Drugs online research references
J Hypertens. 1992 Mar;10(3):265-70.
A study of the interaction between the hypotensive actions of doxazosin and enalaprilat in anaesthetized rats.
Marwood JF, Tierney G, Stokes GS.
Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
OBJECTIVE AND DESIGN: This study was designed to test whether previous work, which showed that the angiotensin converting enzyme (ACE) inhibitor enalaprilat potentiated the alpha 1-adrenoceptor antagonist activity of doxazosin in isolated rat tail arteries, could be extended to demonstrate a synergistic hypotensive effect of these two drugs. METHODS: Groups of untreated or chronically deoxycorticosterone acetate (DOCA)-salt-treated female Sprague-Dawley rats were used. Rats were anaesthetized with Inactin (barbiturate); drugs were administered via a jugular venous catheter; blood pressure was monitored via a carotid arterial catheter. RESULTS: In previously untreated rats, pretreatment with enalaprilat shifted the dose-response curve for the hypotensive effect of doxazosin to the left, indicating synergism. In rats dosed with DOCA-salt (which suppresses renin and angiotensin II production): (1) there was no synergism between the hypotensive actions of enalaprilat and doxazosin; (2) doxazosin was more potent than in untreated rats; and (3) enalaprilat lowered blood pressure, suggesting a hypotensive mechanism separate from ACE inhibition. CONCLUSION: In the absence of angiotensin II (resulting from enalaprilat administration or from chronic DOCA-salt), doxazosin had a greater hypotensive action than in the presence of angiotensin II. This is consistent with the concept that angiotensin II modulates alpha 1-adrenoceptor activity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1315824&dopt=Abstract
J Appl Toxicol. 1992 Feb;12(1):7-11.
Diurnal exposure profile in rats from dietary administration of a chemical (doxazosin) with a short half-life: interplay of age and diurnal feeding pattern.
Charuel C, Comby P, Monro AM.
Centre de Recherche, Laboratoires Pfizer, Amboise, France.
Doxazosin, an alpha-adrenergic blocking agent, has a plasma half-life in male rats of 1-2 h after i.v. administration. Plasma concentrations of doxazosin were measured in male rats receiving the drug mixed in the diet at dose levels from 5 to 40 mg kg-1. Samples taken at 4-h intervals during the light (0700-1900) and dark phases revealed peak concentrations at 0400 which were only about three times higher than the trough concentrations observed ca. 12 h later. The 24-h area under the curve (AUC) values increased disproportionately with dose and with age from 2 months up to 8 months of age; thereafter they were fairly stable to 24 months of age. This age-related effect may have been due to a reduction in clearance and/or a change in the feeding pattern of the rats. Young rats consumed ca. 84% and old rats only 45% of their daily feed during the nocturnal (active) phase. Given the known diurnal rhythms in absorption, protein binding and enzyme metabolising activity, such a change in feeding pattern with age may have wider toxicokinetic implications.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1348752&dopt=Abstract
J Hum Hypertens. 1992 Feb;6(1):9-15.
Reduction of left ventricular hypertrophy after longterm antihypertensive treatment with doxazosin.
Agabiti-Rosei E, Muiesan ML, Rizzoni D, Zulli R, Calebich S, Beschi M, Castellano M, Muiesan G.
Department of Medical Sciences, University of Brescia, Italy.
The aim of this study was to evaluate the effect of antihypertensive treatment with doxazosin on left ventricular anatomy and function. Therefore, after 4 weeks of washout with placebo (phase 1), doxazosin (dosage range from 1 to 16 mg, plus hydrochlorothiazide when necessary) was given to 11 essential hypertensive patients (6 M, 5 F, age range 34-63 years) for 8 weeks (phase 2) in order to achieve diastolic blood pressure values less than 90 mmHg; this dosage was then maintained for a further 20 weeks up to the end of the study (phase 3). Blood pressure was significantly reduced (Anova P less than 0.05), while heart rate did not change. A significant reduction of left ventricular mass index (from 128.5 +/- 26 to 114 +/- 23 g/m2, at the end of phase 1 and 3 respectively, P less than .001)) was observed. Before and during treatment left ventricular systolic function, both at rest and during stress (handgrip and cold pressor tests), evaluated by fractional shortening as related to end-systolic stress, in every case within 95% confidence limits, was calculated in normal subjects. Diastolic function, as evaluated by the ratio between peak early and atrial velocities of transmitral flow examined by pulsed doppler was significantly improved. Plasma catecholamine concentrations, plasma renin activity and plasma aldosterone did not change. A significant reduction of plasma cholesterol concentration was observed. These results confirm that doxazosin is a well tolerated and effective antihypertensive drug, with a favourable effect on blood lipids and they indicate that its longterm administration can induce a significant reduction of left ventricular mass.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1349920&dopt=Abstract
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