Drugs online research references
Am J Cardiol. 1998 Jan 15;81(2):170-4.
Reduction of QT and QTc dispersion during long-term treatment of systemic hypertension with enalapril.
Gonzalez-Juanatey JR, Garcia-Acuna JM, Pose A, Varela A, Calvo C, Cabezas-Cerrato J, de la Pena MG.
Cardiology Department, Hospital General de Galicia and Clinico Universitario, Santiago de Compostela, Spain.
We report, in conjunction with other findings, the evolution of the dispersion of QT and QTc in patients who for the last 7 years have been treated with enalapril for systemic hypertension with left ventricular (LV) hypertrophy. Twenty-four essential hypertensive patients who had received no previous treatment took enalapril (20 mg twice daily) for 7 years. In a pretreatment placebo phase and 8 weeks and 1, 3, 5, 6, and 7 years after the start of therapy, cardiovascular parameters were determined by two-dimensional guided M-mode echocardiography, and the QT interval and corrected QT interval (QTc) and their dispersions were obtained from amplified standard 12-lead electrocardiograms. Therapy rapidly reduced blood pressure (BP) from 156/105 mm Hg to normal values; at 7-year follow-up, BP was 130/84 mm Hg (p <0.001 with respect to the placebo phase). LV mass index decreased progressively until at 5-year follow-up the reduction had reached 39% (p <0.001), after which neither LV mass index nor any structural parameter underwent any further significant change. LV pump function was also significantly better after 7 years of treatment. During this time, QT and QTc decreased significantly, as did the dispersion of both QT (from 61+/-21 to 37+/-14 ms) and QTc (from 67+/-27 to 41+/-16 ms). We conclude that long-term enalapril treatment of hypertensive patients with LV hypertrophy not only induces marked regression of LV mass and improved LV systolic function, but also reduces the dispersions of QT and QTc, which probably reduces the likelihood of ventricular arrhythmias and improves prognosis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9591900&dopt=Abstract
Drug Metab Dispos. 1982 Jan-Feb;10(1):15-9.
The physiological disposition and metabolism of enalapril maleate in laboratory animals.
Tocco DJ, deLuna FA, Duncan AE, Vassil TC, Ulm EH.
N-[1-(S)-carboxy-3-phenylpropyl]-L-alanyl-L-proline (MK-422), is a potent angiotensin I-converting enzyme (ACE) inhibitor, but as a diacid is poorly absorbed in laboratory animals. Enalapril maleate, the monoethyl ester of MK-422, proved to be significantly better absorbed in both rats and dogs. Peak levels of radioactivity in plasma occurred in 30 min in rats and 2 hr in dogs after a single dose of 14C-enalapril maleate (1 mg/kg, po). Rats excreted 26% of the dose in the urine and 72% in the feces in 72 hr; dogs excreted 40% of the dose in the urine and 36% in the feces. After the intravenous dose, the presence of radioactivity in the feces of both species suggested that some biliary excretion had occurred. Absorption was estimated to be 34% in the rat and 61% in the dog. The major metabolite of enalapril maleate in dogs, accounting for 86% of the urine radioactivity, was identified as MK-422 by GC/MS. A procedure was developed for the quantitation of MK-422 and enalapril in plasma and urine by their inhibition of purified ACE. The assays showed that enalapril was absorbed intact in dogs and converted to MK-422 after absorption.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6124377&dopt=Abstract
J Hypertens Suppl. 1989 Dec;7(6):S178-9.
Renal sodium handling abnormalities in hypertensive and normotensive patients with a family history of hypertension.
Ramirez AJ, Gimenez MI, Gallo J, Marco EJ, Sanchez RA.
Instituto de Cardiologia, Academia Nacional de Medicina, Buenos Aires, Argentina.
We measured the effective renal plasma flow, the glomerular filtration rate and the fractional excretion of sodium under low and high sodium intakes in the normotensive offspring of hypertensives and in essential hypertensive patients. During the high sodium intake, 57% of the offspring and 42% of the hypertensive patients showed an increase in effective renal plasma flow and fractional excretion of sodium. In the remaining hypertensives, enalapril improved the renal haemodynamic and sodium-handling responses. Enalapril also reduced the blood pressure in all hypertensives, whether they showed a normal or an abnormal response to a high sodium intake. In the hypertensive patients with an abnormal response to a high sodium intake, the intra-erythrocyte sodium content was higher than in the normal responders. Thus, abnormal renal haemodynamic and sodium-handling responses to a high sodium intake were observed in 50% of the hypertensive patients and the offspring. The high intra-erythrocyte sodium content observed in the hypertensive patients suggests that extrarenal alterations in sodium handling were present.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2561138&dopt=Abstract
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