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PubMedDate not supplied

[Spasmex treatment of patients with hyperactive urinary bladder].

Overactive urinary bladder (HAUB) is encountered in 16-20% patients with various voiding disorders. Etiologically, detrusor hyperactivity can be neurogenic and idiopathic. We studied efficacy of the antimuscarine drug spasmex in patients with imperative voiding disorders and compared its efficacy and tolerance with those of driptan and detrusitol. 193 female patients with imperative voiding disorders were examined. Spasmex given in a dose of 5 mg 3 times a day for 12 weeks produced a good effect in 56 patients: increased the effective capacity of the urinary bladder, reduced the number of voidings and episodes of incontinence for a day. A 3-month course of spasmex proved highly effective as shown by the patients' subjective response and positive changes in objective evidence. Being equally effective with detrusitol and driptan, spasmex is much superior to oxibutynin in safety.

Benzhydryl Compounds↗
PubMed2000

Office evaluation of the patient with an overactive urinary bladder.

Urinary incontinence affects between 13 and 17 million men and women in the United States, with an annual cost exceeding $26 billion. Overactive urinary bladder can be both neurologic (hyperreflexia) and nonneurologic (detrusor instability). The spontaneous involuntary detrusor contractions that occur with the overactive bladder often lead to urinary incontinence. Symptoms vary from patient to patient, with urgency, increased frequency, and urinary urge incontinence being the most bothersome complaints. Multiple components and interactions of the nervous system are required for appropriate storage and evacuation function of the bladder to occur normally. Thorough history taking and physical examination along with appropriate urodynamic testing are necessary for obtaining an accurate diagnosis and treatment planning. The quality of life for many patients with overactive bladder and the resulting incontinence can be dismal. Fortunately, most of these patients can be treated successfully.

Female↗
PubMed2006

Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study.

OBJECTIVE: Estimate the prevalence of urinary incontinence (UI), overactive bladder (OAB), and other lower urinary tract symptoms (LUTS) among men and women in five countries using the 2002 International Continence Society (ICS) definitions. METHODS: This population-based, cross-sectional survey was conducted between April and December 2005 in Canada, Germany, Italy, Sweden, and the United Kingdom using computer-assisted telephone interviews. A random sample of men and women aged >/= 18 yr residing in the five countries and who were representative of the general populations in these countries was selected. Using 2002 ICS definitions, the prevalence estimates of storage, voiding, and postmicturition LUTS were calculated. Data were stratified by country, age cohort, and gender. RESULTS: A total of 19,165 individuals agreed to participate; 64.3% reported at least one LUTS. Nocturia was the most prevalent LUTS (men, 48.6%; women, 54.5%). The prevalence of storage LUTS (men, 51.3%; women, 59.2%) was greater than that for voiding (men, 25.7%; women, 19.5%) and postmicturition (men, 16.9%; women, 14.2%) symptoms combined. The overall prevalence of OAB was 11.8%; rates were similar in men and women and increased with age. OAB was more prevalent than all types of UI combined (9.4%). CONCLUSIONS: The EPIC study is the largest population-based survey to assess prevalence rates of OAB, UI, and other LUTS in five countries. To date, this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions. The results indicate that these symptoms are highly prevalent in the countries surveyed.

Adolescent↗
PubMedDate not supplied

[Temporary sacral and tibial neuromodulation in treating patients with overactive urinary bladder].

The effects of temporary sacral (S3) stimulation and posterior tibial nerve stimulation were studied in patients with the overactive urinary bladder. Unilateral temporal (10 days) electrical stimulation of the S3 sacral spinal nerve (32 patients) and posterior tibial nerve stimulation (18 patients) were used to treat this abnormality. There was a decrease in the average frequency of voiding, in the number of leakage episodes and used pads per day after both stimulations. An over 50% symptomatic improvement was achieved in 19 of the 32 patients and after temporary sacral (S3) stimulation and in 14 of the patients following posterior tibial nerve stimulation. Neuromodulation is an effective treatment in patients with the overactive bladder.

Electric Stimulation↗
PubMed1999

An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder.

Detrusor instability, or urinary incontinence, is common in elderly patients, particularly elderly women. The clinical symptoms of overactive, or unstable, urinary bladder include urge urinary incontinence, urgency, and frequency. Mixed urinary incontinence, which comprises urge urinary incontinence and stress incontinence, is manifested by increased intraabdominal pressure on coughing or sneezing. The detrusor muscle of the bladder is under the control of the parasympathetic, or muscarinic, nervous system. The drug of choice in this condition is oxybutynin chloride, which has the ability to block acetylcholine released from parasympathetic nerves in the urinary bladder, preventing contractions of the muscle and exerting a direct spasmolytic effect on the bladder. A new extended-release oral tablet formulation, OROS oxybutynin, uses osmotic pressure to deliver the drug at a controlled rate over approximately 24 hours. It resembles a conventional tablet but has a two-part core consisting of a drug layer and below it, a "push" layer containing osmotically active components, the whole surrounded by a semipermeable membrane with a laser-drilled opening in the drug side. Water in the gastrointestinal tract enters the tablet and mixes with the drug to form a suspension. The "push" layer expands and pushes the suspended drug out of the orifice and into the gastrointestinal tract for eventual absorption. Pharmacokinetic studies have indicated a slow rise in mean plasma concentration of the isomer R-oxybutynin for 4 to 6 hours after a single dose of OROS oxybutynin, followed by maintenance of steady concentrations for up to 24 hours, minimizing the fluctuations between peak and trough associated with TID dosing of 5-mg immediate-release oxybutynin tablets. Efficacy and safety studies comparing the extended-release with the immediate-release formulation of oxybutynin demonstrated equivalent efficacy in patients with overactive urinary bladder. The adverse-event profile of oxybutynin is similar to that of a typical anticholinergic agent such as atropine--dry mouth, constipation, somnolence, blurred vision, headache, and gastrointestinal pain--although in 2 clinical studies, the incidence of dry mouth was less with the extended-release formulation. Once-daily dosing with OROS oxybutynin appears to be well tolerated and effective, as well as convenient, for the treatment of overactive bladder, particularly for elderly patients using multiple medications.

Cholinergic Antagonists↗
PubMed1997

Pharmacokinetics and pharmacodynamics of tolterodine in man: a new drug for the treatment of urinary bladder overactivity.

The aim of this study was to determine the pharmacokinetics, pharmacodynamics, and safety of tolterodine following single oral and intravenous doses in healthy volunteers. A secondary aim was to identify major urinary metabolites and determine mass balance. Single oral doses of 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 mg of tolterodine (as the tartrate salt) were given to 17 healthy male volunteers. Two intravenous doses (0.64 and 1.28 mg) were administered to 8 of the volunteers and mass balance was studied after a single oral dose of 5 mg (14C)-tolterodine in 6 subjects. Tolterodine was rapidly absorbed following oral administration (time to peak serum concentration 0.9 +/- 0.4 h). The absolute bioavailability was highly variable, ranging from 10 to 70%. The volume of distribution at steady-state ranged from 0.9 to 1.6 l/kg and systemic clearance ranged from 0.23 to 0.52 l/h/kg, which resulted in a terminal half-life of 2-3 h. Tolterodine exhibited high first-pass metabolism and 2 hepatic metabolic pathways were identified: oxidation and dealkylation. Independent of route of administration, < 1% of the parent compound was excreted unchanged in urine. Five metabolites were structurally identified in urine. Following oral administration of (14C)-tolterodine, the excretion of radioactivity into urine and feces was 77 +/- 4.0% and 17 +/- 3.5%, respectively. Tolterodine decreased stimulated salivation after 3.2 mg, increased heart rate after 6.4 mg, and nearpoint of vision after 12.8 mg. Six of 8 subjects reported micturition difficulties after a dose of 12.8 mg. The lack of a direct relationship between tolterodine serum concentrations and effects on stimulated salivation suggested the presence of pharmacologically active metabolite(s).

Adult↗
PubMed2005

Loss of ryanodine receptor calcium-release channel expression associated with overactive urinary bladder smooth muscle contractions in a detrusor instability model.

OBJECTIVE: To investigate the changes in spontaneous bladder smooth muscle contractions that occur during detrusor instability (DI), and to test the possibility that altered function or expression of ryanodine receptors (RyRs) could account for the increased bladder contractions. MATERIALS AND METHODS: After 8 weeks of partial bladder outlet obstruction, DI was confirmed in female experimental rats by filling cystometry. Muscle strips were dissected from freshly isolated bladders, and isometric tension recorded in strips from DI and normal bladders. The contractions were recorded during electrical stimulation or exposure to various agents. Western blot analysis was used to determine RyR expression in DI and normal bladder muscle. RESULTS: In DI bladder muscle, spontaneous contractile activity persisted in the presence of blockers for known neurotransmitter receptors in the bladder wall. The RyR blocker ryanodine significantly increased the spontaneous contractile frequency in normal bladder strips, but failed to affect spontaneous contractions in DI muscle. Caffeine inhibited spontaneous contractile activity in both the DI and normal strips. After administering the l-type Ca(2+) channel antagonist nimodipine, the myogenic contractile activity was abolished in normal strips; in contrast, in DI strips, the amplitude of contractions was reduced but the frequency of contractions was unchanged. Western blot analysis showed that RyR expression was lower in DI muscle than in normal bladder muscle. CONCLUSION: These results provide the first characterization of a loss of regulation of spontaneous contractile activity by RyRs in DI muscle associated with a significant decrease in RyR expression. RyRs in normal detrusor muscle act as negative-feedback regulators of spontaneous contractile activity, presumably by releasing Ca(2+) that activates Ca(2+)-dependent K(+) channels to decrease contractility. This mechanism might be weakened in DI muscle, resulting in spontaneous contractile overactivity.

Animals↗
PubMed2006

Current and future trends in the management of overactive bladder.

Urinary incontinence is a common problem which increases in prevalence in association with advancing age and has a significant adverse effect upon well-being and quality of life. It is not the "benign" condition that many take it for. Overactive bladder (frequency-urgency syndrome) is the commonest bladder problem in late life, affecting up to 41% of over-75-year-old individuals, and the elderly experience more severe disease. This small series should provide the reader with a comprehensive overview of the current thinking in the assessment and management of patients with overactive bladder syndrome, explores the history of the condition and current approaches to its medical and surgical management and explores where management may change in more complex populations. The current state and future developments in pharmacological therapy are also outlined.

Aged↗
PubMed2006

The natural history of overactive bladder and stress urinary incontinence in older women in the community: a 3-year prospective cohort study.

AIMS: This is the first study designed to describe the natural history of stress urinary incontinence (SUI) and overactive bladder (OAB), using validated symptom syndrome severity scores developed for the purpose. METHODS: Two separate but related studies were involved, (i) a clinic sample (N = 2,052) from a randomised controlled trial (RCT) and (ii) a prospective cohort study (N = 12,750) with 3-year follow-up. Subjects in both studies were women aged 40 or more living in the community, approached using similar postal questionnaires. Severity scores using standardised urinary symptoms were derived for SUI and OAB from weightings obtained from logistic regression models of symptoms in relation to urodynamic diagnosis. Symptom severity scores were plotted for baseline and 3 years of follow-up to demonstrate the natural history of the main categories of SUI and OAB. RESULTS: Overactive bladder and SUI syndrome severity scores showed good criterion validity in relation to relevant clinical measures and good test-retest reliability. OAB severity increased progressively with age including a period of accelerated increase in the 60s. In contrast, SUI severity showed two age-related peaks around age 60 and again at age 80. SUI severity also showed a more fluctuating pattern from year to year compared to OAB. CONCLUSIONS: Contrasting patterns of natural history for OAB and SUI syndromes were identified consistent with differences in the patterns of related co-morbidities. Further studies are needed to confirm these findings.

Adult↗
PubMed2006

Impact of stress urinary incontinence and overactive bladder on micturition patterns and health-related quality of life.

We examined the impact of stress urinary incontinence (SUI) and overactive bladder (OAB) on micturition habits and health-related quality of life (QOL). A total of 250 Korean women were included in the study. The Medical Outcomes Study Short Form (SF-36) and the King's Health Questionnaire (KHQ) were used to assess QOL in the patient (SUI, n=158 and OAB, n=92) and control (n=70) groups. A control group was recruited at the Health Promotion Center of our hospital. Each of the dimension scores in the SF-36 represents better health, while that of the KHQ does worse health perception. On the frequency-volume charts, patients with OAB had more nighttime voids than those with SUI (P=0.001). Of the eight domains in the SF-36 questionnaire, four domains were significantly different between the control and OAB groups. Patients with SUI had a significantly lower score on one domain than the controls. Between the SUI and OAB groups, only one domain showed a significant difference. Regarding the KHQ, all domain scores in control subjects were significantly lower than those in the SUI and OAB groups. Between the SUI and OAB groups, the OAB group had higher scores on 'general health perception' and 'sleep/energy disturbances', while the scores of 'physical limitations' and 'severity measures' were higher in the SUI group. Women with OAB have a higher number of nocturic episodes than those with SUI, but the QOL is not less affected by SUI than by OAB. Furthermore, simultaneous disease-specific QOL instruments should be used in the evaluation of urinary incontinence because the generic QOL instrument is not a sensitive tool for measuring QOL in this population.

Female↗
PubMed2006

Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial.

CONTEXT: Men with overactive bladder and other lower urinary tract symptoms may not respond to monotherapy with antimuscarinic agents or alpha-receptor antagonists. OBJECTIVE: To evaluate the efficacy and safety of tolterodine extended release (ER), tamsulosin, or both in men who met research criteria for both overactive bladder and benign prostatic hyperplasia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted at 95 urology clinics in the United States involving men 40 years or older who had a total International Prostate Symptom Score of 12 or higher and, an International Prostate Symptom Score quality-of-life (QOL) item score of 3 or higher, a self-rated bladder condition of at least moderate bother, and a bladder diary documenting micturition frequency (>or=8 micturitions per 24 hours) and urgency (>or=3 episodes per 24 hours), with or without urgency urinary incontinence. Patients were recruited between November 2004 and February 2006, and the study was completed May 2006. INTERVENTIONS: Patients were randomly assigned to receive placebo (n = 222), 4 mg of tolterodine ER (n = 217), 0.4 mg of tamsulosin (n = 215), or both tolterodine ER plus tamsulosin (n = 225) for 12 weeks. MAIN OUTCOME MEASURES: Patient perception of treatment benefit, bladder diary variables, International Prostate Symptom Scores, and safety and tolerability were assessed. RESULTS: A total of 172 men (80%) receiving tolterodine ER plus tamsulosin reported treatment benefit by week 12 compared with 132 patients (62%) receiving placebo (P<.001), 146 (71%) receiving tamsulosin (P=.06 vs placebo), or 135 (65%) receiving tolterodine ER (P=.48 vs placebo). Patients receiving tolterodine ER plus tamsulosin compared with placebo experienced significant reductions in urgency urinary incontinence (-0.88 vs -0.31, P=.005), urgency episodes without incontinence (-3.33 vs -2.54, P=.03), micturitions per 24 hours (-2.54 vs -1.41, P<.001), and micturitions per night (-0.59 vs -0.39, P.02). Patients receiving tolterodine ER plus tamsulosin demonstrated significant improvements on the total International Prostate Symptom Score (-8.02 vs placebo, -6.19, P=.003) and QOL item (-1.61 vs -1.17, P=.003). All interventions were well tolerated. The incidence of acute urinary retention requiring catheterization was low (tolterodine ER plus tamsulosin, 0.4%; tolterodine ER, 0.5%; tamsulosin, 0%; and placebo, 0%). CONCLUSIONS: These results suggest that treatment with tolterodine ER plus tamsulosin for 12 weeks provides benefit for men with moderate to severe lower urinary tract symptoms including overactive bladder. Clinical Trials Registration clinicaltrials.gov Identifier: NCT00147654.

Adrenergic alpha-Antagonists↗
PubMed2006

Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence.

PURPOSE: Urge urinary incontinence is the involuntary leakage of urine commonly occurring in older adults, particularly women. Preclinical evidence suggests that urge urinary incontinence may occur due to up-regulation of tachykinin mediated bladder/spinal reflex signaling. This study tested the hypothesis that aprepitant, a neurokinin-1 receptor antagonist, may be efficacious in the treatment of urge urinary incontinence. MATERIALS AND METHODS: This was a double-blind, randomized, placebo controlled, parallel group pilot study in which postmenopausal women with a history of urge urinary incontinence or mixed incontinence (with predominantly urge urinary incontinence) were assigned to receive a 160 mg capsule of aprepitant (61) or placebo (64) once daily for 8 weeks. The primary end point was percent change from baseline in average daily micturitions assessed by a voiding diary. Secondary end points included average daily total urinary incontinence and urge urinary incontinence episodes, and urgency episodes. RESULTS: Aprepitant significantly decreased the average daily number of micturitions compared with placebo at 8 weeks. The between-group treatment difference expressed as percent change from baseline was -6.8%, 95% CI (-12.5, -1.1) (p = 0.019). The average daily number of urgency episodes was also significantly reduced compared to placebo (p = 0.049). The average daily number of urge urinary incontinence and total urinary incontinence episodes were also reduced, although the difference was not statistically significant. Aprepitant was generally well tolerated and adverse experiences were generally mild. CONCLUSIONS: Results of this initial study suggest that neurokinin-1 receptor antagonism may represent a novel therapeutic approach to treating overactive bladder syndrome.

Adult↗
PubMed2005

New pharmacological treatments for urinary incontinence and overactive bladder.

Lower urinary tract dysfunction encompasses a number of different pathologies, and affects the lives of millions of patients worldwide. Although several pharmaceutical companies have been involved in urological drug discovery over the last several years, therapeutic options remain limited. The mainstay of treatment for overactive bladder and urinary incontinence for several years has been antimuscarinic agents. While additional antimuscarinic compounds are currently undergoing clinical development, next generation compounds aimed at novel targets and mechanisms of action are in clinical and preclinical development. This review highlights new compounds and approaches under clinical investigation by various pharmaceutical companies. These novel therapeutic strategies offer the promise of expanded treatment options for patients suffering from these disorders.

Animals↗
PubMed2006

Do transsexuals have micturition disorders?

OBJECTIVE: Transsexualism occurs with an estimated prevalence of 2.4:100,000 male-to-female (MTF) and 1:100,000 female-to-male (FTM) transsexuals. As sex reassignment surgery involves surgery of the urethra and transsexuals are substituted life-long with the cross gender hormones there could possibly arise micturition disorders. Aim of the study was to determine if transsexuals have an increased risk of micturition disorders and if so which. STUDY DESIGN: Between January and July 2003 we examined 25 transsexuals whereof 18 were MTF and 7 were FTM transsexuals using King's Health Questionnaire, visual analogue scale for patient's well being, perineal and transabdominal ultrasound, urine dipstick and uroflow measurement. RESULTS: 17 out of 25 patients considered themselves very happy. In MTF transsexuals, a diverted stream, overactive bladder and stress urinary incontinence was a common problem. Prostate volume was small with 20 g and palpation did not confirm and solid or suspicious lesions. None of the patients had significant residual urine but MTF transsexuals had a reduced urinary flow. We could not detect a current urinary tract infections in any of the patients. CONCLUSION: Transsexuals have an increased risk for the development of micturition disorders including stress urinary incontinence and overactive bladder compared to age-matched control groups and should be counselled preoperatively. Reasons for the development of incontinence might be surgery including pudendal nerve damage, hormonal reasons and ageing.

Adult↗
PubMed2006

Comparison of electric stimulation and oxybutynin chloride in management of overactive bladder with special reference to urinary urgency: a randomized placebo-controlled trial.

OBJECTIVES: To compare the efficacy of electric stimulation (ES), oxybutynin, and placebo in managing the symptom complex of overactive bladder (OAB), particularly urgency. METHODS: A randomized placebo-controlled trial was conducted for 68 patients with OAB, placing emphasis on urinary urgency. The interventions for the 12-week treatment period, conducted by the physiotherapist, who was unaware of the progress and outcome, included a vaginal ES program using biphasic symmetric, pulsed current with a 10-Hz frequency, 400-micros pulse width, 10/5 duty cycle, and varying intensity; and oxybutynin (2.5 mg) or placebo three times per day. Identical preintervention and postintervention assessments included the measurement of warning time, urodynamics, voiding diaries, and King's Health Questionnaire. RESULTS: Of the 68 women who completed this study, 24 were in the ES, 23 in the oxybutynin, and 21 in the placebo group. The between-group comparison showed that significant improvements in daily voided volume, pad count, number of urgency and nocturia episodes, and the domain 2 score and total score of the King's Health Questionnaire existed between the ES and the other groups (all P < or = 0.050). The changes in warning time, maximal voided volume, number of urgency episodes, and frequency were significantly improved between oxybutynin and placebo (all P < 0.013). Additionally, a comparison of the voided volume in uroflowmetry between the ES and placebo groups revealed a greater difference after treatment (P = 0.013). The reduction rate of OAB was 58.4% for the ES, 39.1% for the oxybutynin, and 9.5% for the placebo group (P = 0.036). CONCLUSIONS: ES had the greatest subjective outcome for OAB and was the most effective of the three treatments. Oxybutynin was more effective than placebo.

Adolescent↗
PubMed2002

Prevalence of overactive bladder and urinary incontinence.

We conducted a cross-sectional study in Italy among men at least 50 years old and women at least 40 years old who consecutively visited their general practitioners. Patients were asked about the frequency of symptoms of overactive bladder and urinary incontinence. A total of 9613 men (mean age, 64.8 years; range, 50-98 years) and 13,365 women (mean age, 60.3 years; range, 40-98 years) were identified by 774 general practitioners. The frequencies of overactive bladder were 3.0% (95% confidence interval, 2.7-3.5) in men and 1.1% (95% confidence interval, 0.9-1.3) in women. The corresponding frequencies for urinary incontinence were 8.3% (95% confidence interval, 7.7-8.9) in men and 10.2% (95% confidence interval, 9.6-10.8) in women.

Adult↗
PubMed2006

The placebo effect in the pharmacologic treatment of patients with lower urinary tract symptoms.

OBJECTIVES: We reviewed placebo responses in randomised controlled trials (RCTs) for pharmacologic treatment of lower urinary tract symptoms (LUTS), including urinary incontinence (UI), overactive bladder, and benign prostatic hyperplasia. Review papers on placebo effects in non-urologic disorders were assessed to compare the magnitude of placebo responses in drugs for LUTS with those reported for other diseases. METHODS: Data were retrieved from registration trials for LUTS drugs on the Web sites of the Food and Drugs Administration and the European Medicines Agency. Reviews were retrieved from Medline using the MeSH term "placebo effect" (English language; published between 1990 and 2005). RESULTS: Placebo treatment of LUTS yields reductions in incontinence episodes (IEs) ranging from 32% to 65%, whereas prostate or UI symptom scores are reduced by 9-34%. Genuine drugs decrease IEs by 45-77% and symptom scores by 22-45%. Placebo responses are much lower when objective changes in voided volume or peak flow rate are assessed. CONCLUSIONS: The placebo effect in LUTS has a strong behavioural component as patients become aware of their voiding habits and potential risk factors. Symptom severity, treatment naivety, study duration, and interaction with health care providers may also influence it. Proper patient selection, study duration, and objective and subjective outcome measures may better separate genuine treatment effects from artefacts. Observational studies with patients representative for real-life situations and covering a sufficient period of time could allow for better understanding of RCT results and their applicability in clinical practice.

Adrenergic Antagonists↗