Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study

ABSTRACT Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

Is Tamsulosin 0.2 mg Effective and Safe as a First-Line Treatment Compared with Other Alpha Blockers?: A Meta-Analysis and a Moderator Focused Study

PURPOSE: Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. MATERIALS AND METHODS: We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. RESULTS: Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. CONCLUSION: This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms.

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

Objective To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). Materials and Methods 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4mg plus sildenafil 50mg in group A and tamsulosin 0.4mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient’s ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Results Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). Conclusion It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone. .

The Effect of Combined Therapy with Tamsulosin Hydrochloride and Meloxicam in Patients with Benign Prostatic Hyperplasia Symptoms and Impact on Nocturia and Sleep Quality

Purpose We aimed to compare the effect and feasibility of a combined therapy with tamsulosin hydrochloride plus meloxicam, and tamsulosin hydrochloride alone in patients with benign prostate hyperplasia symptoms and impact on nocturia and sleep quality. Materials and Methods Four hundred male patients were included in this study between 2008 and 2011. Patients were randomly divided into two groups: one received tamsulosin hydrochloride 0.4 mg (Group 1, 200 patients) and the other tamsulosin hydrochloride 0.4 mg plus meloxicam 15 mg (Group 2, 200 patients) prospectively. Patients were evaluated for benign prostate hyperplasia (BPH) symptoms according to the American Urological Association clinical guidelines and sleep quality according to Pittsburgh Sleep Quality Index (PSQI). Patients were reevaluated after three months of treatment. The International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were recorded at baseline and after three months. Results Mean age was 63.3 ± 6.6 and 61.4 ± 7.5 years in groups 1 and 2, respectively (p = 0.245). There were no statistically significant differences between both groups. Also, baseline prostate specific antigen (PSA), prostate volume, creatinine, International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were similar in both groups. In addition, the total IPSS, IPSS-QoL, PVR, nocturia, and PSQS were significantly lower in Group 2 compared with Group 1 after treatment (p < 0.05). Qmax and AFR were higher significantly in Group 2 compared with Group 1 after treatment (p < 0.05). Conclusions Cyclooxygenase (COX)-2 inhibitors ...

The role of central mechanisms in the anti-inflammatory effect of amitriptyline on carrageenan-induced paw edema in rats

OBJECTIVE: The present study was designed to further investigate the effect of amitriptyline, a classical tricyclic antidepressant, on carrageenan-induced paw edema in rats. METHODS: First, amitriptyline was administered intraperitoneally (i.p.) at doses of 20, 40 and 80 mg kg-1, 30 min before subplantar injection of carrageenan. Second, amitriptyline was given intracerebroventriculary or intrathecally at doses of 25, 50 and 100 μg/rat, 30 min prior to carrageenan challenge. Third, the effect of adrenergic receptor antagonists such as propranolol (10 mg kg-1, i.p.), prazosin (4 mg kg-1, i.p.) and yohimbine (10 mg kg-1, i.p.) and an opioid receptor antagonist (naloxone, 4 mg kg-1, i.p.) on the anti-inflammatory effect of amitriptyline (40 mg kg-1, i.p.) was investigated. RESULTS: Our data confirm that intraperitoneally administered amitriptyline exhibits a marked anti-inflammatory effect on carrageenan-induced paw edema in rats 4 h postcarrageenan challenge (P < 0.001). Intracerebroventricular (i.c.v.) administration of amitriptyline also reduced the development of paw edema at 4 h postcarrageenan (P < 0.001), but intrathecal (i.t.) application of amitriptyline failed to alter the degree of paw swelling. Furthermore, the applied antagonists did not modify the anti-inflammatory effect of amitriptyline. CONCLUSION: These results support the view that amitriptyline has a considerable anti-inflammatory effect on carrageenan-induced paw edema in rats and suggest that at least a part of this property could be mediated through supraspinal sites. Moreover, it seems unlikely that the investigated adrenergic and opioid receptors have a significant role in this effect of amitriptyline.

Alfuzosin hydrochloride transdermal films: evaluation of physicochemical, in vitro human cadaver skin permeation and thermodynamic parameters

Purpose: The main objective of the investigation was to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the effects of polymeric system and loading dose on the in vitro skin permeation pattern. Materials and methods: Principles of experimental design have been exploited to develop the dosage form. Ratio of ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) and loading dose were selected as independent variables and their influence on the cumulative amount of alfuzosin hydrochloride permeated per cm2 of human cadaver skin at 24 h (Q24), permeation flux (J) and steady state permeability coefficient (P SS) were studied using experimental design. Various physicochemical parameters of the transdermal films were also evaluated. Activation energy for in vitro transdermal permeation has been estimated. Results: Ratio of EC and PVP was found to be the main influential factor for all the dependent variables studied. Drug loading dose was also found to influence the dependent variables but to a lesser extent. Physicochemical parameters of the prepared films were evaluated and found satisfactory. Activation energy for alfuzosin permeation has also been estimated and reported. Conclusion: The therapeutic system was found to be dermatologically non-irritant and hence, a therapeutically effective amount of alfuzosin hydrochloride can be delivered via a transdermal route.