Seminal plasma PSA has been found to be a better predictor of the response to alpha-blocker treatment when compared to serum PSA and PSA density.
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The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients' quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. Alpha1-adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled-release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross-over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5alpha-reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well-tolerated, long-term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.
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Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options.
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The Lipid Research Clinic trials established conclusively that lowering serum cholesterol reduces the incidence of coronary heart disease. Yet a number of clinical trials have demonstrated that many pharmacological agents commonly used to lower blood pressure also adversely affect serum lipid levels. Recent studies of prolonged use of beta-blockers and diuretics have failed to show that these agents have any clear primary preventive effect on coronary heart disease; in a few cases, these agents were believed to pose a greater risk of coronary heart disease than no antihypertensive treatment at all. These observations suggest that a reappraisal of current therapeutic schemes is in order. Because coronary heart disease is known to have many causes, primary preventive therapy must logically go beyond the relatively simple goal of lowering blood pressure. The metabolic effects of antihypertensive drugs, particularly on blood lipids, should also be taken into account. These effects could be of special clinical significance in relatively young patients, for whom the long-term risk of developing coronary heart disease is of major concern. This review discusses recent clinical trials examining the effects on lipids of diuretics, beta-blockers, and selective alpha-adrenoceptor blocking agents.
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To assess the long-term efficacy and safety of extended-release doxazosin gastrointestinal therapeutic system (GITS) under routine clinical care conditions over 12 months in Korean men with benign prostatic hyperplasia (BPH) with and without coexisting hypertension.
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The study was conducted between September 2004 and December 2005, and included 90 treatment naïve patients, aged 22-42 yr (mean age: 29.1+/-5.2) with Category IIIB CPPS, who were randomized into three groups: group 1, alpha-blocker; group 2, combination of alpha-blocker, anti-inflammatory, and muscle relaxant; group 3, placebo once daily. The patients were treated for 6 mo and were followed up for a further 6 mo. Changes from baseline in the total and domain scores of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) were evaluated. The primary criterion for response was scoring 50% reduction in NIH-CPSI pain score.
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Data were analyzed from a prospective, multicenter, randomized, open, parallel study of Chinese men aged 50-84 years with LUTS/BPH. Two hundred patients were randomized to receive daily treatment with 4 mg doxazosin-GITS (n=100) or 0.2 mg tamsulosin (n=100) for 8 weeks. Nocturia was assessed by question 7 of the International Prostate Symptom Score (IPSS-question 7) and a frequency-volume chart (FVC) at weeks 4 and 8. Self-reported quality of sleep and quality of life by the last question of the IPSS questionnaire were also evaluated.
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A total of 80 patients with stones sized 10 mm or smaller, located in the distal part of the ureter, were included. They were divided into two groups, according to the gender. Patients were followed-up until passage of the stone or for a maximum of 3 weeks. The number of pain episodes, stone expulsion rate and time, and possible side effects of medications were recorded and compared in both groups.
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A capillary electrophoretic method for the enantiomeric separations of doxazosin and its intermediate was developed. Several tetraalkylammonium reagents were examined for controlling the electroosmotic flow in order to improve resolution of the enantiomers. Tetramethylammonium hydroxide (TMB) was found more suitable than tetrabutylammonium hydroxide (TAB) or hexadecyltrimethylammonium bromide (CTAB) for the enantiomer separation. In addition, the effects of the pH value, the separation voltage and the concentration of the sodiumdihydrogen phosphate on the chiral separation were investigated. A buffer containing 60 mmol/L sodium dihydrogen phosphate (pH 2.2), 30 mmol/L TMB and 12 mmol/L beta-cyclodextrin (beta-CD) resulted in the baseline separation of the doxazosin enantiomers and its intermediate enantiomers. It showed that the presence of TMB was essential in some chiral separations that were previously not achieved by only using the beta-CD as a chiral selector.
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The left coronary artery was hypoperfused by means of a clamped shunt line. Sequential selective postjunctional alpha 1 (doxazosin) and alpha 2 (SK&F 104078) adrenergic antagonism was established following beta adrenergic antagonism with propranolol. Regional myocardial blood flow was measured with radiolabelled microspheres during equal coronary perfusion pressures. Experimental subjects were nine pentobarbitone anaesthetised open chest cats.
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The available data suggest that combination alpha(1)ARA/5ARI therapy is beneficial in the treatment of BPH and the associated symptoms. The greatest efficacy was evident in patients with an enlarged prostate, more severe symptoms, and higher PSA levels. There are limited data suggesting that the presence of prostatic inflammation may indicate a greater likelihood of treatment efficacy with combination therapy.
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Catheterization remains the standard management of acute urinary retention (AUR), followed by a trial without catheter (TWOC) or prostatectomy in men who do not void spontaneously. If AUR is caused by increased sympathetic activity at the level of the prostatic smooth muscles, alpha-blockers (alpha-1 adrenoreceptor antagonists) should increase the likelihood of a successful trial without catheter (TWOC) following AUR. Alpha-blockers effectively reduce the symptoms associated with benign prostatic hyperplasia (BPH) and improve the urodynamic parameters of obstruction. They may diminish the incidence of AUR and the need for prostatectomy in symptomatic men. The adventage of tamsulosin and slow-release alfuzosin over doxazosin and terazosin in the management of AUR is that a therapeutic dose can be administered at the onset of AUR, thereby reducing the time for attempting catheter removal.
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Plasma cholesterol levels are markedly reduced when doxazosin, a selective alpha 1-adrenoceptor inhibitor, is administered for several days to C57BR/cdJ mice that have been fed a high cholesterol diet. This system affords a useful model for investigating the mechanism by which selective alpha 1-adrenoceptor inhibitors decrease circulating lipid levels. The results indirectly suggest that hypercholesterolemia induced by dietary cholesterol may involve activation of the sympathetic nervous system. The basis for linkage between circulating cholesterol levels and sympathetic nervous activity, while not yet understood, may involve changes in the balance among cholesterol pathways in the liver, alteration of vasomotor tone and control of the activity of vascular endothelial lipases. An additive effect is described for cholestyramine and doxazosin, in which low density lipoprotein cholesterol is decreased by 76% by a combination of maximal doses of the 2 agents.
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Although the duration of drug administration was short in this study, 5-ARI monotherapy could maintain the alleviated symptoms and reduce the risk of acute urinary retention and surgery due to prostate regrowth in BPH patients whose symptoms improved with combination therapy.
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The findings suggest that tonocardin exerts an antihypertensive effect and positively affects carbohydrate and lipid metabolisms, and diminishes insulin resistance in patients with type 2 DM concurrent with AH.
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We examined the effect of prazosin on growth and tube formation of human umbilical vascular endothelial cells (HUVECs). We used flow cytometry to assess the effect of prazosin on cell cycle progression and Western blotting to assess its effect on the expression of various apoptotic proteins.
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New uses of cardiovascular drugs with proven experience are emerging, including for treating cancer. Quinazoline is a compound made up of two fused six member simple aromatic rings, benzene and pyrimidine rings, with several biological effects. Cardiologists first used quinazoline-based α1-adrenoceptor antagonists prazosin, doxazosin, and terazosin; currently available data support their use as safe, well tolerated, and effective add-on therapy in uncontrolled hypertension with additional favourable metabolic effects. Recent findings highlight the anticancer effects of quinazoline-based α1-adrenoceptor antagonists, indicating that they may have a significant role in uncontrolled hypertensive cancer patients without signs of ischemia.
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To test whether the combination of calcium antagonism is additive with the other newer antihypertensives, namely alpha-blockers and angiotensin converting enzyme (ACE) inhibitors.
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(-)Doxazosin is one of the enantiomers of (+/-)doxazosin, and it was reported that (-)doxazosin possessed higher selectivity for lower urinary tract between the cardiovascular system and the urinary system in the animal experiments in comparison with that of (+/-)doxazosin and (+)doxazosin. Therefore, it is important to know whether (-)doxazosin has a therapeutic effect on the hyperplastic prostate.
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Blood pressure control (<140/90 mm Hg) rates for hypertension fall far short of the US national goal of 50% or more. Achievable control rates in varied practice settings and geographic regions and factors that predict improved blood pressure control are not well identified.
Sildenafil is the most prescribed oral agent for patients with erectile dysfunction (ED). Vardenafil is a new phosphodiesterase type 5 (Pde-5) inhibitor that was approved by the US Food and Drug Administration last year to treat patients with ED of various causes. Both of these Pde-5 inhibitors have vasodilating properties and effects on blood pressure (BP), and like nitrates, they work through the nitric oxide cyclic guanosine monophosphate pathway. The aim of this study was to investigate the influence of these Pde-5 inhibitors on BP and heart rate (HR) in normotensive men with ED by a crossover comparison. Thirty-five patients with ED were enrolled to evaluate and compare the effect of sildenafil (50 mg) and vardenafil (10 mg) on BP and HR. At the screening (baseline [B]) visit, sitting systolic blood pressure (B-SBP), diastolic blood pressure (B-DBP), and HR were measured. We performed a multiple administration for both drugs and, therefore, multiple measurements of BP and HR changes, 3 doses a week, on alternate days, late in the afternoon, and on an empty stomach. B-SBP, B-DBP, and HR were recorded before each 50-mg sildenafil dosing and after 30, 60, 120, and 240 minutes. Data were averaged over the 4 time points and compared with the baseline values obtained before each dosing. After a 3-week wash-out period, patients were crossed over to vardenafil (10 mg) with the same study design. After administration of both drugs, we observed a statistically significant decrease of BP and an increase of HR. On average, sildenafil caused a decrease of SBP ranging from 5.1 +/- 3.9 mm Hg during the first dosing to 4.7 +/- 4.2 mm Hg during the third dosing, DBP ranged from 4.4 +/- 4.9 to 4 +/- 4.1 mm Hg, and HR increased 1.8 +/- 2.0 bpm (first dose) and 1.2 +/- 0.9 bpm (third dose). With vardenafil, we recorded a greater variation for SBP and DBP. SBP decreased from 8.02 +/- 8.0 mm Hg during the first dosing to 5.4 +/- 5.5 mm Hg during the third dosing, whereas DBP decreased from 6.6 +/- 7.2 to 5.0 +/- 5.3 mm Hg, respectively. Recorded HR showed an increase of 3.1 +/- 3.2 bpm (first dose) and 2.4 +/- 2.3 bpm (third dose). After the first vardenafil administration, we recorded fainting episodes in 3 patients because of a decrease in BP greater than 20 mm Hg. Two of the patients were in therapy with doxazosin for benign prostatic hyperplasia (BPH). Cardiovascular response was not significantly different after the first dose between the 2 treatments. Vardenafil demonstrated clinically significant differences (fainting) with respect to sildenafil only during the first doses. We suggest that before starting therapies with Pde-5 inhibitors, particularly with the newer ones, that baseline cardiovascular parameters are measured and monitored, especially during the first dose, because of the presence of a "first dose effect." Moreover, it is necessary to pay particular attention to those patients in treatment with other drugs that could have a synergistic hypotensive effect as a result of vasodilation potentiation.
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Minimal invasive adrenalectomy has become the procedure of choice to treat adrenal tumors with a benign appearance, ≤ 6 cm in diameter and weighing < 100 g. Authors evaluated medium- and long-term outcomes of laparoscopic adrenalectomy (LA), performed for ten years in a single endocrine surgery unit.
Thirty patients with hypertension were enrolled in this study, 13 had non-insulin-dependent diabetes mellitus (NIDDM) and 17 were nondiabetic. Patients were treated with doxazosin for approximately 4 months, and blood pressure fell significantly (P < .001) in both nondiabetics (149/96 to 134/85 mm Hg) and in those with NIDDM (154/96 to 143/84 mm Hg). In the nondiabetic group, doxazosin treatment was associated with significant improvement in insulin-mediated glucose disposal (P < .05) and lower plasma insulin (P < .001), and triglyceride (P < .001) concentrations measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at noon). In addition, fasting total plasma (P < .001) and VLDL cholesterol (P < .01), and total plasma (P < .05), VLDL (P < .08), LDL (P < .01), HDL (P < .01) triglyceride concentrations were lower following doxazosin treatments in the nondiabetic group, as was the ratio of total to HDL cholesterol (P < .001). Finally, apoprotein B concentrations fell with doxazosin in the nondiabetic group (P < .01). Significant changes seen in the group with NIDDM included a decrease in the ratio of total to HDL cholesterol (P < .001) and a fall in apoprotein B concentration (P < .05). However, values for all other variables did not change significantly with treatment in this group. Thus, doxazosin treatment of nondiabetic subjects with high blood pressure was associated with a series of changes in glucose, insulin, and lipoprotein metabolism that should decrease risk of coronary heart disease (CHD) in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)