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British Journal of Pharmacology Feb 19981. The mechanism underlying the antidiuretic effect of thiazide diuretics in diabetes insipidus (DI) is unknown. This study addressed two specific questions: is the...
1. The mechanism underlying the antidiuretic effect of thiazide diuretics in diabetes insipidus (DI) is unknown. This study addressed two specific questions: is the reduction in urine flow rate (V) related to a decrease in the delivery of fluid from the pars recta of the proximal tubules ('distal delivery'), and are there any changes in the expression and/or intracellular distribution of vasopressin stimulated water channels (AQP2) in the collecting ducts, during chronic thiazide-induced antidiuresis? 2. Nine Brattleboro rats with vasopressin-deficient DI were treated for 5 days with bendroflumethiazide (BFTZ), 9 mg kg(-1) day(-1) orally, and 9 Brattleboro rats were left untreated. BFTZ-treated DI rats showed a fall in V from approximately 200 to approximately 75 ml day(-1) and an increase in urine osmolality from approximately 130 to approximately 400 mosmol kg(-1). 3. BFTZ-induced antidiuresis was associated with a persistent loss of sodium, but not of potassium. After 5 days of treatment, clearance studies in conscious rats showed a tendency towards decreases in effective renal plasma flow (-7%), GFR (-12%) and lithium clearance (C(Li); used as marker for distal delivery) (-25%), compared with untreated controls, but none of these changes were statistically significant. There was no apparent relationship between C(Li) and V in BFTZ-treated or untreated DI rats. 4. BFTZ treatment did not change the expression of AQP2 in homogenates of cortex, outer or inner medulla from DI rats, or from normal Long Evans rats. Light and electron microscopic immunocytochemistry revealed no changes in intracellular distribution of AQP2 in principal cells from inner medullary collecting ducts of BFTZ-treated DI rats. 5. We concluded, (i) that although the antidiuretic effect of BFTZ in rats with DI is associated with a net loss of Na, the decrease in V shows no association with changes in distal delivery, as estimated by C(Li). (ii) Antidiuretic treatment with BFTZ does not alter the expression of subcellular distribution of AQP2 water channels in the collecting ducts. The mechanism underlying the chronic antidiuresis caused by thiazide diuretics in DI remains elusive.
Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Bendroflumethiazide; Diabetes Insipidus; Diuresis; Diuretics; Female; Ion Channels; Kidney; Rats; Rats, Brattleboro; Sodium Chloride Symporter Inhibitors; Subcellular Fractions
PubMed: 9517394
DOI: 10.1038/sj.bjp.0701653 -
Acta Medica Scandinavica 1976The antihypertensive effect and side-effects during 12 months' treatment with bendroflumethiazide and propranolol have been compared in two randomly selected, equally... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The antihypertensive effect and side-effects during 12 months' treatment with bendroflumethiazide and propranolol have been compared in two randomly selected, equally large groups (n= 53) of previously untreated male hypertensives. Systolic BP above 170 or diastolic BP above 105 mmHg on two occasions were defined as hypertension. The same BP reduction was achieved in both groups. During the 12 months' treatment one subject on bendroflumethiazide developed diabetes mellitus and one on propranolol developed cardiac decompensation. None developed gout. Contrary to what had been presumed, glucose tolerance improved during 12 months' treatment with both agents, while there were no changes in fasting blood sugar, insulin or triglyceride concentrations. No changes were found in serum potassium or total body potassium during 12 months' bendroflumethiazide treatment, while serum potassium increased during treatment with propranolol. Uric acid increased slightly during treatment with both agents. Prolongation of the follow-up to 24 months did not change any of the findings regarding metabolic changes during treatment. The frequency of subjective side-effects decreased to the same extent during treatment with both drugs. It is concluded that bendroflumethiazide and propranolol are equally useful as antihypertensive agents and that the risk of impariment of glucose metabolism and potassium balance seems to be very slight during treatment with bendroflumethiazide in mild hypertension.
Topics: Bendroflumethiazide; Blood Glucose; Blood Pressure; Heart Rate; Humans; Hypertension; Insulin; Male; Middle Aged; Potassium; Propranolol; Triglycerides; Uric Acid
PubMed: 937076
DOI: 10.1111/j.0954-6820.1976.tb06770.x -
Acta Crystallographica. Section C,... Nov 2007Bendroflumethiazide, or 3-benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, is reported to crystallize as 1:1 solvates with...
Bendroflumethiazide, or 3-benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, is reported to crystallize as 1:1 solvates with acetone, C(15)H(14)F(3)N(3)O(4)S(2).C(3)H(6)O, and N,N-dimethylformamide, C(15)H(14)F(3)N(3)O(4)S(2).C(3)H(7)NO. A detailed investigation of the crystal packing and intermolecular interactions is presented by means of Hirshfeld surface analysis. This analysis confirms the atomic positions of methyl H atoms of the solvent molecules that were inferred from the X-ray data and provides a useful tool for structure validation.
Topics: Acetone; Antihypertensive Agents; Bendroflumethiazide; Crystallography, X-Ray; Diuretics; Hydrogen; Molecular Conformation; Molecular Structure; Solutions
PubMed: 17989490
DOI: 10.1107/S0108270107044812 -
QJM : Monthly Journal of the... Dec 1994In a double-blind, double-dummy, randomized, multi-centre study, the effects of bendroflumethiazide vs. enalapril on blood pressure, glycaemic control, lipoprotein... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
In a double-blind, double-dummy, randomized, multi-centre study, the effects of bendroflumethiazide vs. enalapril on blood pressure, glycaemic control, lipoprotein concentrations and albuminuria were compared in non-proteinuric, hypertensive type 2 diabetic patients; they were treated for 20 weeks with either bendroflumethiazide 2.5-5.0 mg (n = 59) or enalapril 10-20 mg (n = 55). Age, fasting plasma glucose, HbA1c and BMI were similar in the groups. Systolic and diastolic blood pressure were reduced in both groups. Bendroflumethiazide was accompanied by minor but significant elevations in fasting plasma glucose and serum C-peptide. HbA1c was increased during both treatments. Lipoproteins and urinary albumin/creatinine ratio were stable. Bendroflumethiazide caused a decrease in serum potassium and an increase in serum urate. No significant correlations were observed between the decline in blood pressure and changes in the metabolic risk factors. Baseline levels of age, sex, BMI, blood pressure or urinary albumin/creatinine ratio were not related to changes in blood pressure, metabolic parameters or urinary albumin/creatinine ratio.
Topics: Adult; Aged; Bendroflumethiazide; Diabetes Mellitus, Type 2; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Male; Middle Aged
PubMed: 7859051
DOI: 10.1093/oxfordjournals.qjmed.a068893 -
Journal of Clinical Pharmacology Jan 1987It has been suggested that a diuretic added to a calcium antagonist may not reduce blood pressure further in patients with hypertension. Bendroflumethiazide 5 mg was... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
It has been suggested that a diuretic added to a calcium antagonist may not reduce blood pressure further in patients with hypertension. Bendroflumethiazide 5 mg was given to 17 patients with essential hypertension who had persistent mild to moderate hypertension despite treatment with nifedipine slow-release tablets 20 mg bid. One group received bendroflumethiazide before (N = 8) and the other after placebo (N = 9) in a double-blind, randomized cross-over trial. Supine blood pressure following active bendroflumethiazide administration was significantly reduced in both groups compared with trial entry (166/105 to 150/96 mm Hg, P less than .01; 170/108 to 156/98 mm Hg, P less than .01). A reduction in serum potassium level and a rise in serum uric acid concentration were seen with combined treatment. We cannot substantiate theoretic arguments for the ineffectiveness of a bendroflumethiazide-nifedipine combination on blood pressure.
Topics: Adult; Bendroflumethiazide; Blood Glucose; Blood Pressure; Body Weight; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Humans; Hypertension; Middle Aged; Nifedipine; Potassium; Pulse; Random Allocation; Uric Acid
PubMed: 3316303
DOI: 10.1177/009127008702700106 -
The American Journal of Cardiology Jan 1988Three double-blind Veterans Administration Cooperative Studies are reviewed to determine age-related changes in response to antihypertensive agents. In the first study... (Comparative Study)
Comparative Study
Three double-blind Veterans Administration Cooperative Studies are reviewed to determine age-related changes in response to antihypertensive agents. In the first study 312 patients received hydrochlorothiazide titrated from 25 to 100 mg twice daily to lower diastolic blood pressure (BP) to less than 90 mm Hg. Of 121 patients aged 55 to 65 the decrease in BP averaged -21.8/-12.9 mm Hg, while in the 191 patients younger than 55 the reduction averaged -15.7/-11.5 mm Hg (p less than 0.001; p = 0.048, respectively). Both systolic and diastolic BP reductions averaged significantly more in older whites; in older blacks it was systolic BP only. An additional 298 patients received titrated doses of propranolol alone. In this group there were no significant differences in BP response between younger patients and patients aged 55 to 65 except in the subgroup of white patients older than 60, in whom the systolic reduction was significantly less than in the younger patients. In a second study of bendroflumethiazide alone and with nadolol, systolic BP decreased more in older than in younger patients but there was no age-related reduction with nadolol alone. In the third trial captopril was first given alone and later with hydrochlorothiazide. There were no age-related differences with captopril alone, but after the addition of hydrochlorothiazide there was a trend toward a greater antihypertensive response in the patients aged 55 to 69. Thus, responsiveness of older patients varies with the type of antihypertensive drug. Age appears to increase the antihypertensive response to thiazide diuretics but not to beta-adrenergic blocking drugs or to captopril.
Topics: Adult; Aged; Aging; Bendroflumethiazide; Black People; Blood Pressure; Captopril; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Nadolol; Random Allocation; White People
PubMed: 3276117
DOI: 10.1016/0002-9149(88)91316-1 -
Hypertension (Dallas, Tex. : 1979) Jun 2012Thiazide and thiazide-like diuretics are widely used in the management of hypertension, but recently the equivalence of hydrochlorothiazide and chlorthalidone for blood... (Meta-Analysis)
Meta-Analysis
Thiazide and thiazide-like diuretics are widely used in the management of hypertension, but recently the equivalence of hydrochlorothiazide and chlorthalidone for blood pressure (BP) lowering and prevention of cardiovascular disease has been questioned. We performed a meta-analysis to characterize the dose-response relationships for 3 commonly prescribed thiazide diuretics, hydrochlorothiazide, chlorthalidone, and bendroflumethiazide, on BP, serum potassium, and urate. Randomized, double-blind, parallel placebo-controlled trials meeting the following criteria, ≥ 2 different monotherapy dose arms, follow-up duration ≥ 4 weeks, and baseline washout of medication ≥ 2 weeks, were identified using Embase (1980-2010 week 50), Medline (1950-2010 November week 3), metaRegister of Controlled Trials, and Cochrane Central. A total of 26 trials examined hydrochlorothiazide, 3 examined chlorthalidone, and 1 examined bendroflumethiazide. Studies included a total of 4683 subjects in >53 comparison arms. Meta-regression of the effect of thiazides on systolic BP showed a log-linear relationship with a potency series: bendroflumethiazide>chlorthalidone>hydrochlorothiazide. The estimated dose of each drug predicted to reduce systolic BP by 10 mm Hg was 1.4, 8.6, and 26.4 mg, respectively, and there was no evidence of a difference in maximum reduction of systolic BP by high doses of different thiazides. Potency series for diastolic BP, serum potassium, and urate were similar to those seen for systolic BP. Hydrochlorothiazide, chlorthalidone, and bendroflumethiazide have markedly different potency. This may account for differences in the antihypertensive effect between hydrochlorothiazide and chlorthalidone using standard dose ranges.
Topics: Antihypertensive Agents; Bendroflumethiazide; Blood Pressure; Chlorthalidone; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hydrochlorothiazide; Hypertension; Potassium; Randomized Controlled Trials as Topic; Treatment Outcome; Uric Acid
PubMed: 22547443
DOI: 10.1161/HYPERTENSIONAHA.111.190637 -
Calcified Tissue International Jul 1984Inhibition of dissolution of calcium hydroxyapatite in the presence of bendroflumethiazide, Centyl, and of hydrochlorothiazide has been investigated. The former compound... (Comparative Study)
Comparative Study
Inhibition of dissolution of calcium hydroxyapatite in the presence of bendroflumethiazide, Centyl, and of hydrochlorothiazide has been investigated. The former compound has a pronounced larger inhibitory effect than the latter. The trifluormethyl group in bendroflumethiazide has been shown to hydrolyze, with the release of fluoride and hydrogen ions, presumably forming a carboxylic acid. The inhibitory effect of hydrolyzed bendroflumethiazide is found to be similar to the effect of a potassium fluoride solution with the same fluoride ion concentration, as measured by a fluoride selective ion electrode.
Topics: Bendroflumethiazide; Bone Resorption; Durapatite; Humans; Hydrochlorothiazide; Hydrolysis; Hydroxyapatites
PubMed: 6091853
DOI: 10.1007/BF02405355 -
American Journal of Obstetrics and... Aug 1964
Topics: Bendroflumethiazide; Biomedical Research; Congenital Abnormalities; Diet, Sodium-Restricted; Drug Therapy; Eclampsia; Female; Infant, Newborn; Placebos; Pregnancy; Toxicology; Water-Electrolyte Balance
PubMed: 14207556
DOI: 10.1016/0002-9378(64)90058-4 -
Journal of the American Society of... Nov 2004
Review
Topics: Animals; Bendroflumethiazide; Diabetes Insipidus; Diuresis; Diuretics; Humans; Hydrochlorothiazide; Sodium Chloride Symporter Inhibitors
PubMed: 15504949
DOI: 10.1097/01.ASN.0000146568.82353.04