect all cases. Abnormalities of gut and vasoactive peptides failed to distinguish the two conditions. Flushing in carcinoid patients responds uniformly to octreotide (Sandostatin), but only one third of the patients with IF are relieved of the symptom. Patients with IF have features that distinguish them from individuals with flushing from other causes, such as CS, postmenopausal state, chlorpropamide-alcohol flush, panic attacks, medullary thyroid carcinoma, and autonomic epilepsy. Familiarity with the clinical and biochemical features of IF should facilitate evaluation and identification of these patients.

Adult↗

Drug therapy in patients with diabetes mellitus: an audit.

The drug therapy prescribed for 412 diabetic patients attending an outpatient clinic over a 12 week period was recorded to try and identify potential therapeutic problems. Over 90% of the patients were prescribed at least one drug (including insulin) with oral hypoglycaemic agents prescribed for 86% of non-insulin requiring diabetics. 19% of patients were prescribed more than three drugs and few patients took drug combinations. Of patients prescribed either glibenclamide or chlorpropamide, 63% were aged 65 yr or older. Despite their potential adverse clinical and biochemical effects, diuretics and beta-blockers were commonly prescribed, especially in hypertension. The prescribing of "newer" anti-hypertensive drugs, combination products in patients taking a multiple drug regimen, and the potential dangers of sulphonylureas in the elderly are three areas where alteration of prescribing habits may be of value.

Adrenergic beta-Antagonists↗

[Changes in the electrocardiogram in patients with coma due to poisoning].

The paper deals with changes in the electrocardiogram in a group of 20 patients in a comatose state due to intoxication. They were treated in an Intensive Care Unit. Special attention is directed to the corrected Q-T interval. The etiology of comatose states differed from ethanol, pesticides, antidepressives to anxiolytics, antiepileptics, sedatives, hypnotics, trichloroethylene and chlorpropamide. According to the criteria of Reed, nine patients were in a comatose state of the 0 or I degree, seven in a state of the II or III degree, and four in a state of the IV degree. The length of comatose states was between one hour and six days. Four of these patients died. According to ECG changes, in eleven patients sinus tachycardia, in two atrial fibrillation, and in seven a regular heart rhythm were diagnosed. The corrected Q-T interval was prolonged in fifteen out of 20 patients on the admission and reached the values of 0.664 seconds: it as also prolonged in two of the patients showing a normal range on the admission. In one of the patients malignant ventricular arrhythmia was observed.

Adolescent↗

Drug-induced hypoglycemia. A review of 1418 cases.

The present review catalogues 1418 reported cases of drug-induced hypoglycemia. The main findings are that sulfonylureas (especially chlorpropamide and glyburide), either alone or with a second hypoglycemic or potentiating agent, still account for 63% of all cases; that alcohol, propranolol, and salicylate, either singly or with another hypoglycemic drug, are the next most frequent offenders (19% of the total); and that one older drug (quinine) and three new ones (pentamidine, ritodrine, and disopyramide) have caused an additional 7% of all episodes of severe hypoglycemia. The clinical factors that set the stage for drug-induced hypoglycemia are still restricted food intake, age, hepatic disease, and renal disease, both individually and even more so in combination. Drug-induced hypoglycemia continues to be so common that virtually every unconscious patient should be considered hypoglycemic until immediate estimation of the blood sugar level rules it in or out. If ruled in, the clinician should promptly start 10% intravenous glucose and plan to maintain it uninterruptedly for 1 or more days, with added glucagon, hydrocortisone, and diazoxide administration if necessary, until sustained hyperglycemia guarantees that all drug effects have worn off.

Adolescent↗

[Use of indomethacin in diabetes insipidus].

Papers with evidence of the efficacy of therapy of patients suffering from diabetes insipidus with chlorpropamide, miscleron, carbamazepine, and maninil have appeared of late in the literature. This is the author's first experience in the use of indomethacin for the treatment of 14 patients with diabetes insipidus. Decreased diuresis, thirst and the improved general status were observed.

Adult↗

[Description of Wolfram syndrome (DIDMOAD) on the basis of a new case].

We present a new clinical case of a 25-year-old man with Wolfram's syndrome. Partial central diabetes insipidus was found to cause polyuria, polydipsia and enuresis. The patient had diabetes mellitus for the last 18 years, controlled with diet and/or chlorpropamide during 10 years and showed no typical complications of the disease. The patient was also shown to have a dilated urinary tract and perceptive hypoacusis for high frequencies. The fifth classical component of this syndrome, primary optic atrophy, was not found. Based on the report of this case, Wolfram's syndrome is briefly described.

Adult↗

Drug and nutrient interactions in the elderly diabetic.

Elderly diabetics take more drugs than other groups of elderly patients. Their multiple drug use is largely explained by the drugs that they take for complications of their primary disease; these include cardiovascular drugs for macrovascular disease and antibiotics for secondary infections. They also take more drugs for control of other conditions that are etiologically associated with the development and progression of their diabetes, including antihypertensive agents, antilipemic agents and steroids, and nonsteroidal antiinflammatory drugs (NSAIDs), which are taken for relief of joint pain that is intensified by arthritic joints bearing excess weight. Drugs taken by elderly diabetics that contribute to the high prevalence of drug-nutrient interactions include those taken as antidiabetic agents, including both insulin and sulfonylureas as well as calcium channel blockers; they also include thiazides, loop diuretics, sulfa drugs, cephalosporin antibiotics, tetracyclines, antifungal agents, cholestyramine and colestipol, niacin, prednisone and other corticosteroids, and NSAIDs. These drugs and drug combinations contribute to the risk of hyperglycemia, which can cause nonketotic hyperglycemia in the elderly; to the risk of hypoglycemia, which in the elderly carries the risk of inducing pseudo-stroke; to the risk of drug-induced nutritional deficiencies from antilipemics and cephalosporins, which can induce vitamin K deficiency; to the risk of acute incompatibility reactions, including flush reactions from chlorpropamide, niacin, and calcium channel blockers; and to the risk of edema, anemia, and hyperkalemia from NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The influence of oral hypoglycaemic sulfonyl ureas on prostacyclin release by the rat thoracic aorta.

The influence of some oral hypoglycaemic sulfonyl ureas on PGI2 release by the rat thoracic aorta in vitro was examined using reversed phase HPLC. The column (Micro Pack MCH-10) (30 cm X 4 mm) was eluted using the solvent mixture:acetonitrile:glacial acetic acid:water (23:0.1:76.9v/v/v). Preincubation of the aortae with the sulfonyl ureas (15 microM) enhanced PGI2 release. The control release (measured as 6-oxo-PGF1 alpha) was 1.15 +/- 0.1 ng/mg wet weight. This was significantly increased to 2.30 +/- 0.20, 2.50 +/- 0.30, 2.90 +/- 0.25, 2.10 +/- 0.20 and 2.40 +/- 0.30 ng/mg by glibenclamide, gliclazide, acetohexamide, glibornuride and chlorpropamide, respectively (P less than 0.01, n = 6). Mepacrine (0.5 mM) abolished both basal and stimulated release. Thus, the enhanced PGI2 release may probably involve activation of the enzyme phospholipase A2. None of the compounds affected ADP-induced rat platelet aggregation even when the platelets were preincubated for 10 min at a concentration of 100-180 microM. The enhanced release of PGI2 may help to delay the development and progression of retinopathy, nephropathy, hypertension and thrombosis in diabetic patients prone to these diseases. Furthermore, the enhanced PGI2 release may partly underly some of the previously observed and poorly explained findings following the administration of some sulfonyl ureas into mammals.

6-Ketoprostaglandin F1 alpha↗

Management of the syndrome of inappropriate secretion of antidiuretic hormone.

The etiology, pathophysiology, clinical features, diagnosis, and medical treatment of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are reviewed. SIADH is a common cause of hyponatremia in hospitalized patients. Increased concentrations of antidiuretic hormone (ADH) result in retention of free water, increased excretion of sodium, and hyponatremia. Symptoms generally occur only when hyponatremia is severe (less than or equal to 125 meq/L) and may include anorexia, vomiting, and confusion, followed by seizures, coma, and death. SIADH may result from a variety of diseases, as well as from the use of drugs such as chlorpropamide, carbamazepine, diuretics, and some antineoplastic agents. Diagnosis of SIADH is confirmed by demonstration of a high urine osmolality with a low plasma osmolality, in the absence of diuretic use. Immediate treatment of the symptomatic patient with SIADH includes intravenous furosemide and 3% sodium chloride injection to produce a negative free-water balance. If the underlying cause of SIADH cannot be corrected, the treatment of choice for chronic SIADH is fluid restriction. If this is not tolerated by the patient, demeclocycline can be used to induce a negative free-water balance. Urea, lithium, phenytoin, and loop diuretics have been reported to be effective, but there are few data to support their use. Future research into the treatment of SIADH must be directed at developing effective antagonists of ADH. Treatment of SIADH consists of elimination of underlying causes and restriction of fluid intake; if these measures are unsuccessful or poorly tolerated, long-term drug therapy may be indicated.

Demeclocycline↗

Multicenter comparison of glyburide and glipizide in the treatment of non-insulin-dependent diabetes mellitus.

A multicenter, randomized, open-label comparison of glyburide and glipizide was made in 109 patients with non-insulin-dependent diabetes mellitus whose fasting plasma glucose levels had been maintained at less than or equal to 140 mg/dl by tolbutamide, chlorpropamide, or glyburide. After an initial evaluation, patients entered a dose-adjustment phase to establish the optimal daily dose of the assigned drug--glyburide or glipizide--needed to maintain metabolic control. A second evaluation was made at the end of this phase. Patients then proceeded into the maintenance phase, which lasted approximately three months. A final evaluation was made upon completion of or withdrawal from the maintenance phase. Metabolic control was monitored by means of determinations of fasting plasma glucose and hemoglobin A1c. Comparative efficacy was assessed in relation to the doses of the respective drugs needed to maintain acceptable metabolic control. Safety was evaluated through reports of adverse effects as well as through laboratory tests and measurements of vital signs at each patient visit.

Blood Glucose↗

Effects of paweiwan on streptozotocin-induced hyperglycemia in rats.

The ancient Chinese remedy of Paweiwan was used by patients with polyuria, polydipsia, and polyphagia. The present study investigated the hypoglycemic effects of Paweiwan using streptozotocin-induced hyperglycemic rats. The effects on serum glucose in a 4-day course, in a 7-week course, on the standard oral glucose tolerance test, and on the liver glycogen content were studied. In the glucose tolerance test, chlorpropamide and insulin were used as the positive controls and 0.5% CMC (Carboxymethylcellulose) was used as the negative control. We found that Paweiwan decreased the baseline glucose concentration, ameliorated the blood glucose elevation after glucose challenge, and increased liver glycogen content. The results may imply that Paweiwan increases glucose entrance into cells.

Animals↗

Renal tubular chloride and renin release.

We have suggested that the renal tubular signal for renin release is related to alterations of sodium chloride cotransport in the TALH. Renin release is inhibited by increased sodium chloride transport and stimulated by interrupted sodium chloride transport. Because of the different affinities of the carriers for sodium and chloride, chloride rather than sodium is rate limiting for this cotransport process. Consequently, renin release is related to alterations of chloride delivery rather than sodium delivery to the TALH. The reduction of PRA by selective chloride loading and by short-term infusion of chloride salts is related to increased chloride delivery to the loop and hence increased chloride transport. Alternatively, chlorpropamide and antidiuretic hormone may inhibit renin release by increasing chloride delivery to the loop. Stimulation of renin release may likewise be related either to decreased chloride delivery and hence decreased transport in the loop (hypochloremia related to selective chloride deprivation) or to an intrinsic alteration in the transporting capacity of the loop (loop diuretics, potassium depletion, glucocorticoid deficiency, Bartter's syndrome). The intermediate steps between alterations of sodium chloride transport in the TALH and renin release remain to be defined.

Animals↗

Facial flushing secondary to hypoglycemia.

Facial flushing is usually not associated with hypoglycemia. Diabetics treated with chlorpropamide can have an antabuse-like flushing with ingestion of alcohol, but flushing secondary to hypoglycemia per se has not been reported. The first case demonstrating that facial flushing can occur in insulin-induced hypoglycemia is described. This patient had marked erythematous facial flushing that was repeatable with each instance of hypoglycemia. Endocrine evaluation revealed no evidence of carcinoid or a pheochromocytoma in this patient and the facial flushing was unrelated to alcohol. Without insulin-induced hypoglycemia, this diabetic patient has had no further facial flushing in one year follow-up.

Aged↗

Sulphonylureas and biguanides do not affect insulin binding in H35 hepatoma cells.

Six sulphonylureas (tolbutamide, tolazamide, chlorpropamide, glibornuride, glipizide and gliquidone) and 2 biguanides (metformin and buformin) were tested for possible effects on insulin binding to H 35 rat hepatoma cells in culture. Insulin binding was measured after 24 and 72 hr of culturing cells in medium containing the drugs. Buformin and gliquidone were tested in concentrations from 10(-8)-5 X 10(-5) M, the other drugs in concentrations from 10(-7)-5 X 10(-4) M. All 24-hr experiments were repeated in cells down-regulated with 10 micrograms/ml insulin. None of the oral hypoglycemic agents tested had any significant influence on insulin binding to H 35 hepatoma cells, either in the presence or absence of insulin. We suggest that the insulin receptor status, at least in this type of liver cell, is not influenced by sulphonylureas or biguanides.

Animals↗

Sulphonylureas and glucose metabolism in phenobarbital induced rats.

The addition of phenobarbital (PB) to a sulphonylurea (SU) regimen may improve glycemic control in patients with non- insulin dependent diabetes mellitus (NIDDM, type II). Since SU reactions may be modified, we investigated glucose metabolism in rats with combined PB and SU treatment. Chlorpropamide (CHL) and glibenclamide (GB) were selected as SU drugs. The combination of PB to the CHL or GB regimens induced the drug metabolism enzymes excluding aminopyrine N-demethylase activity, which was enhanced by GB but not CHL. The CHL and GB treatments lowered blood glucose (BG) concentration and decreased hepatic glucose-6-phosphate phosphohydrolase (G6P hydrolase) activity and glycogen reserves in the rats. The concomitant administration of PB and the SUs decreased hepatic G6P hydrolase activity and glycogen content in the animals, whereas the BG level remained unaltered. The hepatic glycogen content was decreased more markedly in the CHL plus PB than in the CHL alone treated animals. The findings suggests that enzyme inducers modify the action of SU in rats. Hepatic drug and glucose metabolizing enzymes seems also to respond to distinct PB plus SU combinations in different ways.

Aminopyrine N-Demethylase↗