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There is no consensus for the optimal treatment program for individuals with mild hypertension, including whether treatment should emphasize life-style changes alone, such as weight loss, reduction of sodium and alcohol intake, and increased physical activity, or whether it should also include a pharmacologic component. The dilemma is accentuated by the availability of many drugs from different classes to lower blood pressure. To study the relative efficacy and safety of a combination of pharmacologic and nutritional-hygienic intervention compared with nutritional-hygienic intervention alone, a double-blind, controlled clinical trial was initiated. Nine hundred two men and women with mild hypertension (average blood pressure, 140/91 mm Hg) were randomized to receive nutritional-hygienic intervention plus one of six treatments: (1) placebo; (2) diuretic (chlorthalidone); (3) beta-blocker (acebutolol); (4) alpha 1-antagonist (doxazosin mesylate); (5) calcium antagonist (amlodipine maleate); or (6) angiotensin-converting enzyme inhibitor (enalapril maleate). After 12 months, weight loss averaged 4.5 kg, urinary sodium excretion was reduced by 23%, and reported leisure-time physical activity was nearly doubled. Systolic and diastolic blood pressure in the group given nutritional-hygienic intervention alone (placebo) were reduced by 10.6 and 8.1 mm Hg, respectively. For participants in the five groups receiving antihypertensive medication in addition to nutritional-hygienic treatment, blood pressure reductions were significantly greater than those achieved with nutritional-hygienic treatment alone (range, 16 to 22 mm Hg for systolic and 12 to 14 mm Hg for diastolic blood pressure). Although differences among treatment groups in certain dimensions of quality of life, self-reported side effects, plasma lipid levels, and biochemical measures were observed, no consistent pattern in the differences was noted. Nutritional-hygienic therapy is an effective first-step treatment for persons with mild hypertension, and significant additional blood pressure lowering with minimal short-term side effects can be achieved by adding one of five different classes of antihypertensive agents.
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Although the pathology of essential hypertension is still unclear, studies have shown that doxazosin, a selective alpha 1-inhibitor, is able to effectively control mild-to-moderate hypertension. The aim of these two, noncomparative studies was to evaluate the efficacy and toleration of doxazosin when used as monotherapy and in combination with other antihypertensive agents. In study I, 154 patients with standing and sitting diastolic blood pressures (DBPs) ranging from 95 to 115 mm Hg were treated with once-daily doxazosin (1 to 8 mg) as monotherapy for 12 weeks. Both sitting and standing blood pressures were significantly reduced by doxazosin monotherapy. Target DBP of less than or equal to 90 mm Hg was achieved in 86% of patients after 12 weeks of therapy with doxazosin, and there was no change in heart rate. Cholesterol and triglyceride levels were significantly decreased by doxazosin, but there was no change in glucose levels. Minor side effects were seen in 17.5% of patients, and 2.6% discontinued therapy. In study II, 65 patients with DBPs ranging from 95 to 115 mm Hg on existing antihypertensive therapies were concomitantly treated with doxazosin (1 to 8 mg) once daily for 12 weeks. Target DBPs of less than or equal to 90 mm Hg was achieved in 71% of patients after 12 weeks of therapy with doxazosin. There was no change in heart rate throughout the treatment period, and plasma cholesterol, triglyceride, and glucose levels remained essentially unchanged. Three patients, each receiving a beta-blocker, a diuretic, and doxazosin, were withdrawn because of side effects. Minor side effects, which were considered drug related were seen in 21% of patients. Doxazosin is a drug with good antihypertensive efficacy and is well tolerated as monotherapy and in combination with beta-blockers, thiazide diuretics, angiotensin converting enzyme inhibitors, and various combinations of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Although the parathyroid hormone-related protein gene is widely expressed in the central nervous system, the role of this protein in blood pressure is unknown. This article examines whether parathyroid hormone-related protein is involved in the central regulation of blood pressure. An intraventricularly injected solution of parathyroid hormone-related protein elicited a dose-dependent increase of mean arterial pressure accompanied by a decrease of heart rate in conscious Sprague-Dawley rats. An anti-parathyroid hormone-related protein monoclonal antibody, given in an intraventricularly injected solution, blocked the pressor effect of parathyroid hormone-related protein. Furthermore, this pressor effect of parathyroid hormone-related protein was also abolished after pretreatment by intravenous administration of either hexamethonium bromide or doxazosin mesylate. These results suggest that central parathyroid hormone-related protein is implicated in the regulation of blood pressure, and that this effect may be mediated through sympathetic activation.
These findings suggest that the arterial stiffness reduction induced by antihypertensive medications is associated with the improvement of renal damage, independent of home/office SBP reduction.
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We retrospectively reviewed 88 consecutive patients undergone LA for lesions of adrenal glands from 2003 to 2013. The first 30 operations were considered part of the learning curve. Doxazosin was preoperatively administered in case of pheochromocytoma (PCC), while spironolactone and potassium were employed to treat Conn's disease. Perioperative cardiovascular status modifications and surgical and medium- and long-term results were analyzed.
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We present a female Jehovah's Witness patient with concomitant severe left main and left anterior descending coronary artery disease and pheochromocytoma who underwent successful off-pump myocardial revascularization. Perioperative management of this patient included alpha-blockade with Doxazosin followed by beta-blockade with Metoprolol. A short-acting Phentolamine was used for alpha-blockade before surgery. Because she refused transfusion of blood and blood products, erythropoietin and iron was used to increase her hemoglobin in both the preoperative and postoperative periods. Intraoperative strategy included off-pump myocardial revascularization, the use of a pulmonary catheter to monitor hemodynamics, the use of norepinephrine and epinephrine to increase blood pressure, the employment of the cell saver, and transesophageal echocardiography.
MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function.
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Thirty-six men (mean age 83.6 years, SD 5.6, range 80-96) received either doxazosin 4 mg (11 men) or 8 mg (10 men), or terazosin 5 mg (five men) or 10 mg (10 men), once daily at night. Twenty-eight men (78%) were on other anti-hypertensive medication; the type and dosage were not changed during the study. Efficacy and safety were assessed using measurements of peak urinary flow rate, symptom scores and the incidence of adverse events.
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Influence of postjunctional alpha 1- and subsequent alpha 2-adrenergic antagonism on myocardial blood flow was measured in a group of anesthetized cats with acute occlusion of the left anterior descending coronary artery (LAD) and a control group (n = 10 for both). The relatively selective postjunctional alpha 1-(doxazosin) and alpha 2-adrenergic (SK&F 104078) antagonists were applied after beta-adrenergic blockade (propranolol). Regional myocardial blood flow was obtained with radiolabeled microspheres. Major hemodynamic determinants for perfusion were kept constant both within and between groups by right atrial pacing and aortic obstruction. Mean coronary resistance in nonischemic myocardium was permanently lower in the occlusion group as compared with controls (p less than 0.01). Subsequent alpha 2-adrenergic antagonism reduced mean coronary resistance in controls only (p less than 0.05). Cardiac output (CO) and dP/dt was reduced in LAD-occluded hearts after alpha 2-adrenergic blockade (p less than 0.01, p less than 0.05). The study demonstrates the significance of postjunctional alpha 2-adrenergic-mediated vasoconstriction in well-perfused myocardium of control hearts, whereas such vasoconstriction was deteriorated in LAD-occluded hearts. A role for myocardial alpha 2-adrenoceptors for maintenance of global cardiac function in acute regional ischemia was also indicated.
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Fifteen patients with arterial hypertension (AH) were examined. Their peripheral venous hemodynamics, central circulation, systolic and diastolic functions were studied and a course therapy with doxazosin (cardura, Pfizer, USA) was performed for 30 days. Cardura (doxazosin) was found to be the drug of choice for antihypertensive therapy in patients with AH concurrent with baseline systemic venous normo- or hypertension. In patients with baseline venous hypervolemia in the presence of venous hypotension, cardura therapy resulted in deterioration of signs of venous insufficiency and promoted the development (in 38% of the cases) or progression (in 38%) of diastolic dysfunction of the left ventricle (LV). Thus, the venous circulation and LV myocardial function should be originally assessed in order to decide whether cardura (doxazosin) is used in antihypertensive therapy in patients with AH.
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Iasi "Sf Spiridon" Emergency Hospital and "Oftaprof" private practice
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alpha1-Adrenoreceptors are thought to be involved in prostate smooth muscle contractions and could hence play a role in the dynamic component of intravesical obstruction associated with symptomatic BPH. Consequently, since the mid-eighties alpha receptor blocking agents have been used for the treatment of BPH. Non-selective alpha blockers are usually associated with systemic side-effects which resulted in an exclusion or withdrawal of many patients from this form of treatment. With the availability of so-called uroselective alpha blockers the management picture has changed since it was anticipated that these compounds cause lesser side-effects with at least the same, or even better, efficacy. Comparative clinical studies are essential for determining the eventual advantages of the uroselective alpha1-antagonists and a large number of such studies have been performed worldwide studying the various available compounds. European studies with terazosin showed clear superiority of the drug over the placebo while causing only limited side-effects. Various other studies using alpha-blocking agents such as doxazosin, tamsulosin and alfuzosin yielded identical results. Especially with tamsulosin and alfuzosin, the side-effects were comparable with those encountered in the placebo group. About 7% of the patients using tamsulosin experienced retrograde ejaculation in one study which did not occur in the alfuzosin studies. Important studies in Europe have also investigated the value of a combination of an alpha blocker with a 5alpha-reductase inhibitor. Comparable studies in which both alfuzosin and doxazosin were combined with the 5alpha-reductase inhibitor Proscar have shown that a combination is not superior to a blocker monotherapy and especially in the ALFIN study the results show that alfuzosin monotherapy is superior to Proscar in the management of symptomatic BPH. European studies have evaluated Quality of Life, sexuality as well as socio-economical outcome of the treatment with alpha1 receptor antagonists. These studies completed the spectrum of clinical research in Europe in the important field of management of symptomatic BPH with uroselective alpha1 antagonists.
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Prostatic and erectile tissues were obtained from nine to 12 patients, respectively. Patients underwent cystoprostatectomy for infiltrating bladder cancer or penile surgery for penile implant, congenital curvature or Peyronie's disease.
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The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in uncontrolled hypertension when used in combination with all other major classes of antihypertensive drug and there is increasing evidence suggesting that they have modest but significant beneficial effects on lipid and glucose metabolism. The availability of extended-release formulations has contributed to an excellent tolerability profile. New data from an observational analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that doxazosin gastrointestinal therapeutic system (GITS) used as a third-line antihypertensive agent lowered blood pressure and caused modest reductions in plasma lipids. Furthermore, use of doxazosin in ASCOT was not associated with an increased risk of heart failure, in contrast to the earlier finding of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Overall, currently available data support the use of alpha-blockers as safe, well tolerated and effective add-on antihypertensive drugs, which have additional favourable metabolic effects.
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Doxazosin may be an antihypertensive agent that decreases both waking and sleeping BP through inhibiting sympathetic nervous activity in macroalbuminuric diabetes patients.
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Patients before TURP were significantly more depressed, worried and psychiatrically morbid than were those before medical treatment. Three months after medical and surgical treatment, there was significantly less depression, anxiety and psychiatric morbidity in the TURP than in the medication group.
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This study investigated the safety and efficacy of doxazosin treatment in a large population of patients (n = 336) with essential hypertension and assessed the effect of doxazosin on the serum lipid profile and the calculated risk of developing coronary heart disease. Patients were assigned to two groups: those with a baseline diastolic blood pressure greater than or equal to 95 mm Hg (group 1) and those with a baseline diastolic blood pressure less than 95 mm Hg (group 2) that was controlled by previous antihypertensive therapy. Doxazosin treatment (monotherapy in 76.2% of patients) significantly (p less than 0.05) reduced the blood pressure of patients in group 1 (-23/-17 mm Hg) after 10 weeks and maintained the control of blood pressure for patients in group 2. Heart rate was essentially unchanged in both groups. Mean final daily doses of 3.6 and 3.2 mg were achieved in groups 1 and 2, respectively. Treatment with doxazosin improved the severity category of hypertension for 88.4% of patients in group 1; 87.3% of patients were considered a therapy success. Doxazosin had a favorable effect on the serum lipid profile in both groups of patients. The majority of lipid changes achieved statistical significance and resulted in a significant 27% decrease in the calculated risk of developing coronary heart disease. Doxazosin was well tolerated; only 24.1% of patients had side effects that were related or possibly related to treatment. In nine (2.7%) patients the dose of doxazosin was reduced and 26 (7.7%) patients withdrew from doxazosin therapy because of side effects.
The use of alpha-blockers for all prescriptions began to decrease after the closure of the alpha-blocker (doxazosin) arm of ALLHAT in January 2000. Prescriptions for the thiazide-type diuretics immediately increased after the ALLHAT publication in December 2002. During the first 6 months of 2003, the percentages of thiazide-type diuretics were statistically significantly higher compared with the predicted values. This pattern held for all as well as for new antihypertensive prescriptions.
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The four alpha(1)-adrenoceptor antagonists were evaluated against norepinephrine-induced phasic contractions in mouse isolated ureteral preparations and against phenylephrine-induced sustained contractions in hamster isolated ureteral preparations using a functional experimental technique.
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In vitro, pharmacological antagonism of alpha(1)-adrenoceptors in endothelial cells from WKY rats by doxazosin enhanced, while stimulation of these adrenoceptors with phenylephrine, inhibited endothelial cell proliferation and DNA synthesis, ERK and retinoblastoma protein (Rb) phosphorylation, cell migration and tubule formation. In vivo, we found increased alpha(1)-adrenoceptor density in the ischaemic hindlimb, compared to non-ischaemic hindlimb, suggesting an enhanced alpha(1)-adrenoceptor tone in the ischaemic tissue. Treatment with doxazosin (0.06 mg kg(-1) day(-1) for 14 days) did not alter systemic blood pressure but enhanced neo-angiogenesis in the ischaemic hindlimb, as measured by all our assays.
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Management of benign prostatic hyperplasia (BPH) is often complicated by concomitant hypertension, a life-threatening condition that must be managed optimally. Many of the alpha blockers used to treat BPH also decrease blood pressure, and terazosin and doxazosin have been shown to have significant cardiovascular side effects, such as asthenia/fatigue, postural hypotension, and dizziness when used to treat BPH patients. Furthermore, these drugs are not first-line therapies for hypertension, and the majority of hypertensive BPH patients will be receiving other antihypertensive agents. Therefore, it is possible that the introduction of these drugs will affect blood pressure control, at least temporarily, with possible adverse effects. In contrast, the selective alpha1A blocker tamsulosin does not appear to have significant cardiovascular side effects and produces minimal blood pressure reductions. Therefore, urologists can choose either to use alpha blockers to treat both hypertension and BPH or to treat BPH using alpha blockers that do not interact with antihypertensive therapy. This review focuses on the alpha blockers currently being used to treat BPH, their effects on the cardiovascular system, and their interaction with antihypertensive drugs.
There were improvements in all urodynamic parameters (Free Qmax: 30.4% and 28%, PVR: 14 ml and 12 ml, invasive Qmax: 29.3% and 26.2%, Pdet at Qmax: -32.7% and -30%, Pdet-max: -29% and -27.7% at end of the 1st and 6th months whereas placebo effects were worsening in all urodynamic parameters.
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Overall antihypertensive use in the autonomous region of Valencia in 2005 was 235.6DDD/1000/day. This consumption was concentrated in pensioners (800DDD/1000p/day vs. 73DDD/1000a/day). Consumption of antihypertensive subgroups oscillated from 442DDD/1000p/day for drugs with action on the renin-angiotensin system to 32DDD/1000p/day for doxazosin. The active population showed similar patterns. Variation in consumption was moderate, with coefficients of variation from 0.20 to 0.40 (slightly greater for the active population). Associations among dispensations of the different therapeutic subgroups were strong.