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[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↗

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↗

[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↗

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↗

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↗

Current and future pharmacological treatment for overactive bladder.

PURPOSE: Urinary incontinence and overactive bladder are important and common conditions that have received little general medical attention. We reviewed the magnitude and impact of these conditions, and discuss pharmacotherapy as well as new drugs under investigation. MATERIALS AND METHODS: The main emphasis of this review is pharmacological therapy for the bladder. We discuss currently available agents, drugs under development and pharmacological targets that would be suitable targets for treating overactive bladder. Drugs such as duloxetine that target not bladder smooth muscle, but rather central nervous system control of the micturition reflex are undergoing clinical trials. We also discuss intravesical therapy and alternative drug delivery methods, such as intravesical capsaicin and botulinum toxin, with special emphasis on approaches to modulate bladder afferent nerve function for preventing overactive bladder. RESULTS: There are many advantages to advanced drug delivery systems, including long-term therapeutic efficacy, decreased side effects and improved patient compliance. Future speculation such as gene therapy holds great promise for overactive bladder because it is possible to access all genitourinary organs via endoscopy and other minimally invasive techniques that are ideally suited for gene therapy. CONCLUSIONS: Traditional anticholinergic therapies are limited in their effectiveness. There is great hope for future research regarding voiding dysfunction and urinary incontinence through a focus on afferent nerve intervention for preventing overactive bladder.

Adult↗

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↗

Lower urinary tract symptoms, benign prostatic obstruction and the overactive bladder.

Lower urinary tract symptoms (LUTS), benign prostatic obstruction (BPO), and the overactive bladder have increasing prevalence with age in both men and women (with the obvious exception). The question is, are they interrelated or independently related to age? The specific issue is whether BPO causes the overactive bladder. There are two pieces of evidence that might appear to suggest such a cause and effect. First, the overactive bladder is more common in men than in women of the same age, although physiologically, men are 5-10 years older at the same biological age. Second, the overactive bladder resolves in two-thirds of individuals after surgical interventions such as transurethral prostatectomy. The symptoms suggestive of an overactive bladder are the most troublesome, even though they may not be the most prevalent. Long-term follow-up studies with repeated urodynamic investigations have shown that the incidence of the overactive bladder and its attendant symptoms increases despite there being no deterioration in outlet obstruction over follow-up periods of 10 and 20 years. These data, and others, indicate that the situation is not as straightforward as some believe. The statement that 'the overactive bladder is secondary to BPO' cannot be made, as there are too many unanswered questions and pieces of the puzzle that do not fit. The overactive bladder is undoubtedly associated with BPO, and it leads to the most troublesome LUTS in older men. Epidemiological research, coupled with urodynamic evaluation, may provide further evidence. We also need better and more relevant models (e.g. ageing animals), together with further histological and other biological data before the waters become crystal clear.

Aging↗

Efficacy of a multimodal conservative rehabilitation program for bladder control in individuals with incomplete spinal cord injury: A randomized controlled trial.

ObjectiveThe study aimed to evaluate the efficacy of a multimodal intervention on urodynamic outcomes, urinary incontinence severity, and pelvic floor muscle strength in individuals with overactive bladder after incomplete spinal cord injury.MethodsA single-blind randomized controlled trial was conducted on 74 male participants diagnosed with overactive bladder and incomplete spinal cord injury. Participants were randomly assigned to an experimental group or a control group. Treatment was conducted for 8 weeks, three sessions per week. Outcomes were assessed at baseline, post-intervention, and the 8-week follow-up.ResultsThe experimental group showed significantly greater improvements in the measured outcomes compared with the control group (P&#x2009;<&#x2009;0.001).ConclusionIncorporating a multimodal regimen demonstrated significant efficacy in enhancing bladder capacity, continence, and muscle function in individuals with overactive bladder due to incomplete spinal cord injury.Clinical trial registry (ID: NCT07008157).https://clinicaltrials.gov/study/NCT07008157?cond=Spinal%20Cord%20Injuries&intr=Multimodal%20Rehabilitation%20Program&viewType=Card&rank=1.

Humans↗

Prevalence and correlation of urinary incontinence and overactive bladder in Taiwanese women.

AIMS: We randomly sampled a community-based, healthy population to evaluate the prevalence and correlation of urinary incontinence and overactive bladder. We also assessed the influences of these conditions on quality of life and associated risk factors. METHODS: Of the 1,581 women sampled (2.92% of registered female residents aged 20 years and older), 1,253 (79.1%) women were successfully interviewed by using the Bristol Female Urinary Tract Symptoms Questionnaire (r=0.87, P<0.05) and the Questionnaire of Impact index regarding the impact on quality of life (r=0.91, P<0.05). RESULTS: A total of 53.7% of the women sampled suffered from urinary incontinence and related symptoms. The prevalence of stress urinary incontinence, overactive bladder, and mixed incontinence, mutually exclusive of each, was 18.0%, 18.6%, and 17.1%, respectively, from the patients' perceptions. Judging by the criteria of the International Continence Society, the prevalence of the above three conditions was 4.3%, 2.4%, and 1.8%, respectively. Of the women who perceived storage symptoms, 21.1% experienced frequency, 12.6% had urgency, 25.5% had nocturia, and 9.1% had urge incontinence. The occurrence of stress urinary incontinence increased with age up to 65 years old (25% in 50-65-year-old cohort), and the number of overactive bladder conditions significantly increased in the elderly women (over 65 years old, 39.3%). Approximately two thirds of the incontinent women had restricted their social activities (due to worrying about wetting or leakage and no toilet facilities available), and approximately 19% of the incontinent women had an affected sexual life. However, only 27.1% of the women with urinary incontinence and related symptoms in this study had reported seeking medical services to solve these problems. CONCLUSIONS: The prevalence of urinary incontinence and overactive bladder in Taiwanese women is similar to that of Western women.

Adult↗

The effect of urinary incontinence and overactive bladder symptoms on quality of life in young women.

OBJECTIVE: To assess the consequences that the symptoms of urinary incontinence and an overactive bladder have on the quality of life in young, community-dwelling women. SUBJECTS AND METHODS: A population-based, cross-sectional cohort study was conducted in women aged 20-45 years. Urogenital symptoms and quality of life were assessed using standardized questionnaires, e.g. the Urogenital Distress Inventory and Incontinence Impact Questionnaire. RESULTS: The prevalence of symptoms of stress incontinence (39%), urge incontinence (15%) and an overactive bladder (12%) was high in this young population. Compared with urge incontinence, the symptoms of an overactive bladder similarly reduced the quality of life, but stress incontinence did not significantly affect the quality of life. Women with symptoms of an overactive bladder were especially limited in their mobility, whereas urge incontinence was especially associated with feelings of embarrassment. Although many women reported to be bothered by their symptoms, only a minority consulted their physician for them. CONCLUSIONS: The symptoms of urinary incontinence and overactive bladder are common among young adult women and have the same detrimental effect on quality of life as urge incontinence. The reduction in mobility associated with overactive bladder symptoms may be especially distressing for these young and active women.

Adult↗

Impact of urinary incontinence and overactive bladder on quality of life.

OBJECTIVE: To assess the quality of life (QOL) of women with urinary incontinence (UI) or overactive bladder (OB) compared with women without UI. METHODS: A case-control study conducted in Italy on risk factors for UI and OB. Information on QOL were collected using the SF-12 questionnaire, validated for Italian women. RESULTS: A total of 1062 cases (258 had stress, 195 urge, 486 mixed UI and 123 OB without incontinence) and 1143 controls were interviewed. QOL, as assessed by the SF-12, was significantly impaired in cases compared with controls (p=0.0001); the mean SF-12 physical health score was 48.3 for controls, but 45.6, 42.0, 44.5 and 40.0 for cases with OB, urge, stress and mixed incontinence, respectively. Women with OB had significantly higher physical health scores than women with urge and mixed UI (p<0.005) (44.6 versus 41.7 and 41.3). Physical and mental health dimensions of cases significantly decreased with increasing severity of symptoms. CONCLUSIONS: QOL was significantly impaired in women with UI or OB compared to controls. Physical and mental functioning tended to be more impaired in patients than in controls.

Adult↗

Health-related quality of life among adults with symptoms of overactive bladder: results from a U.S. community-based survey.

OBJECTIVES: To assess, by means of a survey, the impact of the symptoms of overactive bladder (urinary frequency, urgency, and urge incontinence) on the quality of life in a community-based sample of the U.S. population. METHODS: A telephone survey was conducted in the United States among an age and sex-stratified sample of 4896 noninstitutionalized adults 18 years of age and older. From the responses to the telephone survey, a total of 483 individuals with symptoms of overactive bladder and 191 controls completed a mailed follow-up questionnaire to assess their quality of life using the Medical Outcomes Study Short-Form 20. RESULTS: After adjustment for age, sex, and the use of medical care, the greatest differences in the quality-of-life scores between the patients with incontinent overactive bladders and the controls were in the health perception (17.6 points; P <0.001) and role functioning (13.0 points; P <0.001) scales. Those with an overactive bladder with the symptoms of frequency or urgency, or both, but without incontinence, also had significantly lower scores than did the controls in mental health (P = 0.026), health perception (P = 0.01), and bodily pain (P = 0.016). CONCLUSIONS: These data indicate that individuals with an overactive bladder experience decrements in their quality of life relative to community controls. An important new finding from this study is that individuals with an overactive bladder, even without demonstrable urine loss, also have a poorer quality of life than that of controls.

Adult↗

Epidemiology, pathophysiology, and evaluation of urinary incontinence and overactive bladder.

OBJECTIVES: To present an overview of current knowledge regarding the epidemiology, pathophysiology, and evaluation of urinary incontinence (UI) with a focus on the problem of the overactive bladder. METHODS: The most recent data on the epidemiology of UI are presented. The literature on the pathophysiology of urinary urge incontinence (UUI) is reviewed, and key concepts related to patient evaluation are summarized. RESULTS: The prevalence of UI depends on the population being surveyed. The overactive bladder constitutes a substantial percentage of the overall problem, ranging from > 50% of incontinent men to only 10% to 15% of incontinent younger women. Few data are available on the incidence of the disorder or on racial/ethnic trends. Overactive bladder or urge incontinence is called detrusor hyperreflexia when a neurologic cause is known and detrusor instability when there is no neurologic abnormality. Although the pathophysiology of idiopathic instability is not well understood, some evidence suggests that this condition may result from subclinical neurologic disease or primary smooth muscle disease. Most patients with UUI can be adequately evaluated with a history, physical examination, determination of postvoid residual volume, and urinalysis. When neurologic disease or other complicating factors are present, or if initial treatment fails, sophisticated urodynamic testing is appropriate. CONCLUSIONS: Urinary incontinence is prevalent in all strata of the population, although it affects women and the elderly disproportionately. With the exception of cases in which a neurologic lesion can be demonstrated, the etiology of UUI remains elusive. A thorough history, physical examination, determination of postvoid residual, and urinalysis will be adequate to classify and treat the majority of patients.

Female↗

Vanilloid receptor ligands: hopes and realities for the future.

Neurons possessing C-fibers transmit nociceptive information into the central nervous system and participate in various reflex responses. These neurons carry receptors that bind capsaicin, recently identified as the vanilloid VR1 receptor. Excitation of these cells by capsaicin is followed by a lasting refractory state, termed desensitisation, in which the neurons fail to respond to a variety of noxious stimuli. Desensitisation to capsaicin has a clear therapeutic potential in relieving neuropathic pain and ameliorating urinary bladder overactivity, just to cite 2 important examples. Vanilloids may also be beneficial in the treatment of benign prostate hyperplasia (BPH). Since the majority of elderly patients have neuropathic pain co-existent with urinary incontinence and/or BPH, a drug that ameliorates pain and improves urinary symptoms at the same time promises to be of great clinical value in geriatric medicine. In fact, capsaicin has already been shown to have a role in the treatment of conditions that can arise in the elderly, including herpes zoster-related neuropathic pain, diabetic neuropathy, postmastectomy pain, uraemic itching associated with renal failure, and urinary incontinence. The potent VR1 agonist resiniferatoxin, now in phase II clinical trials, appears to be superior to capsaicin in terms of its tolerability profile. Recent discoveries enhance the therapeutic potential of vanilloids. The recognition that VR1 also functions as a principal receptor for protons and eicosanoids implies that VR1 antagonists may be of value in the treatment of inflammatory hyperalgesia and pain. Animal experimentation has already lent support to this assumption. The discovery of VR1-expressing cells in the brain as well as in non-neural tissues such as the kidney and urothelium places VR1 in a much broader perspective than peripheral pain perception, and is hoped to identify further, yet unsuspected, indications for vanilloid therapy. The realisation that VR1 and cannabinoid CB1 receptors have overlapping ligand recognition properties may also have far-reaching implications for vanilloid therapy. In fact, arvanil, a combined agonist of VR1 and CB1 receptors, has already proved to be a powerful analgesic drug in the mouse. From academic molecular biology laboratories to industrial drug discovery centres to the clinics, there is a steady flow of new data, forcing us to constantly revise the ways we are thinking about vanilloid receptor ligands and their hopes and realities for the future. This review covers the most promising current trends in vanilloid research with special emphasis on geriatric medicine.

Aged↗

Costs of urinary incontinence and overactive bladder in the United States: a comparative study.

OBJECTIVES: To update the cost of urinary incontinence (UI) for year 2000 and compare it with the cost of overactive bladder (OAB). METHODS: Using the cost-of-illness framework, disease epidemiologic data were combined with treatment rates, consequence probabilities, and average cost estimates. All costs reflect the costs during 2000. RESULTS: The total cost of UI and OAB was 19.5 billion dollars and 12.6 billion dollars, respectively (year 2000 dollars). With UI, 14.2 billion dollars was borne by community residents and 5.3 billion dollars by institutional residents. With OAB, 9.1 and 3.5 billion dollars, respectively, was incurred by community and institutional residents. CONCLUSIONS: OAB affected 34 million individuals compared with 17 million with UI. Despite the differences in epidemiology, the total and per-person costs of UI were higher than the OAB costs because OAB individuals without incontinent episodes incurred fewer costs, on average.

Accidental Falls↗

Effect of muscarinic antagonists on micturition pressure measured by cystometry in normal, conscious rats.

OBJECTIVES: To establish an in vivo model to screen new muscarinic antagonists for the treatment of overactive urinary bladder and to calculate the respective ID(50) values. METHODS: The conscious rat cystometry model was modified to determine a complete dose-response curve in each animal. Spontaneous micturition was induced by infusion of room-temperature saline into rat bladders at a constant rate of 12 mL/hr. Cumulative doses of muscarinic antagonists administered in the femoral vein caused dose-dependent inhibition of the urinary bladder contraction measured as the micturition pressure. In addition, the in vitro pK(B) values for atropine, PNU-200577 (DD01), tolterodine, oxybutynin, and terodiline were determined in carbachol-contracted rat bladder strips. RESULTS: The rank order of the in vivo ID(50) values were atropine (14 +/- 4 nmol/kg), PNU-200577 (22 +/- 12 nmol/kg), tolterodine (94 +/- 20 nmol/kg), oxybutynin (175 +/- 89 nmol/kg), darifenacin (236 +/- 144 nmol/kg), desethyloxybutynin (313 +/- 209 nmol/kg), propiverine (4561 +/- 2079 nmol/kg), and terodiline (18,339 +/- 5348 nmol/kg). Tolterodine and PNU-200577 caused a parallel shift of the in vitro concentration-response curve to the right and did not alter the maximal contraction. The ID(50) values correlated significantly with the in vitro rat pK(B) and human bladder pA(2) values. CONCLUSIONS: The present results suggest that the rat cystometry model can be used in in vivo screening for new muscarinic antagonists.

Animals↗