Correlation between rhodamine 123 accumulation and azole sensitivity in Candida species: possible role for drug efflux in drug resistance.
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.
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 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.
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.
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.