Drugs online research references
Am J Physiol. 1992 Dec;263(6 Pt 2):H1682-8.
Alpha-adrenergic vasoconstriction in normal and hypoperfused myocardium during sympathetic nerve stimulation.
Westby J, Birkeland S, Rynning SE, Myking OL, Lekven J, Grong K.
Department of Surgery, Haukeland Hospital, University of Bergen, Norway.
Coronary vasoconstriction mediated by postjunctional alpha 1- and alpha 2-adrenergic receptors was studied in normally perfused (control group) and left coronary hypoperfused (stenosis group) hearts of vagotomized, beta-blocked (propranolol) cats. Cardiac sympathetic nerve stimulation was combined with alpha 1- and subsequent alpha 2-adrenergic antagonism (doxazosin and SK&F 104078). Coronary perfusion pressure and heart rate were kept constant within groups; regional myocardial blood flow and cardiac output were obtained by means of microspheres with concomitant measurement of left ventricular myocardial oxygen consumption (MVO2). alpha 1-Adrenergic antagonism alone did not significantly alter blood flow in any wall layer in either group. Subsequent alpha 2-adrenergic antagonism increased epicardial as well as composite transmural flow in the stenosis group (P < 0.025). The inverse correlation between coronary resistance and MVO2 vanished in the stenosis group following alpha 1- and alpha 2-adrenergic antagonism. Maximal first derivative of the left ventricular pressure-time relation (dP/dt) and cardiac output were reduced simultaneously (P < 0.001). Hence, the significance of alpha 1- and alpha 2-adrenergic stimulation of inotropy and cardiac performance are augmented by myocardial hypoperfusion. Furthermore, alpha 2-adrenergic receptors are responsible for epicardial vasoconstriction in hypoperfused myocardium.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1362330&dopt=Abstract
J Cardiovasc Pharmacol. 1992 Apr;19(4):479-86.
Combination of nifedipine and doxazosin in essential hypertension.
Donnelly R, Elliott HL, Meredith PA, Howie CA, Reid JL.
University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland.
Pharmacodynamic and pharmacokinetic interactions have been reported when an alpha 1-antagonist is combined with a calcium antagonist. We evaluated the clinical usefulness of the combination of nifedipine (20 mg twice daily, b.i.d.) and doxazosin (2 mg once daily, o.d.) in hypertensive patients in whom blood pressure (BP) control was suboptimal after doxazosin (group A) or nifedipine (group B) as monotherapy and investigated the underlying kinetic and dynamic interactions, including changes in vascular responsiveness to i.v. infusions of angiotensin II (ANGII) and phenylephrine (PE). The combination was well tolerated and associated with further significant reductions in BP. After 4 weeks of combined therapy, average supine BP over 8 h was 122/77 in group A and 137/80 in group B as compared with 140/86 and 150/88 mm Hg, respectively, during monotherapy + placebo. The combination attenuated both phenylephrine and ANG-induced pressor responses: e.g., the mean PD15 values (dose of agonist required to increase systolic BP by 15 mm Hg) for group A at 1.5-3 h were 3.5 micrograms/kg/min for PE and 7.5 ng/kg/min for ANGII as compared with 2.9 and 2.3, respectively, during treatment with doxazosin and placebo. There was no evidence of a significant kinetic interaction between the two drugs and, in particular, addition of nifedipine had no effect on the steady-state kinetics of doxazosin. In conclusion, doxazosin and nifedipine are an effective antihypertensive combination in patients who require treatment with more than one drug.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1380588&dopt=Abstract
J Cardiovasc Pharmacol. 1992 Aug;20(2):274-81.
Vasodilator therapy for acute heart failure: haemodynamic comparison of hydralazine/isosorbide, alpha-adrenoceptor blockade, and angiotensin-converting enzyme inhibition.
Verma SP, Silke B, Reynolds GW, Kelly JG, Richmond A, Taylor SH.
University Department of Cardiovascular Studies, General Infirmary, Leeds, England.
Haemodynamic comparison of three vasodilation regimens [intravenous (i.v.) hydralazine and isosorbide dinitrate (ISDN) combined, i.v. doxazosin, and i.v. enalaprilat] was undertaken in 36 patients with acute left ventricular (LV) failure due to recent myocardial infarction. Each regimen achieved similar reductions in pulmonary artery occluded pressure (PAOP, preload) and systemic arterial pressures (afterload), with increased cardiac and stroke volume (SV) indexes (p less than 0.01). Only the hydralazine and isosorbide combination induced resting tachycardia. Balanced vasodilatation after selective alpha-adrenoceptor blockade (doxazosin) and angiotensin-converting enzyme (ACE) inhibition (enalaprilat) without increase in heart rate (HR) suggests that these therapies may have definite haemodynamic advantages over the hydralazine/ISDN combination.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1381019&dopt=Abstract
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