Current pharmacotherapy of overactive bladder

ABSTRACT Overactive bladder is a symptom complex consisting of bothersome storage urinary symptoms that is highly prevalent among both sexes and has a significant impact on quality of life. Various antimuscarinic agents and the beta-3 agonists mirabegron and vibegron are currently available for the treatment of OAB. Each drug has specific pharmacologic properties, dosing schedule and tolerability profile, making it essential to individualize the medical treatment for the patient's characteristics and expectations. In this manuscript, we review the most important factors involved in the contemporary pharmacological treatment of OAB.

Combination of topical agents and oxybutynin as a therapeutic modality for patients with both osmidrosis and hyperhidrosis / Uso combinado de agentes tópicos e oxibutinina para tratamento de pacientes com osmidrose e hiper-hidrose

Summary Introduction: The association of osmidrosis and hyperhidrosis often causes emotional and social problems that may impair the patients' quality of life. The purpose of our study was to analyze the therapeutic results of oxybutynin and topical agents in 89 patients with both osmidrosis and hyperhidrosis. Method: We conducted an observational study at two specialized centers of hyperhidrosis between April 2007 and August 2013. Eighty-nine (89) patients with both osmidrosis and hyperhidrosis were treated with oxybutynin and topical agents. Patients were evaluated before treatment and at 3 and 6 weeks after treatment started, by using the Quality of Life Questionnaire and the Sweating Evolution Scale. Results: Before treatment, 98% of the patients presented with poor or very poor quality of life. After six weeks of treatment, 70% stated their quality of life as being slightly better or much better (p<0.001) and nearly 70% of the patients experienced a moderate or great improvement in sweating and malodor. Improvement in osmidrosis was significantly greater when the axillary region was the first most disturbing site of hyperhidrosis. Conclusion: There was a significant improvement in quality of life and a reduction in sweating and malodor after six weeks of treatment with topical agents and oxybutynin in patients with both hyperhidrosis and osmidrosis. Therefore, clinical treatment should be considered before invasive techniques.

Resumo Introdução: A associação entre osmidrose e hiper-hidrose com frequência causa problemas emocionais e sociais que podem deteriorar a qualidade de vida dos pacientes. O objetivo deste estudo foi analisar os resultados terapêuticos do uso de oxibutinina associada a agentes tópicos em 89 pacientes com osmidrose e hiper-hidrose. Método: Nós conduzimos um estudo observacional em dois centros especializados em hiper-hidrose entre abril de 2007 e agosto de 2013. Oitenta e nove (89) pacientes com osmidrose associada a hiper-hidrose foram tratados com oxibutinina e agentes tópicos. Os pacientes foram avaliados antes do tratamento e após 3 e 6 semanas do início do tratamento, por meio do Questionário de Qualidade de Vida e da Escala de Evolução da Sudorese. Resultados: Antes do tratamento, 98% dos pacientes apresentavam qualidade de vida ruim ou muito ruim. Após seis semanas de tratamento, 70% classificou sua qualidade de vida como sendo pouco ou muito melhor (p<0.001) e aproximadamente 70% dos pacientes relataram melhora moderada ou grande de sudorese e odor. Houve melhora significativamente maior da osmidrose quando a região axilar era o sítio em que a hiper-hidrose mais incomodava. Conclusão: Houve melhora significativa da qualidade de vida e uma redução da sudorese e do odor após seis semanas de tratamento com agentes tópicos e oxibutinina em pacientes com hiper-hidrose associada a osmidrose. Dessa maneira, a terapia clínica deve ser considerada antes de técnicas invasivas.

Influence of the Short-term Intake of High Doses of Solifenacin and Trospium on Cognitive Function and Health-Related Quality of Life in Older Women With Urinary Incontinence / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to investigate the safety and the effects of elevated doses of solifenacin and trospium on cognitive function and health-related quality of life (HRQoL) in elderly women receiving treatment for urinary incontinence. METHODS: The study included 312 women aged 60–83 years (mean age, 69.4 years). All participants had scored at least 24 points on the Mini-Mental State Examination (MMSE) scale, and all of them had been diagnosed with urge urinary incontinence (UUI) or mixed urinary incontinence (MUI). The women were randomly assigned to 3 groups: group A, individuals who were simultaneously administered solifenacin at a high dosage of 20 mg per day and trospium at a high dosage of 60 mg per day; group B, persons taking solifenacin and trospium at the usual dosage of 10 and 30 mg per day, respectively; and group C, persons who received a placebo. Participants’ cognitive status was assessed by the MMSE, Controlled Oral Word Association Test, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale III, Colour Trails Test, and California Verbal Learning Test scales. The HRQoL assessment was performed using the Medical Outcomes Study 36-Item Health Survey. RESULTS: The cognitive function parameters did not differ at the start and end of the study across the groups (P>0.05). Additionally, the cognitive function parameters did not differ significantly within each group between the start and end of the study (P>0.05). The values of most HRQoL parameters regarding the functional state of the lower urinary tract (LUT) after the termination of treatment significantly improved in groups A and B (P < 0.05). A significant correlation between cognitive status and HRQoL or LUT parameters was absent (r < 0.3), while the correlations between HRQoL and LUT parameters were r=0.31–0.83, P < 0.05. CONCLUSIONS: The use of elevated doses of solifenacin and trospium did not increase the risk of cognitive impairment in women with UUI and MUI. The combination of solifenacin and trospium at a double dosage may be recommended to elderly women with treatment-resistant symptoms of UUI and MUI. However, the safety of combining antimuscarinic drugs in women with an increased volume of residual urine requires further study.

Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis / Antagonistas muscarínicos de longa duração vs. β 2 -agonistas de longa duração em exacerbações da DPOC: revisão sistemática e meta-análise

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

RESUMO Objetivo: Determinar se long-acting muscarinic antagonists (LAMAs, antagonistas muscarínicos de longa duração) são superiores a long-acting β2 agonists (LABAs, β2-agonistas de longa duração) na prevenção de exacerbações da DPOC. Métodos: Revisão sistemática e meta-análise de ensaios clínicos controlados aleatórios com pacientes com DPOC estável, de moderada a grave, conforme os critérios da Global Initiative for Chronic Obstructive Lung Disease, tratados com LAMA (brometo de tiotrópio, aclidínio ou glicopirrônio), acompanhados durante pelo menos 12 semanas e comparados a controles que usaram LABA isoladamente ou com um corticosteroide. Resultados: Foram analisados 2.622 estudos para possível inclusão com base em seu título e resumo; 9 estudos (17.120 participantes) foram incluídos na análise. Em comparação com LABAs, LAMAs resultaram em maior diminuição da razão da taxa de exacerbações [risco relativo (RR) = 0,88; IC95%: 0,84-0,93]; menor proporção de pacientes que apresentaram pelo menos uma exacerbação (RR = 0,90; IC95%: 0,87-0,94; p < 0,00001); menor risco de hospitalizações em virtude de exacerbação da doença (RR = 0,78; IC95%: 0,69-0,87; p < 0,0001) e menor número de eventos adversos sérios (RR = 0,81; IC95%: 0,67-0,96; p = 0,0002). A qualidade geral das evidências foi moderada para todos os desfechos. Conclusões: O principal achado desta revisão sistemática e meta-análise foi que LAMAs reduziram significativamente a taxa de exacerbações (episódios de exacerbação/ano), os episódios de exacerbação, as hospitalizações e os eventos adversos sérios.

Advances of muscarinic antagonists slowing the progression of myopia / 中华实验眼科杂志

The myopic population is growing rapidly worldwide,the treatment of myopia become one of the hot spots in ophthalmology.Medicine therapy of myopia is now commonly used to slow down the progression of myopia,and it has already been the most expected one.Among all the drugs,the effect of muscarinic antagonists has been recognized at home and abroad.Muscarinic antagonists,according to their different M receptors,own different interventional approaches and therapeutic effects.Muscarinic antagonists,such include atropine,pirenzepine,tropicamide and cyclopentolate,their pharmacology and adverse effects are analyzed in order to explore their safety and efficacy and evaluate their clinical value.This paper reviewed these aspects of muscarinic antagonists and raise the discussion and prospect of muscarinic antagonists in the treatment of myopia.

Positioning of Long-Acting Muscarinic Antagonists in the Management of Asthma

Despite a range of efficacious therapies for asthma, including inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA), a significant proportion of patients have poor asthma control and retain a risk of future worsening of their symptoms. Long-acting muscarinic antagonist (LAMA) bronchodilators offer a well-tolerated, efficacious, and cost-effective add-on to a patient's treatment. Of the LAMAs currently under investigation or available for the treatment of asthma, evidence from a comprehensive clinical trial program in adults and children shows that once-daily treatment with tiotropium provides benefits for patients with uncontrolled asthma despite the use of ICS and LABAs. Tiotropium is included in the Global Initiative for Asthma (GINA) strategy document as an add-on therapy option for patients at Step 4 or 5 with a history of asthma exacerbations. Tiotropium Respimat® has demonstrated safety and efficacy in patients with a range of disease severities, ages, and phenotypes. This review describes the evidence for the use of LAMA as add-on therapy for patients with asthma who remain uncontrolled despite the use of ICS and LABA treatments.

Impact of long-term treatment with inhaled corticosteroids and bronchodilators on lung function in a patient with post-infectious bronchiolitis obliterans / Impacto do tratamento de longo prazo com corticosteroides e broncodilatadores inalatórios na função pulmonar em um paciente com bronquiolite obliterante pós-infecciosa

ABSTRACT Post-infectious bronchiolitis obliterans (PIBO) is a small airways disease characterized by fixed airflow limitation. Therefore, inhaled bronchodilators and corticosteroids are not recommended as maintenance therapy options. The management of PIBO currently consists only of close monitoring of affected patients, aimed at the prevention and early treatment of pulmonary infections. In recent years, there has been an increase in the incidence of PIBO in the pediatric population. Patients with PIBO are characterized by a progressive decline in lung function, accompanied by a decrease in overall functional capacity. Here, we report the case of a relatively young man diagnosed with PIBO and followed for three years. After short- and long-term therapy with an inhaled corticosteroid/long-acting 2 agonist combination, together with an inhaled long-acting antimuscarinic, the patient showed relevant improvement of airway obstruction that had been irreversible at the time of the bronchodilator test. The lung function of the patient worsened when he interrupted the triple inhaled therapy. In addition, a 3-week pulmonary rehabilitation program markedly improved his physical performance.

RESUMO A bronquiolite obliterante pós-infecciosa (BOPI) é uma doença das pequenas vias aéreas caracterizada por limitação fixa do fluxo aéreo. Portanto, os broncodilatadores e os corticosteroides inalatórios não são recomendados como opções de terapia de manutenção. Atualmente, o manejo da BOPI consiste apenas de um acompanhamento rigoroso dos pacientes afetados, visando à prevenção e ao tratamento precoce de infecções pulmonares. A incidência de BOPI tem aumentado na população pediátrica nos últimos anos. Os pacientes com BOPI caracterizam-se por um declínio progressivo da função pulmonar, associado a uma diminuição da capacidade funcional global. Relatamos aqui o caso de um homem relativamente jovem diagnosticado com BOPI, acompanhado por três anos. Após terapia de curto e de longo prazo com uma combinação de corticosteroide/2-agonista de longa duração inalatórios, associada a um agente antimuscarínico de longa duração inalatório, o paciente apresentou uma melhora relevante da obstrução das vias aéreas, a qual fora irreversível durante o teste de broncodilatação. A função pulmonar do paciente piorou quando ele interrompeu a terapia inalatória tripla. Além disso, um programa de reabilitação pulmonar de três semanas significativamente melhorou seu desempenho físico.

Overactive bladder - 18 years - Part I

ABSTRACT Abstract: Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals – including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years.

Overactive bladder - 18 years - Part II

ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.

Clinical efficacy of combination therapy of Tamsulosin plus Tolterodine sustained-release capsules on benign prostatic hyperplasia with overactive bladder in elderly men / 中华老年医学杂志

Objective To evaluate the efficacy of combination therapy of cholinergic receptor blocker Tolterodine and Alpha-adrenergic receptor blocker Tamsulosin sustained-release capsules on benign prostatic hyperplasia(BPH)with overactive bladder(OAB) in elderly men.Methods A total of 97 male BPH patients aged 80 years and over(80～98 years old,mean 87.7 years old)were enrolled in this study,who met the diagnosis and treatment guidelines of OAB formulated by Chinese Urological Association and were admitted to our hospital from Jan.2015 to July.2015.Patients were randomly divided into Tamsulosin group(n＝ 51,treated with Tamsulosin) and combination group(n＝ 46,treated with Tamsulosin and Tolterodine).Results In Tamsulosin group after treatment,the international prostate symptom score(IPSS) was reduced from (18.3 ± 2.7) to (13.3 ± 3.1) (t ＝ 14.94,P ＜ 0.05),OAB symptom score(OABSS) from (9.3 ± 2.7) to (6.8 ± 1.9) (t ＝ 3.92,P ＜ 0.05),and post void residual volume(PVRV)from(36.5±32.3)ml to(16.2±12.1)ml(t＝14.98,P＜0.01).And the daily frequency of urgency,urgency incontinence and nocturia were improved in Tamsulosin group after treatment.IPSS,OABSS and PVRV were improved more significantly in combination group after treatment than in Tamsulosin group,and the daily frequency of urgency,urgency incontinence and nocturia were reduced more significantly in combination group than in tamsulosin group(t＝-5.23,-3.98,9.01,11.5,14.8,P＜0.01).While there was no significant difference in prostate volume (PV)and PVRV between the two groups after 8 weeks of treatment(t＝ 1.22,-0.94,P＞0.05).The total incidences of adverse events (mainly mouth dryness)had no significant differences between the Tamsulosingroup and the combination group(8.7％ vs.5.9％,x2 ＝99.47,P＞0.05).No acute urinary retention was found in the two groups.Conclusions The combination therapy of Tamsulosin and Tolterodine has better efficacy and safety than single Tamsulosin application in the treatment of BPH with OAB in elderly men.

Social, Economic, and Medical Factors Associated With Solifenacin Therapy Compliance Among Workers Who Suffer From Lower Urinary Tract Symptoms / 대한배뇨장애요실금학회지

PURPOSE: The prevalence of hyperactive-type lower urinary tract symptoms is 45.2%, with shares of overactive bladder (OAB) and urge incontinence (UI) symptoms of 10.7% and 8.2%, respectively. We investigated the possible impact of a wide range of social, economic, and medical factors on compliance with solifenacin treatment in the working population. METHODS: Social, economic, and medical factors as well as the Overactive Bladder questionnaire – the OAB-q Short Form (OAB-q SF), bladder diaries, and uroflowmetry of 1,038 people who were administered solifenacin for a year were gathered from employer documentation. RESULTS: Among the subjects, 32% maintained their compliance with solifenacin treatment throughout the year. Only 65% of the patients had compliance exceeding 80%, and 17% of patients had compliance of ≥50%, yet less than 80% were still taking solifenacin 12 months after the beginning of this experiment. Working people whose compliance level was, at least, 80% had reliably higher (P≤0.01) average age, annual salary, and treatment efficacy, and a greater treatment satisfaction level, as well as a lack of satisfaction with other antimuscarinic treatments and higher rate of urge UI diagnosis. The same cohort also featured a lower level (P≤0.01) of caffeine abuse and lower share of salary spent purchasing solifenacin. CONCLUSIONS: This study has shown that compliance with solifenacin treatment is associated with a number of significant medical, social, and economic factors. The medical factors included the type of urination disorder, severity of incontinence symptoms, presence of side effects, treatment efficacy and patients’ satisfaction with it, and experience using other antimuscarinic treatments. Among the social and economic factors, those with the strongest correlation to compliance were patient age, employment in medicine and education, annual income level, percentage of solifenacin purchase expenditures, and caffeine abuse. Factors with a weaker, but still significant, association were gender, employment in the transportation industry, and monthly income level.

An Acute Therapeutic Evaluation of Three Regimens of Tiotropium and Formoterol in COPD Patients: A Randomized, Double-blind, Placebo-Controlled Clinical Study.

Aims: To evaluate therapeutic rationality of combining long-acting β2-agonists (formoterol) with duration of action of 12 hours and anticholinergics (tiotropium) with 24 hours as fixed dose inhaled combination (FDC) still widely prescribed in developing countries in COPD patients. Study Design: A randomized, double-blind, placebo-controlled, parallel design study. The three regimens that were used; tiotropium 18 μg once a day in the morning along with the formoterol matched placebo in the evening, the FDC of tiotropium 18 μg plus formoterol 12 μg once a day in the morning and formoterol matched placebo in the evening and the same FDC of the two drugs once a day in the morning and once a day formoterol 12 μg in the evening in patients of COPD without any co-morbidity. Place and Duration of Study: Tertiary care pulmonary medicine university teaching government hospital of Delhi, India; 1 year. Methodology: Sixty COPD patients (Male, Avg. age 56±11 years) divided into 3 groups of 20 each without any comorbidity were admitted in the hospital for 24 hours. The spirometry, perception of dyspnea on Borg's scale and vitals such as blood pressure (BP) and pulse rate (PR) were recorded at the following interval 30 minutes, 2 hours, 12 hours after the morning dose and 30 minutes and 12 hours after the evening dose. Results: Addition of formoterol in the evening along with the FDC in the morning enhanced the peak effects in percentage predicted FEV1 (82.55+/-12.639), FEV1/FVC (0.592±0.097) that remained till the next dose (24 hours) which was statistically (P=.05) superior to the tiotropium alone group (75.55+/-17.981) as well as FDC alone group (74.55+/-12.655). Conclusion: There is no advantage of FDC once a day over tiotropium alone. However addition of evening dose of formoterol has shown therapeutic superiority over once a day FDC of the two in COPD.

Status Asmaticus: lenda ou realidade? Como tratar melhor? / Status Asmathicus: legend or reality? How to treat better?

A história natural do status asmaticus é na maioria das vezes de resolução com mortalidade geral menor que 1%. Cerca de 80% dos pacientes com exacerbação de asma brônquica são liberados da emergência nas primeiras duas horas de tratamento. No entanto, nos pacientes com necessidade de ventilação mecânica a mortalidade pode chegar a 8%. O tratamento rápido e eficaz é essencial para o sucesso do tratamento e a prevenção de complicações. Neste artigo são abordadas as recomendações atuais do tratamento das exacerbações graves de asma brônquica nos setores de emergência e terapia intensiva...

The natural history of status asthmaticus is, most of the time, sorted out with overall mortality less than 1%. About 80% of patients with exacerbation of asthma emergency are released within the first two hours of treatment. However, in patients requiring mechanical ventilation mortality can reach 8%. The rapid and effective treatment is essential for the success of the treatment and the prevention of complications. This paper addresses the current recommendations the treatment of severe exacerbations of asthma in the emergency department and intensive care...

Factors affecting medication discontinuation in patients with overactive bladder symptoms

OBJECTIVE: To find out the factors affecting medication discontinuation in patients with overactive bladder (OAB) symptoms. METHODS: The clinical data of 125 patients with OAB symptoms who had taken antimuscarinics and behavioral therapy were retrospectively reviewed. Antimuscarinics related outcomes were evaluated by an independent observer with telephone interview. All patients were asked about duration of medication and reason of continuation or discontinuation of antimuscarinics. To determine pre-treatment factors predicting self-report discontinuation of antimuscarinics, variables of only those with P-values <0.25 on the univariate analysis were included in the Cox proportional hazard modeling. RESULTS: Mean follow-up was 39.6 months and the proportion of discontinuation of antimuscarinics was 60.0% (75/125). The mean duration of medication was 21.2 months in the continuation group and 3.3 months in the discontinuation group. The reasons of discontinuation of antimuscarinics were improved OAB symptoms (46.7%), tolerable OAB symptoms (33.3%), no change of OAB symptoms (1.3%), side-effects (8.0%) and no desire to take long-term medication (10.7%). The variables affecting remaining cumulative probability of antimuscarinics were age, history of anti-incontinence surgery or vaginal surgery, and having stress predominant urinary incontinence on urodynamic study. CONCLUSION: The lower rate of cumulative continuation of antimuscarinics encourages us to give a more detailed counseling and education to the patients with OAB symptoms before prescription. And explorations about newer agent and non-pharmacologic treatment with good efficacy and lower side-effects are needed.

Clinical Factors Associated With Dose Escalation of Solifenacin for the Treatment of Overactive Bladder in Real Life Practice / 대한배뇨장애요실금학회지

PURPOSE: To determine the baseline clinical characteristics associated with dose escalation of solifenacin in patients with overactive bladder (OAB). METHODS: We analyzed the data of patients with OAB (micturition frequency > or =8/day and urgency > or =1/day) who were treated with solifenacin and followed up for 24 weeks. According to our department protocol, all the patients kept voiding diaries, and OAB symptom scores (OABSS) were monitored at baseline and after 4, 12, and 24 weeks of solifenacin treatment. RESULTS: In total, 68 patients (mean age, 60.8+/-10.0 years) were recruited. The dose escalation rate by the end of the study was 41.2%, from 23.5% at 4 weeks and 17.6% at 12 weeks. At baseline, the dose escalator group had significantly more OAB wet patients (53.6% vs. 20.0%) and higher total OABSS (10.2+/-2.4 vs. 7.9+/-3.5, P=0.032) than the nonescalator group. OAB wet (odds ratio [OR], 4.615; 95% confidence interval [CI], 1.578-13.499; P<0.05) and total OABSS (OR, 1.398; 95% CI, 1.046-1.869; P<0.05) were found to be independently associated with dose escalation. CONCLUSIONS: Patients who have urgency urinary incontinence and high total OABSS have a tendency for dose escalation of solifenacin.

Maintenance of the Therapeutic Effect of Two High-Dosage Antimuscarinics in the Management of Overactive Bladder in Elderly Women / 대한배뇨장애요실금학회지

PURPOSE: To improve the long-term efficiency of the pharmacologic management of overactive bladder (OAB) in elderly women. METHODS: The study comprised 229 women (mean age, 66.3 years; range, 65-77 years) with urodynamically and clinically confirmed OAB. All patients received the most effective treatment regimen based on the data obtained in the initial part of the study (trospium 60 mg/day + solifenacin 40 mg/day, for 6 weeks), and positive results similar to those in the first phase were obtained. They were then divided into four groups, based on the maintenance therapy: group A (59 women), trospium (60 mg/day) + solifenacin (40 mg/day) for 1 month; group B (51 women), electrical stimulation of the detrusor muscle for 1 month; group C (63 women), laser puncture for 1 month; group D (56 women), placebo. Maintenance therapy was administered 2.5 months after completion of primary treatment. The patients' condition was monitored through the OAB questionnaire for 1 year and by urodynamic examination at months 6 and 7 from the start of the study. RESULTS: In group A, the clinical and urodynamic results achieved after the initial + main treatment phase (two high-dosage antimuscarinics of different generations, trospium and solifenacin, for a total of 2.5 months) were maintained for at least 7 months. Electrical stimulation of the urinary bladder as a method of maintenance therapy proved to be less effective. In groups C and D, deterioration in results was observed at 6-8 months, which led us to conclude that laser puncture was an inefficient method of maintenance therapy in elderly women with OAB. CONCLUSIONS: Maintenance treatment of OAB in elderly women with a combination of high-dosage antimuscarinics is an effective method for reducing the risk of recurrence of the disease.

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.

Bladder Wall Thickness is Associated with Responsiveness of Storage Symptoms to Alpha-Blockers in Men with Lower Urinary Tract Symptoms

PURPOSE: Bladder wall thickness (BWT) is reported to be related to detrusor overactivity and bladder outlet obstruction. We investigated the relationship between BWT and the responsiveness of storage symptoms to alpha-blockers in men with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 74 patients with LUTS were enrolled. International Prostate Symptom Score, uroflowmetry with post-void residual urine volume, and transrectal ultrasonography (TRUS) were investigated. BWT was measured by performing TRUS at the midsagittal plane view, and the average value of BWT at the anterior, dome, and trigone areas was used. After 4 weeks of alpha-blocker medication, patients were reevaluated and divided into two groups. The responder group consisted of patients who reported improvement in the storage symptom subscore of 2 points or more; the non-responder group consisted of patients who reported improvement of less than 2 points. Clinical parameters including BWT were compared between the two groups. RESULTS: A total of 52 patients were followed. BWT was positively correlated with intravesical prostate protrusion (IPP) (9.26+/-4.99, standardized beta=0.393, p=0.002) and storage symptom subscore (0.35+/-0.43, standardized beta=0.458, p=0.002). Compared with that in the responder group, BWT was thicker in the non-responder group, and improvement in the storage symptom score was correlated with BWT (0.58+/-0.09 cm vs. 0.65+/-0.11 cm, p=0.018) and prostate volume (27.08+/-16.26 ml vs. 36.44+/-10.1 ml, p=0.018). CONCLUSIONS: BWT was correlated with IPP, the storage symptom subscore, and the responsiveness of storage symptoms to alpha-blockers in LUTS/benign prostatic hyperplasia (BPH) patients. As BWT increased, the responsiveness of storage symptoms to alpha-blocker decreased in LUTS/BPH patients.

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.

Application of solifenacin for female overactive bladder failed in tolterodine treatment / 中华泌尿外科杂志

ObjectiveTo investigate the clinical efficacy and safety of solifenacin for female overactive bladder (OAB) who failed in toherodine treatment. MethodsFrom Jan 2010 to Oct 2010,48 cases of female OAB were treated with 5 mg/d solifenacin for 4 weeks after the failure of tolterodine treatment.The improvement of the perception of bladder condition as well as the mean numbers of day-time micturition,urgency episodes,urge incontinence episode per day,nocturia and pads usage were used as objective indexes for the evaluation of therapeutic effect. ResultsAfter 4-week solifenacin treatment,the mean numbers of day-time micturition,urgency episodes,urge incontinence episode per day,nocturia and pads usage were respectively decreased from the baselines ( 8.7 ± 1.5),(3.4 ± 2.1 ),( 2.4 ± 1.8 ),(2.1 ± 1.8 ) and (2.2 ±1.6) to be (7.2 ±2.5),(2.0 ±1.8),(1.5 ±1.2),(1.2 ±0.8) and (1.4 ±0.8).The perception of bladder condition was improved in 42 cases.The withdrawal from the treatment was seen in 3 cases due to headache and dry mouth.No severe adverse event was found in the rest 45 patients. Conclusion Solifenacin might be an effective and safe alternative agent in the treatment of female OAB who failed in tolterodine treatment.