INTRODUCTION: Diabetes mellitus is one of the most common endocrine disorders with increasing prevalence. Cardiovascular complications are among the major causes of death in diabetic patients. Type II diabetes mellitus is generally treated by sulfonylureas. There are contraversial reports regarding cardiovacular side effects of these drugs. Evidence exists about differences in side effects between the first and the second generatins of sulfonylureas. In the present study, the vascular effects of CHLORPROPAMIDE and glibenclamide belong to the first generation of sulfonyloreas were investigated in healthy male rats. MATERIAL & METHODS: Healthy rats were treated by the above mentioned drugs for periods of one and two months and the response of aortic rings to phenylephrine was examinde and compared to control.RESULTS: The results showed that after two months administration of CHLORPROPAMIDE the smooth muscle function was changed. These changes included a significant decrease in phenylephrine-induced contraction. Since such changes were not observed after one month chloropropamdie administration it may be concluded that these changes are time-dependent. Such changes were not observed after one or two months Glibenclamide administration.CONCLUSION: Phenylephrine EC50s was not differ in test groups when compared to control. Thus it is suggested that changes in the characteristics of aortic smooth muscle alpha-adrenoceptors may not be involved in the observed responses. With respect to the result of this study we concluded that at least part of the vascular effect of CHLORPROPAMIDE can be attributed to the changes in post-receptor cellular components which are involved in signal transduction.

Diabetes mellitus is one of the most common endocrine disorders with increasing prevalence. Cardiovascular complications are among the major causes of death in diabetic patients. Type II diabetes mellitus is generally treated with sulfonylureas. There are controversial reports regarding adverse cardiovascular effects of these drugs. Also evidence exists about differences in side effects between first and second generation sulfonylureas. Thus, an experimental and prospective study was performed. In this study, the vascular effects of two sulfonylureas belonging to the first(CHLORPROPAMIDE) and second generation(glibenclamide) were investigated in healthy male rats. Healthy rats were treated with CHLORPROPAMIDE(8mg/kg/day; i.p.) and glibenclamide(0.285mg/kg/day; i.p.) for oneand two-month periods and the response of isolated aortic rings to phenylephrine, acetylcholine and isosorbide dinitrate were then examined and compared to control. The results showed that chlopropamide pretreatment after two months caused a significant reduction in contractile response to phenylephrine. Moreover, a significant increase in endothelium-dependent relaxation in response to ACh was also observed after a two-month period of pretreatment with CHLORPROPAMIDE. Such changes were not observed after one month administration so it appears that these changes are time dependent. Glibenclamide did not cause such changes after one-or two-month pretreatment. Calculated EC50s for either phenylephrine or ACh did not differ in test groups compared to control. So it is suggested that changes in the characteristics of smooth muscle alpha-1 adrenoceptors or endothelial muscarinic receptors may not be involved in the observed responses. The alpha-1 adrenoceptor-induced vasocontriction appears to be caused both by the release of intracellular Ca2+ and by the transmembranous influx of extracellular Ca2+ It has been demonstrated that glibenclamide may interfere with Ca2+ influx which in turn affects intracellular Ca2+ levels in arterial smooth muscle, leading to reduction to muscle contractility. Inhibitory effect of glibenclamide in the protein kinase-C mediated contractile mechanism has also been suggested. The observed effect of CHLORPROPAMIDE on phenylephrine-induced contraction can be attributed to such mechanisms and a longer pretreatment may be needed for glibenclamide to show its inhibitory effect on contractile response to phenylephrine. On the other hand, it has been shown that sulfonylureas may stimulate the proliferation of endothelial cells from large vessels. There may be a difference between CHLORPROPAMIDE and glibenclamide in the time needed to cause such an effect. Also, it is possible that vascular effects of CHLORPROPAMIDE are due, at least in part, to changes in the post-receptor cellular components which are involved in signal transduction. Results obtained in this study indicate that up to two months pretreatment with CHLORPROPAMIDE and glibenclamide in healthy rats did not affect the aortic function in such a way to contribute to hypertension.

Background and Aim: Diabetes mellitus is the most common endocrine disorder with an ever-increasing prevalence. Cardiovascular complications are the major cause of death in diabetic patients. Type II diabetes mellitus is usually treated by sulfonyureas. There are controversial reports regarding cardiovascular side effects of these drugs. Conflicting evidences exist about side effects of the first and second-generation sulfonylureas. In this study, the vascular effects of CHLORPROPAMIDE and glibenclamide (first and second generations of sulfonylureas respectively) were investigated in healthy male rats.Materials and Methods: Male rats were treated by the above-mentioned drugs for six months and the response of aortic rings to acetylcholine, isosorbide dinitrate and phenylephrine were studied and compared to normal control group. Data were analyzed by means of ANOVA test.Results: There was no significant difference between the response of aortic rings of treated and control group to acetylcholine, isosorbide dinitrate and phenylepherine.Conclusion: Sulfonylureas through closing ATP dependent potassium channels, which exist in beta-cells of pancreas and other organs such as heart and vascular smooth muscles may affect the vascular tone. Based on the results of this study long term oral consumption of CHLORPROPAMIDE and glibenclamide in normal rats did not affect aortic contractile property. Further studies are needed to clarify the vascular effects of sulfonylureas.

Ibuprofen sodium solution (a hydrotropic solubilizing additive) has been utilized to analyze two poorly water-soluble drugs; CHLORPROPAMIDE (by titrimetric method) in the bulk drug and gatifloxacin (by spectrophotometric method) in tablet form. The results of analysis of CHLORPROPAMIDE bulk drug were found to be very much close to the results of analysis by a standard method (British pharmacopoeial method) which proves the accuracy of proposed method. Low values of standard deviation, coefficient of variation and standard error have confirmed the validation of proposed method. In the case of gatifloxacin tablets, Beer’s law was obeyed in the concentration range of 10-60 mg/ml at 333 nm when ibuprofen sodium was used as a hydrotropic agent. Recovery studies and statistical data proved the accuracy, reproducibility and the precision of the proposed method. In both cases, the proposed methods did not involve use of organic solvents. Major drawbacks of organic solvents include high cost, volatility and toxicity. Safety of analyzer is also affected by toxicity of the solvent used. The proposed methods are new, simple, eco-friendly, cost-effective, accurate, safe and precise which can be successfully employed in the routine analysis of CHLORPROPAMIDE bulk drug and gatifloxacin tablets. Ibuprofen sodium may also be tried for analysis of other poorly water-soluble drugs.

There are many reports for involvement of ATP-sensitive potassium channels in pancreatic, cardiac and vascular smooth muscle cells. This study examined the effect of single doses of K+ channel openers; diazoxide, minoxidil and K+ channel blockers; CHLORPROPAMIDE, glibenclamide on serum concentration of aldosterone in male rats. Blood samples were obtained 60 minutes after drug treatment and serum aldosterone level was determined by RIA. The basal serum aldosterone was 659.32 ± 71.48 pg/ml and after diazoxide or minoxidil administration increased to 1188.53 ± 99.45 pg/ml and 1392.69 ± 177.83 pg/ml, respectively. CHLORPROPAMIDE or glibenclamide treatment did not produce any change in basal serum aldosterone concentration, but in early streptozotocin-induced diabetic rats decreased serum aldosterone level significantly (P<0.001). Pretreatment with glibenclamide blocked aldosterone response to diazoxide but did not affect aldosterone response to exogenous ACTH to the same extent. Effect of diazoxide in insulin-treated rats was approximately similar to that of normal rats. Comparison of blood glucose concentration determined in normal, insulin treated and diabetic rats after different drug administration showed that there is no correlation between blood glucose level and the responses observed in serum hormone concentration. The results indicate that regulatory processes involved in the secretion of aldosterone are responsive to drugs affecting glibenclamide–sensitive K+ channels

Background: Idiopathic central diabetes insipidus (DI) is a rare endocrine disorder that results from total or partial deficiency of vasopressin secretion. It is idiopathic when the cause is unknown, but in many cases, is associated with autoimmune disorders. Case presentation: We present the case of a 44-year-old male with vitiligo and a family history of diabetes mellitus and thyroid disease. The patient presented with polydipsia and polyuria greater than 8 L/day. After water deprivation test, the patient was diagnosed with partial central diabetes insipidus. Contrast-enhanced pituitary magnetic resonance imaging showed decreased brightness of the neurohypophysis and normal thickness of the pituitary stalk. Because desmopressin was not initially available, the patient was managed with CHLORPROPAMIDE, carbamazepine, and hydrochlorothiazide, and afterwards substituted. During his outpatient checkups, he presented many episodes of polyuria, the last after 13 years, with polyuria of up to 15 L associated with weight loss, and abnormal blood glucose levels; anti-GAD 65 and IA-2 antibodies were negative. He was subsequently diagnosed with diabetes mellitus and received metformin and insulin; this latter was suspended in subsequent check-ups due to hypoglycemic episodes. Conclusion: We highlight the importance of treatment and adequate control of these pathologies, since they share similar clinical manifestations, can easily have electrolyte imbalance and represent a challenge for endocrinologists and internists.