Microzide
Enalapril in essential hypertension.

Herrera-Acosta J, Perez-Grovas H, Fernandez M, Arriaga J.

It is now well recognised that the renin-angiotensin system plays a key role in the control of blood pressure not only through circulating angiotensin II but through its interaction with the autonomic and central nervous systems. Angiotensin-converting enzyme (ACE) inhibitors have proved to be effective in lowering blood pressure in different types of hypertension. This study evaluates the antihypertensive effects of enalapril, a new, potent, long acting ACE inhibitor. 50 patients with uncomplicated essential hypertension were included in 4 groups. Group I was used to compare the effects of enalapril and propranolol on blood pressure, renal function, plasma renin activity, aldosterone excretion and plasma lipids in 24 patients after 23 weeks. Group II was used to evaluate long term effects (48 weeks) of these drugs in 13 patients. Group III included 32 patients that received enalapril as monotherapy for 6 to 12 weeks. Group IV was studied to estimate the antihypertensive effect of low doses of hydrochlorothiazide in 18 patients receiving enalapril. The effect on mean blood pressure was similar with enalapril and propranolol (enalapril 117 versus 103 mm Hg and propranolol 115 versus 104 mm Hg); however, the glomerular filtration rate decreased with propranolol (105 versus 87 ml/min; p less than 0.05) and was unaltered with enalapril (102 versus 98 ml/min). Triglycerides rose with propranolol (179 versus 231 mg/dl; p less than 0.05) and did not change with enalapril (157 versus 121 mg/dl). In the long term, antihypertensive effects were similar and no significant side effects were observed. In 14/32 patients blood pressure became normal with enalapril alone. Low doses of hydrochlorothiazide (12.5 to 25 mg) decreased mean blood pressure by 10mm Hg when added to enalapril. The antihypertensive effect of enalapril was similar to that of propranolol; however, the lowering effect on glomerular filtration rate of propranolol did not occur with enalapril. A slight rise in triglycerides occurred only with propranolol. No significant side effects were observed with either propranolol or enalapril. Used as monotherapy, enalapril normalised blood pressure in 44% of cases. Addition of low doses of hydrochlorothiazide significantly increased the antihypertensive effect of enalapril.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2994986&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Hydrochlorothiazide abolishes the anti-atherosclerotic effect of quinapril.

Fonseca FA, Ihara SS, Izar MC, Silva EP, Kasinski N, Lopes IE, Pinto LE, Paiva TB, Tufik S, de Paola AA, Carvalho AC.

Division of Cardiology, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil. lipides.dmed unifesp.epm.br

1. Antihypertensive treatment has been demonstrated to result in persistent reductions in morbidity and mortality due to stroke. However, the coronary risk attributable to hypertension has been only partially reversed. We hypothesized that diuretics could have unfavourable effects on atherosclerosis. 2. New Zealand rabbits were fed a 0.5% cholesterol-enriched diet for 12 weeks, followed by a 0.1% cholesterol diet for another 12 weeks. During the last 12 week period, 40 animals were randomly assigned to one of four groups: (i) group I was the control group; (ii) group II received hydrochlorothiazide (10 mg/day); (iii) group III received quinapril (30 mg/day); and (iv) group IV was treated with hydrochlorothiazide (10 mg/day) plus quinapril (30 mg/day). 3. The treatments did not affect either the lipid profile or serum electrolytes and oxidative stress. However, endothelium-dependent vasorelaxation in isolated aortic rings was significantly improved with quinapril (group III) treatment (P < 0.001 vs other groups). In addition, therapy with quinapril promoted a significant reduction in atherosclerosis (intima area, intima/media ratio and perimeter of vessel with plaque; P < 0.05 vs other groups), as well as in cholesterol content of the aorta (P < 0.05 vs groups II and IV). 4. In conclusion, hydrochlorothiazide did not modify atherosclerosis and, when added to quinapril treatment, impaired the anti-atherosclerotic effect seen with quinapril alone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14516418&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Rest and exercise hemodynamic and adrenergic responses to enalapril, hydrochlorothiazide, and combination treatment in patients with systemic hypertension.

Stroh JA, Saltzberg S, Weinberg P, Shamoon H, Charlap S, Frishman W.

The effects of enalapril (10-20 mg twice daily), hydrochlorothiazide (25-50 mg twice daily), and combination enalapril-hydrochlorothiazide therapy (10-20 mg enalapril/25-50 mg hydrochlorothiazide in combination tablet twice daily) were evaluated and compared to no therapy (control) in eight patients with mild to moderate hypertension at rest and during treadmill exercise. All active treatments reduced standing blood pressure in patients at rest compared to the control group (p less than 0.05); however, none produced significant reductions of standing blood pressure in patients at peak exercise. Standing heart rates of patients at rest and at peak exercise were not changed with active therapy. However, standing heart rate in patients at rest was lower with enalapril than with hydrochlorothiazide and combination therapy (p less than 0.05). Heart rate of patients on hydrochlorothiazide was higher than with control and other therapies at Stage I of exercise (p less than 0.01). Supine norepinephrine levels in patients at rest were elevated with both hydrochlorothiazide and combination therapy when compared to that in patients with enalapril and control (p less than 0.05). Treatment with enalapril alone produced no changes in plasma catecholamine levels compared to control. There were no differences between control and all treatment regimens in peak exercise levels of catecholamines. Thus, enalapril, hydrochlorothiazide, and combination therapy, although effective in lowering resting blood pressure, may not be effective in blunting the blood-pressure response to exercise. The drugs do not appear to have any significant effects on catecholamine levels in patients at peak exercise.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3014075&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Postmarketing study of timolol-hydrochlorothiazide antihypertensive therapy.

Bannon JA, Stewart KA, Schrogie JJ, Delisser O.

A postmarketing surveillance study was conducted to determine the safety and efficacy of a fixed-ratio combination containing 10 mg of timolol maleate and 25 mg of hydrochlorothiazide, administered twice daily for one month to hypertensive patients. Data on 9,037 patients were collected by 1,455 participating physicians. Mean systolic blood pressure decreased 25 mmHg and mean diastolic blood pressure declined 15 mmHg after one month of timolol-hydrochlorothiazide therapy (P less than 0.01, both comparisons). Age, race, and sex appeared to have no influence on the decrease in blood pressure. The antihypertensive effect of the drug was greater in patients with more severe hypertension. Overall, 1,453 patients experienced a total of 2,658 adverse events, the most common being fatigue, dizziness, and weakness. Treatment in 590 patients was discontinued because of adverse events.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3833372&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Hydrochlorothiazide-amiloride in the treatment of congenital nephrogenic diabetes insipidus.

Alon U, Chan JC.

The effects of treatment with hydrochlorothiazide combined with amiloride were compared to hydrochlorothiazide treatment alone in 2 brothers with congenital nephrogenic diabetes insipidus. Whereas both modalities of treatment resulted in reduction in voiding frequency and urine volume, decrease in daily fluid intake and increase in urine osmolality, the two-drug combination was found to be superior to hydrochlorothiazide alone by preventing urinary potassium losses, hypokalemia, and alkalosis. It was also found that amiloride had a certain additive effect to the thiazide in terms of increasing initial urinary sodium excretion, reducing urine volume and free water clearance, and lowering serum sodium concentration and osmolality. Similar comparison of the hydrochlorothiazide-amiloride regimen to treatment with the hydrochlorothiazide-tolmetin combination in 1 of the patients revealed that the effectiveness of both diuretic modalities was close with slight advantage of the former. Treatment of the 2 patients for 10 months with hydrochlorothiazide and amiloride showed no adverse effects and consistent reduction in fluid intake and urine volume. It is concluded that the hydrochlorothiazide-amiloride regimen is superior to hydrochlorothiazide alone and can be a satisfactory alternative to the hydrochlorothiazide-prostaglandin synthetase inhibitor combination in the treatment of congenital nephrogenic diabetes insipidus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3970081&dopt=Abstract hydrochlorothiazide Microzide