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PubMed2001

Tolterodine: a review of its use in the treatment of overactive bladder.

UNLABELLED: Tolterodine is a competitive muscarinic receptor antagonist that shows in vivo selectivity for the bladder over the salivary glands compared with oxybutinin. Results of randomised double-blind placebo-controlled studies indicate that tolterodine 4 mg/day (administered as immediate-release tablets 2mg twice daily or extended-release capsules 4mg daily) is superior to placebo in improving micturition diary variables in patients with overactive bladder. Moreover, tolterodine 2mg twice daily is as effective as oxybutynin 5mg 3 times daily. Maximum treatment effects with both drugs occurred after 5 to 8 weeks of treatment and improvements were maintained during long term treatment for up to 24 months. In a pooled analysis of four 12-week studies, equivalent and significant reductions in micturition frequency (-2.3 and -2.0 vs -1.4, p < 0.001) and the incidence of urge incontinence episodes (-1.6 and -1.8 vs -1.1, p < 0.05) were reported for tolterodine 2mg twice daily and oxybutynin 5mg 3 times daily compared with placebo. Functional bladder capacity was also significantly increased. Improvements in patient perceptions of their urgency symptoms and of problems caused by their bladder condition were significantly greater during treatment with tolterodine than with placebo. Tolterodine was generally well tolerated in clinical trials of up to 24 months' duration. Dry mouth was the most frequent adverse event. The incidence (40 vs 78%, p < 0.001) and intensity of this event was lower with tolterodine 2mg twice daily than oxybutynin 5mg 3 times daily. Additionally, a 23% lower incidence of dry mouth was reported with once daily extended-release tolterodine capsules than with twice daily immediate-release tablets (p < 0.02). The incidence of adverse CNS events with tolterodine was low and similar to that of placebo. Tolterodine was well tolerated in elderly patients and no serious tolerability concerns were identified. CONCLUSION: Tolterodine is the first antimuscarinic agent to specifically developed for the treatment of overactive bladder. The functional selectivity of tolterodine for the bladder translates into good efficacy and tolerability in patients, including the elderly, with overactive bladder. Tolterodine is as effective as oxybutynin in improving micturition diary variables but is associated with a significantly lower incidence and intensity of dry mouth. This favourable tolerability profile, together with sustained clinical efficacy during long term treatment, places tolterodine as valuable treatment for the symptoms of overactive bladder.

Benzhydryl Compounds↗

PubMed2006

Trospium chloride: Distinct among other anticholinergic agents available for the treatment of overactive bladder.

Trospium chloride is an antimuscarinic agent indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. It has been available in Europe for over 20 years and in the United States since May 2004. Trospium has pharmacologic properties that are distinct from other antimuscarinic agents. The safety and efficacy profiles of trospium and how its pharmacologic properties contribute to these profiles form the basis for this review. The low incidence of adverse event of central nervous system effects and the efficacy parameters of "urgency" and "onset of action" are highlighted.

Benzilates↗

PubMed2006

Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder.

1. The effectiveness of antimuscarinic agents in the treatment of the overactive bladder (OAB) syndrome is thought to arise through blockade of bladder muscarinic receptors located on detrusor smooth muscle cells, as well as on nondetrusor structures. 2. Muscarinic M3 receptors are primarily responsible for detrusor contraction. Limited evidence exists to suggest that M2 receptors may have a role in mediating indirect contractions and/or inhibition of detrusor relaxation. In addition, there is evidence that muscarinic receptors located in the urothelium/suburothelium and on afferent nerves may contribute to the pathophysiology of OAB. Blockade of these receptors may also contribute to the clinical efficacy of antimuscarinic agents. 3. Although the role of muscarinic receptors in the bladder, other than M3 receptors, remains unclear, their role in other body systems is becoming increasingly well established, with emerging evidence supporting a wide range of diverse functions. Blockade of these functions by muscarinic receptor antagonists can lead to similarly diverse adverse effects associated with antimuscarinic treatment, with the range of effects observed varying according to the different receptor subtypes affected. 4. This review explores the evolving understanding of muscarinic receptor functions throughout the body, with particular focus on the bladder, gastrointestinal tract, eye, heart, brain and salivary glands, and the implications for drugs used to treat OAB. The key factors that might determine the ideal antimuscarinic drug for treatment of OAB are also discussed. Further research is needed to show whether the M3 selective receptor antagonists have any advantage over less selective drugs, in leading to fewer adverse events.

Animals↗

PubMed2007

Redefining response in overactive bladder syndrome.

OBJECTIVE: To evaluate three potential definitions of treatment response in overactive bladder (OAB) syndrome, based on the International Continence Society (ICS) definition of OAB, using pooled data from two large clinical trials of the antimuscarinic agent solifenacin succinate. PATIENTS AND METHODS: As the ICS definition of OAB does not rely on urodynamic observations for a diagnosis, the use of composite endpoints, such as in the definitions examined here, might provide a more relevant measure of patient benefits. Each definition was tested to assess the impact of pharmacotherapy, comparing treatment response rates based on composite endpoints. Responder definitions were validated based on the impact on quality of life (QoL). Pooled data from two 12-week multinational, multicentre, double-blind randomized studies of solifenacin, a once-daily oral antimuscarinic for treating OAB symptoms, were used for this analysis. Based on the symptom data from these studies (episodes of urgency, incontinence, nocturia and voiding frequency per 24 h), response was defined as being: (i) a reduction by half or more in all baseline symptoms; (ii) a reduction by half or more in urgency and at least one other symptom; or (iii) resolution of urgency episodes and at least one other symptom. Health-related QoL changes were recorded using the King's Health Questionnaire (KHQ). RESULTS: Solifenacin at 5 mg or 10 mg once daily resulted in significantly higher response rates than with placebo, irrespective of the definition of a responder (P < or = 0.001). When assessing the most challenging definition of response (resolution of urgency and at least one other symptom), solifenacin at 5 mg and 10 mg resulted in 20% and 25% of patients, respectively, meeting the response criteria, vs 12% of placebo-treated patients (P < or = 0.001 for both solifenacin doses). For all three definitions of response, responders showed greater improvements in all KHQ domains than did nonresponders, and the differences were statistically significant. CONCLUSIONS: The two strictest definitions of response (halving or more in all baseline symptoms or resolution of urgency and more than one other symptom) appeared to capture QoL changes most effectively. Establishing the most appropriate definition to assess treatment-related changes in OAB will require further investigation, but it is clear from this analysis that composite clinical endpoints, based on the ICS definition of OAB, are a valid approach for assessing the effect of treatments for OAB.

Double-Blind Method↗

PubMed2003

The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women.

OBJECTIVES: To investigate the role of diet and other lifestyle factors in the incidence of overactive bladder and stress incontinence in women. Studies have suggested relationships between different aspects of lifestyle and symptoms of urinary incontinence, but there is a lack of firm evidence about their role in its cause. SUBJECTS AND METHODS: A random sample of women aged >or= 40 years living at home took part in a prospective cohort study. Baseline data on urinary symptoms, diet and lifestyle were collected from 7046 women using a postal survey and food-frequency questionnaire. Follow-up data on urinary symptoms were collected from 6424 of the women in a postal survey 1 year later. Logistic regression was used to investigate the association of food and drink consumption and other lifestyle factors with the incidence of overactive bladder and stress incontinence. RESULTS: In the multivariate model for the onset of an overactive bladder, there were significantly increased risks associated with obesity, smoking and consumption of carbonated drinks, and reduced risks with higher consumption of vegetables, bread and chicken. Obesity and carbonated drinks were also significant risk factors for the onset of stress incontinence, while consumption of bread was associated with a reduced risk. CONCLUSIONS: Causal associations with obesity, smoking and carbonated drinks are confirmed for bladder disorders associated with incontinence, and additional associations with diet are suggested. Behavioural modification of lifestyle may be important for preventing and treating these disorders.

Adult↗

PubMed2001

Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial.

PURPOSE: We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Ireland. MATERIALS AND METHODS: In a randomized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder (a urinary frequency of 8 or more voids per 24 hours with urgency and/or urge incontinence, that is 1 or more urge incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg. tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily, increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessments. RESULTS: Patients treated with tolterodine had significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6% versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin caused a significant decrease (p = 0.0001) in the mean number of voids per 24 hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment. CONCLUSIONS: Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability. The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition.

Aged↗

PubMed2003

Estimated economic costs of overactive bladder in the United States.

OBJECTIVES: To estimate the economic costs of overactive bladder (OAB), including community and nursing home residents, and to compare the costs in male versus female and older versus younger populations. METHODS: The National Overactive Bladder Evaluation Program included a representative telephone survey of 5204 community-dwelling adults 18 years and older in the United States and a follow-up postal survey of all individuals with OAB identified and age and sex-matched controls. The postal survey asked respondents about bladder symptoms, self-care use, treatment use, work loss, and OAB-related health consequences. Survey data estimates were combined with year 2000 average cost data to calculate the cost of OAB in the community. Institutional costs were estimated from the costs of urinary incontinence in nursing homes, limited to only those with urge incontinence or mixed incontinence (urge and stress). RESULTS: The estimated total economic cost of OAB was 12.02 billion dollars in 2000, with 9.17 and 2.85 billion dollars incurred in the community and institutions, respectively. Community female and male OAB costs totaled 7.37 and 1.79 billion dollars, respectively. The estimated total cost was sensitive to the estimated prevalence of OAB; therefore, we calculated the average cost per community-dwelling person with OAB, which was 267 dollars per year. CONCLUSIONS: By quantifying the total economic costs of OAB, this study-the first obtained from national survey data-provides an important perspective of this condition in society. The conservative estimates of the total cost of OAB were comparable to those of osteoporosis and gynecologic and breast cancer. Although this provides information on the direct and indirect costs of OAB, quality-of-life issues must be taken into account to gain a better understanding of this condition.

Adolescent↗

PubMed2002

Surgical management of overactive bladder.

The majority of patients with overactive bladder (OAB) can be managed with office-based techniques. When medical therapy fails as treatment for OAB, surgical intervention ranging from electric stimulation administered in the office to extensive procedures, such as augmentation or urinary diversion, may be needed. Any surgical intervention should be tailored to the patient with consideration of the degree of his or her discomfort, underlying pathology, general health, and obviously, the patient's own motivation.

Electric Stimulation Therapy↗

PubMed2006

Using anticholinergics to treat overactive bladder: the issue of treatment tolerability.

Overactive bladder (OAB) is a chronic syndrome with debilitating symptoms that negatively affect health-related quality of life. Although anticholinergic agents have been first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Anticholinergic agents prevent involuntary contractions of the bladder detrusor muscle by preventing acetylcholine from binding to the M2 and M3 muscarinic receptor subtypes. Anticholinergics are not tissue specific, and their use for treatment of OAB has been associated with side effects such as dry mouth, constipation, and blurred vision. Recent studies with extended-release formulations and newly developed receptor subtype-specific anticholinergic agents demonstrate that side effects are typically mild to moderate and generally tolerable, seldom leading to patient withdrawal. By incorporating patient-initiated dose adjustment into the protocol, the primary care physician can effectively manage adverse events associated with OAB without compromising efficacy. Recent dose-adjustment data with extended-release oxybutynin suggest that, given some control in the process, patients are willing to tolerate certain side effects in exchange for symptom relief.

Benzhydryl Compounds↗

PubMed2006

Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis.

BACKGROUND: Overactive bladder (OAB) syndrome is characterized by urinary frequency and urgency with or without urge incontinence, and often accompanied by nocturia. The prevalence of OAB increases with aging; it is a particularly common condition among the elderly, affecting at least 25% of people aged > or = 65 years. OBJECTIVE: The goal of this study was to assess the efficacy and tolerability of solifenacin 5 and 10 mg once daily for treating elderly subjects with OAB. METHODS: This was a retrospective analysis of pooled data from 4 studies. Data were analyzed from elderly subjects (aged > or = 65 years) with OAB who were treated with solifenacin in four 12-week, double-blind, Phase III, international, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled studies and from elderly subjects who received solifenacin in a 40-week, open-label, flexible-dose extension trial that enrolled subjects who completed 2 of the double-blind studies. Micturition data were collected from diaries completed during the 3 days before each study visit. Efficacy end points included mean change from baseline for the number of incontinence episodes/24 hours, urgency episodes/24 hours, number of micturitions/24 hours, and volume voided/micturition. The proportion of subjects who became continent or had no urgency episodes at end point was also evaluated. RESULTS: The mean age of the subjects in the 12-week, double-blind studies (N = 1045; 781 women, 264 men) was 71.9 years; mean age in the 40-week extension trial (N = 509; 359 women, 150 men) was 71.2 years. The majority of subjects (74.7% in the 12-week, double-blind studies and 70.5% in the 40-week extension trial) were female, and >90% of the elderly subjects were white. The duration of OAB ranged from 0 to 66 months, and 43.7% had received previous medical therapy for OAB. The completion rate for elderly subjects was 85.5% for the 12-week, double-blind studies and 80.0% for the 40-week extension trial. Efficacy end points at week 12 of double-blind treatment demonstrated statistically significant improvements in the symptoms of OAB with solifenacin compared with placebo. Mean (SE) changes in number of incontinence episodes/24 hours were -1.5 (0.17) for the 5-mg dose and -1.9 (0.14) for the 10-mg dose compared with -1.0 (0.14) for placebo (P = 0.013 for the 5-mg dose and P < 0.001 for the 10-mg dose, vs placebo); mean (SE) changes in the number of urgency episodes/24 hours were -3.2 (0.27) for the 5-mg dose and -3.2 (0.19) for the 10-mg dose compared with -1.6 (0.18) for placebo (P < 0.001 for both doses vs placebo); mean (SE) changes in the number of micturitions/24 hours were -2.0 (0.17) for the 5-mg dose and -2.5 (0.13) for the 10-mg dose compared with -1.1 (0.13) for placebo (P < 0.001 for both doses vs placebo); mean (SE) changes in the volume voided/micturition were 30.2 (3.24) mL for the 5-mg dose and 46.2 (2.55) mL for the 10-mg dose, compared with 9.1 (2.39) mL for placebo (P < 0.001 for both doses vs placebo). The proportion of subjects with restoration of continence was 49.1% and 47.3% of the 5- and 10-mg treatment groups, respectively, compared with 28.9% of the placebo group (P < 0.001 for both doses vs placebo). The proportion of subjects with resolution of urgency was 34.6% and 24.9% for the 5- and 10-mg treatment groups, respectively, compared with 16.9% of the placebo group (P < 0.001 for the 5-mg dose and P < 0.01 for the 10-mg dose). Improvements in incontinence, urgency, and micturitions were maintained during the 40-week extension trial. The most common adverse events in both the double-blind and extension trials were dry mouth, constipation, and urinary tract infection. Most adverse events were mild to moderate in nature and did not result in treatment discontinuation. CONCLUSIONS: In these pooled analyses, solifenacin 5 and 10 mg once daily were efficacious and well tolerated in the treatment of these elderly subjects with OAB. Solifenacin therapy was also associated with a high level of persistence in a 40-week extension trial.

Aged↗

PubMed2004

Defining overactive bladder: epidemiology and burden of disease.

Overactive bladder (OAB) is a common, disabling condition associated with considerable negative impact on quality of life, quality of sleep, and mental health. The age-specific prevalence of OAB is similar among men and women. Urge incontinence affects only a portion of the OAB population: 33% of patients have OAB with urge incontinence ("OAB wet"), while 66% have OAB without urge incontinence ("OAB dry"). The symptoms of OAB can affect social, psychological, occupational, domestic, physical, and sexual aspects of life. OAB can also lead to depression and low self-esteem. The shift away from urodynamic observation (essential in the identification of OAB) reflects increased emphasis on the symptom-specific nature of this common disorder. The overall costs of OAB to society are in the billions. Yet the condition often goes unrecognized, largely because of the reluctance of those with OAB to seek medical attention.

Cost of Illness↗

PubMed2001

Factors associated with clinical assessment of overactive bladder and selection of treatment.

BACKGROUND: Overactive bladder (OAB) affects >17 million individuals in the United States, but the symptoms of OAB are frequently underreported by patients and therefore untreated by physicians. OBJECTIVE: The purpose of this observational study was to investigate the demographic and clinical factors associated with the decision to treat OAB pharmacologically and identify factors associated with physicians' assessment of symptom severity. METHODS: We studied 31 physicians treating 217 patients with OAB and collected data on patient demographic characteristics, OAB symptoms, previous management strategies, physicians' assessments of OAB severity, and treatment prescribed. Stepwise logistic regression was used to identify factors associated with selecting pharmacologic treatment and with physician assessment of severity of OAB symptoms. RESULTS: The mean age of the patients was 61.3 years; approximately 82% were female, and approximately 73% were white. Participants with urinary incontinence were significantly (P < 0.001) more likely to be treated with medication than were those with only symptoms of nocturia or urinary frequency. Other significant factors associated with pharmacologic treatment were being white (odds ratio [OR], 9.5; 95% CI, 2.9-30.8); being black (OR, 5.9; 95% CI, 1.2-29.7); physician's clinical assessment of OAB as moderate (OR, 3.5; 95% CI, 1.5-8.2) or severe (OR, 3.8; 95% CI, 1.1-13.7); previous use of medication (OR, 2.9; 95% CI, 1.1-8.1); and number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.0-1.5). Factors associated with physician assessment of OAB severity included distress due to OAB symptoms (OR, 2.1; 95% CI, 1.3-3.2), number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.1-1.4), and use of previous treatment(s) (OR, 0.4; 95% CI, 0.2-0.8). CONCLUSIONS: Both demographic and clinical symptoms of OAB were associated with the decision to treat OAB with medication, whereas physicians' assessment of OAB severity was associated only with clinical symptoms. Urinary incontinence was the key symptom associated with the decision to treat patients with medication and with the assessment of OAB symptom severity.

Aged↗

PubMed2001

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

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

Cholinergic Antagonists↗

PubMed2000

Overactive bladder significantly affects quality of life.

Overactive bladder (OAB), with symptoms of frequency, urgency, and urge incontinence, substantially affects the lives of millions of people. The symptoms associated with OAB can significantly affect the social, psychological, occupational, domestic, physical, and sexual aspects of those who suffer from it. Unfortunately, many sufferers are reluctant to discuss their condition with their healthcare provider or family members. As a result, OAB remains underreported, despite increased awareness and improved diagnosis and treatment. Health-related quality of life can be measured objectively, and several instruments have been developed, validated, and used in research. Currently, there are 2 major types of quality-of-life questionnaires: generic and disease specific. Although these questionnaires have been helpful and are widely used, the goal is to establish a single questionnaire that is acceptable throughout the world for use by urologists, gynecologists, urogynecologists, geriatricians, and epidemiologists.

Adult↗

PubMed2000

Economic considerations in overactive bladder.

Many costs are associated with overactive bladder (OAB). They include direct costs, such as those associated with treatment, diagnosis, routine care, and the consequences of the disease; indirect costs of lost wages and productivity; and intangible costs associated with pain, suffering, and decreased quality of life. Quantification of all these costs is essential for establishing the total economic burden of a disease on society. Currently, the total economic burden of OAB is unknown. However, various studies have determined that the economic burden of urinary incontinence, one of the symptoms of OAB, is substantial. It is also important to establish the economic impact of various interventions for OAB. Cost-minimization, cost-outcome, cost-utility, and cost-benefit models can be used for these analyses. The most difficult aspect of evaluating the economic impact of a treatment is estimating the intangible costs.

Cost Allocation↗

PubMed2004

Stating the case for overactive bladder: a nurse practicioner's perspective.

Overactive bladder (OAB) is a widespread syndrome characterized by symptoms of urgency, with or without urge urinary incontinence, frequency of micturition, and nocturia. Urgency is a sudden, intense, difficult-to-defer desire to pass urine and must be differentiated from normal urge or desire to void that can be deferred. It is the core symptom of OAB in the International Continence Society definition. Many misconceptions surround OAB, including that it is a normal part of aging; these contribute to the barriers to OAB diagnosis. Women are more likely than men to have OAB with incontinence; these women report diminished quality of life and are more susceptible to sleep disorders, fractures, and infections. The nurse practitioner plays an important role in diagnosing OAB during examination by eliciting specific information about symptoms from patients in their care, and in determining which treatment approaches (i.e., behavioral, pharmacologic, or a combination of both) will help them achieve optimal outcomes.

Age Distribution↗

PubMed2004

Antimuscarinics for treatment of overactive bladder.

For many years, antimuscarinic drugs have been the first-line pharmacological treatment for urgency, frequency, and urge incontinence, all symptoms of the disorder termed overactive bladder. Antimuscarinic treatment is not always effective and is associated with side-effects that limit its clinical use. The clinical significance of the effects of antimuscarinic drugs has been questioned lately. In this review, the rationale for the use of these drugs in the management of overactive bladder is re-examined and the results of treatment are discussed. I conclude that these drugs are the only treatment with undisputed effectiveness in the treatment of overactive bladder. They may not be the perfect treatment for all patients with this disorder, but their value for individual patients should not be underestimated. Further clinical trials with improvement in quality of life as the primary endpoint are needed and may give a fair reflection of the clinical value of antimuscarinic drugs.

Clinical Trials as Topic↗

PubMed2002

Overactive bladder--pharmacological aspects.

The micturition reflex can be initiated by contraction or distension of detrusor smooth muscle cells, or by signals from the urothelium. It has been shown that bladder distension causes release of ATP from the urothelium, and that ATP can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, most probably the activation of afferent fibres during bladder filling involves not only ATP, but a cascade of inhibitory and stimulatory transmitters/mediators. These mechanisms may be targets for future drugs. Both in the normal and functionally disturbed bladder, muscarinic receptor stimulation produces the main part of detrusor contraction, but evidence is accumulating that in disease states, such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, interstitial cystitis, and also in the ageing bladder, a non-cholinergic activation via purinergic receptors may occur. If this component of activation is responsible not only for part of the bladder contractions, but also for the symptoms of the overactive bladder, it should be considered an important target for therapeutic interventions. Drags blocking different P2X receptor subtypes, or counteracting bladder contraction via other mechanisms, e.g. beta3-adrenoceptor stimulation, may be developed for treatment of the overactive bladder.

Adenosine Triphosphate↗