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At least 757 records · Page 42Linked to original sources
PubMed1977

[Pharmacological studies on diuretics (8). Diuretic activity and mechanism of action of a new hypotensive diuretic, SE-1520 (author's transl)].

Effects of SE-1520 were compared with those of thiazide diuretics, hydrochlorothiazide (HCT) and trichlormethiazide (TCM) in rats and dogs. SE-1520 in an oral dose of 0.1 approximately 10.0 mg/kg resulted in a strong and dose-dependent increase in urine volume as well as in the urinary excretion of Na+ and Cl-, while that of K+ significantly increased with an oral dose over 3.0 mg/kg. In experimental acidotic, alkalotic, nephritic and spontaneously hypertensive rats, almost the same strong natriuretic activity seen in normal rats was observed with SE-1520. The diuretic potency of these three diuretics in rats was MCT greater than or equal to SE-1520 greater than HCT. SE-1520 also exhibited a strong diuretic activity in dogs. In the renal clearance test of dogs, SE-1520 0.1 approximately 1.0 mg/kg i.v. did not influence the renal plasma flow (RPF) or glomerular filtration rate (GFR). The renal tubular Na+ reabsorption rate decreased by a maximum of 2.11% and the urinary Na+ excretion increased by 15.3 times the normal level 20 min after the injection of SE-1520 in a dose of 1.0 mg/kg i.v. From the results of clearance test and stop flow test in dogs, the site of action of SE-1520 was observed to be mainly in the distal tubules.

Acidosis↗
PubMed2006

Perindopril/indapamide combination in the first-line treatment of hypertension and end-organ protection.

This article examines evidence-based findings in the literature on the efficacy of perindopril 2 mg/indapamide 0.625 mg, a first-line, low-dose antihypertensive drug combination. In regulatory Phase II and III trials, perindopril/indapamide significantly lowered blood pressure compared with other first-line therapies (atenolol, losartan and irbesartan). This was also the case in STRAtegies of Treatment in Hypertension: Evaluation, a postregistration study versus current monotherapies and stepped-care therapy with different classes of antihypertensive agents. The efficacy/safety ratio (both clinical and with regard to laboratory parameters) of perindopril/indapamide was good. Perindopril/indapamide provides additional antihypertensive efficacy compared with each component used alone and with current monotherapies, with major efficacy on systolic blood pressure, an important predictor of cardiovascular risk. It also reduces pulse pressure, an independent cardiovascular risk factor, large-vessel arterial stiffness and microcirculatory alterations. The fixed dosage of a once-daily tablet, ensures optimal ease of use and enhances patient compliance. Perindopril/indapamide also reduces target organ damage in patients at high cardiovascular risk, such as patients with cardiac hypertrophy and Type 2 diabetics with albuminuria. These benefits, together with the good efficacy/tolerability ratio, fulfill the requirements of the European Society of Hypertension and of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines for low-dose, first-line combination therapy in hypertension.

Adrenergic beta-Antagonists↗
PubMed1995

Factors determining the blood pressure response to enalapril and nifedipine in hypertension associated with NIDDM.

OBJECTIVE: To examine the factors that determine the blood pressure response to enalapril and nifedipine monotherapy in the treatment of hypertension associated with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: After a 6-week placebo baseline period, 102 hypertensive NIDDM patients were randomly assigned, double-blindly, to treatment with nifedipine retard (slow release) (n = 52) or enalapril (n = 50). The daily dosage of enalapril was increased, if required, from 10 to 20 to 40 mg and that of nifedipine from 40 to 60 to 80 mg at 4-week intervals during the 12-week titration period. Blood pressure, 24-h urinary albumin excretion (UAE), biochemical data, and serum angiotensin-converting enzyme (ACE) activity were measured at weeks -6, -4, 0, 4, 8, and 12. At week 0, venous blood was also sampled for baseline plasma atrial natriuretic peptide, renin, aldosterone, and serum insulin concentrations. RESULTS: At week 12, the mean daily dose of enalapril was 35 +/- 11.4 mg, and 27 (57%) patients were receiving the maximum daily dose of 40 mg. In the nifedipine group, the mean daily drug dose was 50 +/- 12.9 mg, and 4 (8%) were receiving the maximum daily dose of 80 mg. Despite a dose-dependent fall in the serum ACE activity in the enalapril group, the mean arterial pressure (MAP) was reduced by only 8 mmHg throughout the 12-week titration period compared to a decline of 15, 18, and 19 mmHg at weeks 0, 4, and 12, respectively, in the nifedipine group (P = 0.01 between groups). In the enalapril group, changes in MAP between weeks 0 and 12 correlated significantly with baseline plasma glucose (r = 0.45, P = 0.001) and aldosterone concentrations (r = -0.32, P = 0.02) and UAE (r = 0.3, P = 0.04). There was no statistically significant correlation between the changes in MAP and baseline plasma renin concentration. On multivariate analysis, the baseline renal function, glycemic control, and plasma aldosterone and serum insulin concentrations were all independently related to the changes in blood pressure in the enalapril-treated patients. No such statistical associations were observed in the nifedipine group. CONCLUSIONS: In hypertensive NIDDM patients, the activity of the renin-angiotensin-aldosterone system, the level of serum insulin, glycemic control, renal function, and proteinuria may be important determinants of the blood pressure response to ACE inhibition. Good glycemic control may optimize the antihypertensive efficacy of concomitant ACE inhibitor therapy.

Albuminuria↗
PubMedDate not supplied

[Evaluation of different approaches to the treatment of arterial hypertension: combination treatment with low dose perindopril/indapamide versus sequential treatment of stepped-dose treatment].

A randomised double-blind comparison of three treatment strategies in 533 patients with mild-to-moderate hypertension over 6-9 months. The low-dose perindopril/indapamide (PER/IND) combination (2 mg and 0.625 mg, respectively) daily resulted in a significantly better blood pressure control and systolic blood pressure decrease. In addition, the low-dose PER/IND combination showed superior efficacy/safety criteria than the sequential strategy of atenolol (50 mg) then losartan (50 mg) then amlodipine (5 mg), and the step-by-step strategy of valsartan (40 mg then 80 mg then 80 mg plus hydrochlorothiazide 12.5 mg).

Adrenergic beta-Antagonists↗