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At least 19 recordsLinked to original sources
PubMed1985

Blood pressure lowering and potassium conservation by triamterene-hydrochlorothiazide and amiloride-hydrochlorothiazide in hypertension.

Effects of once-daily doses of 50 mg triamterene with 25 mg hydrochlorothiazide and 5 mg amiloride with 50 mg hydrochlorothiazide were compared in a randomized, multicenter study of 84 adult subjects with mild to moderate hypertension (diastolic blood pressure 90 to 114 mm Hg). After a 3-wk placebo lead-in period, the subjects entered a 6-wk treatment period. The two drug regimens were compared with respect to antihypertensive effects and effects on serum potassium and magnesium levels during the final week of drug therapy, with the use of the last week of placebo therapy as a covariate. Both drug regimens substantially reduced mean supine systolic and diastolic blood pressures to well within normal limits; there was no significant difference the two groups. Twenty-four of the 41 subjects receiving triamterene-hydrochlorothiazide (59%) and 29 of the 43 patients receiving amiloride-hydrochlorothiazide (67%) had diastolic blood pressure less than 90 mm Hg at week 9. Five subjects receiving amiloride-hydrochlorothiazide (12%) and two subjects receiving triamterene-hydrochlorothiazide (5%) had hypokalemia (serum potassium level less than 3.5 mEq/l) at week 9. The average decrease in serum potassium levels during amiloride-hydrochlorothiazide therapy (-0.33 +/- 0.08 mEq/l) was greater than that after triamterene-hydrochlorothiazide (- 0.08 +/- 0.07 mEq/l). Serum magnesium levels were not changed by either regimen. Weight loss was greater in the amiloride-hydrochlorothiazide group than in the triamterene-hydrochlorothiazide group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

An equivalence study of the safety and efficacy of a fixed-dose combination of perindopril with indapamide versus fixed-dose combinations of captopril with hydrochlorothiazide and enalapril with hydrochlorothiazide in the treatment of hypertension.

OBJECTIVE: The aim of this multicenter, randomly allocated, double-blind, parallel-group study was to evaluate the equivalence of three fixed-dose combination drugs in mild to moderate hypertension: perindopril + indapamide (4 + 1.25 mg), captopril + hydrochlorothiazide (50 + 25 mg) and enalapril + hydrochlorothiazide (20 + 12.5 mg). PATIENTS AND METHODS: After a single-blind, 4-week, placebo run-in phase, 527 patients (mean +/- SD age 54.5 +/- 1.2 years) with a supine diastolic blood pressure of 101.2-101.7 mmHg were randomly assigned to one of the three treatments for 8 weeks. The main evaluation criteria were diastolic blood pressure and serum potassium concentration. Equivalence was assessed on an intention-to-treat basis, using Schuirmann's method, which involves performing two one-tailed statistical tests on the data. Thirty-five patients were withdrawn from the study but there were no differences between groups in the reasons for withdrawal. RESULTS: Diastolic blood pressure decreased by between 13.1 and 14.2 mmHg in the three groups. The 90% confidence intervals for the differences between perindopril + indapamide and the other treatments were -1.1, +1.7 mmHg for captopril + hydrochlorothiazide and -0.4, +2.6 mmHg for enalapril + hydrochlorothiazide. Schuirmann's test was highly statistically significant (P<0.001 for perindopril + indapamide versus captopril + hydrochlorothiazide; P<0.002 for perindopril + indapamide versus enalapril + hydrochlorothiazide), so that the two one-sided hypotheses that the treatments were not equivalent were rejected at the nominal level of alpha = 0.05. Similarly, the safety of the treatments was equivalent in terms of serum potassium. The 90% confidence intervals of the differences between perindopril + indapamide and the other treatments were -8.7, -1.6% for captopril + hydrochlorothiazide (P = 0.004) and -1.5, +2.7% for enalapril + hydrochlorothiazide (P<0.001). CONCLUSIONS: We conclude that the safety and efficacy of perindopril + indapamide, captopril + hydrochlorothiazide and enalapril + hydrochlorothiazide were equivalent after 8 weeks of treatment in patients with mild to moderate hypertension.

Adolescent↗
PubMed1981

Multiclinic comparison of amiloride, hydrochlorothiazide, and hydrochlorothiazide plus amiloride in essential hypertension. Multicenter Diuretic Cooperative Study Group.

A randomized, double-blind, multicenter study comparing amiloride hydrochloride, amiloride hydrochloride plus hydrochlorothiazide, and hydrochlorothiazide was conducted in 179 patients with mild to moderate essential hypertension (diastolic pressure, 95 to 115 mm Hg). After 12 weeks of treatment, significant reductions in pressure were observed for all three treatment groups. Systolic pressure reduction was greatest for amiloride plus hydrochlorothiazide. Baseline vs 12-week average supine pressures were 153/101 vs 139/93 mm Hg for amiloride, 160/100 vs 137/90 mm Hg for amiloride plus hydrochlorothiazide, and 154/101 vs 134/89 mm Hg for hydrochlorothiazide. Baseline vs treatment mean serum potassium levels were 4.24 vs 4.47 mEq/L for amiloride, 4.24 vs 3.86 mEq/L for the combination, and 4.15 vs 3.56 mEq/L for hydrochlorothiazide. The changes in serum potassium level from the baseline for amiloride plus hydrochlorothiazide were significantly different from those for hydrochlorothiazide throughout the study (except for week 6). All drugs were well tolerated, and no drug-related toxic reaction was detected. This study demonstrates the efficacy of amiloride and amiloride plus hydrochlorothiazide as diuretic antihypertensive potassium-conserving agents.

Adult↗
PubMed1994

Interaction of allopurinol and hydrochlorothiazide during prolonged oral administration of both drugs in normal subjects. II. Kinetics of allopurinol, oxipurinol, and hydrochlorothiazide.

The kinetics of allopurinol and hydrochlorothiazide were investigated in seven healthy male subjects during prolonged coadministration of two drugs. Subjects were maintained on an isoenergetic, purine-free formula diet with RNA supplementation for 24 days. Allopurinol (300 mg) was given orally on days 1-24. Hydrochlorothiazide (50 mg daily) was added to days 11-21. On day 43 a single oral dose of 50 mg hydrochlorothiazide was administered. Plasma concentration-time profiles of allopurinol and its main metabolite oxipurinol were obtained on days 1, 10, and 21; hydrochlorothiazide profiles were assessed on days 21 and 43. In addition, 24-h plasma concentrations of oxipurinol were measured repetitively, and 24 h urine samples were collected for the determination of allopurinol, oxipurinol, and hydrochlorothiazide. For oxipurinol, mean Cmax was not altered on hydrochlorothiazide treatment (13.8 +/- 1.4 micrograms/ml and 14.7 +/- 2.6 micrograms/ml, respectively); mean AUC0-24 was 259 and 290 micrograms h-1 ml-1, respectively. The small difference in AUC0-24 values does not explain the increase in plasma uric acid concentration during hydrochlorothiazide treatment, nor do the variations in allopurinol and hydrochlorothiazide kinetics.

Administration, Oral↗
PubMed1986

Comparison of low doses of hydrochlorothiazide plus amiloride and hydrochlorothiazide alone in hypertension in elderly patients.

A randomised, double-blind study comparing 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride with 25 mg of hydrochlorothiazide alone was conducted in 40 elderly patients with mild to moderate hypertension. After 8 weeks of treatment, the target blood pressure, supine diastolic blood pressure less than 90 mm Hg, was obtained in 73% of the hydrochlorothiazide plus amiloride treated patients (n = 17) and in 41% of the hydrochlorothiazide treated patients (n = 19; p less than 0.05). However, there was no statistically significant difference in blood pressure reduction between the 2 groups. Four patients dropped out, 3 of them due to side-effects. Serum potassium and magnesium concentrations were reduced in the hydrochlorothiazide group and serum sodium concentration in the hydrochlorothiazide plus amiloride group. Our results suggest that in elderly hypertensive subjects, a higher proportion of patients could be managed with the low dose hydrochlorothiazide plus amiloride regimen than with the low dose hydrochlorothiazide regimen.

Aged↗
PubMed1986

Antihypertensive therapy with triamterene-hydrochlorothiazide vs amiloride-hydrochlorothiazide. Comparison of effects on urinary prostaglandin E2 excretion.

Amiloride hydrochloride has now been recognized as a safe and effective potassium-sparing diuretic alternative to triamterene with a similar mechanism of pharmacologic activity. Studies were undertaken to assess the difference between therapy with the triamterene-hydrochlorothiazide combination (Dyazide) and an amiloride hydrochloride-hydrochlorothiazide combination (Moduretic) on renal prostaglandin production, since an increase in renal prostaglandin synthesis has been shown to mediate or enhance the pharmacologic action of certain diuretic drugs. Eight subjects treated for four weeks with triamterene-hydrochlorothiazide were compared with nine patients similarly treated with amiloride-hydrochlorothiazide. A 24-hour urine sample for prostaglandin E2 (PGE2) assay was collected under control conditions and after six weeks of therapy with either diuretic in all patients. The PGE2 excretion increased in the amiloride-hydrochlorothiazide-treated group; in the other group PGE2 excretion actually declined. It is concluded from these studies that therapy with amiloride-hydrochlorothiazide enhanced renal PGE2 production, whereas that with triamterene-hydrochlorothiazide actually decreased renal PGE2 production. This difference is an important renal consequence of the use of either drug and should be considered in the choice between these diuretic combinations.

Amiloride↗
PubMed1986

Clinical efficacy and cost comparison of an amiloride-hydrochlorothiazide combination versus hydrochlorothiazide and wax-matrix potassium supplement in the treatment of essential hypertension.

To compare the clinical efficacy and cost of therapy with an amiloride-hydrochlorothiazide combination versus hydrochlorothiazide and a wax-matrix potassium supplement, we reviewed the medical records of 20 hypertensive men who had received both treatments. The review period included 5.9 +/- 0.9 (mean +/- SE) months on hydrochlorothiazide and wax-matrix potassium and 5.3 +/- 0.7 months after changeover to the amiloride-hydrochlorothiazide combination. Control of blood pressure, maintenance of serum potassium levels, and number of outpatient visits were similar before and after the change in therapy. The monthly cost of medication, based on the lowest listed price in the Drug Topics Red Book and also in the Red Book Update, was approximately 12% higher for the hydrochlorothiazide and wax-matrix potassium regimen than for the amiloride-hydrochlorothiazide combination, whereas the federal agency contract price for the latter was significantly higher. The change to the amiloride-hydrochlorothiazide combination reduced the mean number of tablets taken daily from 5.3 +/- 0.6 to 1.25 +/- 0.1, suggesting a more convenient therapeutic regimen.

Adult↗
PubMed1985

Hydrochlorothiazide-amiloride versus hydrochlorothiazide alone for essential hypertension: effects on blood pressure and serum potassium level.

In a double-blind randomized controlled trial the effects on the blood pressure and the serum potassium concentration of hydrochlorothiazide-amiloride hydrochloride (Moduret) and hydrochlorothiazide alone were compared in 266 adults who were normokalemic and had a diastolic blood pressure greater than 95 mm Hg at the time of entry into the study. The mean ages (52.2 and 53.8 years) and the proportions of men (66% and 56%) in the groups given the combination drug and hydrochlorothiazide alone respectively were similar. In the group given the combination drug the mean blood pressure, measured while the patients were supine, and the mean serum potassium level fell significantly, from 156/99 to 138/88 mm Hg and from 4.23 to 3.91 mmol/L, after 8 weeks of treatment. In the other group both measures also fell significantly, the blood pressure from 157/99 to 138/87 mm Hg and the potassium level from 4.16 to 3.69 mmol/L. The proportions of patients in the two groups with hypokalemia (14% and 29% respectively), defined as a serum potassium level below 3.5 mmol/L, differed significantly (p = 0.0026), whereas the proportions with a potassium level exceeding 4.5 mmol/L (4.5% and 3.9% respectively) were similar. Thus, the combination drug reduced the blood pressure to the same extent as hydrochlorothiazide alone but significantly less often caused hypokalemia. In light of growing concerns about the cardiovascular complications of hypokalemia, hydrochlorothiazide-amiloride appears preferable to hydrochlorothiazide alone for the treatment of some patients with hypertension.

Adolescent↗
PubMed1985

Hydrochlorothiazide and potassium chloride in comparison with hydrochlorothiazide and amiloride in the treatment of mild hypertension.

A randomized, double-blind, cross-over study comparing 50 mg hydrochlorothiazide plus 5 mg amiloride (HCTZ/A) with 50 mg hydrochlorothiazide plus 26 mmol potassium chloride (HCTZ/K) was conducted in 18 patients with mild essential hypertension (diastolic pressure 90-105 mmHg). The sequence of treatment was: placebo for 2 weeks, one active drug for 3 weeks, placebo for 2 weeks, the other active drug for 3 weeks. The two agents were significantly and equally efficacious in lowering the systolic and diastolic blood pressure. Baseline vs. treatment mean serum potassium levels were 3.82 vs. 3.78 mmol/l for HCTZ/A and 3.82 vs. 3.70 mmol/l for HCTZ/K. The decrease in serum potassium level from baseline was significant for both agents but not significantly different when the two treatment forms were compared. Both treatment forms elevated fasting serum cholesterol and glucose. Serum triglycerides and uric acid rose significantly with HCTZ/K. Amiloride may affect the tubular handling of uric acid causing increased uric acid excretion, thus counteracting thiazide-induced hyperuricemia. During 3 weeks' extension of the main study, 5 patients received HCTZ/A in double the original dose (100 mg/10 mg) and 6 patients received HCTZ/K in double the original dose (100 mg/52 mmol). No further blood pressure reduction was observed on treatment with these doses. The mean serum potassium levels did not decrease further on doubling the HCTZ/A dose, while a significant fall was observed for HCTZ/K (3.60 vs. 3.42 mmol/l) (p less than 0.05, single tailed t-test). Both drug combinations were well tolerated and side-effects were not significantly different from those during placebo administration. This study demonstrates that 50 mg hydrochlorothiazide plus 26 mmol potassium chloride are as effective as 50 mg hydrochlorothiazide plus 5 mg amiloride, both in reducing blood pressure and preventing hypokalaemia in the treatment of essential hypertension. A small extension study indicates that amiloride might be more effective than potassium chloride in preventing hypokalaemia when high doses (100 mg/day) of hydrochlorothiazide are administered.

Adult↗
PubMed1981

Comparative study of hydrochlorothiazide and a fixed combination of metoprolol and hydrochlorothiazide essential hypertension.

In a double-blind study comprising 31 patients with essential hypertension not satisfactorily controlled on hydrochlorothiazide 25 mg o.m., a fixed-ratio combination of metoprolol 100 mg and hydrochlorothiazide 12.5 mg, given as 2 tablets o.m. has been compared with hydrochlorothiazide 50 mg o.m. monotherapy. With the combination regimen a significant reduction of blood pressure was achieved while doubling of the thiazide dose did not adequately control the blood pressure. In 7 patients in the thiazide-group the therapy was changed to the combination during a follow-up period and their blood pressure was normalised. During the follow-up period, 22 patients were thus treated with the fixed combination; 50% of them were controlled on one tablet o.m. The tolerability was good in both groups and no changes were observed regarding laboratory variables except for an increase in serum uric acid in the thiazide-group. The study indicates that a fixed-ratio combination of hydrochlorothiazide 12.5 mg and metoprolol 100 mg in a dose of one or two tablets once daily is a well tolerated and more effective therapy than hydrochlorothiazide 50 mg once daily monotherapy.

Adult↗
PubMed1981

Antihypertensive effect of oral timolol maleate and hydrochlorothiazide once daily compared with hydrochlorothiazide once daily.

The efficacy and safety of timolol maleate combined with hydrochlorothiazide given once daily compared with hydrochlorothiazide given once daily to patients with hypertension was investigated in a double-blind, randomized study. Patients with uncomplicated, mild to moderate hypertension were admitted to the study. Ten patients received two tablets once daily of timolol maleate 10 mg and hydrochlorothiazide 25 mg (T/H). Nine patients received hydrochlorothiazide 25 mg (HCTZ). Blood pressure and pulse rate measurements and laboratory tests were performed after a six-week placebo baseline period and throughout the 12-week study. Mean supine systolic blood pressure decreased by 21-35 mm Hg for the T/H group and by 10-24 mm Hg for the HCTZ group. Mean supine diastolic blood pressure decreased by 15-22 mm Hg for the T/H group and by 10-13 mm Hg for the HCTZ group. Changes observed in the laboratory variables were not statistically significant between the two treatment groups. One patient in each group had an adverse experience considered unrelated to the drug, and no patient had to discontinue the drug therapy because of an adverse reaction. Although both drug regimens effectively and safely treated uncomplicated mild to moderate hypertension, the timolol maleate and hydrochlorothiazide combination had a greater antihypertensive effect.

Adult↗
PubMedDate not supplied

Enalapril and enalapril-hydrochlorothiazide in the treatment of essential hypertension. The Enalapril-Hydrochlorothiazide in Essential Hypertension Canadian Working Group.

A total of 217 patients with essential hypertension were enrolled by 25 Canadian centers in this double-blind, parallel study to compare the efficacy and safety of enalapril administered alone or in combination with hydrochlorothiazide. After a 4-week placebo period, patients were given 10 mg of enalapril for 2 weeks. At the end of the 2 weeks of therapy, patients were maintained on the same dose of enalapril, titrated to a higher dose of enalapril, or received combination therapy with hydrochlorothiazide if their diastolic blood pressure remained > 90 mmHg. Patients in group 1 received enalapril 10 mg or 20 mg and those in group 2 received enalapril 10 mg alone or combined with hydrochlorothiazide 25 mg. The maintenance phase lasted 8 weeks. A standard mercury sphygmomanometer was used to measure blood pressure at each visit. The mean decrease in supine diastolic blood pressure (SDBP) was 16 mmHg in groups 1 and 2; the mean decrease in supine systolic blood pressure (SSBP) was 19 mmHg in group 1 and 20 mmHg in group 2. Eighty percent of the patients in group 1 and 81% of those in group 2 had an SDBP < or = 90 mmHg at the final visit. To achieve this control, 67% of the patients received enalapril 10 mg and 33% received enalapril 20 mg in group 1. In group 2, 70% of the patients received enalapril 10 mg and 30% received enalapril 10 mg plus hydrochlorothiazide 25 mg. Eighteen patients in group 1 and 17 patients in group 2 experienced one or more minor adverse events. The most frequently reported adverse events were headache, asthenia, abdominal pain, nausea, and dizziness. No major adverse events were observed. We conclude that enalapril used alone reduces blood pressure in the majority of patients with mild to moderate essential hypertension. When blood pressure is not controlled by enalapril alone, hydrochlorothiazide can safely be added to the regimen.

Adult↗
PubMed1997

The effects of antihypertensive combination therapy on lipid and glucose metabolism: hydrochlorothiazide plus sotalol vs. hydrochlorothiazide plus captopril.

Metabolic side-effects of antihypertensive drugs may increase the risk of coronary heart disease despite an adequate blood pressure reduction. Since combinations of different antihypertensive drugs are often necessary and frequently used, we performed a randomized study comparing the effects of a fixed combination of hydrochlorothiazide and sotalol (group A), or hydrochlorothiazide and captopril (group B) on blood pressure and on lipid and glucose metabolism in 40 men with essential hypertension over 1 year. Significant blood pressure reductions (p < 0.001) were achieved in both treatment groups: from 160/105 to 128/88 mmHg in group A (mean doses: hydrochlorothiazide 33 and sotalol 197 mg) and from 162/106 to 135/89 mmHg in group B (hydrochlorothiazide 33 and captopril 64 mg) after 12 months, respectively. No significant changes in body weight were observed in either treatment group. Triglycerides increased (p < 0.05) in both treatment groups (from 183 to 262 mg/dl in A, and from 160 to 196 mg/dl in B) and HDL cholesterol decreased (p < 0.001 and < 0.05) in both groups (from 45.1 to 35.7 mg/dl in A, and from 49.3 to 46.3 mg/dl in B), whereas LDL cholesterol increased significantly (p < 0.05) only in group A from 153 to 164 mg/dl. No significant changes were observed in total cholesterol nor in lipoprotein(a) concentrations in either treatment group. Fasting plasma glucose and hemoglobin A1 increased significantly (p < 0.05) only in group A after 1 year of treatment (from 91.6 to 98.0 mg/dl, and from 6.3 to 6.9%, respectively). Serum levels of creatinine and potassium decreased, and uric acid increased significantly under either combination. Our data show that the diuretic/beta-blocker combination has adverse effects on lipid and glucose metabolism after long-term therapy. The effects of the diuretic/ACE inhibitor combination on lipid metabolism are less pronounced and there are no adverse effects on glucose metabolism. However, the ACE inhibitor component could not completely counteract the metabolic effects of the diuretic. Both combinations have no effects on Lp(a). We conclude that the combination of hydrochlorothiazide with an ACE inhibitor has a better metabolic profile for the treatment of essential hypertension than the combination with a beta-blocker.

Adrenergic beta-Antagonists↗
PubMed1989

[Efficacy and tolerability of captopril-hydrochlorothiazide vs amiloride-hydrochlorothiazide combination in mild to moderate arterial hypertension].

Forty patients, mean age 56.87 yrs. with light or moderate essential arterial hypertension were randomized double-blind into two subgroups of 20 subjects each, and submitted to daily combined drug treatment with either captopril 50 mg + hydrochlorothiazide 25 mg (group A) or amiloride 5 mg + hydrochlorothiazide 50 mg (group B). Patients were monitored after the washout period and after 4 and 8 weeks of treatment approximately 20-24 after the last dose. The following parameters were studied: blood pressure, heart rate, body weight, untoward side effects. Standard laboratory tests were performed in all patients after washout and at the end of the 8-week treatment period. Both combinations significantly reduced pressure values but the captopril-hydrochlorothiazide combination reduced blood pressure more readily and proved more effective in reducing diastolic values. There were no dropouts due to subjective side effects which were of little relevance and were equally distributed among the two groups. As for laboratory data, patients taking the captopril-hydrochlorothiazide combination had a statistically significant increase in blood glucose. Neither combination induced significant changes in the other parameters, especially as far as potassemia was concerned.

Aged↗
PubMed1984

Reserpine plus hydrochlorothiazide and sotalol plus hydrochlorothiazide in Black and Indian hypertensive patients.

Fifty patients (25 Blacks and 25 Indians) suffering from mild-to-moderate hypertension (supine diastolic blood pressure 100 - 105 mmHg) were studied in order to compare the antihypertensive effect of a combination of a beta-blocker (sotalol hydrochloride 160 mg/d) plus a thiazide derivative (hydrochlorothiazide 25 mg/d) ( Sotazide ; B-M) with that of a combination of reserpine 0,1 mg/d ( Serpasil ; Ciba) plus hydrochlorothiazide 25 mg/d ( Dichlotride ; Frosst MSD). The combination of reserpine plus hydrochlorothiazide was found to be as effective as that of sotalol plus hydrochlorothiazide in lowering the blood pressure in both the Black and the Indian patients. Two patients taking the combination containing reserpine developed side-effects, but this did not occur in any of those taking the combination containing sotalol. We feel that in developing countries, where the cost of therapy is important, reserpine in a dosage of less than 0,1 mg/d plus a thiazide derivative in low dosage is preferable to a beta-blocker plus a thiazide derivative in the treatment of hypertension.

Blood Pressure↗
PubMed1977

Long term effect of timolol and hydrochlorothiazide, or hydrochlorothiazide and amiloride, in essential hypertension.

Twenty-four patients with mild to moderate hypertension were treated for up to 60 weeks with hydrochlorothiazide and either placebo, timolol, or timolol and amiloride. The effect of adding timolol and amiloride to hydrochlorothiazide was evaluated in a double blind trial. In 22 of the 24 patients a supine diastolic blood pressure below or equal to 95 mm Hg was produced by hydrochlorothiazide and timolol. Replacing a potassium supplement with amiloride increased the antihypertensive effect.

Adult↗
PubMedDate not supplied

Double-blind comparison of triamterene plus hydrochlorothiazide and spironolactone plus hydrochlorothiazide in the treatment of hypertension.

The results from this double-blind, multi-investigator study showed that a combination of 50 mg triamterene plus 25 mg hydrochlorothiazide and a combination of 25 mg spironolactone plus 25 mg hydrochlorothiazide were equally efficacious in lowering blood pressure in hypertensive outpatients, and that they produced the same type and incidence of adverse effects. Likewise, the two drug combinations produced similar effects on blood chemistry and hematology. There were no significant differences between the two combination drugs in efficacy laboratory studies, or adverse effects.

Adult↗