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PubMed1980

Pharmacokinetics of atenolol in hypertensive subjects with and without co-administration of chlorthalidone.

The pharmacokinetics of atenolol with and without the co-administration of chlorthalidone were studied in five hypertensive subjects. Concomitant administration of chlorthalidone appears to have little if any effect on the pharmacokinetics of atenolol during treatment for 7 days. The atenolol elimination half-lives were 6.7 +/- 1.1 and 6.3 +/- 0.9 h, respectively, with and without chlorthalidone. Two healthy volunteers also received a single 50 mg oral dose of chlorthalidone. Their blood profiles and pharmacokinetics were similar to those observed in hypertensive subjects, but a statistically significant difference (p < 0.01) was found between the urinary excretion half-lives of chlorthalidone. This difference may be because chronic administration of the drug caused saturation of red cell binding.

Adult↗

PubMed1976

Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses.

A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorathidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n = 10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those preducted from the single oral dose studies in healthy volunteers.

Adult↗

PubMed1976

Cardiovascular response to exercise under increasing doses of chlorthalidone.

Five male subjects with essential hypertension received chlorthalidone at each of four dose levels (25, 50, 100, and 200 mg/day) for eight week periods each preceded by an eight week placebo period. Dosage order was randomized and double-blind. During the last week of each active and placebo period an upright bicycle exercise study was carried out at three loads (100, 200, 300 kpm/min) for 6 min each. Oxygen consumption at the maximal workload was 42% of predicted at a heart rate of 170. During placebo therapy, increasing workloads were associated with a progressive increase in blood pressure, heart rate, and pressure-rate index (systolic pressure times heart rate). With increasing doses of chlorthalidone up to 100 mg/day, there was a progressive reduction in blood pressure and pressure-rate index. At 200 mg/day there were paradoxical increases in diastolic pressures, heart rates and pressure-rate indices above values observed at 100 mg/day. With increasing doses of chlorthalidone, there was a progressive increase in arterial blood CO2 content and pH. Increasing workloads were associated with increased arterial blood lactate and decreased arterial blood lactate and decreased arterial blood pH. The changes in lactate and pH were not different at the different dose levels. The best antihypertensive effect in these exercising subjects was observed at a daily dose of 100 mg of chlorthalidone. The exercise response was useful in the determination of potentially adverse hemodynamic consequences of the larger dose of chlorthalidone.

Adult↗

PubMed1985

Systolic Hypertension in the Elderly Program (SHEP): antihypertensive efficacy of chlorthalidone.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, blinded test of the efficacy of antihypertensive drug treatment. In a large feasibility trial, 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone (25 to 50 mg/day) or matching placebo as the step I drug. After 1 year, 83% of the chlorthalidone group and 80% of the placebo group were still taking SHEP medications. Of those still taking chlorthalidone, 88% had reached goal blood pressure (BP) without requiring a step II drug, and most had responded to the lower dose (25 mg/day). The BP response was similar in all age, sex and race subgroups, with an overall mean difference between randomized groups of 17 mm Hg for systolic BP (p less than 0.001) and 6 mm Hg for diastolic BP (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum levels of potassium (0.5 mEq/liter lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001) and creatinine (0.08 mg/dl higher, p = 0.02). This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease.

Aged↗

PubMed1986

A comparison of celiprolol and chlorthalidone in hypertensive patients with reversible bronchial obstruction.

The objective of this study was to evaluate the effects of celiprolol, a new beta-blocking drug, on the clinical condition and pulmonary function of hypertensive patients with reversible bronchial obstruction. Celiprolol was compared with chlorthalidone, an antihypertensive drug without known effect on bronchial tone. The study consisted of a 4-week placebo run-in period and a 12-week titration period in which the dose of both drugs was increased at 4-week intervals if blood pressure was not reduced adequately. The doses of celiprolol were 200, 400, or 600 mg once daily; those for chlorthalidone 12.5, 25, or 37.5 mg once daily. Entry criteria were a diastolic blood pressure between 90 and 115 mg Hg, and FEV-1 between 40% and 80% of predicted value, increasing by 15% or more after salbutamol, and a need for occasional bronchodilator therapy. Prophylactic medication for asthma was given in constant dosage for a month before the study and throughout the study. Preliminary results on 66 patients demonstrate that neither drug had a clinically significant effect on FEV-1, FEF 25-75, or FVC. Clinical variables were not significantly changed by either drug: the average monthly asthma attacks fell from 18 to 13 with celiprolol and from 11 to 7 with chlorthalidone. FEF was reduced by more than 50% in two patients on celiprolol and three on chlorthalidone. Monthly asthma attacks increased by more than 100% in five patients on celiprolol and four on chlorthalidone. Thus, preliminary results are unable to demonstrate adverse effects from celiprolol in patients with asthma and hypertension.

Adrenergic beta-Antagonists↗

PubMed1989

Effects of chlorthalidone, oxprenolol, and their combination in hypertensive blacks: a randomized double-blind crossover study.

One hundred twenty black patients with mild to moderate essential hypertension participated in a double-blind placebo-controlled crossover study of the efficacy and tolerability of slow release oxprenolol versus chlorthalidone singly and in combination. Oxprenolol as monotherapy produced no effect on blood pressure as compared with placebo even after doubling the dose. Chlorthalidone as monotherapy produced a significant decrease in blood pressure (p less than 0.01). Combining oxprenolol with chlorthalidone yielded hypotensive effects in excess of those of either of the components given singly. Oxprenolol produced a significant decrease in plasma renin activity (PRA) whereas chlorthalidone produced a significant increase in PRA. These results indicate that a beta-blocking agent alone is ineffective in lowering blood pressure in hypertensive blacks, even when the dose is high. Oxprenolol may increase the hypotensive effect of chlorthalidone by counteracting the hypokalemic effect of the diuretic and by attenuating the diuretic-induced increase in plasma renin activity.

Adrenergic beta-Antagonists↗

PubMed1976

Effects of chlorthalidone on serum and total body potassium in hypertensive patients.

Total body potassium has been estimated in 26 hypertensive patients who were hypokalaemic as a result of long-term chlorthalidone treatment (mean 20.5 months), while they were on chlorthalidone and 4 weeks after this had been discontinued. The mean difference amounted to only 95 mEq (not significant). In 6 additional patients not previously treated with chlorthalidone, serial total body potassium estimations revealed a mean potassium deficiency of 245 mEq after 33 days and of 106 mEq after 100 days. These results suggest that the mechanism causing the initial potassium loss is partly reversed or compensated later on. In patients with uncomplicated hypertension, no significant potassium deficiency was detected during long-term treatment. Eighteen of our patients received 39 mEq potassium chloride supplements daily for 4 weeks; this caused a mean rise in serum potassium from 3.23 mEq/l to 3.38 mEq/l (not significant). Total body potassium did not change at all. We conclude that potassium chloride supplements are not an effective treatment of hypokalaemia in this condition. Correction of the extracellular pH by ammonium chloride in 6 patients on chlorthalidone, who demonstrated a slight metabolic alkalosis, gave rise to a mean increase in plasma potassium from 2.78 mEq/l to 2.96 mEq/l (not significant). The hypokalaemia in hypertensive patients on long-term chlorthalidone treatment cannot be explained by either a potassium deficiency or the change in extracellular pH.

Adult↗

PubMed1984

Mechanism of chronic hypocalciuria with chlorthalidone: reduced calcium absorption.

Chlorthalidone, like other benzothiadiazides, lowers urine calcium excretion chronically. If intestinal calcium absorption did not fall or bone accretion did not increase, serum calcium and the filtered load of calcium would increase and urine calcium would return to pretreatment levels. To determine whether overall intestinal calcium absorption fell, we fed chlorthalidone (5 mg X kg body wt-1 X 24 h-1) to 10 adult male rats eating 15 g/day of a 0.6% calcium diet. Compared with 10 control rats, chlorthalidone reduced urine calcium [2.1 +/- 0.1 (SE) vs. 5.8 +/- 0.5 mg/6 days; P less than 0.001]. Fecal calcium rose (307 +/- 9 vs. 257 +/- 12; P less than 0.005) because percent intestinal calcium absorption fell (41 +/- 2 vs. 52 +/- 2; P less than 0.002). Twenty other rats given the same diet were injected subcutaneously with 1,25(OH)2D3 (50 ng/day). In these rats, chlorthalidone reduced urine calcium (23 +/- 3 vs. 59 +/- 3; P less than 0.001) and percent intestinal calcium absorption (60 +/- 1 vs. 66 +/- 1; P less than 0.01). With or without 1,25(OH)2D3, chronic administration of chlorthalidone reduces intestinal calcium absorption, and this reduction seems to be the mechanism that permits urine calcium excretion to remain low.

Animals↗

PubMed1994

Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.

Diuretics have been the mainstay of long-term treatment of hypertension, but there is no evidence suggesting that diuretics may be effective in reducing cardiac hypertrophy associated with hypertension. Thus, the present study was carried out to elucidate if long-term treatment with chlorthalidone (8 mg per animal per day added to food) affects the development of and reverses the ventricular hypertrophy in deoxycorticosterone acetate (DOCA) (8 mg/kg SC twice a week)-salt hypertensive rats. Chlorthalidone was given to one group during all 20 days of DOCA administration (preventive regimen) and to another group 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). Chlorthalidone was found to reduce or prevent the development of ventricular hypertrophy, as assessed by a reduction in ventricular mass and cardiac protein as well as arterial hypertension. Both chlorthalidone regimens prevented the increase or induced a significant decrease in the plasma concentration of sodium and in cardiac sympathetic tone, which were both increased in DOCA-salt-treated rats. These data provide evidence that long-term chlorthalidone treatment is effective in preventing or reducing ventricular hypertrophy along with arterial hypertension. However, whether this is due to a reduction in plasma sodium or other additional mechanisms, such as a reduction in cardiac sympathetic tone, remains to be determined.

Animals↗

PubMed2001

Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease.

OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6+/-4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5+/-3.8) and diltiazem (3.2+/-4.2) when compared with placebo (7.9+/-8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2+/-31.9min; diltiazem: 19.3+/-29.6min; placebo: 46.1+/-55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Aged↗

PubMed2002

Relationship of antihypertensive treatment regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly assigned to doxazosin or chlorthalidone: further analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial.

BACKGROUND: The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial reported that treatment initiated with doxazosin compared with chlorthalidone doubled the risk for heart failure in high-risk hypertensive patients (relative risk, 2.04 [95% CI, 1.79 to 2.32]). Patients assigned to doxazosin therapy had a mean in-trial systolic/diastolic blood pressure 3/0 mm Hg higher than that in patients assigned to chlorthalidone. Sixty-eight percent (6167 of 9061) of the former patients and 59% (9081 of 15 256) of the latter patients were given additional medications to achieve a target blood pressure of less than 140/90 mm Hg. OBJECTIVE: To ascertain the influence of open-label antihypertensive drugs and subsequent blood pressure on relative risk for heart failure. DESIGN: Randomized, double-blind, active-controlled clinical trial. SETTING: 623 sites in the United States and Canada. PATIENTS: Hypertensive patients 55 years of age or older with at least one additional risk factor for cardiovascular disease. INTERVENTION: Chlorthalidone (12.5 to 25 mg/d) or doxazosin (2 to 8 mg/d) for a planned follow-up of 4 to 8 years. MEASUREMENTS: Data on blood pressure, medication, and incident heart failure (treated outside hospital, hospitalized, or fatal) from February 1994 through December 1999. RESULTS: After the treatment groups were categorized as having no exposure to open-label medications (monotherapy) or exposure to open-label therapy, the relative risk for heart failure with doxazosin versus chlorthalidone was 3.10 (CI, 2.51 to 3.82) and 1.42 (CI, 1.20 to 1.69), respectively. After adjustment for follow-up systolic/diastolic blood pressure, the overall relative risk was 2.00 (CI, 1.72 to 2.32). CONCLUSION: In high-risk patients with hypertension, the higher risk for heart failure while taking doxazosin compared with chlorthalidone is attenuated but not eliminated by adding other antihypertensive drugs. The small observed difference in systolic blood pressure does not explain this increased risk.

Antihypertensive Agents↗

PubMed1992

[An open comparative study of captopril + hydrochlorothiazide versus chlorthalidone for the treatment of mild and moderate primary hypertension].

PURPOSE: To compare the antihypertensive and metabolic effects of captopril combined with hydrochlorothiazide (C+HCTZ) versus chlorthalidone (CT) in mild and moderate primary hypertensive patients. METHODS: Fifty five patients, without treatment or treated with 15 days placebo were randomized for treatment with the combination of captopril 50mg and hydrochlorothiazide 25mg (n = 29) against chlorthalidone (n = 26). The clinical evaluation was done during placebo and monthly throughout three months, and the laboratory tests were done before and at the end of the study. RESULTS: The blood pressure were similar between groups during placebo period (C + HCTZ: 161 +/- 25/102 +/- 6-CT: 155 +/- 18/101 +/- 6 mmHg); the diastolic blood pressure decreases significantly at first month already in the group C + HCTZ (89 +/- 8 mmHg) compared to group CT (94 +/- 8 mmHg, p < 0.05). The percentile diastolic and mean blood pressure dropped, in average, 12% in C + HCTZ group and in CT varied between 7 (1st and 2nd month) to 11% (3rd month). Without statistical difference, the blood pressure normalization was obtained in 69% of the patients with the association captopril and diuretic and in 50% of the patients in the chlorthalidone group. It was observed a significant reduction of potassium in patients treated with chlorthalidone (4.2 +/- 0.7 to 3.7 +/- 0.4 mEq/L, p < 0.01) that was not observed with the captopril and the thiazide associated. The last treatment also significantly reduced the cholesterol levels (219 +/- 39 mg/dl to 202 +/- 39 mg/dl, p < 0.04). CONCLUSION: Our results indicate that captopril combined with low diuretic dose normalize the blood pressure in 69% mild to moderate primary hypertensive patients, and acts faster than chlorthalidone in this control. In addition has metabolic benefits reducing cholesterol levels with no alteration in potassium levels.

Adolescent↗

PubMed1991

Effects of chlorthalidone and metoprolol alone or in combination (logroton) on blood pressure, lipids, lipoproteins and circulating plasma ANF levels in essential hypertension.

The effects of chlorthalidone (mean dose 25 mg/day), metoprolol (mean dose 200 mg/day) or their combination (logroton) on blood pressure, lipids, lipoproteins and circulating atrial natriuretic factor (ANF) were evaluated in a controlled trial of 42-week duration in 33 hypertensive patients. There was a significant reduction in mean arterial pressure after chlorthalidone and metoprolol treatments. This effect was more pronounced with the chlorthalidone/metoprolol combination (logroton). There were no significant changes in mean ANF levels after any drug regimen, although a tendency to increase was observed after six weeks of treatment with metoprolol. Both chlorthalidone and metoprolol as monotherapy increased the total triglycerides. This effect was less pronounced with logroton. During metoprolol treatment, HDL cholesterol decreased significantly, whereas VLDL-C increased. When combined drug therapy was administered, the unfavorable effects on HDL-C were partially blunted and VLDL-C returned to baseline. LDL-cholesterol did not change significantly during any drug regimen nor did the ratio of LDL-C/HDL-C. Logroton significantly increased the VLDL apo B levels in patients who had received chlorthalidone as monotherapy but had no effect in patients already treated with metoprolol. Neither treatment had a significant influence on the ratio of LDL-C/B. There were no serious adverse events reported throughout the study. It is concluded that logroton may be an effective combination therapy that produces less adverse effects on lipid and lipoprotein metabolism than chlorthalidone or metoprolol monotherapies.

Atrial Natriuretic Factor↗

PubMed1990

Assessment of a fixed-dosage combination of atenolol and chlorthalidone (Tenoretic) in hypertensive Nigerians.

The antihypertensive effect of a fixed dosage combination of the cardioselective beta-adrenoceptor blocker, atenolol, and the oral thiazide-like diuretic, chlorthalidone (Tenoretic) was studied in 24 hypertensive Nigerians in a double-blind, cross-over comparison with three other treatments. These were atenolol alone, 100 mg daily, chlorthalidone alone, 25 mg daily, and atenolol (100 mg) plus chlorthalidone (25 mg) daily taken as separate formulations. Tenoretic was taken as a once-daily tablet containing 100 mg atenolol plus 25 mg chlorthalidone. The order of administration of the drugs was randomized. Each drug was taken for 4 weeks. The results showed that atenolol and chlorthalidone lowered blood pressure to the same extent. Combination of the two drugs whether taken separately or in fixed-dosage combination was better than either product singly. The drugs were well tolerated.

Adult↗

PubMed1981

[Pharmacokinetics of clonidine and chlorthalidone following subacute administration of a fixed combination compared with a sustained release formulation of clonidine alone (author's transl)].

Clonidine concentrations in urines and blood plasma samples analysed by RIA were observed over a period of 240 h in 6 male, healthy, normotensive volunteers being treated for 7 days with sustained-release formulations of 2-(2,6-dichloroanilino)-2-imidazoline (clonidine, Catapresan) alone (0.15 mg/d) and subsequently with a combination containing 0.15 mg clonidine plus 15 mg chlorthalidone. Chlorthalidone was determined in blood samples using a newly developed massfragmentographic method. The trials revealed: 1. There is no influence of chlorthalidone on the pharmacokinetics of clonidine. 2. the steady-state levels of the plasma or blood concentrations being reached on the 2nd (clonidine) and on the 5th day (chlorthalidone) were adjusted subsequently in therapeutically relevant ranges ranging between minima and maxima of 0.2 and 0.6 ng/ml (clonidine) and between 2.4 and 2.6 microgram/ml (chlorthalidone) respectively. From pharmacokinetic aspects therefore a fixed combination of two synergistic antihypertensive agents can be considered as useful. 3. Following 7 administrations of either clonidine formulation 63% of the total clonidine doses were excreted renally.

Adult↗

PubMedDate not supplied

[The vasodilating effect of chlorthalidone in mild hypertension evaluated by impedance venous plethysmography].

Thirty hypertensive outpatients of both sexes having diastolic blood pressure below 110 mmHg were included in a randomized trial. Their mean age was 50.4 +/- 8.6 years. After a two-week placebo period, the patients were treated with chlorthalidone in a single daily dose of 25 or 12.5 mg over the one-month period, and the next month the alternative dose (i.e. 12.5 or 25 mg) was administered. Changes in vascular reactivity were measured by occlusive plethysmography (mercury strain-gauge) at the end of the placebo period, and then post the first and second month of therapy. All the observed parameters, i.e. rest flow (RF), peak flow (PF), venous capacity (VC), and maximal venous outflow (MVO) increased with 25 mg of chlorthalidone, and similar findings were registered when a dose of 12.5 mg was given. There was a significant increase in venous capacity of both groups (from 2.6 to 3.2 and from 3.0 to 3.4 ml/100/min) and in peak flow of the group that was on 25 mg of chlorthalidone as the first dose (from 18.6 to 23.9 ml/100ml/min). Both doses had similar antihypertensive effect. It is concluded that antihypertensive effect of chlorthalidone is partly due to changes in vascular reactivity in the sense of vasodilation which is more prominent at the venous side of the blood flow, Low-dosed chlorthalidone is equipotent in antihypertensive efficiency, its side effects are rare, and the cost of therapy is by far the lowest.

Chlorthalidone↗

PubMed2002

Validation of Heart Failure Events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants Assigned to Doxazosin and Chlorthalidone.

BACKGROUND: The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor (lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% CI, 1.17-1.33; P <.001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% CI, 1.79-2.32; P <.001). Questions about heart failure diagnostic criteria led to steps to validate these events further. METHODS AND RESULTS: Baseline characteristics (age, race, sex, blood pressure) did not differ significantly between treatment groups (P <.05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly (RR 0.96; 95% CI, 0.67-1.38; P = 0.83). CONCLUSION: Results of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm.

Journal Article↗

PubMed1995

Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in hypertensive patients.

A double-blind clinical trial was conducted to compare the efficacy of and electrolyte changes caused by ramipril-chlorthalidone combination treatment (5 mg + 25 mg) and chlorthalidone monotherapy (25 mg daily) in patients with hypertension. After a 4-week placebo period, 32 patients (mean age, 51 +/- 9 years) with essential hypertension (average blood pressure of 181.4/104.5 +/- 13.0/6.9 mmHg) were randomly assigned to receive combination therapy (group A, n = 17) or monotherapy (group B, n = 15). After 12 weeks of active treatment, systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively, for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for patients taking monotherapy. The difference was significant for between-group comparisons. There were no changes in serum sodium concentration, but a significant similar increase in 24-hour urinary sodium excretion was seen in both groups. Serum calcium levels increased slightly and 24-hour urinary calcium excretion decreased significantly in both groups, probably due to chlorthalidone administration. Serum potassium levels increased slightly in group A (from 4.16 +/- 0.39 mmol/L to 4.30 +/- 0.42 mmol/L) and decreased slightly in group B (from 4.18 +/- 0.32 mmol/L to 3.99 +/- 0.49 mmol/L). Urinary potassium excretion did not change significantly in group A, but increased by approximately 15% in group B. There was a decrease in 24-hour urinary magnesium excretion (from 4.01 +/- 1.24 mmol/24 hours to 3.50 +/- 0.93 mmol/24 hours) in group A and an increase (from 3.49 +/- 0.98 mmol/24 hours to 4.35 +/- 1.12 mmol/24 hours) in group B. At the end of the trial these changes were significant in between-group comparisons. Consistent with the previously shown amelioration by ramipril of thiazide-induced metabolic side-effects, ramipril appears to improve magnesium balance during cotreatment with chlorthalidone.

Adult↗