Drugs online research references
An Med Interna. 1995 Mar;12(3):122-6.
[Efficacy and tolerance of doxazosin in the treatment of isolated systolic hypertension in hypertensive patients over 60 years of age]
[Article in Spanish]
Calvo C, Lopez E, Barrio E, Espejo J, Ruiz M, Vega A.
Departamento de Medicina, Hospital General de Galicia Clinico Universitario, Santiago de Compostela.
Isolated Systolic Arterial Hypertension (ISAH) is the most frequent form of AHT in the aged population, resulting in an increase of the cardiovascular risk, mainly at the cerebrovascular level. In this open non-comparative study, we analyze the effect of doxazosin, an alpha-adrenergic blocker in 40 patients older than 60 years, diagnosed of isolated systolic hypertension. After 2 weeks of lavage, the patients received treatment with doxazosin according to a monotherapy scheme, with progressive increase of the dose, from 1 to 16 mg/day during a period of 14 weeks. Doxazosin significantly reduces the systolic and diastolic arterial pressure (p < 0.001) with a therapeutical response in 86.5% of the cases, using an average dose of 3.4 mg/day and without observing modifications in the heart rate. This drug improves the lipidic profile, with a reduction of the plasmatic levels of total cholesterol and cholesterol linked to low density proteins (LDL) with p < 0.05 and a reduction of triglycerides. Among the 40 patients included in the study, 10 (25%) referred side effects; there were 2 drop-outs (5%) and the dose had to be reduced in 2 patients (5%). In conclusion, doxazosin shows its antihypertensive effectiveness in the treatment of isolated systolic hypertension in patients older than 60 years and it is well tolerated by most of the patients, improving at the same time the lipidic profile. Hence, it contributes to the reduction of the cardiovascular morbidity-mortality in this group of patients.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7795118&dopt=Abstract
Blood Press Suppl. 1994;4:19-24.
Comparison of the hemodynamic effects of urapidil and flesinoxan in healthy volunteers.
Van Zwieten PA, Bruning TA.
Department of Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
The possible role of peripheral 5HT1A-receptors in the vasodilation caused by urapidil was studied by means of venous occlusion plethysmography in the forearm vascular bed of healthy volunteers. Urapidil is known to be an alpha 1-adrenoceptor antagonist and an agonist of 5HT1A-receptors. The hemodynamic effects of urapidil were compared with those of flesinoxan, a selective 5HT1A-receptor agonist virtually devoid of alpha 1-adrenoceptor antagonistic activity, and with the selective alpha 1-adrenoceptor antagonist doxazosin, which has no affinity for 5HT1A-receptors. Urapidil, as well as doxazosin, caused a dose-dependent decrease in forearm vascular resistance (FVR), thus reflecting vasodilation. Both urapidil and doxazosin were competitive antagonists of the vasoconstrictor effect of the selective alpha 1-adrenoceptor agonist methoxamine. On a molar base doxazosin proved more potent than urapidil (more than 10-fold). Flesinoxan slightly decreased FVR only at high doses. The nitric oxide (NO)-synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) depressed the vasodilatation caused by serotonin and also that by high-dose flesinoxan. The serotonin-induced vasodilatation is known to be NO-dependent. From the experiments it is concluded that peripheral 5HT1A-receptors cannot play an important role in the vasodilator response caused by urapidil, which is predominantly the result of postsynaptic alpha 1-adrenoceptor blockade. 5HT1A-receptors are clearly not involved in the NO-dependent dilatation caused by serotonin. During chronic treatment of hypertension with urapidil central but not peripheral 5HT1A-receptors may be assumed to play a role.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7804508&dopt=Abstract
Arzneimittelforschung. 1994 Oct;44(10):1117-21.
Influence of doxazosin on the activity of the endothelium-derived relaxing factor.
Yeates RA.
Pfizer Mack, Heinrich Mack Nachf. Chem.-Pharmazeutische Fabrik, Illertissen, Fed. Rep. of Germany.
This work examined the effect of the selective a1-inhibitor, doxazosin (CAS 74191-85-8), on the activity of endothelium-derived relaxing factor (EDRF). In vitro, the intact thoracic aortic rings of rabbits were contracted with the a-agonist, phenylephrine, and then relaxed by sequentially increasing concentrations of the EDRF-releasing agent adenosine triphosphate (ATP). In parallel experiments, doxazosin (10(-8) mol/l) was added after the contraction but before the addition of ATP. Doxazosin enhanced the ATP-induced vasodilation by a factor of 3. Control experiments suggested that this was due to the enhanced activity of EDRF, which was related to displacement of phenylephrine from a1-adrenoceptors by doxazosin. Physiologically relevant concentrations of 6- or 7-hydroxydoxazosin (5 x 10(-10) mol/l) had no effect on EDRF activity in vitro. In vivo experiments in the rabbit were carried out using bolus, intravenous injections of acetylcholine (ACh), which stimulated EDRF release. Threshold doses of doxazosin (2 x 10(-6) g/kg) enhanced the hypotensive activity of ACh. Prefeeding the rabbits for 4 weeks with a 2% cholesterol diet significantly reduced the sensitivity of the aorta to isosorbide-5-mononitrate, a stable EDRF-analog. However, the impairment in endothelium-dependent relaxation was attenuated in the presence of doxazosin (2 x 10(-9) mol/l). The results that in addition to its known antiplatelet activity, doxazosin enhances EDRF activity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7818583&dopt=Abstract
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