Urodynamic effects of terazosin treatment for Japanese patients with symptomatic benign prostatic hyperplasia

PURPOSE: For treating benign prostatic hyperplasia (BPH) 5 or 10 mg. terazosin hydrochloride daily has been routinely used in North America and Europe. We investigated the urodynamic effects of 2 mg. terazosin daily on Japanese patients with symptomatic BPH using pressure flow study. MATERIALS AND METHODS: A total of 20 Japanese patients 50 years old or older with symptomatic BPH underwent symptomatic and urodynamic evaluations, including pressure flow study, before and after terazosin treatment. Patients were given 1 mg. terazosin once daily for the first 7 days and they continued to receive 1 mg. terazosin twice daily for the following 3 weeks. RESULTS: At 4 weeks after terazosin treatment the International Prostate Symptom Score, quality of life index and maximum and average flow rates were significantly improved. Pressure flow study demonstrated decreased detrusor pressure at maximum flow, and minimum detrusor pressure during voiding and urethral resistance factor after terazosin treatment. Of the 20 patients 13 (65%) showed improvement in the linear passive urethral resistance relation. There was no significant difference in the maximum W. factor before and after terazosin treatment. CONCLUSIONS: Terazosin treatment, even 2 mg. daily, urodynamically relieved bladder outlet obstruction in Japanese patients with symptomatic BPH without any changes in detrusor contractility.     

A multicenter, fixed-flexible dose study of terazosin hydrochloride in the treatment of symptomatic benign prostatic hypertrophy]

In this study the multicenter, fixed-flexible dose regimen was taken to evaluate the effective dose range of Terazosin for the treatment of micturition disturbance in benign prostatic hypertrophy (BPH) and to clarify the characteristics of patients who are more responsive to Terazosin therapy. After a 1-week washout (placebo) the first two weeks 1 mg/day of Terazosin was administered, then depending on efficacy of subjective symptoms, Terazosin doses were increased up to 2 mg/day and 4 mg/day at intervals of two weeks. After six weeks the final efficacy and safety were assessed. The subjective symptom improvement rate was 18.5% by 1 mg/day, 55.6% by 2 mg/day and 65.4% by 4 mg/day cumulatively. The objective symptom improvement rate were 13.2% by 1 mg/day, 42.1% by 2 mg/day and 50.0% by 4 mg/day cumulatively. The global improvement rate was 14.5% by 1 mg/day, 50.0% by 2 mg/day and 61.8% by 4 mg/day cumulatively. The patients who had a higher subjective symptom score in the lead-in period were more improved rather than those who had a lower score. In objective symptoms, voided volume, maximum flow rate (MFR), MFR nomogram score and average flow rate improved and the ratio of residual urine volume decreased. There was no relationship between clinical improvement on either subjective or objective symptoms and prostatic weight. Adverse reactions, such as dizziness, vertigo, tinnitus, nausea and blurred vision; were seen in 10 cases. In conclusion Terazosin was effective and well tolerated for the treatment of patients who had micturition disturbance with BPH in the dose range of 2 to 4 mg/day.     

A comparative study of terazosin and tamsulosin for symptomatic benign prostatic hyperplasia in Japanese patients

OBJECTIVE: To compare the efficacy and safety of an incremental-dose regimen of terazosin (1-2 mg daily) and a fixed-dose regimen of tamsulosin (0.2 mg daily), on Japanese patients with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: This multicentre, single-blind, randomized trial compared terazosin and tamsulosin over 4 weeks, in 61 patients with symptomatic BPH randomly assigned to terazosin (n = 31) or tamsulosin (n = 30). Terazosin 0.5 mg twice daily was administered for 2 weeks, followed by 1 mg twice daily for 2 weeks. Tamsulosin (0.2 mg) was administered once daily for 4 weeks. Symptoms were evaluated using the International Prostate Symptom Score (IPSS), and quality of life (QOL) was assessed subjectively before treatment, and again after 2 and 4 weeks of treatment. Objective measurements taken before and after the treatment period were the maximum (Qmax) and average (Qave) urinary flow rates, and the percentage residual urine volume. Improvement was defined as a 25% decrease from baseline in IPSS, > 1 point increase in QOL score, and > 2.5 mL/s increase in Qmax. Adverse reactions potentially related to the study drugs were recorded throughout the treatment period. RESULTS: Both terazosin and tamsulosin produced statistically significant improvements in subjective and objective variables. Neither treatment affected systolic or diastolic blood pressure or pulse rate. Adverse reactions were noted in four patients (three in the terazosin group and one in the tamsulosin group). However, there was no statistically significant difference in the incidence of adverse effects between the groups. CONCLUSIONS: Despite the limitations of small sample size and relatively short treatment periods, terazosin and tamsulosin were equally effective in the treatment of symptomatic BPH in Japanese patients, using relatively lower doses than those used in Western countries.     

Comparison of prazosin, terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia: A short-term open, randomized multicenter study

BACKGROUND: The objective of this open randomized clinical study was to compare the short-term efficacy and safety of three alpha-1 blockers, prazosin, terazosin and tamsulosin, in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS: The study comprised 121 patients with symptomatic BPH who were randomized to receive 0.5 mg of prazosin twice daily, 0.5 mg of terazosin twice daily or 0.1 mg of tamsulosin once daily for the initial 2 weeks. The doses were doubled for the next 2 weeks. The primary variables assessed were a symptom score, changes in maximum and average urinary flow rate (Qmax and Qave), postvoid residual urine volume and blood pressure. RESULTS: The percentage changes in the total symptom score from baseline were 38, 39 and 26% at 4 weeks by prazosin, terazosin and tamsulosin, respectively. Terazosin produced significantly higher improvement in four out of nine individual symptoms than tamsulosin (P < 0.05). A significant increase in Qmax or Qave in uroflowmetry was obtained in the prazosin and tamsulosin groups. Blood pressure remained unchanged in normotensive patients, but significantly decreased in hypertensive patients except for the tamsulosin group. Adverse events were minimal in all treatment groups. CONCLUSIONS: The efficacy and safety profiles were different among the alpha-1 blockers at standard doses. Tamsulosin appears to be safer than the others for aged patients or patients with hypertension who have impaired blood pressure regulation, while terazosin is significantly effective in improving symptomatic score when compared with the others examined. It is recommended that the alpha-1 blocking agent and its optimal dose are selected on the basis of the baseline characteristics of the patients with symptomatic BPH.     

Laser treatment of symptomatic benign prostatic hyperplasia

The treatment of lower urinary symptoms secondary to benign prostatic hyperplasia (BPH) after failure of medical therapies remains controversial for most urologic surgeons. The complications of traditional surgery are the driving force behind the development of several minimally invasive treatments of symptomatic BPH. Laser prostatectomy is one of the most investigated such modalities. In this article we reviewed the results of the most common types of lasers used in prostatic surgery.     

选择性α1受体阻滞剂治疗前列腺增生的尿动力学研究

用选择性α１肾上腺素能受体阻滞剂盐酸四喃唑嗪（商品名高特灵）治疗有症状ＢＰＨ患者，并用非选择性α受体阻滞剂酚苄明和安慰剂作对照治疗。３０例患者随机分为三组，每组１０例，实验组用高特灵４ｍｇ／ｄ，对比治疗组用酚苄明２０ｍｇ／ｄ，对照组用安慰剂２片／ｄ，均３周为一个疗程。结果表明：两种药物均能明显改善排尿困难等主观症状，显著增加尿流率（Ｐ＜０．０５），非常显著降低前列腺压（Ｐ＜０．０１），但对于降低膀     

Effect of terazosin on the lipid profile in patients with symptomatic benign prostatic hyperplasia

INTRODUCTION: To determine the changes in plasma lipid levels in symptomatic benign prostatic hyperplasia (BPH) patients receiving terazosin treatment. MATERIALS AND METHODS: The study included 99 patients with BPH aged 44-74 years. The patients were divided into 3 groups: in group 1 (n = 25) with baseline total cholesterol levels of >220 mg/dl, terazosin 5 mg/day was used; in group 2 (n = 56) with basal total cholesterol levels of < 220 mg/dl, terazosin 5 mg/day was used, and group 3 (n = 18) did not use terazosin and was defined as the control group. Plasma levels of total cholesterol, low-density lipoprotein, high-density lipoprotein and triglyceride were recorded, and the high-density lipoprotein to total cholesterol ratio was calculated at the beginning of the study and after 12 weeks. RESULTS: The total cholesterol level decreased from the baseline level by 10.88% after 12 weeks (p < 0.05) in group 1. The decrease was observed in 22 of 25 patients (88%). In group 1, the mean plasma total cholesterol level decreased significantly (p < 0.05), but the decrease was not significant in group 2 and no change was observed in group 3. The mean plasma low-density lipoprotein level decreased significantly in group 1 (p < 0.05), but no change was observed in the other 2 groups. The mean plasma high-density lipoprotein level increased in group 1, whereas no change was observed in the other 2 groups. The mean plasma triglyceride level decreased significantly in groups 1 and 2 (p < 0.05), but no change was observed in group 3. The high-density lipoprotein to total cholesterol ratio increased significantly in group 1, but no change was observed in the other 2 groups. CONCLUSION: We suggest that terazosin may be a reasonable choice because of the beneficial effect on the lipid profile in older symptomatic BPH patients with a higher ratio of dyslipidemia.     

A randomized comparative study assessing once versus twice a day treatment of benign prostatic hyperplasia with terazosin

We compared the efficacy of once a day administration of terazosin hydrochloride with that of twice a day administration for benign prostatic hyperplasia (BPH) patients. Forty-two patients with BPH were randomly assigned to receive a maximum dose of 2 mg terazosin either once (n = 21) or twice (n = 21) a day. International prostate symptom score (IPSS), uroflowmetry and side effect profile were determined before and 4 weeks after randomization. Both groups were similar with respect to patient age, baseline IPSS and prostate volume. After 4 weeks of treatment with terazosin, significant improvement in IPSS, maximum flow rate and mean flow rate were observed in both groups. However, these improvements did not differ significantly between them. In addition, there were no differences in side effects between the groups. In conclusion, once a day administration of terazosin hydrochloride is as effective and safe as twice a day administration in patients with BPH.     

A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.

The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.     

Efficacy of terazosin in patients with benign prostatic hyperplasia.

Terazosin, a selective, long-acting alpha 1-adrenergic blocker, was evaluated in 44 men with benign prostatic hyperplasia. The dose was titrated from 2 to 20 mg nightly depending on improvement in symptoms and flow rate. All men completed at least 3 months of therapy, 26 had 6 months and 19 received 9-12 months of terazosin. There was an average increase of 2 ml/s in the peak urinary flow rate compared to baseline. This was statistically significant at the 3-month level. Residual urine decreased under treatment at each 3-month time interval. Prior to initiation of terazosin the mean was 165 ml, and it was 62, 100, and 41 ml at 3, 6 and 9 months respectively. There was a statistically significant improvement in both the obstructive and irritative symptom scores. Side effects were minimal; only 1 patient discontinued terazosin due to a hypotensive episode. Terazosin was found to be safe and effective in the dose range of 2-20 mg taken at bedtime in men with symptoms related to benign prostatic hyperplasia. The present study did not identify any baseline parameters such as initial prostate volume, peak flow rates, or obstructive or irritative symptom scores that correlated with clinical outcome.     

The safety, efficacy and compliance of terazosin therapy for benign prostatic hyperplasia.

The primary objective of the present interim analysis of an open label study initiated in December 1988 is to provide further insight into the long-term safety, efficacy and compliance of terazosin, a long-acting selective alpha 1-blocker, for the treatment of symptomatic benign prostatic hyperplasia (BPH). A total of 45 normotensive patients with symptomatic BPH was enrolled into this study. The dose of terazosin was titrated to 5 mg. during a 1-month period provided adverse reactions and orthostatic hypotension were not observed. The subjects were maintained on 5 mg. terazosin throughout the 24-month followup. The peak and mean urinary flow rates, obstructive and irritative Boyarsky symptom scores, and systolic and diastolic blood pressures were evaluated at 2, 6, 12, 18 and 24 months after initiation of therapy. Of the 45 subjects 21 (47%) exhibited a durable clinical response with no significant adverse events during the 24-month followup. The obstructive and irritative symptom scores decreased by 63% and 35%, respectively, after 2 months of terazosin therapy. These improvements in obstructive and irritative symptom scores were maintained throughout the 2-year followup. The peak and mean urinary flow rates improved by 42% and 48%, respectively, after 2 months of terazosin therapy. The changes in mean urinary flow rate increased, whereas the changes in peak urinary flow rate decreased during followup. Of the patients 6 (13%) were withdrawn from the study due to an adverse event. Our study demonstrates the safety, efficacy and compliance of terazosin therapy for BPH during a 2-year followup.     

A selective alpha1A-adrenoceptor antagonist inhibits detrusor overactivity in a rat model of benign prostatic hyperplasia

PURPOSE: Alpha(1)-adrenoceptor antagonists relax the obstructed prostatic urethra and suppress the irritative symptoms frequently observed in patients with benign prostatic hyperplasia. We investigated the effects of 3 alpha(1)-adrenoceptor antagonists on urodynamics in rats with hormone induced benign prostatic hyperplasia to determine which alpha(1)-adrenoceptor subtype selective antagonists would suppress irritative symptoms. MATERIALS AND METHODS: Rats were treated with testosterone and 17beta-estradiol by weekly intramuscular injections. After 4 weeks a pressure flow study was done and the effects of the alpha(1)-adrenoceptor antagonists KMD-3213 silodosin, tamsulosin and prazosin on urodynamics were compared. We especially investigated the involvement of the bladder and prostatic urethra to clarify the mechanism of detrusor overactivity expression. RESULTS: Hormone treatment induced benign prostatic hyperplasia and resulted in detrusor overactivity, as determined by cystometry. Baseline perfusion urethral pressure and the phenylephrine induced increase in it were significantly higher in rats with vs without benign prostatic hyperplasia. Cystometry in hormone treated female rats did not show detrusor overactivity. KMD-3213 decreased detrusor overactivity, similar to other alpha(1)-adrenoceptor antagonists. CONCLUSIONS: These results suggest that an excessive response to sympathetic nerve stimulation, which is mainly mediated via alpha(1A)-adrenoceptor, in the hypertrophied prostate gives rise to detrusor overactivity. Furthermore, the alpha(1A)-adrenoceptor selective antagonist KMD-3213 would be suitable for improving irritative symptoms in patients with benign prostatic hyperplasia.     

Examination of the mechanism of ameliorating effect of alpha 1-blocker on storage symptoms associated with benign prostatic hyperplasia

To investigate the mechanism of the ameliorating effect of alpha1-blocker on storage symptoms associated with benign prostatic hyperplasia (BPH), we evaluated the effect of tamsulosin on the bladder blood flow in rats with bladder outlet obstruction (BOO). BOO was produced by ligature in the part around a proximal urethra and kept for 2 weeks. Tamsulosin was subcutaneously administered with an osmotic pump for 2 weeks immediately after the BOO operation. Bladder blood flow in the sham-operated rats, the control BOO rats and the tamsulosin-treated BOO rats was measured by the fluoro-microsphere method. Bladder blood flow was significantly reduced in BOO rats compared with sham-operated rats, and tamsulosin significantly increased the bladder blood flow in BOO rats. The present results suggest that the increase in bladder blood flow by tamsulosin contributes to the improvement of storage symptoms associated with BPH.     

Role of long-acting selective alpha-1 blockers in the treatment of benign prostatic hyperplasia.

Alpha blockers are effective for the treatment of symptomatic BPH, although the long-term response to and compliance with alpha blockers remain critical issues. The ultimate role of alpha blockade for the management of symptomatic BPH is undefined pending their resolution. The effectiveness of nonselective alpha blockers such as phenoxybenzamine is counterbalanced by the incidence and severity of adverse reactions. Selective alpha blockers such as prazosin and terazosin are far better tolerated while providing similar degrees of subjective and objective relief of bladder outlet obstruction. The preliminary experience with alpha blockers demonstrates statistically and clinically significant improvements in the symptoms of prostatism and urinary flow rates, and the majority of patients receiving alpha blockers have been extremely satisfied. The data on alpha blockers are preliminary, and therefore the role of these drugs at present must be decided upon by the individual urologist. There is sufficient evidence to justify the use of alpha blockers for men with moderate symptoms of prostatism, yet urologists may validly interpret the clinical experience with alpha blockers as preliminary. Nevertheless, urologists should at least present this option to patients before performing a prostatectomy. The patients selected for alpha blockade must be advised that the drugs alleviate the symptoms of prostatism rather than permanently reversing the pathophysiology of BPH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of alpha 1 adrenoceptors in the prostate capsule of men with symptomatic and asymptomatic benign prostatic hyperplasia.

The objective of this study was to compare the binding and functional properties of alpha 1 adrenoceptors in prostate capsules obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH) undergoing simple retropubic prostatectomy and cystoprostatectomy respectively. Saturation experiments using 125I-Heat demonstrated that the density and binding affinity of alpha 1 adrenoceptors in the prostate capsules obtained from men with symptomatic and asymptomatic BPH were similar. Non-cumulative dose response experiments using phenylephrine demonstrated that the magnitude of the contractile response to phenylephrine was 4-fold greater in the prostate capsules from men with symptomatic BPH than from those with asymptomatic BPH. The EC50 of phenylephrine in the prostate capsules of men with symptomatic and asymptomatic BPH was similar. A correlation between alpha 1 adrenoceptor density and phenylephrine Emax was not observed, implying that either alpha 1 adrenoceptors are not localised exclusively to the prostate smooth muscle or that spare alpha 1 adrenoceptors exist. This study suggests that the neuropharmacological properties of the prostate capsule may play a significant role in the development of infravesical obstruction in the ageing male population.