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Combinations of a beta-blocker and a diuretic often produce a greater fall in blood pressure than does either drug alone. Furthermore, beta-blockers prevent an increase in plasma renin activity, thereby attenuating diuretic-induced potassium excretion and also the reduction in hypotensive response to the diuretic. This study was designed to compare the effects of the two fixed-dose combinations atenolol 100 mg plus chlorthalidone 25 mg (Tenoretic; ICI) and sotalol 320 mg plus hydrochlorothiazide 50 mg (Sotazide; B-M) on the pattern of diuresis and the biochemical composition of the urine in normal subjects. These preparations differ mainly in that the plasma half-lives of chlorthalidone and hydrochlorothiazide are 60 hours and 6 hours respectively; the former therefore accumulates when given once daily while the latter does not. These two preparations were found to have similar effects on the pattern of diuresis and the biochemical values. It is therefore concluded that the relationship between the serum chlorthalidone level and the fall in serum potassium level is in keeping with the flat dose-response curves for the thiazide and phthalimide diuretics.
The authors conducted a clinical investigation in twenty-five patients affected with essential hypertension of mild or moderate grade associated with type II diabetes mellitus, the purpose being to assess the effect of 8 weeks of combined treatment with atenolol (100 mg) and chlorthalidone (25 mg) on arterial blood pressure, heart rate, and glycaemia. It is, indeed, generally known that both beta-blockade agents and diuretics can interfere with carbohydrate metabolism. The results indicate that 92% of the patients treated in this trial had significant reduction of systolic and diastolic blood pressure readings, in the absence of bradycardia or other adverse effects. Glycaemia values were lower at the end of treatment, probably as a result of better diet control during the trial, as suggested by the general tendency to body-weight reduction.
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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.
A patient is presented who suffered for 3 years from increasing photosensitivity with chronic eczematous lesions in sun-exposed areas. He had taken one Neotri (triamterene, xipamide) tablet daily for 6 years. After discontinuation of the drug, phototesting and a photopatch test failed to reveal pathological reactions. Eczematous lesions, however, were induced in test areas upon systemic photochallenging with Neotri. One year later, after the antihypertensive medication had been changed from Adalat (nifedipine) to Teneretic (atenolol, chlortalidone) the eczematous photosensitive reaction recurred. Since both xipamide and chlortalidone have a chlorsulfamoyl-substituted aromatic ring in common, it seems that a photoallergic cross-reaction occurred.
The pharmacological treatment, mainly based on diuretics, of isolated systolic hypertension (ISH) has recently been shown to reduce the risk of stroke and coronary heart disease in the elderly. The purpose of this study was to compare the antihypertensive effect and tolerability of different drug regimens in elderly subjects with ISH (systolic blood pressure--SBP-- > or = 160 mmHg and diastolic blood pressure--DBP-- < 90 mmHg). A multicentre, randomized, controlled open trial was planned in the general practice setting. Four widely used treatment schedules were tested: hydrochlorothiazide 25 mg plus amiloride 2.5 mg (H+Am), nifedipine slow release 20 mg (N), atenolol 50 mg (At) and atenolol 25 mg plus chlorthalidone 6.25 mg (At+C). After a baseline evaluation, 308 patients (76.3% female, mean age 75.3 +/- 7.1 years) were randomized and followed up for 6 months. After 3 months the drug dosage was doubled if the systolic blood pressure goal (SBP < 160 mmHg and SBP reduction of at least 20 mmHg) had not been reached. Ninety-four subjects (30.5%) presented contraindications to beta-blockers. At the 3rd- and 6th-month visits all treatment groups, except At, showed a significant reduction in SBP compared to the control group; DBP showed no significant reduction in any group at any time. At the end of the follow-up the percentage of hypertensives who had reached the BP goal was 14.6% in the control group, 52.9% in H+Am, 54.8% in N, 28.6% in At and 52.2% in At+C.(ABSTRACT TRUNCATED AT 250 WORDS)
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The optimal first-line treatment of hypertension has been a contentious issue. Despite the probable advantage of diuretics, which was demonstrated in early clinical trials, concern about their metabolic effects meant that therapy was often commenced with drugs of other types. The results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which compared agents of three groups of new antihypertensive drugs with a diuretic, demonstrated the equivalence between these drugs and chlorthalidone (Tenoretic AstraZeneca) in the prevention of incident fatal coronary heart disease and nonfatal myocardial infarction. The diuretic was superior to other drugs in preventing some major secondary end-points, such as cerebrovascular disease and heart failure. These findings, together with other very practical reasons, such as easy administration, few side effects and low cost, demonstrate that diuretics are the first option for drug management of hypertension.
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.
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A large-scale postmarketing survey was conducted in the United States to evaluate the antihypertensive efficacy and safety of a combination of 50 mg of the long-acting cardioselective beta-blocker atenolol and 25 mg of the monosulfonamyl diuretic chlorthalidone. The program included 28,585 patients (of whom 26,892 provided sufficient information by questionnaire for an assessment of efficacy and race), and the participation of 7,009 primary-care physicians. After four weeks of treatment, patients had a mean reduction in systolic blood pressure of 21 mmHg and in diastolic blood pressure of 13 mmHg. The magnitude of these reductions did not differ appreciably with respect to age, sex, race, or previous therapy. Diastolic blood pressure was reduced by at least 11 mmHg in 55% of patients and systolic blood pressure was reduced by at least 16 mmHg in 59% of patients. Physicians' assessments indicated that 86% of patients achieved satisfactory control of blood pressure by the end of the study. The physicians' global assessment of the effectiveness of treatment indicated that the combination was better than previous therapy in 82% of patients; 91% of physicians planned to continue treatment with the fixed combination. There were no adverse experiences that had not been reported previously, and only dizziness exceeded an incidence of 1%. It was concluded that the fixed combination provides added blood pressure control and the convenience of a simplified once-daily regimen without added side effects, regardless of age, sex, race, or prior antihypertensive therapy.
The antihypertensive efficacy and tolerance of a new fixed combination of 50 mg atenolol and 12.5 mg chlorthalidone (Tenoretic Mite, TM) was studied in 37 patients with arterial hypertension, aged 61-80 years (mean, 70.2 years), who had been randomized to either 50 mg atenolol or 12.5 mg chlorthalidone for a 4-week period. At the end of this period, the fixed combination of atenolol and chlorthalidone was given to all patients for 6 months at a dose of one tablet daily in the morning. In both atenolol- and chlorthalidone-pretreated patients, treatment with the fixed combination resulted in a further significant drop in blood pressure, whereas the heart rate decreased only in the latter group. The mean blood pressure reduction achieved by the fixed combination was 30/15 mmHg in the standing position. Serum potassium levels significantly increased with the fixed combination compared with values on chlorthalidone alone. Unwanted effects were rare, and their frequency tended to decrease over time. In conclusion, the fixed combination of 50 mg atenolol plus 12.5 mg chlorthalidone tested in this study proved highly effective in lowering elevated blood pressure values in a population of elderly hypertensive patients treated over a 6-month period without noticeable unwanted effects.
The clinical effects of Tenoric, a long-acting combined drug (atenolol and chlorthalidone in a tablet), were studied in 31 patients with Stages I and II hypertensive disease, by using echocardiography, daily automatic blood pressure monitoring, bicycle ergometry, measurements of plasma renin and aldosterone. The drug was found to be highly clinically effective in labile and sustained hypertension. When given once or twice a day, it makes it possible to reliably monitor blood pressure, improve hemodynamic parameters, as reflected by lower cardiac output and decreased peripheral vascular resistance, reduce the estimated mass of the left myocardium, alleviate a pressor response to exercise and enhance its tolerance, lower plasma renin levels. The side effects of the drug are minimal and include moderate bradycardia. Peripheral vasospasm and systemic weakness were observed in single cases. There were no atherogenic changes in lipid spectrum and disturbed glucose and uric acid metabolism during the drug therapy.
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Two cyclodextrin micellar liquid chromatographic methods were developed and applied to the simultaneous determination of bisoprolol/hydrochlorothiazide and atenolol/chlorthalidone combinations in urine matrices without sample pretreatment. These combined β-blockers and diuretics chemotherapies are commonly used in the treatment of hypertension and cardiovascular diseases. Hybrid isocratic mobile phases containing hydroxypropyl-β-cyclodextrin, sodium dodecyl sulfate, phosphate buffer and methanol on a Luna C18 column with 0.5 mL min(-1) flow rate and 25.0°C column temperature were used. The methods were sensitive enough for the determination of analytes at the therapeutic urine levels with limits of detections down to 1.0 µg mL(-1); relative standard deviations and recoveries were ranged between 1.5-4.4% and 98.00-109.52%, respectively. Urinary excretion studies showed that the detection of drugs is possible up to 24 h after their ingestion. The selective proposed separations with less consumption of organic solvents over the hitherto ones could be attributed to the four point competitive interactions among analysts, pseudostationary phases and a real stationary phase.