Pharmacological agents for the treatment of urinary incontinence due to overactive bladder

Although the exact aetiology of overactive bladder is unknown to date, pharmacological therapy has been targeted to both the central and peripheral nervous systems. Potential CNS targets include GABA, opioid, serotonin (5-HT), dopamine and glutaminergic receptors as well as the α-adrenoceptors. Potential PNS targets include muscarinic receptors, calcium and potassium channels and α- and β-adrenergic receptors. Since acetylcholine is the primary excitatory neurotransmitter involved in bladder (detrusor) contraction and emptying, anticholinergic agents are the primary compounds used clinically to decrease involuntary detrusor contractions. Anticholinergic therapy has a stabilising effect on the bladder (detrusor muscle); increases bladder capacity; decreases frequency of involuntary detrusor contractions; and delays the initial urge to void, but does not affect warning time. However, the clinical utility of antimuscarinic therapy is limited by the lack of receptor selectivity, resulting in the classic anticholinergic side effects of dry mouth, blurred vision, constipation and potentially, CNS effects such as somnolence and impaired cognitive function. These unwanted side effects often result in premature discontinuation of therapy and poor compliance. Previous attempts to develop uroselective α-adrenergic receptor antagonists have not been successful and although research continues, the hope that this class of agents would be viable alternatives to the anticholinergics remains to be proven in the clinical setting. The recent demise of several potassium channel openers does not augur well for the future of this class of agent. The reasons for the discontinuation of trials with these agents have not been fully elucidated, but one must assume that they were not uroselective and the cardiovascular side effects rendered them less than useful clinically. The serotonin re-uptake inhibitors appear to be promising novel therapeutic agents aimed at controlling bladder over-activity through specific CNS pathways. The sensory side of the micturition reflex is a potential therapeutic target. Agents to desensitise afferent nerve endings involved in C-fibre afferent reflexes include capsaicin and resiniferatoxin. Their clinical applicability is currently being evaluated. Finally, the recent findings related to the role of the P2X3 receptor in the sensory aspects of bladder filling have created new interest in the future development of agents that will improve the management of this prevalent and debilitating condition.     

Tolterodine for the treatment of overactive bladder

Background: The overactive bladder syndrome is a common condition affecting ～ 12% of men and women. It is extremely disturbing with a great impact on quality of life. Its treatment involves a combination of behavioural and pharmacological therapy. The latter includes antimuscarinic drugs such as tolterodine. Objective: To review the safety and efficacy of tolterodine in the treatment of overactive bladder in comparison with other available antimuscarinic agents. Methods: A Pubmed search was carried out differentiating randomised, clinical trials; longitudinal, retrospective studies; and metanalysis on the use of tolterodine for overactive bladder treatment. In the comparison with other antimuscarinic agents, only randomised, clinical trials were considered. Results/conclusion: Tolterodine is available as immediate- or extended-release formulations. It has been extensively evaluated with long-term, randomised trials for safety and efficacy showing a significant improvement in overactive bladder symptoms with an excellent tolerability profile.     

Dose-ranging study of tolterodine in patients with detrusor hyperreflexia

Tolterodine is a potent antimuscarinic agent specifically developed for the treatment of urinary urge incontinence and other symptoms related to the overactive bladder. In order to assess the optimum dosage for use in future clinical studies, a double-blind, randomized, placebo-controlled, parallel-group, multicenter study was performed in 90 patients with detrusor hyperreflexia and symptoms of urinary urgency, frequency, and/or urge incontinence. Urodynamic variables, micturition diary variables, and subjective urinary symptoms were measured before and after 2 weeks' treatment with either placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily (bd). Serum drug concentrations, electrocardiogram recordings, blood pressure, and incidence of adverse events were also assessed. Linear regression analysis showed a significant dose-response relationship for several clinically relevant urodynamic variables, while there was a trend towards an improvement in micturition diary variables and subjective assessment of symptoms with increasing dosages of tolterodine. There were no safety or tolerability concerns regarding any of the dosages of tolterodine investigated, although 2 patients treated with a dosage of 4 mg bd experienced urinary retention that necessitated dosage reduction. The results of this study suggest that tolterodine is well-tolerated and exerts a dose-dependent effect on bladder function in patients with detrusor hyperreflexia. The optimum dosage of tolterodine for use in future studies is 1–2 mg bd. Neurourol. Urodynam. 17:499–512, 1998. © 1998 Wiley-Liss, Inc.     

Comparisons of the therapeutic safety of seven oral antimuscarinic drugs in patients with overactive bladder: a network meta-analysis

ObjectivesThis network meta-analysis aimed to assess the safety profiles of seven commonly used oral antimuscarinic drugs (darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, and tolterodine) in patients with overactive bladder (OAB).MethodsPubMed, Cochrane Library, EMBASE, CNKI, and Wanfang databases were searched for randomized controlled trials (RCTs). Studies comparing one or more antimuscarinic drugs for treating OAB with reported adverse effects (AEs) were eligible. Data were extracted, and a network meta-analysis was performed by two authors independently.ResultsForty-five RCTs and 124,587 patients were included. The results demonstrated that tolterodine had better safety outcomes for 7 out of 12 major AEs, including dry mouth, constipation, urinary retention, dizziness, urinary tract infection, dry eyes, and dry skin. Darifenacin, fesoterodine, imidafenacin, oxybutynin, and solifenacin presented comparable safety profiles.ConclusionsTolterodine may be preferable as it showed a reduced association with important AEs. Darifenacin, fesoterodine, imidafenacin, oxybutynin, and solifenacin have similar safety profiles in treating patients with OAB. Taken together, this analysis provides a valuable overview of the therapeutic safety for oral antimuscarinic drugs and is useful for personalized medicine in patients with OAB.Trial registration: This trial was retrospectively registered at INPLASY (https://inplasy.com/) with the registration number 202170095.     

坦索罗辛联合舍尼亭治疗严重尿频相关性睡眠障碍的疗效观察

目的 探讨坦索罗辛联合舍尼亭治疗尿频相关性睡眠障碍的疗效.方法 对严重夜尿所致睡眠障碍73例患者在常规导眠药物治疗基础上,联合服用坦索罗辛、舍尼亭治疗8周.症状改善评估采用尿频综合征症状评分(USS)、匹兹堡睡眠质量指数(PSQI)、生活质量评分(QOL)为主要疗效指标,观察治疗效果.结果 治疗后患者睡眠质量及生活质量改善,PSQI、USS、QOL分值明显降低,差异有统计学意义(P<0.01).结论 坦索罗辛(0.4mg/d)联合舍尼亭可提高夜尿性睡眠障碍患者的睡眠质量.     

萘哌地尔联合舍尼亭治疗女性膀胱过度活动症的疗效观察

目的探讨萘哌地尔联合舍尼亭治疗女性膀胱过度活动症的疗效。方法对31例诊断为女性膀胱过度活动症的患者行萘哌地尔加舍尼亭治疗。以自由尿流率的主要参数如最大尿流率（Qmax）、平均尿流率（Qave）、排尿量（VV）和尿道综合征症状评分（FUSS）、生活质量评分（QOL）为主要疗效指标，来观察治疗效果。砖栗治疗前后的尿流率参数值（Qmax、Qave、VV）、FUSS、QOL相比较，差异显著（P〈0．05），总有效率为83．88％。砖论萘哌地尔加舍尼亭联合应用可作为女性膀胱过度活动症的一种有效治疗手段。     

Correlations between the ICIQ-SF score and urodynamic findings

AIMS: The primary aim of this prospective study was to examine the correlations between "The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)" score and urodynamic findings in patients with urge incontinence. In addition, we aimed to observe the alterations of these parameters with antimuscarinic therapy. METHODS: Between January and December 2005, patients referred to our department with urge incontinence were examined. After taking a detailed clinical history, physical examination, and urinalysis, each patient was asked to complete an ICIQ-SF questionnaire. We carried out subtracted cystometry according to a fixed protocol on all patients. Patients who were defined as detrusor overactivity incontinent were given antimuscarinic therapy for 3 months. Following treatment, filling cystometry and ICIQ-SF scoring were repeated in all patients. All pre- and post-treatment data of 18 male and 42 female patients were transferred to the SPSS 11.0 for Windows program, and statistical analyses were performed. RESULTS: The patients' ages ranged from 28 to 70 (mean 49.8) years. We found statistically significant differences between the pre- and post-treatment parameters (mean ICIQ-SF score, first sensation, cystometric capacity, maximum detrusor pressure, compliance; P<0.01). We found negative correlation between pre-treatment mean ICIQ-SF score and first sensation (correlation coefficient -0.266, P<0.05) and positive correlation between pre-treatment mean ICIQ-SF score and maximum detrusor pressure (correlation coefficient 0.4, P<0.01). CONCLUSIONS: ICIQ-SF scoring is a practical and reliable method for baseline and post-treatment evaluation of patients with urge incontinence. Significant correlation exists between ICIQ-SF score and urodynamic parameters.     

Does urodynamic verification of overactive bladder determine treatment success? Results from a randomized placebo‐controlled study

OBJECTIVE

To determine whether subjects with or with no detrusor overactivity (DO) determined by urodynamic assessment respond differently to treatment with the antimuscarinic agent tolterodine (extended release formulation, ER).

SUBJECTS AND METHODS

Adult subjects with urinary frequency (average ≥8 voids/24 h) and urgency with or without urgency urinary incontinence (UUI) underwent urodynamic assessment and were stratified according to whether they had DO (positive urodynamics) or not (negative urodynamics). Subjects in each urodynamic stratum were randomized to receive tolterodine‐ER (4 mg once daily) or placebo for 12 weeks. Diary cards were completed for 7 days before each study visit (at baseline, week 4, and week 12). The volume per void was recorded for 3 of the 7 days.

RESULTS

The difference between the positive and negative urodynamic groups in mean change in volume voided between baseline and 12 weeks was 5.38 mL (95% CI, ?93 mL to +15.71 mL). This difference is within the pre‐stipulated range defined for equivalence (±20 mL, P = 0.31). There was also no significant difference in the change from baseline to 12 weeks between the urodynamics groups in mean number of voids per day or UUI episodes. However, there was significant improvement in the treatment group compared with the placebo group, in the number of voids per 24 h (P = 0.003) and in the mean change in volume voided (P = 0.03), from baseline to 12 weeks, but not in UUI episodes (P = 0.35).

CONCLUSIONS

Urodynamics status could not predict treatment outcomes between patients treated with tolterodine‐ER or placebo. The results add support to evidence suggesting that urodynamic assessment is not a prerequisite for the treatment of overactive bladder (OAB). Therefore, we recommend that anticholinergic treatment may be initiated to patients with OAB symptoms without the need for urodynamics studies.     

舍尼亭治疗留置气囊导尿管尿液渗漏的效果观察

目的观察舍尼亭（酒石酸托特罗定）治疗留置气囊导尿管尿液渗漏的效果。方法将2011年发生在本科留置气囊导尿管尿液渗漏的56例患者随机分为对照组和观察组。对照组使用传统方法处理,观察组在使用传统方法处理的基础上应用舍尼亭治疗,比较2组尿液渗漏总有效率。结果观察组总有效率（100％）高于对照组（643％）。结论舍尼亭在治疗留置气囊导尿管尿液渗漏中疗效显著。