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At most time points tamsulosin inhibited phenylephrine-induced diastolic blood pressure elevations significantly less than terazosin (5 h time point: median difference in inhibition 35%, 95% CI: 18.7-50.3%). On the other hand, phenylephrine-induced changes of cardiac output, heart rate and stroke volume were similar during both active treatments.
1,624 patients suffering from BPH and requiring medical treatment were included in this multicentre open clinical trial performed by 983 general practitioners. After a one-week titration phase, terazosin was administered for 4 weeks at the dosage of 5 mg per day as a single dose in the evening at bedtime. The efficacy of treatment was assessed by the variation of the IPSS score between inclusion and the end of treatment, the treatment response rate (at least 3 point reduction of the IPSS score) and the course of the quality of life score. The safety of treatment was evaluated by clinical interview and physical examination at each visit and by analysis of all adverse events occurring during the trial.
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The effects of long-term monotherapy with terazosin, an alpha-1 blocker, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 53 hypertensive patients: 19 with normal glucose tolerance (NGT) and 34 with impaired glucose tolerance (IGT). The plasma glucose, serum lipids, fructosamine, and glycosylated hemoglobin A1c (HbA1c) levels were determined before and during long-term (6 months) therapy with terazosin. A 75-g oral glucose tolerance test was performed before and during long-term terazosin therapy. Significant falls in both systolic and diastolic blood pressure in both patient groups were maintained during the long-term therapy with terazosin. Neither fasting nor postglucose-load venous plasma glucose levels were altered in either group of patients, and diabetes mellitus did not develop in any patient with NGT during the study. There was no significant change in the insulinogenic index (delta IRI/delta BS at 30 minutes after glucose load) in either patient group. In patients with IGT, glucose intolerance was slightly improved with significant reductions in HbA1c and fructosamine during terazosin therapy. Serum total cholesterol (TC) and triglyceride levels were significantly decreased in patients with IGT. In addition, TC and low density lipoprotein (LDL) cholesterol were significantly decreased in patients with hypercholesterolemia (TC > 220 mg/dL). These results suggest that long-term therapy with terazosin may improve glucose and lipid metabolism in hypertensive patients and terazosin seems to be an antihypertensive agent with beneficial effects for hypertensive patients with either dyslipidemia or impaired glucose metabolism.
OBJECTIVES To evaluate the number of medical and urological conditions associated with nocturia in a cohort of older men who were primary-care enrolees, and to assess the feasibility and efficacy of using a multicomponent intervention to reduce nocturia and its bother. SUBJECTS AND METHODS Men aged > or =50 years and with two or more episodes of nocturia were recruited from the primary-care clinics at one Veterans Affairs Medical Center to participate in a 4-week, open-label, prospective pilot study. A multicomponent intervention composed of behavioural therapy and targeted drug therapy was administered according to a specified protocol based upon identified risk factors for nocturia. Outcome measures included self-reported nocturia and bother on the American Urological Association (AUA)-7 Symptom Index, 3-day bladder diaries and self-reported sleep-related measures recorded using 7-day sleep diaries. RESULTS Fifty-five men completed the protocol (mean age 67 years, sd 8.3); they had a mean of 4.5 of nine defined conditions potentially related to nocturia. Highly prevalent conditions included moderate-to-severe benign prostatic hyperplasia (87%), hypertension (86%) and urinary frequency (71%). The mean diary-recorded nocturia decreased from 2.6 to 1.9 (P < 0.001), and bother score reduced from 3.1 to 1.1, representing a change from a 'medium' to a 'very small' problem (on a 5-point scale). Sleep diary-derived measures also improved significantly (time to initiate sleep, time to return to sleep after awakening, quality of sleep). CONCLUSIONS Given that individual older patients often have multiple coexistent risk factors for nocturia, identifying a principal cause of nocturia, a concept emphasized in treatment guidelines, proved to be difficult. Implementing a multicomponent behavioural intervention combined with drug(s) was feasible in older men and reduced nocturia frequency, bother from nocturia, and time to initiate sleep, within 4 weeks. These promising results merit repeating using a randomized, controlled trial.
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All patients with insufficient blood pressure control with either a calcium channel blocker or an ACE inhibitor and evidence of hyperlipidemia (total serum cholesterol > 5.69 mmol/L) were included into an open, randomized and prospective study to evaluate the effects of terazosin and atenolol on lipid profile in hypertensive patients. The patients received either terazosin (n = 26; dose 1 to 10 mg) or atenolol (n = 28; dose 25 to 100 mg). Blood pressure was assessed by 24-hour ambulatory blood pressure measurement and serum lipids were evaluated at the time of inclusion and 12 weeks later.
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Terazosin is a post-synaptic alpha 1-adrenoceptor antagonist with a similar pharmacodynamic profile to prazosin. It differs from prazosin in having a longer duration of action, with an elimination half-life some 2 to 3 times that of prazosin, allowing the convenience of once daily administration. Moreover, its absorption from the gastrointestinal tract is more complete and predictable than that of prazosin which may facilitate dose titration. Terazosin therapy results in a significant reduction in blood pressure in patients with mild to moderate essential hypertension, with little influence on heart rate. The drug is an effective antihypertensive when administered as monotherapy or in combination with a range of antihypertensive agents including beta-blockers, diuretics and combinations of the two. In the few patients with congestive heart failure studied, terazosin produced an increase in cardiac output with a reduction in ventricular filling pressure and systemic vascular resistance, but no studies have been performed to assess the therapeutic potential of terazosin in this indication. Reductions in total plasma cholesterol and low density plus very low density lipoprotein cholesterol fractions have been reported after terazosin therapy, while high density lipoprotein cholesterol concentrations have tended to increase. Should such beneficial changes be confirmed in long term clinical studies they would suggest a therapeutic advantage of terazosin over some other antihypertensive drugs, particularly diuretics, which have been reported to adversely affect the plasma lipid profile. The most common side effects associated with terazosin treatment are dizziness, headache, asthenia and nasal congestion, but these are usually mild and do not require treatment discontinuation. Terazosin is normally administered once daily, starting at a dose of 1 mg/day and gradually titrating upwards as the blood pressure stabilises at each new dose, until blood pressure is adequately controlled or to a maximum dose of 20mg daily. First-dose syncope occurs rarely after terazosin, and can largely be avoided by giving the first dose at bedtime. Thus, terazosin offers a useful alternative to the drugs currently available for the management of mild to moderate essential hypertension either as monotherapy or in combination with other antihypertensive drugs.
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Further characterization of the alpha1AR gene family indicates that 3 receptor subtypes exist in humans. Their different distribution between urinary tract and cardiovascular tissues has provided a strategy for the development of improved therapeutic agents. Since excessive activity of the alpha1aAR and alpha1dAR subtypes appears to be a common feature in symptomatic BPH and alpha1aARs are enriched in prostatic tissue, drugs that demonstrate high alpha1aAR selectivity have attracted attention. Tamsulosin, which has high affinity for alpha1aAR and alpha1dAR subtypes but not for alpha1bAR, shows efficacy similar to the nonsubtype selective agents terazosin and doxazosin. It is associated with fewer cardiovascular side effects, although it has some ejaculatory side effects. The nonsubtype selective agent alfuzosin also demonstrates efficacy and offers an enhanced side effect profile, particularly minimizing hypotension. Other agents with super selective specificity for the alpha1aAR subtype are under investigation.
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Human prostate tissue was obtained at prostatectomy for benign prostatic hyperplasia in 37 adult male patients. Tissues were suspended in tissue bath chambers connected to force displacement transducers. Specimens were subjected to agonist induced contractions, the first always being norepinephrine (NE). Specimens were pretreated with antagonist (adrenergic, cholinergic, nonadrenergic noncholinergic or none if control), followed by contraction with a second agonist (NE or other). Contractile tensions were recorded on a polygraph and then statistically analyzed.
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These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarisation resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarisation, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy. This article is protected by copyright. All rights reserved.
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The treatment of benign prostate hyperplasia (BPH) presents 2 options: medical or surgical, and there are doubts about what is the best treatment since 80% of patients who undergo surgery become asymptomatic and 10 to 40% of those under medical regimen undergo surgery within a 5 years period. It is difficult to assess the actual costs of treating BPH in Brazil due to several factors, among them regional particularities and the scarcity of current statistical data.
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At day 28 of the trial, the Amlodipine plus terazosin group demonstrated comparable efficacy in lowering the total International Prostate Symptom Score and significant improvement in the presence of overactive bladder compared with the terazosin group (P < .05) and significant improvement in quality of life compared with the Amlodipine group (P < .05). The Amlodipine plus terazosin group also achieved the greatest blood pressure control compared with either the terazosin group (P < .01) or Amlodipine group (P < .05). All 3 treatment regimens were well tolerated by the study patients.
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Randomized, double-blind, multicenter (eight government and private facilities), placebo-controlled study.
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To evaluate the effect of antihypertensive therapy on platelet activation in essential hypertension, the plasma levels of beta-thromboglobulin (beta-TG) were examined in 45 patients with essential hypertension and 20 age-matched normotensive control subjects. Hypertensive patients were assigned to monotherapy with one of five different antihypertensive drugs for 6 months, and the change of plasma levels of beta-TG was reexamined after the completion of the monotherapy. The plasma beta-TG increased in hypertensive patients compared with levels in normotensive control subjects. Monotherapy with each drug resulted in sufficient blood pressure control in all hypertensive patients. The plasma beta-TG decreased significantly after monotherapy with an alpha-blocker or an angiotensin-converting enzyme inhibitor (ACEI). The plasma beta-TG increased with the use of a diuretic but did not change with the use of a beta-blocker or calcium antagonist. The platelet activation observed in patients with essential hypertension is reversed by monotherapy with an alpha-blocker or an ACEI. It is possible that these drugs reduce the development of hypertensive vascular complications due to suppression of platelet activation in patients with essential hypertension.
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EA at Zhongliao and Huiyin points can markedly improve the symptoms of difficult urination in mild or moderate patients with BPH, increase their Qmax and reduce PVR. Its efficacy is better than that of terazosin.
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Middle-aged men with essential hypertension were enrolled by their primary care physicians in community practice. Those with symptoms of benign prostatic hyperplasia were identified by a Boyarsky scale score. The study was a 12-week, dose-escalation, open-label protocol for men aged 45 years and older.
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A working classification system for prostatitis was developed in 1999, but there are few randomized controlled trials that distinguish between the various treatment options. Bacterial prostatitis can be acute or chronic but always requires some degree of antimicrobial therapy. Pharmacologic features of fluoroquinolones make them the preferred agents for most patients. These antibiotics can become trapped in a chronically inflamed prostate due to pH differences between prostatic tissue and serum. Many fluoroquinolones have penetration ratios (prostate level:serum level) of up to 4:1. A study in European men (N = 117) who received levofloxacin 500 mg/d with a diagnosis of chronic bacterial prostatitis demonstrated clinical success rates of 92% (95% CI 84.8%-96.5%), 77.4% (95% CI, 68.2-84.9%), 66.0% (95% CI, 56.2%-75.0%), and 61.9% (95% CI, 51.9%-71.2%) at 5-12 days, 1 month, 3 months, and 6 months after treatment. Additionally, there have been numerous randomized, placebo-controlled trials in patients with chronic prostatitis that have studied α-blockers, steroid inhibitors, anti-inflammatory agents, and bioflavonoids. Treatment responses to α-blockers appear to be greater with longer durations of therapy in α-blocker-naïve patients (National Institutes of Health-Chronic Prostatitis Symptom Index [NIH-CPSI] score reduction of at least 3.6 points after 6 weeks of tamsulosin therapy [P = 0.04] and up to 14.3 and 9.9 point NIH-CPSI score reductions with 14 weeks of terazosin and 24 weeks of alfuzosin therapy, respectively [P = 0.01 for both]). Combination therapy with an α-blocker, an anti-inflammatory, and a muscle relaxant does not appear to offer significant advantages over monotherapy (12.7 vs 12.4 point reduction in NIH-CPSI scores) and a stepwise approach to therapy involving antibiotics followed by bioflavonoids and then α-blockers appears to effectively reduce symptoms for up to 1 year in patients with chronic prostatitis (mean NIH-CPSI point reduction of 9.5 points compared with baseline, P < 0.0001). Patients who have had multiple unsuccessful treatment regimens may benefit from direct stimulation of the pelvic muscles through electromagnetic or electroacupuncture therapy.
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When medical therapy is indicated for moderate or severe BPH, alpha-adrenergic antagonists exhibit a faster onset of action and produce greater improvement of voiding symptoms than does finasteride.
Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) have a significant impact on the lifestyle of older men. Transurethral resection of the prostate (TURP) is the most effective surgical therapy for this condition but an increasing number of patients are electing conservative medical therapy. Alpha-Adrenoceptor antagonists and 5alpha-reductase inhibitors are the 2 categories of drug therapy currently available for BPH. Use of alpha-adrenoceptor antagonists in the treatment of BPH is based on their ability to prevent the neural stimulation which induces prostate smooth muscle contraction, producing lower urinary tract symptoms. Several studies have demonstrated that alpha-receptors predominate in the prostatic stroma, capsule and bladder neck. Initial work focused on the use of phenoxybenzamine, a nonspecific alpha-blocker, in the treatment of BPH. While results were promising, significant adverse effects and concern over potential mutagenicity have resulted in a lack of use of this medication for this indication. Subsequent attention was directed towards the short-acting alpha-specific antagonist prazosin. Results conflicted regarding whether an actual sustained improvement in lower urinary tract symptoms could be achieved with this medication, and because of twice daily dosing compliance issues were a drawback. Thus, the mainstay in pharmacological treatment of BPH over the past decade has been 2 once-a-day alpha-specific antagonists, doxazosin and terazosin. Over 75% of all prescriptions written for BPH are for one of these 2 medications. Despite their tremendous success in both decreasing urinary symptoms and increasing urinary flow rates, systemic adverse effects can be bothersome. Recently, efforts have focused on use of alpha1A-urospecific antagonists such as tamsulosin and alfuzosin in an attempt to achieve similar clinical results as doxazosin and terazosin without systemic adverse effects. Thus far, results are promising, but long term studies must be done to determine whether pharmacological uroselectivity is actually clinically relevant.
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The quinazoline based alpha1-adrenoceptor antagonists doxazosin and terazosin suppress prostate tumor growth via the induction of apoptosis and decrease in tissue vascularity. To assess the effect of alpha1-blocker exposure on the incidence of prostate cancer we performed an exploratory, observational cohort study.
A total of 24 women with obstructive voiding symptoms or retention were evaluated with video pressure flow electromyography, and diagnosed with functional bladder neck obstruction due to high pressure and low flow on silent electromyography and bladder neck appearance on fluoroscopy. Patients were initially treated with clean intermittent self-catheterization and alpha-blockers. Catheterization was stopped when post-void residual was less than 50 ml. and only alpha-blocker therapy was continued. Bladder neck incision was performed in patients who had a poor response to or side effects of alpha-blocker therapy, or when therapy was discontinued due to economic reasons. Clean intermittent self-catheterization was continued in patients who had a poor response to alpha-blockers or refused to undergo bladder neck incision. Bladder neck incision was performed in the initial 2 cases with an adult resectoscope using a Collin's knife and subsequently a pediatric resectoscope (13F). Uroflow and post-void residual measurements were performed in all cases.
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Primary bladder neck dysfunction is a nonneurogenic voiding disorder frequently overlooked in pediatrics. The diagnosis classically is made by videourodynamics but can also be made with noninvasive uroflow studies with pelvic floor electromyography. We report our long-term results using alpha-blocker therapy in patients with primary bladder neck dysfunction.