Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis.

Effects of Terazosin and Tolterodine on Ureteral Stent Related Symptoms: A Double-Blind Placebo-Controlled Randomized Clinical Trial

Objective To evaluate the effects of terazosin and tolterodine on ureteral stent discomfort. Materials and Methods Of 163 patients assessed for eligibility, 104 patients were randomly assigned to receive placebo, 2 mg of terazosin twice daily, 2 mg of tolterodine daily, or both terazosin plus tolterodine during the stenting period. Prior to stenting and at stent removal, the International Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) subscore and the Visual Analog Scale for Pain were determined. The patients also reported their analgesic use during the stenting period. Results Ninety-four patients completed the study. We noted significant decreases in the total IPSS scores (p = 0.002), irritative subscore (p = 0.039), QoL (p = 0.001), flank pain (p = 0.013), voiding pain (p = 0.01) and amount of analgesics used (p = 0.02) in the groups. However, neither the obstructive subscore nor the suprapubic pain improved significantly (p = 0.251 and p = 0.522, respectively). The patients receiving terazosin plus tolterodine experienced significant reductions in the total IPSS, irritative symptoms, QoL, flank pain, voiding pain and decreased analgesics use compared with those patients receiving placebo. However, compared with placebo, terazosin monotherapy did not affect pain levels, and tolterodine monotherapy did not improve QoL, flank pain or analgesics use. Conclusions Terazosin plus tolterodine improves ureteral stent-related complications, including irritative symptoms, the amount of analgesics used, QoL, flank pain and voiding pain but does not decrease obstructive symptoms or suprapubic pain. This trial was registered at www.clinicaltrials.gov as NCT01530243. .

Efficacy and safety of propiverine and terazosine combination for one year in male patients with luts and detrusor overactivity

Purpose To evaluate the long term efficacy and safety of the use of propiverine and terazosine combination in patients with LUTS and DO by a placebo controlled study. Materials and Methods One hundred patients were enrolled in the study. They were randomized into two groups (each group consisted of 50 patients). Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2. The patients were evaluated by international prostate symptom score (IPSS), the first four questions of IPSS (IPSS4), the 8th question of IPSS (quality of life-QoL), overactive bladder symptom score questionnaire (OAB-q V8), PSA test, urodynamic studies, post voiding residue (PVR). All patients were followed for one year and were reassessed for comparison. Results IPSS, IPSS4, OAB symptoms, QoL score, PVR, and Qmax scores of the groups did not differ. After one year treatment, there was significant improvement in IPSS, IPSS4, OAB symptoms, QoL and Qmax values in Group 2. No significant improvement was noted for the same parameters in Group 1. Conclusion This is the first study to show long term safety and efficacy of anticholinergic therapy for patients with LUTS. In patients with OAB or DO, long term anticholinergic treatment may be regarded as a treatment option. .

Efficacy of three different alpha 1-adrenergic blockers and hyoscine N-butylbromide for distal ureteral stones

PURPOSE: To evaluate hyoscine N-butyl bromide (HBB) and three different alpha-1 blockers in the treatment of distal ureteral stones. MATERIALS AND METHODS: A total of 140 patients with stones located in the distal tract of the ureter with stone diameters of 5 to 10mm were enrolled in the present study and were randomized into 4 equal groups. Group 1 received HBB, Group 2 received alfuzosin, Group 3 received doxazosin and Group 4 received terazosin. The subjects were prescribed diclofenac injection (75 mg) intramuscularly on demand for pain relief and were followed-up after two weeks with x-rays of the kidneys, ureters, bladder and urinary ultrasonography every week. The number of pain episodes, analgesic dosage and the number of days of spontaneous passage of the calculi through the ureter were also recorded. RESULTS: The average stone size for groups 1, 2, 3 and 4 was comparable (6.13, 5.83, 5.59 and 5.48 mm respectively). Stone expulsion was observed in 11 percent, 52.9 percent, 62 percent, and 46 percent in groups 1, 2, 3 and 4 respectively. The average time to expulsion was 10.55 ± 6.21 days in group 1, 7.38 ± 5.55 days in group 2, 7.85 ± 5.11 days in group 3 and 7.45 ± 5.32 days in group 4. Alpha blockers were found to be superior to HBB (p < 0.05). CONCLUSIONS: Medical treatment of distal ureteral calculi with alfuzosin, doxazosin and terazosin resulted in a signi?cantly increased stone-expulsion rate and decreased expulsion time when compared with HBB. HBB seems to have a negative effect on stone-expulsion rate.

[Comparison between efficacy of Tamsulosin and Terazosinin alpha-adrenergic blockers in spontaneous passage of ureter stones after ESWL [A double blind clinical trial]]

Nephrolithiasis has a high prevalence in population. Our objective was to compare time of stone passage, severity of pain, frequency of the use of analgesics and the course of disability between groups A, B and C. In this randomized controlled trial study, 240 patients were selected .inclusion criteria was all patient with 5-9mm stone diameter, and exclusion criteria was opium addiction. All of patients were categorized in 3 groups with Block Balance Randomize and double blind method. Each group consisted of 80 persons. In group A [i.e. control group] patients were given daily Diclofenac suppositories of 100mg and Diclofenac tablets of 25mg.In group B patients were given Tamsulosin tablets of 0.4 mg in addition to routine treatment and in group C patients were given Terazosin tablets of 2 mg in addition to routine treatment. Patients were visited three months after lithotripsy. The rate of ureteral stone passage in group B [85.5%] was more than group A [80%] and group C [83.3%], the mean expulsion time group A with 14.9 days was more than group B [12.1 days] and group C [12.2 days],also severity of pain on the basis of VAS chart in group B [4.7] less than group A [5.5] and C [5.2], extra analgesic requirement in alpha blockers group [B:4 patients and C:2 patients] less than control group [8 patients], and all of these were non significantly different. alpha blockers are decrease symptoms of pain and no effective response on expulsion of stones

[ effect of terazocin and prednislone in the epulsion therapy for symptomatic distal urethral stones]

[alpha]1-Adrenergic blockers have recently been shown to increase the rate of spontaneous passage of distal urethral stones. In this study the clinical role of Terazocin and Prednisolone in expulsion therapy of symptomatic distal urethral stones was assessed. The total number of 106 patients between 20-68 years old [Mean 39.05 years] who had lower ureteral stones with size of 5-10mm were selected in this prospective study. The patients were randomly divided into 2 equal groups; treatment group received Terazocin [5mg daily] plus Prednisolone [5mg daily], and control group received only analgesics. Hydration was recommended simultaneously. The treatment duration considered for 10 days to prevent the side effects resulting from prolonged corticosteroid therapy. Two groups had no significant difference based on age, sex and stone location. In treatment group mean stone diameter was 7.45 +/- 1.705mm and in control group it was 6.7 +/- 1.75mm. The rate of expulsion for the treatment and control groups were 62.3% and 37.7% respectively that showes a significant difference between two groups [P<0.001]. In the treatment group the number of pain episodes and analgesic [Morphin] intake was found to be lower compared to the control group. Simultaneous administration of terazosin [[alpha] 1-Adrenergic blocker] and Prednisolone [corticosteroid] can increase the frequency of spontaneous passage of distal urethral stones

Efficacy of terazosin as a facilitator agent for expulsion of the lower ureteral stones

To determine the efficacy of terazosin as a facilitator agent for the passage of lower ureteral stones. Since February 2004 to December 2004, 64 patients with lower ureteral stones who came to the emergency department were enrolled in this study. Exclusion criteria were the presence of urinary tract infection, severe hydronephrosis, elevated serum creatinine, hypertension, history of peptic ulcer disease and history of spontaneous stone passage. Patients were randomized into 2 groups of 32. Group 1 patients received terazosin tablets, 10 mg daily and analgesic [indomethacin capsules] for a maximum of 4 weeks, but patients in Group 2 received only analgesic. In cases of incomplete pain control, intravenous pethidine was administered. The 2 groups were compared with regard to stone passage rate, time to stone passage, the amount of received pethidine and the need for intervention. Statistical analysis was performed by student t-test. The mean age of Group 1 was 44 years and Group 2 was 39 years. The median stone size was 6.9 +/- 2.3 mm in Group 1 and 6.6 +/- 3.1 mm in Group 2, which was not significantly different. Stone expulsion rate was 90.62% in Group 1 and 62.5% in Group 2, with a significant statistical difference [p=0.041]. The mean expulsion time was 76.3 +/- 60 hours and 141 +/- 64 hours in Groups 1 and 2, [p=0.001]. Extra analgesic [pethidine] requirement averaged 34.4 +/- 12.7 mg and 62.1 +/- 10.5 mg in Groups 1 and 2 [p=0.036]. Seven patients in Group 1 and 15 patients in Group 2 required ureteroscopy after 4 weeks due to lack of the stone passage. Terazosin is a safe and effective treatment for lower ureteral stones. By using this medication, stone passage rate increases and the time of stone passage and the need for intervention decreases

Efficacy of terazosin and finasteride in symptomatic benign prostatic hyperplasia: A comparative study.

Medical treatment for symptomatic Benign Prostatic Hyperplasia (BPH) has become popular for the last few years. This study was designed to find out and compare the efficacy of terazosin, a alpha1 adrenoceptor blocker and finasteride, a 5alpha-reductase inhibitor in symptomatic BPH. A total of 60 patients (30 in terazosin group and 30 finasteride group) of symptomatic BPH were selected. Terazosin group received 1 mg daily at bedtime for 3 days, 2 mg at bedtime for 7 days, thereafter 5 mg at bedtime daily for 6 months. Finasteride group received 5 mg once daily. In terazosin treated patients, improvement after 3 months were as follows, IPSS 3.93 +/- .74 points reduction, Qmax 2.13 +/- .68 ml/s increase, post-voided residual urine volume (PVR) 20.67 +/- 10.56 ml reduction (significant, p<0.001) and prostate volume 0.57 +/- 1.54 ml reduction (not significant). Similar statistical differences were observed at 6 months follow up. In finasteride treated patients, improvements after 3 months were as follows, International Prostate Symptom Score (IPSS) 1.38 +/- .63 points reduction, Qmax 0.55 +/- 0.78 ml/s increase, PVR 5.93 +/- 7.64 ml reduction (significant, p<0.001) and prostate volume 0.17 +/- 5.6 ml reduction (non-significant). At 6 month follow up statistical differences were significant in all parameters including prostate volume 4.57 +/- 5.30 ml reduction (p<0.001). In comparison, statistically significant superiority of terazosin over finasteride was found in improving IPSS, Qmax and PVR in both follow up visits. But terazosin had nonsignificant effect in reducing prostate volume; in contrast, finasteride had significant effect in second visit. It can be concluded from this study that terazosin 5mg once daily is effective in mild to moderate cases of symptomatic BPH. On the other hand, finasteride 5mg once daily may be useful in large prostate and to be given for at least 6 months.

Comparative evaluation of Prostina and terazosin in the treatment of benign prostatic hyperplasia.

The objective of the present study was to evaluate the efficacy and safety of Prostina, a multi-ingredient herbal formulation in benign prostatic hyperplasia (BPH) in comparison with terazosin. A randomised, open, parallel, controlled clinical trial was carried out in ambulatory men aged between 40-80 years suffering from BPH, with American Urological Association (AUA) symptom index score of at least 8 or more at recruitment. One group received 2 Prostina capsules twice daily for 12 weeks; the other received terazosin 2 mg at bedtime for 12 weeks. Urodynamic parameters, AUA score, biochemical and clinical adverse effects were assessed. Twenty subjects completed the study in Prostina group and 20 in terazosin group. The groups were comparable at baseline in age and assessment criteria. Majority of urodynamic parameters showed improving trends in both the groups. AUA symptom score declined significantly from 19.50 +/- 1.40 (mean +/- standard error) to 1.04 +/- 0.68 in Prostina group and from 16.95 +/- 1.23 to 4.14 +/- 0.88 in terazosin group. The AUA symptom score in 12 weeks follow-up was significantly lower in Prostina group than terazosin group (p = 0.005). Other laboratory-parameters remained unaltered in both the groups. Prostina is as effective as terazosin in providing symptomatic relief in BPH.

Management of the lower urinary tract symptoms [LUTS] due to benign prostatic hyperplasia [BPH], with terazosin

This study was designed to assess the efficacy, safety and compliance of terazosin in the management of lower urinary tract symptoms due to benign prostatic hyperplasia. Study was conducted in the department of urology, DHQ Hospital Vehari, in about 1-year i-e from July 2004 to June 2005. Sixty patients with an age range of 45-85 years were included in the study. Data was collected prospectively. Patients were assessed according to the international prostate symptom score [I-PSS] at the start of study, during follow up and at the end of study. Out of sixty patients, fifty-two were able to complete the study. It was observed that most of the patients obtained a significant decrease in the prostate symptoms score and improvement in QoL score, with only a few side effects. Terazosin is a safe and effective treatment for BPH with good compliance

Baroreceptor mediated blood pressure regulation is not affected during dose dependent inhibition of prostatic contractions by terazosin.

Benign prostatic hyperplasia (BPH), common in aging males is often treated with alpha1-adrenoceptor (AR) antagonists. In view of known hypotensive effect of most of the alpha1-AR antagonists, this work examined the effect of a selected alpha1-AR antagonist, terazosin on the baroreceptor mediated regulation of blood pressure. The three doses of terazosin (10, 100, 300 microg/kg body weight) used in anesthetized dogs inhibited in a dose-dependent manner the prostatic contractions and rise in blood pressure induced by phenylphrine. Impairment of arterial baroreflex, an important neural regulatory mechanism for the maintenance of normal arterial pressure, by alpha1-AR antagonist (prazosin) has been suggested in an earlier study. Hence, the effects of terazosin in doses 10, 100 and 300 microg/kg on baroreflex sensitivity (calculated as the ratio of heart rate change to acute increase in blood pressure by phenylephrine) were investigated. Terazocin did not produce any change in the baroreflex sensitivity. Therefore, in the absence of any adverse effect on the baroreceptor mediated regulation of the blood pressure, terazosin can be treated as a safer drug for the symptomatic treatment of BPH.

The use and rationale of selective alpha blockade in children with non-neurogenic neurogenic bladder dysfunction

INTRODUCTION: We present here a long-term observation of 2 children with a rare syndrome with a non-neurogenic neurogenic bladder dysfunction (Hinman's syndrome), and we investigated the safety and efficacy of long-term use of terazosine in association with prophylactic antibiotics, timed voiding and a bowel regimen. MATERIALS AND METHODS: Two children, 7 years-old (22 kg) and 11 years-old (36 kg) presented in 1997 to our pediatric urology clinic with symptoms of urgency, frequency, urge incontinence and nocturnal enuresis. Both children were placed in a regimen of terazosine (starting with 0.5 mg increasing until 2 mg). RESULTS: There were no significant side effects throughout the entire treatment. The first 7-year old boy however developed some dizziness when the dose of terazosine was increased to 2 mg (after 4 weeks of administrating 1 mg), and this disappeared immediately when the dosage was reduced back to 1 mg daily. The urgency symptoms improved in both boys after 3 weeks of 1 mg terazosine. The secondary enuresis in the 11 year-old boy resolved after 2 months of 2 mg terazosine. CONCLUSION: It is possible to say that the alpha-blocker medication, terazosine can be administered safely to children with a non-neurogenic bladder dysfunction, also known as the Hinman's syndrome. These results have shown that dysfunctional voiding, postvoiding residual and upper tract involvement can disappear over time when long term terazosine is given in combination with timed voiding, prophylactic antibiotic therapy and treatment of the associated constipation. Our observations also suggest a permanent effect after discontinuing the medication.