CLINICAL EXPERIENCE WITH A NEW DIURETIC, TRIAMTERENE, IN CONJESTIVE HEART FAILURE.
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Triamterene therapy was evaluated in 35 patients with congestive heart failure over a period of two and one-half years. The parameters used were: clinical assessment; daily 24-hour urine sodium, potassium, chloride, and total volume; bi-weekly serum sodium, potassium, chloride, uric acid, and SGOT; hemogram, and BUN.Triamterene is a moderately potent diuretic and natriuretic, with the added desirable property of potassium conservation. It acts synergistically with spironolactone and not only potentiates the effects of hydrochlorothiazide but greatly minimizes its kaluretic effect.It is particularly useful in patients in whom cardiac arrhythmias are associated with digitalis intoxication or with inadvertently induced hypokalemia. Its main therapeutic value, used either alone or in combination with other diuretics, is in the longterm management of chronic edema, especially in certain patients refractory to the currently used diuretics.No significant undesirable side effects were noted. (+info)
SMALL BOWEL ULCERATION ASSOCIATED WITH ENTERIC-COATED POTASSIUM CHLORIDE AND HYDROCHLOROTHIAZIDE.
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Three cases of intestinal obstruction due to solitary localized ulceration, inflammation and stenosis of the small bowel are described. All three patients had been treated with a pill containing hydrochlorothiazide and an enteric-coated centre of potassium chloride. The occurrence of this lesion in these patients, and in similar cases reported from other centres, suggests that such a combination should not be prescribed. (+info)
TREATMENT OF CONGESTIVE HEART FAILURE WITH TRIAMTERENE.
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Triamterene, a newer oral diuretic, was administered to nine hospitalized patients with congestive heart failure for an average of 15 days, and to 22 ambulatory patients for a period of three to 11 months. The daily dosage of triamterene ranged from 50 to 250 mg., but usually 100-200 mg. was administered daily in two divided doses, with or without the addition of 50 mg. of hydrochlorothiazide daily.Triamterene is a safe and effective diuretic at doses of 100-200 mg. daily and no drug tolerance develops with long-term therapy. However, when used alone, it is not as effective as hydrochlorothiazide, but in combination with the latter drug the resultant diuresis is unsurpassed by any other oral diuretic therapy that we have used to date.Triamterene itself does not produce kaliuresis and it blocks thiazide-induced kaliuresis. Serum uric acid levels may rise slightly, but no clinical gout was seen in this study. (+info)
A PHARMACOLOGY TEACHING EXERCISE IN DRUG EVALUATION: A COMPARISON OF THE DIURETIC EFFICACY OF CLOREXOLONE, HYDROCHLOROTHIAZIDE AND A PLACEBO IN NORMAL SUBJECTS.
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In 63 healthy medical students, grouped in 21 randomized blocks, the comparative effects of clorexolone, hydrochlorothiazide and placebo on the quantity of urine excreted and on weight loss were studied. Each subject ingested a single 50-mg. dose of one of the medications. An oral saltloading technique was employed. Measurements were recorded during the four hours following administration. This experiment, which was an integral part of a teaching program in pharmacology, permitted a practical demonstration to medical students of the four fundamental control measures in clinical pharmacology: the comparison with a standard medication and/or a placebo, the random distribution of treatments, the double-blind technique and the statistical analysis of data. In this study hydrochlorothiazide proved to have significantly greater diuretic activity than placebo and clorexolone; the latter medication did not demonstrate effects statistically superior to those of the placebo. A highly significant positive correlation was found to exist between the measurements of urine volume and weight loss. (+info)
Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party.
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OBJECTIVE: To establish whether treatment with diuretic or beta blocker in hypertensive older adults reduces risk of stroke, coronary heart disease, and death. DESIGN: Randomised, placebo controlled, single blind trial. SETTING: 226 general practices in the MRC general practice research framework. SUBJECTS: 4396 patients aged 65-74 randomised to receive diuretic, beta blocker, or placebo. Patients had mean systolic pressures of 160-209 mm Hg and mean diastolic pressures less than 115 mm Hg during an eight week run in and were not taking antihypertensive treatment. INTERVENTION: Patients were randomised to atenolol 50 mg daily; hydrochlorothiazide 25 mg or 50 mg plus amiloride 2.5 mg or 5 mg daily; or placebo. The regimens were adjusted to achieve specified target pressures. Mean follow up was 5.8 years. MAIN OUTCOME MEASURES: Strokes, coronary events, and deaths from all causes. RESULTS: Both treatments reduced blood pressure below the level in the placebo group. Compared with the placebo group, actively treated subjects (diuretic and beta blocker groups combined) had a 25% (95% confidence interval 3% to 42%) reduction in stroke (p = 0.04), 19% (-2% to 36%) reduction in coronary events (p = 0.08), and 17% (2% to 29%) reduction in all cardiovascular events (p = 0.03). After adjusting for baseline characteristics the diuretic group had significantly reduced risks of stroke (31% (3% to 51%) p = 0.04), coronary events (44% (21% to 60%), p = 0.0009), and all cardiovascular events (35% (17% to 49%), p = 0.0005) compared with the placebo group. The beta blocker group showed no significant reductions in these end points. The reduction in strokes was mainly in non-smokers taking the diuretic. CONCLUSION: Hydrochlorothiazide and amiloride reduce the risk of stroke, coronary events, and all cardiovascular events in older hypertensive adults. (+info)
Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study.
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BACKGROUND: Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension. METHODS AND RESULTS: A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was >90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (-14.5+/-3.36 g; n=50) similarly to enalapril (-19.7+/-3.20 g; n=54; P=0.258), but eplerenone/enalapril (-27.2+/-3.39 g; n=49) was more effective than eplerenone alone (P=0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, -23.8 and -11.9 mm Hg; enalapril, -24.7 and -13.4 mm Hg; and eplerenone/enalapril, -28.7 and -14.4 mm Hg, P=0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone (P=0.033), and elevated potassium was more common with eplerenone. CONCLUSIONS: Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone. (+info)
Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability.
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Thiazide diuretics are one of the preferred pharmacologic treatments for hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most commonly used diuretics in major clinical trials. Treatment guidelines and compendia often consider these 2 drugs interchangeable agents within the class of thiazide or thiazide-like diuretics. Many sources list them as equipotent. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. We conducted a literature search from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and blood pressure-lowering effects of these 2 agents. There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Chlorthalidone is approximately 1.5 to 2.0 times as potent as hydrochlorothiazide, and the former has a much longer duration of action. Whether these pharmacokinetic and pharmacodynamic features cause differences in outcomes is not known. (+info)
Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat.
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1. Adult male spontaneously hypertensive rats (SHR) were given captopril plus hydrochlorothiazide mixed in the diet for 10 weeks. Calculated daily doses were 44 mg kg-1 per day for captopril, and 22 mg kg-1 per day for hydrochlorothiazide. Separate groups received captopril or hydrochlorothiazide alone, at similar doses, or no treatment. A final group of WKY normotensive rats received no drug. 2. Systolic arterial blood pressure, measured at regular intervals throughout the 10 weeks' period was lowered but not normalized, in groups receiving either captopril plus hydrochlorothiazide, or captopril alone, but not in the group receiving hydrochlorothiazide alone. 3. Following pentobarbitone anaesthesia, systolic arterial blood pressure, measured in the femoral artery, was found to be lower in all treated groups, but the greatest effect was observed in SHR previously treated with captopril plus hydrochlorothiazide. Aortic pulse wave velocity was also lower in treated SHR, and once again the greatest decrease was observed in the group previously treated with captopril plus hydrochlorothiazide. 4. Following pithing, systolic arterial blood pressures were similar in all SHR groups. Aortic pulse wave velocity was lower in pithed rats previously treated with captopril and hydrochlorothiazide. 5. In conclusion, antihypertensive treatment of SHR produces falls in blood pressure and pulse wave velocity, an indicator of aortic distensibility. Results in pithed rats suggest that treatment with the combination of captopril plus hydrochlorothiazide may increase aortic distensibility independently of blood pressure. (+info)