A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial

ABSTRACT Introduction: Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. Objectives: In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. Patients and Methods: This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. Results: The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. Conclusion: Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.

Overactive bladder - pharmacological treatment

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

The effect of extended release tolterodine used for overactive bladder treatment on female sexual function

ABSTRACT Introduction Overactive bladder (OAB) is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER) used for OAB treatment on the sexual function of women. Materials and Methods Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI) questionnaire. 73 patients of group A (control group) received no treatment and 85 patients of group B received an anticholinergic regimen - tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. Results A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment), arousal (3.1±0.2 to 3.1±0.2 respectively), lubrication (3.4±0.3 to 4.3±0.3 respectively), orgasm (3.5±0.3 to 4.5±0.3 respectively), satisfaction (2.6±0.2 to 4.2±0.3 respectively) and pain (2.4±0.2 to 4.6±0.4 respectively) after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05). Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5) compared to pre-treatment values (17.4±1.4, p<0.01) and to control group A (17.7±1.2 and 17.9±1.5, p>0,05) respectively. Conclusions This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.

A dosage regimen of M-receptor blocker after TURP for severe BPH with predominant urine storage symptoms / 中华男科学杂志

Objective@#To study the dosage regimen of oral M-receptor blocker following transurethral resection of the prostate (TURP) for severe benign prostate hyperplasia (BPH) with predominant urine storage period symptoms (USPSs) and its clinical effect.@*METHODS@#Severe BPH patients with predominant USPSs received oral tolterodine (2 mg q12d or 4 mg qd) 6 hours after TURP for 4 weeks. The medication continued for another 2 weeks in case of recurrence of USPSs or until the 12th week in case of repeated recurrence. Before and at 1, 4, 8 and 12 weeks after TURP, we analyzed the International Prostate Symptoms Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) of the patients.@*RESULTS@#Complete clinical data were collected from 106 cases, of which 33 achieved successful drug withdrawal with no aggravation of USPSs at 4 weeks after TURP, 51 at 6－8 weeks, 13 at 10－12 weeks, and 9 needed medication after 12 weeks. Before and at 1, 4, 8 and 12 weeks after TURP, the total IPSSs were 25.33 ± 3.45, 19.33 ± 3.62, 11.56 ± 2.45, 8.38 ± 2.0 and 7.74 ± 1.87, those in the urine storage period were 11.97 ± 1.53, 10.76 ± 1.82, 6.16 ± 1.22, 4.08 ± 1.19 and 3.91 ± 1.15, those at urine voiding were 9.80 ± 1.60, 5.59 ± 1.45, 3.40 ± 0.92, 2.85 ± 0.71, and 2.61 ± 0.67, and the QoL scores were 4.70 ± 0.78, 3.92 ± 0.75, 2.55 ± 0.74, 1.83 ± 0.72 and 1.66 ± 0.75, respectively, with statistically significant differences between the baseline and the scores at 1 and 4 weeks (P 0.05). Qmax and PVR were improved progressively and significantly at 1 and 4 weeks (P 0.05).@*CONCLUSIONS@#Four to eight weeks of oral administration of M-receptor blocker may be an effective dosage regimen for severe BPH with predominant USPSs after TURP.

Efficacy and Safety of Medium-to-long-term Use of Tolterodine Extended Release with or without Tamsulosin in Patients with Benign Prostate Hyperplasia and Larger Prostate Size: A Double-blind, Placebo-controlled, Randomized Clinical Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release (ER) with or without tamsulosin in patients with benign prostate hyperplasia (BPH) and larger prostate size.</p><p><b>METHODS</b>Totally, 152 patients (age ≥50 years) with BPH, International Prostate Symptom Score (IPSS) ≥12, quality-of-life (QoL) score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups (n = 38 in each) to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS (total, storage, and voiding subscales), QoL, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) were collected at baseline, and at weeks 4, 12, and 24.</p><p><b>RESULTS</b>Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS (-7.15, -12.20, and -14.66 vs. -3.51, -5.78, and -7.23), storage IPSS (-3.56, -5.63, and -6.66 vs. -1.52, -1.21, and -2.43), voiding IPSS (-2.88, -5.10, and -6.48 vs. -1.52, -3.03, and -2.97), QoL (-1.21, -2.40, and -3.21 vs. -0.39, -1.41, and -1.60), Qmax (2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s), and PVR (-17.88, -26.97, and -27.89 ml vs. -12.03, -11.16, and -16.73 ml) at weeks 4, 12, and 24, respectively; the differences were all statistically significant (P < 0.05). Adverse events (AEs) were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS (-4.61, -6.79, and -5.70), voiding IPSS (-0.64, -1.83, and -1.45), QoL (-0.69, -1.21, and -1.41), or Qmax(-0.79, 2.83, and 1.11 ml/s), compared with placebo (all P > 0.05). However, a gradual increase in PVR (10.03, 10.41, and 12.89 ml) and more urinary AEs suggestive of urinary retention (11/38 vs. 4/38) were observed.</p><p><b>CONCLUSION</b>Medium-to-long-term use of tolterodine ER plus tamsulosin should be recommended in patients with BPH and an enlarged prostate volume.</p><p><b>TRIAL REGISTRATION</b>www.chictr.org.cn, ChiCTR-TRC-09000596; http://www.chictr.org.cn/showproj.aspx?proj=8939.</p>

Duration of Antimuscarinic Administration for Treatment of Overactive Bladder Before Which One Can Assess Efficacy: An Analysis of Predictive Factors / 대한배뇨장애요실금학회지

PURPOSE: To determine the duration of antimuscarinic therapy for overactive bladder syndrome (OAB) appropriate for assessment of the efficacy of treatment, and to evaluate the possible predictive factors for response to therapy. METHODS: All OAB patients who visited a urology outpatient clinic of a tertiary referral center and who were prescribed 5 mg of solifenacin or 4 mg of tolterodine extended release capsules daily were enrolled in the study. Patients were asked to continue therapy for 6 months. All enrolled patients completed the patient perception of bladder condition, overactive bladder symptom score (OABSS), and the modified Indevus Urgency Severity Scale questionnaires. All patients underwent uroflowmetry. RESULTS: A total of 164 patients were enrolled and 125 patients (76%) had at least one follow-up visit. The mean follow-up interval was 1 month (range, 0.5-6 months). Sixty-two patients (49.6%; 95% confidence interval [CI], 40.7-58.5) responded to antimuscarinic treatment. The median time for the onset of response was 3 months (95% CI, 1-6). Multivariate Cox proportional-hazards model revealed that elevated baseline OABSS was an independent predictor of responsiveness to therapy. Receiver operating characteristic (ROC) curve analysis revealed an optimal OABSS cutoff value of > or =7, with an area under the ROC curve of 0.79 (95% CI, 0.70-0.88; sensitivity, 91.9%; specificity, 60.7%). CONCLUSIONS: The median time for a therapeutic response was 3 months, and OABSS was the only predictor for responsiveness. These findings may serve as a guideline when prescribing antimuscarinic treatment for OAB patients.

Efectividad y seguridad de la oxibutinina o tolterodina comparado con darifenacina, solifenacina, fesoterodina y placebo para el tratamiento de la incontinencia / Effectiveness and safety of oxybutynin or tolterodine compared to darifenacin, solifenacin, fesoterodine and placebo for the treatment of incontinence

Introducción: Alrededor del 16% al 45% de los adultos tiene síntomas de vejiga hiperactiva, que se manifiestan con urgencia para orinar, aumento en la frecuencia de micciones o incontinencia urinaria de urgencia, o ambos, denominado síndrome de vejiga hiperactiva. Los fármacos anticolinérgicos son los tratamientos más comunes para el tratamiento farmacológico y entre ellos la oxibutinina y la tolterodina. Esta evaluación tecnológica se desarrolló en el marco de la actualización integral del Plan Obligatorio de Salud para el año 2015. Objetivo: evaluar la efectividad y seguridad de la oxibutinina o la tolterodina para la incontinencia urinaria, comparadas con otros medicamentos antimuscarínicos como: solifenacina, darifenacina, fesoterodina para informar la toma de decisiones. Metodología: la evaluación fue realizada de acuerdo al protocolo definido previamente por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS, sin restricciones de idioma y limitada a revisiones sistemáticas publicadas en los últimos cinco años. Las búsquedas electrónicas fueron hechas entre octubre y noviembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por dos revisores de forma independiente y los desacuerdos fueron resueltos por consenso. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad. La calidad de los estudios fue valorada con la herramienta AMSTAR. Las características de los estudios fueron extraídas a partir de las publicaciones originales. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés a partir de los estudios de mejor calidad con AMSTAR. Resultados: se seleccionó una revisión sistemática que incluyó un total de 86 ensayos clínicos (31,249 pacientes) con medicamentos muscarínicos incluyendo a la Oxibutinina y la Tolterodina. Se realizaron comparaciones directas entre medicamentos y comparaciones intratecnología (dosis y presentaciones). Cuando se comparó la Tolterodina versus la Oxibutinina, no se encontró diferencia estadisticamente significativa en los desenlaces de calidad de vida, la percepción de cura o mejora y cuantificación de los síntomas. Cuando se comparó solifenacina versus tolterodina, se encontró diferencia estadisticamente significativa en los mismos desenlaces a favor de la solifenacina, e igual se reportó en la comparación fesoterodina versus tolterodina, a favor de la fesoterodina. Respecto a seguridad se comparó tolterodina versus oxibutinina y el retiro por eventos adversos fue más frecuente en el grupo de la oxibutinina RR 0.52 IC95% 0.40 a 0.66. En la comparación de soliferacina versus oxibutinina el retiro por eventos adversos fue más frecuente en el grupo de oxibutinina RR 0.45 IC95% 0.22 a 0.91 y al comparar la fesoterodina versus la tolterodina el retiro por eventos adversos fue más frecuente en el grupo de la fesoterodina RR 1.45 IC95% 1.07 a 1.98. Conclusiones: Efectividad: No se evidenció diferencia en efectividad entre la Oxibutinina y Tolterodina en los desenlaces de calidad de vida y la percepción de cura o mejora. Para la comparación de efectividad entre Oxibutinina versus Darifenacina y Solifenacina, no se reportaron resultados. La Solfenacina y Fesoterodina son más efectivas que la Tolterodina, en los desenlaces de calidad de vida y la percepción de cura o mejora. Seguridad: Tolterodina fue más seguro que la Oxibutinina, respecto al abandono por eventos adversos. La comparación entre Darifenacina versus oxibutinina no reportó resultados. Solifenacina fue más seguro que la oxibutinina, respecto al abandono por eventos adversos. Tolterodina fue más seguro que Fesoterodina, respecto al abandono por eventos adversos y boca seca.(AU)

Cardura monotherapy versus combination therapy of cardura and tolterodine L-tartrate tablets for II° ? benign prostatic hyperplasia with overactive bladder / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of the monotherapy of Cardura and the combination therapy of Cardura and Tolterodine L-Tartrate Tablets for II° ? benign prostate hyperplasia (BPH) with overactive bladder (OAB).</p><p><b>METHODS</b>This study included 87 cases of BPH with OAB, with a disease course > or = 3 months, daily urination > or = 8 times, nocturnal urination > or = 2 times, urine volume < 200 ml per time, International Prostate Symptom Score (IPSS) > or = 8, OAB symptom score (OABS) > or = 3, quality of life score (QOL) > or = 3, post-void residual (PVR) < or = 100 ml, maximum urinary flow (Qmax) > or = 5 ml/s, prostate weight 25-50 g, and PSA < 4 microg/L. We randomized the patients to a monotherapy group (n = 44) and combination group (n = 43), the former treated with Cardura 4 mg qd, and the latter with Cardura 4 mg + Tolterodine L-Tartrate Tablets 4 mg qd, both for 8 weeks. Then we recorded the IPSS, OABS, Qmax, PVR, PSA, and adverse events.</p><p><b>RESULTS</b>The baseline parameters showed no significant differences between the two groups (P > 0.05). In comparison with the baseline, both the monotherapy group and the combination therapy group showed significant decreased in the IPSS (16.50 +/- 4.27 vs 13.68 +/- 3.69 and 15.51 +/- 3.80 vs 11.49 +/- 2.75), urine storage symptom score (10.48 +/- 2.75 vs 7.98 +/- 2.34 and 9.47 +/- 2.31 vs 5.74 +/- 1.66), OABS (8.55 +/- 2.69 vs 6.32 +/- 1.97 and 8.21 +/- 2.55 vs 4.44 +/- 1.62), urgent micturition score (4.25 +/- 1.06 vs 3.23 +/- 0.99 and 4.07 +/- 0.83 vs 2.26 +/- 1.05), QOL (5.36 +/- 0.72 vs 3.43 +/- 0.66 and 5.07 +/- 0.86 vs 2.37 +/- 0.76) and PVR ([44.55 +/- 22.39] vs [38.30 +/- 20.20] ml and [36.19 +/- 21.21] vs [24.98 +/- 17.60] ml) (P < 0.01). All the six parameters were significantly more improved in the combination therapy group than in the monotherapy group (P < 0.01), but there were no remarkable differences between the groups in Qmax and voiding symptom score (P > 0.05). Neither group exhibited significant changes in the PSA level and prostate weight after treatment as compared with the baseline (P > 0.05). No acute urinary retention and other severe adverse reactions were observed during the medication.</p><p><b>CONCLUSION</b>Both Cardura monotherapy and the combination therapy of Cardura + Tolterodine L-Tartrate Tablets can improve II ? BPH with OAB, and the latter has an even better efficacy than the former.</p>

Oxybutynin and tolterodine for treatment of neurogenic detrusor overactivity: a pharmacoeconomic evaluation in the Brazilian context

Antimuscarinic agents are the first-line choice for the treatment of neurogenic detrusor overactivity (NDO). The currently available antimuscarinic drugs have been widely studied in patients presenting idiopathic detrusor overactivity; however, investigations evaluating the effects of these drugs on NDO are scant, particularly with regard to cost-effectiveness analyses. A pharmacoeconomic evaluation was performed to compare the costs and effectiveness of oxybutynin and tolterodine in two different formulations, extended (ER) and immediate-release (IR), for the treatment of NDO (based on Brazilian maximal consumer price index). A systematic review of literature was conducted in order to obtain significant clinical and urodynamic data (based on expert opinion), concerning the effects of these drugs in the neurogenic population. Furthermore, a pharmacoeconomic evaluation was performed and costs involved were calculated based on percentage effectiveness obtained for the timeframes of one month and of one year. The best cost-effectiveness ratio (CER) was observed with oxybutynin IR for the urodynamic parameters. In terms of clinical parameters, oxybutynin IR and ER showed the best CER. Based on the key urological parameters analyzed, oxybutynin IR was considered the most cost-effective antimuscarinic agent.

A terapia antimuscarínica é vista como primeira escolha para o tratamento da hiperatividade detrusora de origem neurológica (HDON). No entanto, a maioria dos antimuscarínicos existentes é amplamente estudada em pacientes portadores de hiperatividade detrusora idiopática. Assim, existe escassez de pesquisas que avaliam esses fármacos na problemática da HDON, principalmente em termos de estudos de custo-efetividade. Diante isso, um estudo farmacoeconômico foi realizado (baseado no índice de preço máximo ao consumidor) para comparar os custos e a efetividade da oxibutinina e da tolterodina, em duas diferentes formulações, cápsulas de liberação imediata (LI) e controlada (LC), para o tratamento da HDON. Uma revisão sistemática da literatura foi conduzida para obtenção de dados urodinâmicos e clínicos relevantes (baseado em opinião de especialistas), quanto aos efeitos desses fármacos em pacientes com distúrbios urológicos de origem neurológica. Após essa etapa, um estudo farmacoeconômico foi conduzido e os custos envolvidos foram calculados sobre cada percentual de efetividade obtido, num horizonte temporal de 1 mês e 1 ano. A melhor razão de custo-efetividade (RCE) quanto aos parâmetros urodinâmicos foi obtida com uso de oxibutinina LI. Quantos aos parâmetros clínicos, oxibutinina LI e LC tiveram as melhores RCE. Baseando-se nos principais parâmetros urológicos analisados, oxibutinina LI foi considerada o antimuscarínico mais custo-efetivo.

Overactive bladder after transurethral resection of prostate treated with electroacupuncture therapy and tolterodine / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of overactive bladder after transurethral resection of prostate (TURP) preventively treated with electroacupuncture and Tolterodine.</p><p><b>METHODS</b>One hundred and twenty cases of benign prostate hyperplasia of TURP were randomly divided into an electroacupuncture and medicine group, an electroacupuncture group, a medicine group and a control group, 30 cases in each group. All the patients were treated with TURP under the continuous epidural anesthesia, and the catheter was retained for 5-7 days. In electroacupuncture group, before the surgery of the same day, Huiyang (BL 35), Ciliao (BL 32), Qugu (CV 2) and Huiyin (CV 1) were acupunctured with electroacupuncture for 30 min, once a day, 5-7 days' treatment was applied. In medicine group, Tolterodine Tartrate tablet was taken for 2 mg in the morning of surgery day, twice a day and treatment was applied for 5-7 days. In electroacupuncture and medicine group, the comprehensive therapies above in both electroacupuncture group and medicine group were applied. In control group, Pethidine of 50 mg was given by intramuscular injection when bladder was overactive, combined with Anisodamine injection of 10 mg according to the symptoms. The frequency and lasting time of bladder overactivity were compared within 72 hours after TURP in each group.</p><p><b>RESULTS</b>After TURP, the frequency of bladder overactivity were 2-4 times a day, and lasted for 5-15 min each time in control group. The frequency and lasting time of bladder overactivity in treatment groups at different time were less than those in control group (P < 0.01, P < 0.001). There was no significant difference in comparison of frequency and lasting time of bladder overactivity between electroacupuncture and medicine group (all P > 0.05). The frequency and lasting time of bladder hyperactivity in electroacupuncture and medicine group were less than those in the electroacupuncture group and the medicine group at 24 hours, 24-48 hours, 48-72 hours after TUPR (P < 0.05, P < 0.01, P < 0.001).</p><p><b>CONCLUSION</b>After TURP, early prevention of combined therapy of electroacupuncture and Tolterodine with oral administration is superior to that of electroacupuncture therapy or Tolterodine for overactive bladder treatment, and it is the safe and effective method to treat overactive bladder.</p>

Parkinson's disease combined with overactive bladder syndrome treated with acupuncture and medication / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of Parkinson's disease combined with overactive bladder syndrome (GAB) treated with combined therapy of oral administration of Tolterodine with low dose and electroacuponcture.</p><p><b>METHODS</b>Sixty cases of Parkinson's disease combined with GAB were randomly divided into a combined acupuncture and medication group (group A) and a medication group (group B), 30 cases in each group. In both groups, Madopar basic doses were same, and anticholinergic agents such as Artane were stopped. In group A, Tolterodine was orally taken for 1 mg, twice a day; Baihui (GV 20), Sishengcong (EX-HN 1) and Yintang (EX-HN 3) were punctured with electroacupuncture, once a day. In group B, Tolterodine was orally taken for 2 mg, twice a day. After 6 weeks, the changes of urination and UPDRS III scores were observed, and the adverse reactions were recorded in both groups.</p><p><b>RESULTS</b>After treatment, the frequency of average urination of 24 hours, frequency of incontinence of 24 hours and average urine volume at a time were obviously improved (all P < 0. 01), of which, the above items in group A were superior to those in group B (all P < 0. 05) the UPDRSIII score in group A was superior to that in group B (P < 0.05). The adverse reactions in group A were less than those in group B.</p><p><b>CONCLUSION</b>The therapeutic effect of Parkinson' s disease combined with GAB treated with combined therapy of Tolterodine with low dose and electroacupuncture is superior to that of complete dose of Tolterodine with oral administration, with less adverse reactions. And it also can improve the motor symptom of Parkinson's disease patients.</p>

Characterization of Bladder Selectivity of Antimuscarinic Agents on the Basis of In Vivo Drug-Receptor Binding / 대한배뇨장애요실금학회지

The in vivo muscarinic receptor binding of antimuscarinic agents (oxybutynin, solifenacin, tolterodine, and imidafenacin) used to treat urinary dysfunction in patients with overactive bladder is reviewed. Transdermal administration of oxybutynin in rats leads to significant binding of muscarinic receptors in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral oxybutynin. Oral solifenacin shows significant and long-lasting binding to muscarinic receptors in mouse tissues expressing the M3 subtype. Oral tolterodine binds more selectively to muscarinic receptors in the bladder than in the submaxillary gland in mice. The muscarinic receptor binding of oral imidafenacin in rats is more selective and longer-lasting in the bladder than in other tissues such as the submaxillary gland, heart, colon, lung, and brain, suggesting preferential muscarinic receptor binding in the bladder. In vivo quantitative autoradiography with (+)N-[11C]methyl-3-piperidyl benzilate in rats shows significant occupancy of brain muscarinic receptors with the intravenous injection of oxybutynin, solifenacin, and tolterodine. The estimated in vivo selectivity in brain is significantly greater for solifenacin and tolterodine than for oxybutynin. Imidafenacin occupies few brain muscarinic receptors. Similar findings for oral oxybutynin were observed with positron emission tomography in conscious rhesus monkeys with a significant disturbance of short-term memory. The newer generation of antimuscarinic agents may be advantageous in terms of bladder selectivity after systemic administration.

Dissimilar Effects of Tolterodine on Detrusor Overactivity in Awake Rats with Chemical Cystitis and Partial Bladder Outlet Obstruction / 대한배뇨장애요실금학회지

PURPOSE: We investigated bladder function, with a special focus on nonvoiding contractions (NVCs), in awake rats with chronic chemical cystitis and bladder outlet obstruction (BOO) by use of simultaneous registrations of intravesical and intraabdominal pressures. In addition, we tested the effects of tolterodine on the NVCs in these models. METHODS: A total of 20 female Sprague-Dawley rats were used in this study. In eight rats, chemical cystitis was induced by intravesical instillation of HCl. Twelve rats were subjected to sham instillations or partial BOO. Four weeks after intravesical instillation or 2 weeks after partial BOO, cystometrograms were obtained by use of simultaneous recording of intravesical and intraabdominal pressure in all unanesthetized, unrestrained rats in metabolic cages. RESULTS: A total of 17 rats survived. In the rats with acute injury by HCl, 50% showed detrusor overactivity (DO), which was not seen in the sham group. The cystitis group had lower DO pressure without a difference in DO frequency compared with the BOO group. After the administration of tolterodine, the cystitis group showed no difference in DO frequency or pressure, whereas the BOO group showed decreased values for both parameters. CONCLUSIONS: Our study showed that toleterodine produced no effect on DO during the filling phase in rats with chronic chemical cystitisbut decreased the frequency and pressure of DO in rats with BOO. Clinically, studies are needed to improve the treatment effect of anticholinergic drugs ininterstitial cystitis patients with overactive bladder.

Tolterodine tartrate combined with alpha-receptor blocker for benign prostatic hyperplasia with detrusor overactivity / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Tolterodine Tartrate combined with the alpha-receptor blocker in the treatment of benign prostatic hyperplasia with detrusor overactivity (BPH-DO).</p><p><b>METHODS</b>A total of 113 patients with BPH-DO were randomly assigned to receive Tolterodine Tartrate combined with Cardura (Group A) and Cardura alone (Group B), both for 12 weeks. Then we recorded and compared their average 24 h urinary frequency, IPSS and QOL score, maximum urinary flow rate, residual urine volume and urinary retention times before and after the treatment.</p><p><b>RESULTS</b>After the treatment, Group A showed significantly better improvement in the average 24 h urinary frequency and scores on IPSS and QOL than Group B. No significant differences were found between the two groups in the maximum urinary flow rate and residual urine volume. No acute urinary retention occurred in either group.</p><p><b>CONCLUSION</b>The combined use of Tolterodine Tartrate and the alpha-receptor blocker can effectively relieve the symptoms of dysuria, urinary frequency and urinary urgency in patients with BPH-DO, with neither significant adverse effects on the maximum flow rate and residual urine volume nor increase in the incidence of acute urinary retention.</p>

Comparisons of efficacy and safety of tolterodine and oxybutynin in children with idiopathic overactive bladder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of tolterodine and oxybutynin in the treatment of idiopathic overactive bladder in children.</p><p><b>METHODS</b>A total of 204 children with idiopathic overactive bladder were randomly divided into three groups (n=68 each): placebo, tolterodine-treated and oxybutynin-treated. The efficacy and safety were evaluated two weeks after treatment.</p><p><b>RESULTS</b>The effective rate was 25% in the placebo group, 89% in the tolterodine-treated group, and 92% in the oxybutynin-treated group. The effective rate in the two treatment groups was significantly higher than that in the placebo group (P<0.05). There was a similar efficacy between the two treatment groups. The incidence of adverse events in the tolterodine-treated group (28%) was significantly lower than that in the oxybutnin-treated group (57%) (P<0.05).</p><p><b>CONCLUSIONS</b>Tolterodine has a similar efficacy to oxybutynin in the treatment of idiopathic overactive bladder in children, with better safety in pharmacotherapy.</p>

Stent Position Is More Important than alpha-Blockers or Anticholinergics for Stent-Related Lower Urinary Tract Symptoms after Ureteroscopic Ureterolithotomy: A Prospective Randomized Study

PURPOSE: To evaluate the clinical factors that impact ureteral stent-related lower urinary tract symptoms (LUTS) after ureteroscopic ureterolithotomy, including the stent position and medication. MATERIALS AND METHODS: Fifty-three patients who underwent ureteroscopic ureterolithotomy with indwelling a stent were distributed into three groups. On demand analgesics were given to the group 1 (n=18). Daily tamsulosin 0.2 mg was added for group 2 (n=15) and daily tamsulosin 0.2 mg and tolterodine 4 mg was added for group 3 (n=20). The patients were also subclassified into appropriate or inappropriate group according to stent position. All the patients completed a visual analogue scale (VAS) and International Prostate Symptom Score (IPSS) on the 1st and 7th postoperative days. The VAS and IPSS were analyzed according to the medication groups and the stent position. RESULTS: In the appropriate stent potion group, only the storage symptom scores of groups 2 and 3 on the 1st postoperative day were significantly lower than those of the group 1 (p=0.001). This medication effect on LUTS was not observed in the inappropriate stent position group. In this group, total IPSS (p=0.015) and storage symptom scores (p=0.002) were higher than in the appropriate stent position group on the 7th postoperative day. CONCLUSIONS: Correct placement of the stent was more important than medication for lessening stent-related storage symptoms.

Combination of tamsulosin and tolterodine alleviates refractory lower urinary tract symptoms in male patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate and compare the clinical efficacy and safety of the highly selective alpha receptor antagonist tamsulosin and its combination with the M receptor antagonist tolterodine in the treatment of refractory lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We included in this study 184 BPH patients with refractory LUTS with the disease course of 4 weeks to 2 years, whose LUTS were not alleviated after a week's treatment with tamsulosin. The patients were randomly divided into Groups A and B, the former (n=89) treated with tamsulosin at 0.2 mg qd and the latter (n=95) given tolterodine at 2 mg bid in addition to tamsulosin medication, both for 4 weeks. Scores on IPSS, QOL and Qmax were obtained before and after the treatment, and the improvement of LUTS evaluated after the medication.</p><p><b>RESULTS</b>The tamsulosin group showed no significant differences before and after the treatment in the scores on IPSS (13.23 +/- 4.39 vs. 12.21 +/- 4.07), QOL (4.23 +/- 1.27 vs 3.53 +/- 0.95) and Qmax ([12.3 +/- 8.39] ml/s vs. [14.1 +/- 8.62] mls) (P > 0.05), while the combination group exhibited significantly higher scores on IPSS and QOL and lower score on Qmax after the medication than before it (IPSS: 14.45 +/- 5.31 vs. 6.56 +/- 2.03, P < 0.05; QOL: 4.45 +/- 0.79 vs. 2.34 +/- 0.73, P < 0.05; Qmax: [11.4 +/- 9.21] ml/s vs. [15.5 +/- 8.35] ml/s, P < 0.01). No severe complications were found in any of the cases.</p><p><b>CONCLUSION</b>Combination of tamsulosin and tolterodine can significantly alleviate refractory LUTS and improve QOL without causing serious adverse events in BPH patients.</p>

The Effect of tolterodine Via Oral and Intravenous Administrations on Voiding in Awake Spontaneously Hypertensive Rats as an Overactive Bladder Model

PURPOSE: We investigated the effect of oral or intravenous tolterodine on cystometric parameters in awake spontaneously hypertensive rats (SHRs) as a model of overactive bladder (OAB). The aim of our study was to observe the experimental conditions required to reproduce the clinical pharmacological effects of tolterodine, as seen in humans, to decrease bladder pressure or increase bladder capacity. MATERIALS AND METHODS: We studied the effects of the most widely used antimuscarinic drug, tolterodine, on cystometric parameters via two different administrations (oral and intravenous) in awake SHRs. RESULTS: Oral administration of tolterodine 10 mg/kg(-1) body weight in awake rats did not change any cystometric parameters significantly. Intravenous administration of tolterodine 0.3 mg/kg(-1) body weight significantly decreased basal pressure (BP) and micturition pressure (MP), but showed no effect on micturition interval (MI) or bladder capacity (BC). CONCLUSION: Despite a high dose of tolterodine via an oral or an intravenous route, a decrease in BP or MP was the only effect on cystometrographic parameters in awake rats, whereas MI and BC were not significantly affected. Therefore, it is difficult to reproduce in awake rats as an acute response the cystometric increase in the MI that is observed in humans after chronic administration of antimuscarinic agents.

Review of the Anticholinergics for the Treatment of Overactive Bladder: 2009 Update

Overactive bladder is a chronic condition defined by bothersome urgency with or without urgency incontinence, usually associated with daytime frequency and nocturia. The treatment of this condition is to control bothersome urinary symptoms and is therefore to improve quality of life. The Korean Continence Society published the overactive bladder guideline in 2007, which suggested the mainstay of management is behavioral therapy and antimuscarinic pharmacotherapy. With growing awareness toward overactive bladder and quality of life, clinical information regarding antimuscarinic agents should be updated. There are several agents with good level of evidence and good grade of recommendation. Newer antimuscarinic agents are available or will be available in near future. The pharmacological properties, efficacy and tolerability of oxybutynin, trospium, propiverine, tolterodine, darifenacin, solifenacin, fesoterodine and imidafenacin are reviewed and discussed here. The results of major clinical studies are summarized.

The Effect of Tolterodine and Oxybutyninin on Nocturia in Patients with Benign Prostatic Hyperplasia

PURPOSE: Nocturia has been one of the most bothersome symptoms in benign prostatic hyperplasia (BPH) patients. Therefore, the authors evaluated the effect of tolterodine and oxybutyninin on nocturia in BPH patients. MATERIALS AND METHODS: From September 2006 to March 2007, 82 patients who presented over than 2 in nocturnal bladder capacity index (NCBI) in spite of having alpha blockers for 6 months were enrolled. Group I (n=38) took alpha blocker with tolterodine, group II (n=44) took alpha blocker with oxybutynin. The number of their nocturia episodes was separately evaluated by the time before and after the medication. The complications were assessed using a questionnaire. RESULTS: The number of nocturia episodes decreased by at least 1 in 68.4% (26/38), 84.1% (37/44) of patients in group I, II, respectively, and decreased by 2 or more, 1 and were unchanged or increased were 36.8, 31.6, 31.6% in group I patients and 45.5, 38.6, 15.9% in group II patients, respectively. In baseline nocturia > or =6 group, the nocturia decreased by 1 or more in 66.7%, 77.8% in group I, II, respectively. Adverse events, including dry mouth, dizziness, headache, etc, occurred in 21.1% (8/38) in group I and 27.3% (12/44) in group II patients. The complications between two groups showed no significant differences. CONCLUSIONS: Alpha blockers with tolterodine or oxybutynin can be effectively combined as a treatment option for patients with BPH complaining of unresolved nocturia.