Drugs online research references
Am Heart J. 1988 Dec;116(6 Pt 2):1826-32.
A single-blind study of doxazosin in the treatment of essential hypertension when added to nonresponders to angiotensin-converting enzyme inhibitor therapy.
Englert RG, Mauersberger H.
Doxazosin, a selective alpha 1-inhibitor, was assessed in hypertensive patients with sitting diastolic blood pressures (DBPs) of 95 to 114 mm Hg while receiving a stable dose of captopril or enalapril. Fifty-six patients were entered into the study that involved three phases: (1) a 2-week baseline period, (2) a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks of doxazosin treatment, 95% of the patients were therapy successes (sitting DBP either less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction or greater than or equal to 10 mm Hg reduction) at a mean daily dose of 2.4 mg. Ninety-three percent achieved blood pressure control (sitting DBP less than or equal to 90 mm Hg) at a mean dose of 2.3 mg once daily. By the final treatment visit, systolic/diastolic sitting blood pressures for efficacy evaluable patients were reduced by 16/17 mm Hg from a mean baseline of 158/101 mm Hg to a final value of 143/84 mm Hg. Throughout the study (2 to 14 weeks), all blood pressure reductions from baseline were significant (p less than 0.05). There was only one side effect (vertigo) that warranted dose reduction, and only one patient was withdrawn from therapy (nausea). Most side effects were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2904758&dopt=Abstract
Br J Pharmacol. 1988 Oct;95(2):619-29.
The modulatory role of vascular endothelium in the interaction of agonists and antagonists with alpha-adrenoceptors in the rat aorta.
Alosachie I, Godfraind T.
Laboratoire de Pharmacodynamie Generale et de Pharmacologie, Universite Catholique de Louvain, Brussels, Belgium.
1. We have examined the effect of endothelium on the antagonistic action of prazosin, doxazosin, yohimbine and phentolamine against phenylephrine, clonidine and noradrenaline. 2. The action of prazosin against phenylephrine was similar to that earlier reported against noradrenaline, acting as a non-competitive antagonist in the presence of endothelium and as a competitive antagonist in the absence of endothelium. Prazosin also acted as a non-competitive antagonist against clonidine in the absence of endothelium. 3. Doxazosin behaved in a similar way to prazosin against noradrenaline, phenylephrine and clonidine acting as a non-competitive antagonist in the presence of endothelium and as competitive antagonist after removal of endothelium. In contrast, yohimbine and phentolamine acted as competitive antagonists both in the presence and in the absence of endothelium. 4. Analysis of the concentration-response curves for noradrenaline, phenylephrine and clonidine in the presence and in the absence of endothelium showed that the affinity for all three agonists was the same but not the efficacy and the receptor reserve, both of which were lower in the presence than in the absence of endothelium. 5. The rank order of agonist potency in the absence of endothelium was noradrenaline greater than phenylephrine greater than clonidine. The rank order of antagonist potency was prazosin greater than or equal to doxazosin greater than phentolamine greater than yohimbine. 6. The results show that vascular endothelium modulates the contractile response to alpha-adrenoceptor agonists and also modifies the action of the antagonists prazosin and doxazosin but not that of yohimbine and phentolamine. This effect of endothelium was related to a change in agonist efficacy and receptor reserve. These results also suggest that the alpha-adrenoceptors of the isolated aorta of the rat are predominantly, if not exclusively of the alpha 1-subtype.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2906562&dopt=Abstract
Scand J Clin Lab Invest. 1988 Jun;48(4):313-7.
Studies of serum lipids in hypercholesterolaemic rabbits treated with doxazosin.
Leren TP, Berg K.
Department of Medical Genetics, City of Oslo, Blindern, Norway.
Serum lipids were studied in hypercholesterolaemic rabbits treated with the selective alpha 1-adrenoreceptor antagonist doxazosin. Hypercholesterolaemia had been induced by cholesterol feeding which raised mean (+/- SEM) total serum cholesterol from 1.4 (+/- 0.1) mmol/l to 84.1 (+/- 3.6) mmol/l. A cross-over design was used to compare the effect of doxazosin with placebo in 20 rabbits of which 16 completed the study. Doxazosin (2 mg/kg) or placebo vehicle was administered subcutaneously once daily for three weeks. Compared with placebo, doxazosin produced an 8.6% greater reduction in total serum cholesterol. This difference did not, however, reach statistical significance.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2907180&dopt=Abstract
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