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PubMed1988

Atenolol and chlorthalidone therapy for hypertension: a double-blind comparison.

In a randomized, double-blind, parallel-group study of 31 patients with mild to moderate hypertension, we compared a placebo regimen with a regimen of atenolol and chlorthalidone (Tenoretic). The study, which lasted seven weeks, began with a single-blind two-week placebo lead-in period, followed by a four-week double-blind treatment phase, and concluded with a one-week single-blind placebo washout period. Of 24 patients included in the analysis of efficacy, seven received one Tenoretic 50 tablet per day (atenolol, 50 mg; chlorthalidone, 25 mg), nine received one Tenoretic 100 tablet per day (atenolol, 100 mg; chlorthalidone, 25 mg), and eight received placebo. Supine systolic/diastolic blood pressure (mean +/- SD) decreased from 154 +/- 15.2/102 +/- 4.6 mm Hg during the baseline period to 128 +/- 8.5/85 +/- 4.0 mm Hg during treatment in the group receiving Tenoretic 100, from 153 +/- 12.6/104 +/- 5.4 mm Hg to 137 +/- 4.5/91 +/- 4.4 mm Hg in the group receiving Tenoretic 50, and from 150 +/- 11.9/101 +/- 1.6 mm Hg to 145 +/- 11.6/93 +/- 5.1 mm Hg in the group receiving placebo. Reductions in systolic and diastolic blood pressures in the active treatment groups were significantly greater than the pressure reductions in the group receiving placebo (P less than .05 to .1). The combination of atenolol and chlorthalidone was well tolerated, and in no case was treatment discontinued because of side effects. This study showed that one tablet per day of either Tenoretic 50 or Tenoretic 100 is effective and well tolerated in the treatment of mild to moderate hypertension.

Adult↗

PubMed1979

Atenolol and chlorthalidone in combination for hypertension.

1 The hypotensive effect of single daily dosing with atenolol 100 mg and chlorthalidone 25 mg given alone or in combination has been assessed in a double-blind, crossover, placebo controlled trial in fifteen hypertensive patients. 2 Average lying blood pressures were: Placebo 155.4/103.9 mm Hg, atenolol 134.6/85.8 mm Hg, chlorthalidone 139.5/90.1 mm Hg, combination 127.7/82.5 mm Hg. 3 The effect of the combination therapy in reducing lying diastolic pressure compared with placebo (a fall of 21.4 mm Hg) was significantly less than the 31.9 mm Hg fall predicted from the sum of the individual effects (P = 0.01). 4 Observations on blood pressure at rest and under mental, isometric and bicycle ergometer stress were made pre-dose and post-dose for a 12 h period at the end of the last treatment period. 5 Lying blood pressure declined from the zero hour (pre-dose) reading on all treatments to a low at 15.00--18.00 h and then rose again. 6 The rise in systolic blood pressure after isometric exercise and mental stress was of a similar magnitude with all four treatment regimes. 7 Atenolol, alone and in combination with chlorthalidone, reduced the blood pressure and the pulse rate increase on exercise 2 h post-dose when compared with readings 24 h post-dose. 8 Once daily dosing with a combination of atenolol and chlorthalidone produced a fall in supine blood pressure over a 24 h period but the effect on exercise induced changes was not uniform over this period.

Adolescent↗

PubMed1986

Isolated systolic hypertension in the elderly. A placebo-controlled, dose-response evaluation of chlorthalidone.

One hundred seventy-one patients, 60 years of age or older with isolated systolic hypertension, were randomly assigned to receive chlorthalidone 12.5, 25.0, or 50.0 mg or placebo once daily for 12 weeks. The majority of the patients receiving chlorthalidone 12.5 mg achieved therapeutic success with no clinically significant biochemical changes or side effects. The 50.0-mg dose level enhanced efficacy only minimally over the 25.0-mg dose level. Drug-related side effects were significantly more prevalent in the chlorthalidone 50.0-mg group than in the placebo group. The data suggest that most elderly patients with isolated systolic hypertension, regardless of the severity, could be treated effectively and safely with chlorthalidone 12.5 mg per day.

Age Factors↗

PubMed2005

Chlorthalidone improves endothelial-mediated vascular responses in hypertension complicated by nondiabetic metabolic syndrome.

BACKGROUND: The study was conducted to evaluate the vascular effects of chlorthalidone, a distal tubule-acting natriuretic agent, in hypertensive patients with nondiabetic metabolic syndrome, an insulin-resistant condition characterized by endothelial dysfunction and high risk for diabetes mellitus development. METHODS: Thirteen untreated hypertensive patients with Adult Treatment Panel-III-defined nondiabetic metabolic syndrome were assigned to 3-month treatment with chlorthalidone. The end-points were baseline and post-treatment evaluation of (1) forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine infusion to test endothelial-mediated vasomotor function, with sodium nitroprusside as a control for endothelium-independent vasodilatation; (2) minimum forearm vascular resistance, the ratio of mean blood pressure and maximal blood flow in response to 13-minute arterial occlusion, as a hemodynamic correlate of arteriolar structure; and (3) transcapillary albumin escape rate (the 1-hour decay rate of (125)I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Additional measurements included baseline and posttreatment lipids, fasting, and postload glucose and insulin as well as the homeostasis model assessment, an index of insulin sensitivity. RESULTS: Chlorthalidone reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum forearm resistance, and slowed the transcapillary albumin escape rate. Metabolic parameters did not change significantly except for an increase in low-density lipoprotein cholesterol levels. CONCLUSIONS: Chlorthalidone improved endothelial function, reversed abnormal arteriolar structure, and slowed albumin permeation in hypertensive patients with nondiabetic metabolic syndrome.

Antihypertensive Agents↗

PubMed1981

Comparison of the antihypertensive activities of xipamide and chlorthalidone: a double-blind, randomized, crossover trial.

The effectiveness of a new potent diuretic, xipamide, was evaluated in the treatment of patients with mild to moderate essential hypertension. The effects of daily doses of 40 mg xipamide were compared with those of 100 mg chlorthalidone with respect to systolic and diastolic blood pressure, using a double-blind crossover design. Patients received each drug for 6 weeks, the order of treatments being at random and the periods being separated by a 'washout' period of 7 days. The results showed that xipamide was as effective as chlorthalidone in controlling blood pressure, both in the upright and supine positions, and when administered after chlorthalidone produced a further reduction. No such further reduction occurred when chlorthalidone was given after xipamide. Serum electrolyte changes induced by the two diuretics were comparable. Both drugs were well tolerated and caused few side-effects.

Adult↗

PubMed1990

Efficacy and tolerability of long term oxprenolol and chlorthalidone singly and in combination in hypertensive blacks.

Sixty two black patients who had confirmed but untreated hypertension participated in a double blind clinical trial of the efficacy and tolerability of slow-release oxprenolol in a daily dose of 160 mg initially and 320 mg subsequently versus chlorthalidone 50 mg daily. Thereafter, a combination of oxprenolol with chlorthalidone in an initial dose of 160 mg and 25 mg and a subsequent dose of 320 mg and 50 mg, respectively, was administered and the effects compared with those of the same drugs given singly. The trial lasted for 3 years, but each participant took active medication for 1 year. Oxprenolol as monotherapy had no effect on the blood pressure, irrespective of the dose. Chlorthalidone as monotherapy produced a significant fall in blood pressure (p less than 0.01). Combining the 2 drugs enhanced their blood pressure lowering effects (p less than 0.001). Oxprenolol as monotherapy and as part of combination therapy was well tolerated by all patients. Chlorthalidone as monotherapy was well tolerated by most patients while a fraction of the patients developed biochemical derangements. These results confirm the findings that a beta-blocker alone may be ineffective in lowering blood pressure in hypertensive blacks. The results also show that the efficacy and tolerability of a beta-blocker and a diuretic are enhanced by their combined administration. Finally, the results show that increasing the dose of a beta-blocker or a diuretic does not produce a further increase in its blood pressure lowering effect.

Adult↗

PubMed1992

Chlorthalidone reduces vascular hyperresponsiveness in DOCA-salt hypertensive rats.

The mechanisms of anti-hypertensive effect of diuretics remain unknown. The purpose of this study was to test the hypothesis that long-term treatment with chlorthalidone decreases the responsiveness of resistance vessels to neurohormones. The study was performed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats with and without treatment with chlorthalidone (Chlor. 8 mg/day, for 20 days). Resting mean arterial pressure in freely moving state was significantly reduced in DOCA-salt-Chlor rats when compared to DOCA-salt rats (116 +/- 3 vs 147 +/- 7 mmHg, respectively). Chlorthalidone treatment reduced the high plasma sodium content observed in DOCA-salt rats to the same levels observed in normotensive control groups. Results obtained in isolated perfused mesenteric arteries showed: a) the increase in perfusion pressure elicited by norepinephrine (NE), serotonin (SE) and vasopressin (VP) was significantly greater in DOCA-salt than in DOCA-salt + Chlor rats or control normotensive rats; b) the endothelium removal increased the pressor responses to NE, SE and VP in a similar way in all groups. These data provide evidence that long-term chlorthalidone treatment reduces vascular hyperresponsiveness to these neurohormones. In addition, these results indicate that this reduction in vascular hyperresponsiveness, associated with a decrease in extracellular sodium level, could be a possible mechanism by which the diuretics reduce the high blood pressure.

Animals↗

PubMed1975

[Spironolactone combined with chlorthalidone in the treatment of essential arterial hypertension].

The antihypertensive effect and the tolerance of the association of spironolactone and chlorthalidone were evaluated clinically and by numerous laboratory examinations in a group of 18 patients affected with non-complicated essential hypertension. All the patients were treated for 30 consecutive days with chlorthalidone (100 mg/day) and then for another 30 days with the two drugs administered contemporaneously (100 mg/day of spironolactone + 100 mg/day chlorthalidone). The balanced combination of the two drugs showed to be significantly more active than the treatment with just chlorthalidone and the margin of safety wider; the therapeutic activity showed to be independent from the variations of the plasma renin activity.

Aged↗

PubMed1990

Bisoprolol vs. chlorthalidone: a randomized, double-blind, comparative study in arterial hypertension.

The antihypertensive effect and tolerance of bisoprolol and chlorthalidone were evaluated in a randomized, double-blind, controlled trial during 4 weeks of treatment. A total of46 patients, aged 18-65 years, were initially included; 41 patients presenting with a diastolic blood pressure between 95 and 120 mm Hg at the end of a previous placebo period completed the trial. They were randomly allocated to two groups: 22 patients were treated with bisoprolol 10 mg o.d., and 19 patients with chlorthalidone 50 mg o.d. Both treatments induced a significant reduction in systolic and diastolic blood pressure (p < 0.001). No difference in antihypertensive efficacy was found between the two treatments after 4 weeks. However, with chlorthalidone, significant changes were found with regard to serum potassium (decrease; p < 0.001) and uric acid (increase: p < 0.05) and the incidence of clinical side effects was higher in the chlorthalidone group (37%) in comparison to the patients treated with bisoprolol (13%).

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Acute antihypertensive, diuretic and metabolic effects of etozolin and chlorthalidone.

Etozolin, a new diuretic agent, has shown a dose-dependent diuretic and saluretic effect in both experimental and clinical studies. Etoxolin, when compared to furosemide or thiazides, exerts a similar effect on urinary excretion of water and Na+, but induces a lower urinary K+ and Cl- excretion and a smaller activation of the renin-angiotensin-aldosterone system. Furthermore, the E series of the prostaglandin system seems to play a role in the mechanism of action of the drug. Seven uncomplicated hypertensive patients were included in this double blind, placebo controlled study, according to a latin square design. Each patient received three single oral doses of etozolin (200 mg, 400 mg, 600 mg), of chlorthalidone (25 mg, 50 mg, 75 mg) and one dose of placebo. Etozolin and chlorthalidone caused a similar, dose-dependent antihypertensive and diuretic effect. However, several haemodynamic and metabolic differences were observed between the two drugs. Etozolin, unlike chlorthalidone, caused no increase of heart rate, no decrease of serum K+ levels and a marked rise plasma PGE2. Moreover, etozolin caused a significantly smaller decrease of serum Na levels compared to chlorthalidone, and a significantly lower increase of supine and standing PRA, of plasma aldosterone and of the urinary excretion of Na and K. These results confirm that the acute antihypertensive and diuretic activity of etozolin occur with little involvement of the RAA system and with a significant but still unclear activation of the prostaglandin system.

Antihypertensive Agents↗

PubMed1991

Effects of chlorthalidone and mechanical ventilation on hydroxyprolinuria during immobilization by means of muscle relaxants.

The influence of chlorthalidone on bone resorption in immobilized patients treated with mechanical ventilation was studied. Bone resorption was measured by means of urinary excretion of hydroxyproline and calcium. Blood pH was measured because of a possible effect of mechanical ventilation on calcium metabolism. Twenty-five patients were examined, 14 receiving and 11 not receiving chlorthalidone. Patients receiving chlorthalidone over a period of at least five and a maximum of 27 days showed lower hydroxyprolinuria and a higher blood pH value than the non-users. No differences were observed concerning calcium and phosphate metabolism. It is suggested that this slight alkalosis resulting from chlorthalidone may inhibit bone resorption.

Adolescent↗

PubMed1990

Chlorthalidone alters the vascular reactivity of DOC-salt hypertensive rats to norepinephrine.

Hypertension caused by deoxycorticosterone-salt (DOC-salt) may involve enhanced sympathetic tone and some diuretics may exert their antihypertensive action by modulating presynaptic adrenergic sensitivity. This study analyzes the noradrenergic sensitivity of the perfused mesentery isolated from DOC-salt hypertensive rats treated or not with chlorthalidone. Chlorthalidone treatment reduced arterial hypertension in DOC-salt treated rats (from 160 +/- 7 to 127 +/- 5 mmHg). The diuretic completely prevented the increase in sympathetic tone and blunted the decreased vagal tone observed in DOC-salt rats. Norepinephrine-induced vasoconstriction was enhanced in perfused mesenteries isolated from DOC-salt rats. This alteration was attenuated in preparations from chlorthalidone-treated DOC-salt animals. Blockade of neuronal catecholamine uptake using cocaine did not change these responses. These data suggest that chlorthalidone reduces the vascular hyperresponsiveness to catecholamines observed in DOC-salt treated hypertensive rats.

Animals↗

PubMed1989

Long-term effect of acetazolamide and chlorthalidone on the hearing loss of Menière's disease.

A retrospective computerized analysis of the records of patients with Meniere's disease was made to evaluate the effect of acetazolamide and chlorthalidone on the rate of hearing loss. Three groups were compared as follows: (1) 79 patients treated with chlorthalidone for 5 to 13.4 years; (2) 42 patients medicated with acetazolamide between 5 and 7.8 years; and (3) a control group of 71 patients who received only intermittent symptomatic treatment for vertigo, followed for 5 to 24.1 years. In the short term, after 2 to 6 weeks of treatment, a statistically significant decrease of the average hearing loss was observed with both chlorthalidone and acetazolamide. In the long term, more than 5 years, no preventive effect on the deterioration of the hearing loss could be detected. Both acetazolamide and chlorthalidone can be useful for diagnostic purposes by causing a fluctuation of hearing, as well as for the management of the vertigo attacks, but it is not useful for the long-term prevention of the hearing deterioration in Meniere's disease.

Acetazolamide↗

PubMed1986

Effect of chlorthalidone on zinc levels, testosterone, and sexual function in man.

This study was designed to test the hypothesis that chlorthalidone, a diuretic used to treat hypertension, depletes body zinc enough to interfere with testosterone production and thereby cause sexual dysfunction. Serum and hair zinc, serum testosterone, and sexual function were measured in 19 middle-aged hypertensive men who had been taking chlorthalidone in average daily doses of between 11 and 50 mg per day for at least 6 months, and a control group of 31 unmedicated middle-aged normotensive men. Although the medicated group had a higher incidence of sexual dysfunction (42% as compared to 16% in the control group), use of chlorthalidone did not significantly affect serum testosterone levels. When other variables were controlled for, medicated men had significantly higher serum zinc levels, and men on the highest dosage of chlorthalidone had higher hair zinc levels than all other men. There was no significant correlation between hair zinc, serum zinc, testosterone, and sexual function. Serum zinc decreased significantly with age (p = 0.043) and with ethanol intake after controlling for age (p = 0.032). Sexual dysfunction occurred more often in older men (p = 0.002). In the unmedicated controls, prevalence of dysfunction increased slightly with increasing serum potassium levels.

Adult↗

PubMed1994

Hemodynamic effects of cadralazine or chlorthalidone in verapamil-treated elderly hypertensives.

Fourteen hypertensives aged > 66-77 years, whose diastolic blood pressure (DBP) was > or = 95 mmHg at the end of 1-month treatment with verapamil 240 mg SR, took part in this clinical-hemodynamic study. Patients were randomized to add the long-acting hydralazine derivative, cadralazine, 10 mg once daily, or chlorthalidone 25 mg once daily for 1 month each, to their previous verapamil regimen, according to a double-blind crossover design. Echo-Doppler hemodynamics were performed before starting verapamil, 1 month after verapamil and then after each phase of the crossover study. A significant reduction in DBP both in supine and upright position was observed with both drugs, while the reduction in systolic blood pressure was not significant. Criteria for a satisfactory response were DBP < or = 90 mmHg or a DBP reduction > or = 10 mmHg; this goal was achieved in 9 patients with cadralazine, 9 patients with chlorthalidone, 5 patients with both. The hemodynamic study in responders showed that both cadralazine and chlorthalidone acted through a reduction of peripheral resistances without inducing reflex tachycardia. Thus, cadralazine and chlorthalidone represent a suitable second-step treatment in elderly hypertensives insufficiently controlled by verapamil monotherapy: both drugs act through a reduction in total peripheral resistance (TPR).

Aged↗

PubMedDate not supplied

Efficacy and reduced metabolic side effects of a 15-mg chlorthalidone formulation in the treatment of mild hypertension. A multicenter study.

We compared a new low-dose chlorthalidone formulation consisting of 15 mg of this compound and a biocompatible polymer in a double-blind placebo-controlled trial with the standard 25-mg dose of chlorthalidone in the management of mild essential hypertension. Two hundred twenty-two patients, ranging in age from 21 to 69 years, with an average standing diastolic blood pressure between 91 and 104 mm Hg participated in this trial. At the end of 12 weeks, the percentage of patients who had a decrease in their standing diastolic blood pressure of 5 mm Hg or more was statistically similar in both of the active-treatment groups and significantly different from the placebo group. With the lower-dose compound, the metabolic side effect of hypokalemia was less of a problem and there was no evidence of glucose intolerance. Thus, this new 15-mg formulation of chlorthalidone appears to be an effective antihypertensive agent with fewer metabolic side effects compared with the standard 25-mg dose in the management of mild essential hypertension.

Adult↗

PubMed1980

Serum lipoprotein levels during chlorthalidone therapy. A Veterans Administration-National Heart, Lung, and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

In a joint Veterans Administration-National Heart, Lung, and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age and with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups. Subjects in the active group received chlorthalidone or chlorthalidone plus reserpine, while the other subjects received matching placebo tablets. After one year of treatment, the chlorthalidone group had increases of 10.0 +/- 1.8 (SE) mg/dL in total cholesterol level, 9.8 +/- 5.2 mg/dL in triglyceride level, and 12.6 +/- 3.4 mg/dL in low-density lipoprotein-cholesterol level above the changes in the placebo group. There was no difference in high-density lipoprotein changes between the two groups (0.1 +/- 0.8 mg/dL). The possible net effect on risk of increasing lipid values while lowering pressure in the long-term treatment of mild hypertension with thiazides or related diuretics must be further evaluated.

Adult↗

PubMed1978

Dose response to chlorthalidone in patients with mild hypertension. Efficacy of a lower dose.

A multicenter study of chlorthalidone was performed to determine the relative antihypertensive efficacy and side effects of doses lower than those usually recommended for therapy. After a 4-wk placebo control period 100 patients with mild hypertension were randomly assigned doubleblind to 12.5-, 25-, 50-, or 75-mg regimens of chlorthalidone or to placebo for 12 wk. The groups of patients taking 25, 50, and 75 mg had declines in blood pressure which were not significantly different from each other. Serum potassium decreased in the 50- and 75-mg groups but not significantly in the 25-mg group. We conclude that chlorthalidone, 25 mg daily, was at least as effective for hypertension as 50 and 75 mg with less perturbation of potassium. Use of smaller initial diuretic doses may provide equal efficacy with fewer side effects for many patients.

Adult↗