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PubMed2006

Determining the importance of change in the overactive bladder questionnaire.

PURPOSE: The overactive bladder questionnaire assesses symptom bother and health related quality of life in patients with overactive bladder. It has been shown to be reliable, valid and responsive. We established the minimally important difference of the overactive bladder questionnaire. MATERIALS AND METHODS: Post hoc analyses from 2 clinical trials were performed. Distribution based, eg effect size, and anchor based analyses using perception of treatment benefit and clinical variables were used. RESULTS: The mean age of the 2 study populations was 58.8 and 58.7 years, respectively. Patients were predominantly female (51.8% and 75.1%) and white (83.9% and 87%, respectively). Half SD of the overactive bladder questionnaire symptom bother subscale was 9.1 to 9.3, and half SD of the overactive bladder questionnaire health related quality of life subscales (coping, concern, sleep and social interaction) was 9.8 to 13.2. Questionnaire subscales had moderate to large effect sizes with the largest effect sizes for symptom bother (-0.85 to -1.09). Anchor based analyses showed that significantly greater change scores were associated with greater patient perceived treatment benefit and satisfaction. The difference between change scores in patients perceiving no and little benefit was 7.4 to 16.5 for all questionnaire scales except social interaction with the majority greater than 10 points. Greater change scores were consistently associated with greater improvements in micturition diary variables. CONCLUSIONS: Multiple methodologies provide strong justification for the recommendation of a 10-point minimally important difference for all overactive bladder questionnaire subscales. This minimally important difference may be conservative for some subscales, although a uniform minimally important difference is recommended to facilitate interpretation of the overactive bladder questionnaire.

Female↗

PubMed2003

Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo.

Bladder overactivity associated with outflow obstruction is a common human condition recapitulated in the female rat by narrowing the diameter of the urethra. The goal of these studies was to evaluate the role of intercellular communication through connexin43 (Cx43)-derived gap junction channels to bladder overactivity following partial urethral outflow obstruction of 3-day to 6-wk duration. Cx43 mRNA and protein expression were barely detectable by Northern or Western blots, respectively, in the detrusor layer of normal bladders, but bands were found with both techniques after 6 wk of obstruction. Linear regression analysis of the RT-PCR data revealed a statistically significant positive correlation between the duration of obstruction (again, ranging from 3-day to 6-wk duration) and Cx43 mRNA transcript levels, such that after 6 wk of obstruction, Cx43 transcript levels were approximately 15-fold greater than initial control values. When taking into account the approximately fivefold increase in bladder weight over this same time frame, the absolute amount of Cx43 mRNA in the bladder apparently increased by approximately 75-fold. In that regard, as anticipated, and consistent with previous observations, 6 wk of obstruction was also associated with a significant increase in spontaneous bladder contractions between micturitions. The amplitude of these contractions was significantly reduced by heptanol given intravesically. Furthermore, carbachol-precontracted bladder strips from obstructed animals were more sensitive to heptanol-induced relaxation (100 microM) than their unobstructed counterparts (n = 6; P < 0.01). When bladder strips were equivalently precontracted via electrical field stimulation (EFS; 20 Hz), similar heptanol-induced relaxation responses were observed. However, the tetrodotoxin-resistant portion of the EFS-induced contraction was greater in the obstructed than in the unobstructed animals, and this portion of the contractile response was more sensitive to heptanol-induced relaxation in obstructed than unobstructed bladders (n = 7; P < 0.01). Taken together, these observations indicate that partial outlet obstruction produces an overactive bladder that may be more dependent on intercellular communication through gap junctions for modulation of contractile responses than its normal counterpart.

Animals↗

PubMed2005

Urodynamic properties and neurotransmitter dependence of urinary bladder contractility in the BK channel deletion model of overactive bladder.

Overactive bladder and incontinence are major medical issues, which lack effective therapy. Previously, we showed (Meredith AL, Thornloe KS, Werner ME, Nelson MT, and Aldrich RW. J Biol Chem 279: 36746-36752, 2004) that the gene mSlo1 encodes large-conductance Ca2+-activated K+ (BK) channels of urinary bladder smooth muscle (UBSM) and that ablation of mSlo1 leads to enhanced myogenic and nerve-mediated contractility and increased urination frequency. Here, we examine the in vivo urodynamic consequences and neurotransmitter dependence in the absence of the BK channel. The sensitivity of contractility to nerve stimulation was greatly enhanced in UBSM strips from Slo-/- mice. The stimulation frequency required to obtain a 50% maximal contraction was 8.3 +/- 0.9 and 19.1 +/- 1.8 Hz in Slo-/- and Slo+/+ mice, respectively. This enhancement is at least partially due to alterations in UBSM excitability, as muscarinic-induced Slo-/- contractility is elevated in the absence of neuronal activity. Muscarinic-induced Slo-/- contractility was mimicked by blocking BK channels with iberiotoxin (IBTX) in Slo+/+ strips, whereas IBTX had no effect on Slo-/- strips. IBTX also enhanced purinergic contractions of Slo+/+ UBSM but was without effect on purinergic contractions of Slo-/- strips. In vivo bladder pressure and urine output measurements (cystometry) were performed on conscious, freely moving mice. Slo-/- mice exhibited increased bladder pressures, pronounced pressure oscillations, and urine dripping. Our results indicate that the BK channel in UBSM has a very significant role in urinary function and dysfunction and as such likely represents an important therapeutic target.

Animals↗

PubMed2006

How many uncomplicated male and female overactive bladder patients reveal detrusor overactivity during urodynamic study?

OBJECTIVE: We retrospectively evaluated the incidence of detrusor overactivity (DO) in uncomplicated overactive bladder syndrome (OAB) patients. METHODS: From December 1993 to October 2003, 139 adult patients were referred to an urodynamic clinic for urodynamic evaluation of frequency and/or urinary incontinence. Of these, 50 patients (12 males and 38 females) with urgency, without any overt pathological conditions, were retrospectively evaluated in regard to patient age, storage symptoms, urodynamic parameters, and the presence or absence of DO (DO patients or no DO patients, respectively). RESULTS: The overall incidence of DO was 75% (nine of 12 patients) and 36.8% (14 of 38 patients) in male and female patients, respectively. Two of nine male DO patients and five of 14 female DO patients revealed DO after provocative maneuvers. In male patients, all DO patients were OAB wet. In female patients, 13 of 14 DO patients were OAB wet (92.9%), whereas 17 of 24 no DO patients were also OAB wet (70.8%). Compared with no DO patients, female DO patients revealed statistically significant lower maximum cystometric capacity (P = 0.0139) and lower vesical compliance (P = 0.0002). Although aged 60 years or more was associated with DO in univariate analysis in female patients, any symptoms, even incontinence, were not associated with DO in both sexes. CONCLUSION: It is supposed that, in contrast to male OAB, DO might not be a major underlying cause of uncomplicated female OAB.

Aged↗

PubMedDate not supplied

Gabapentin treatment of neurogenic overactive bladder.

OBJECTIVE: Detrusor overactivity is a well-recognized and distressing medical condition affecting both men and women, with a significant prevalence in the population and with a higher incidence rate in people older than 70 years. This pathological condition is characterized by irritative symptoms: urinary urgency, with or without incontinence, and urinary frequency, often seriously compromising the quality of life of the people who have it. The complaint of these symptoms is defined by the International Continence Society (www.continet.org) as "overactive bladder." Many neurological patients experience irritative symptoms of the lower urinary tract related to their disease, and this condition drastically limits their social life. Various drugs have been introduced in therapy protocols to treat neurogenic detrusor overactivity; however, in many cases, the outcomes of these treatments have proven to be unsatisfactory. This fact is probably related to the incomplete understanding of the pathophysiological aspects of detrusor overactivity. Recent studies suggest the possible role in the detrusor overactivity pathogenesis of bladder receptors, afferent pathways, and spinal cord interneurons; consequently, the modulation of bladder receptor and/or spinal cord centers activity has been proposed as a possible approach to control involuntary detrusor contractions, using drugs capable of acting on bladder afferent pathways. The aim of this study was to evaluate the efficacy of gabapentin, an anticonvulsive agent used by neurologists in the treatment of epilepsy and neurogenic pain, in the treatment of detrusor overactivity of neurogenic origin. METHODS: Sixteen patients affected by neurogenic overactive bladder were enrolled in the study. The clinical outcomes were assessed by symptomatic score evaluations, voiding diary, and urodynamic test before and after 31 days of gabapentin treatment. RESULTS: The preliminary results showed significant modifications of urodynamic indexes, particularly of the detrusor overactivity, whereas the symptomatic score evaluation and the voiding diary data demonstrated a significant lowering of the irritative symptoms. Furthermore, we did not record significant adverse effects and no patient interrupted the drug treatment. CONCLUSIONS: These data support the rationale that detrusor overactivity may be controlled by modulating the afferent input from the bladder and the excitability of the sacral reflex center and suggest a novel method to treat overactive bladder patients.

Aged↗

PubMed2006

Evaluation and management of refractory overactive bladder.

The refractory overactive bladder patient is a complex new entity for the urologic community. We present the most current review of this difficult subject matter with an emphasis on evaluation and new treatment options such as sacral neuromodulation and botulinum toxin injection. It is hoped that in this new era of medical innovation, extirpation and reconstruction of the bladder will become historic in nature and refractory therapy can be transitioned to the office and outpatient operation rooms.

Female↗

PubMed2006

The bladder epithelium and overactive bladder: what we know.

Although the urothelium has been traditionally thought of as a passive barrier between urine and detrusor muscle, new studies have shown that the urothelium is a highly specialized structure involved in antigen presentation, micturition reflex, metabolic secretion, inflammatory regulation, and sensory afferent functioning. Data from several laboratories have shown that the urothelium can respond to thermal, mechanical, and chemical stimuli. The earlier findings (activation of urothelial transient receptor potential channel vanilloid 1 producing the second messenger nitric oxide, which in turn triggers suburothelial sensory nerves) demonstrate how the urothelium acts as a transducer, releasing chemicals that target adjacent bladder cells and sensory neurons. We now know that bladder urothelium acts also as a transducer whereby afferent neurons, via urothelial mechanoafferent transduction, are involved in the micturition process and the pathogenesis of bladder disorders. This paper highlights the important role that the urothelium has in bladder pathophysiology.

Humans↗

PubMed2002

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↗

PubMed1997

The overactive bladder: pharmacologic basis of drug treatment.

OBJECTIVES: To provide an overview of the basis for drug treatment of the overactive bladder. METHODS: Published information is evaluated. RESULTS: The causes of bladder overactivity are not known, but theoretically, increased afferent activity, decreased inhibitory control in the central nervous system (CNS) or peripheral ganglia, and increased sensitivity of the detrusor to efferent stimulation may be involved. Several CNS transmitters can modulate voiding, but few useful drugs with a defined CNS site of action have been developed. Drugs that stimulate gamma-aminobutyric acid receptors are used clinically. Potentially, drugs affecting opioid, 5-hydroxytryptamine, norepinephrine, dopamine, and glutamatergic receptors and mechanisms can be developed, but a selective action on the lower urinary tract may be difficult to obtain. Traditionally, drugs used for treatment of bladder overactivity have had a peripheral site of action, mainly efferent neurotransmission or the detrusor itself. Antimuscarinic drugs, beta-adrenoceptor agonists, alpha-adrenoceptor antagonists, drugs affecting membrane channels, prostaglandin synthetase inhibitors, and several other agents have been used with limited success. New information on the alpha-adrenoceptor and muscarinic receptor subtypes in the human detrusor has emerged and may be the basis for the development of new compounds with effects on bladder overactivity. Decreasing afferent activity seems an attractive therapeutic approach, and drugs affecting afferent nerves by causing release of tachykinins, such as capsaicin and analogs, as well as agents blocking tachykinin receptors, may be of therapeutic interest. CONCLUSIONS: New drugs, specifically designed for the treatment of bladder overactivity, are desirable.

Central Nervous System↗

PubMed2002

Prevalence and burden of overactive bladder in the United States.

CONTEXT: the National Overactive BLadder Evaluation (NOBLE) Program was initiated to better understand the prevalence and burden of overactive bladder in a broad spectrum of the United States population. OBJECTIVE: to estimate the prevalence of overactive bladder with and without urge incontinence in the US, assess variation in prevalence by sex and other factors, and measure individual burden. DESIGN: US national telephone survey using a clinically validated interview and a follow-up nested study comparing overactive bladder cases to sex- and age-matched controls. SETTING: noninstitutionalized US adult population. PARTICIPANTS: a sample of 5,204 adults >/=18 years of age and representative of the US population by sex, age, and geographical region. MAIN OUTCOME MEASURES: prevalence of overactive bladder with and without urge incontinence and risk factors for overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and MOS sleep scores were used to assess impact. RESULTS: the overall prevalence of overactive bladder was similar between men (16.0%) and women (16.9%), but sex-specific prevalence differed substantially by severity of symptoms. In women, prevalence of urge incontinence increased with age from 2.0% to 19% with a marked increase after 44 years of age, and in men, increased with age from 0.3% to 8.9% with a marked increase after 64 years of age. Across all age groups, overactive bladder without urge incontinence was more common in men than in women. Overactive bladder with and without urge incontinence was associated with clinically and significantly lower SF-36 quality-of-life scores, higher CES-D depression scores, and poorer quality of sleep than matched controls. CONCLUSIONS: the NOBLE studies do not support the commonly held notion that women are considerably more likely than men to have urgency-related bladder control problems. The overall prevalence of overactive bladder does not differ by sex; however, the severity and nature of symptom expression does differ. Sex-specific anatomic differences may increase the probability that overactive bladder is expressed as urge incontinence among women compared with men. Nonetheless, overactive bladder, with and without incontinence, has a clinically significant impact on quality-of-life, quality-of-sleep, and mental health, in both men and women.

Adolescent↗

PubMed2004

Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder.

OBJECTIVE: To assess the efficacy of combined treatment with doxazosin and tolterodine, as although alpha-blockers are commonly used and generally effective in men with symptomatic bladder outlet obstruction (BOO), a subset of men with BOO and overactive bladder (OAB) symptoms often complain of persistent symptoms. PATIENTS AND METHODS: In a prospective study of 144 consecutive men with BOO at one tertiary urology centre, all had a baseline pressure-flow urodynamic study and were then subdivided into those with BOO or BOO + OAB, based on absence or presence of involuntary detrusor contractions. The Abrams-Griffiths nomogram was used to determine obstructive BOO. After the initial evaluation, all patients were treated with doxazosin 4 mg/day for 3 months. In patients with no symptomatic improvement, tolterodine 2 mg twice daily was added for an additional 3 months. RESULTS: Of the 144 patients, 76 (53%) were diagnosed as having BOO and 68 (47%) BOO + OAB. The patients with BOO + OAB were older (P < 0.05) and had a higher International Prostate Symptom Score. After 3 months of treatment with doxazosin, 60 (79%) with BOO and 24 (35%) BOO + OAB reported a symptomatic improvement. In those patients with no improvement, six of 16 with BOO and 32 of 44 (73%) with BOO + OAB improved after adding tolterodine. Acute urinary retention developed in only two of 60 men (3.3%) treated with the combined therapy. CONCLUSION: About half of men with symptomatic BOO had an OAB; while about three-quarters of men with symptomatic BOO and no OAB improved with doxazosin, only a third with BOO + OAB were helped with doxazosin alone. Combining tolterodine with doxazosin was effective in three-quarters of men with BOO + OAB. Overall, most men with BOO with or with no OAB were helped with doxazosin alone or with the addition of tolterodine.

Adrenergic alpha-Antagonists↗

PubMed2005

Overactive bladder: epidemiology and social impact.

PURPOSE OF REVIEW: Overactive bladder epidemiology is a rapidly evolving field. The new terminology of lower urinary tract function, introduced in 2002, modified the definitions of all four components of overactive bladder. In the same year, the lack of specific information on overactive bladder prevalence was identified and consequently new studies were launched and recently published. RECENT FINDINGS: Following the new terminology, overactive bladder now includes both a purely sensory disorder and a condition related to an altered bladder behaviour. Studies conducted in selected countries and populations suggested comparable prevalence data worldwide, although the syndrome is considered to be underreported. 'Urge' is now considered the cornerstone symptom of overactive bladder. Recent epidemiological data confirm the increase in overactive bladder prevalence with age and suggest that most diet and lifestyle factors are not associated with the condition, with the exception of body mass index. Among the symptoms, urge and urinary incontinence were considered to be more significantly related to patients' quality of life compared with frequency and nocturia. The socioeconomic consequences of the overactive bladder syndrome were recently estimated in a large US study and a total cost of 12.6 billion US dollars was calculated. SUMMARY: Specific data on overactive bladder epidemiology are now available, providing new evidence about its relevance as a clinical issue. Both wet and dry overactive bladder cause a significant reduction in quality of life. In our daily practice we have to consider that overactive bladder is frequently underreported as patients believe that no treatment is available and urinary incontinence is considered a natural consequence of aging.

Female↗

PubMed1998

Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder.

OBJECTIVE: To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition. RESULTS: After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily. CONCLUSION: Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.

Adult↗

PubMed2006

Anticholinergic drugs versus non-drug active therapies for overactive bladder syndrome in adults.

BACKGROUND: Overactive Bladder Syndrome (OAB) is defined as urgency, with or without urgency incontinence, usually with frequency and nocturia. Pharmacotherapy with anticholinergic drugs is often the first line medical therapy, either alone or as an adjunct to various non-pharmacological therapies. The commonest non-pharmacologic therapies are: bladder training, pelvic floor muscle training with or without biofeedback and electric stimulation to affect detrusor muscle activity. OBJECTIVES: To compare the effects of various anticholinergic drugs with various non-pharmacologic therapies for idiopathic overactive bladder syndrome in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register (searched 29 November 2005), The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to September 2004), PREMEDLINE, Dissertation Abstracts and the reference lists of relevant articles. SELECTION CRITERIA: All randomised, or quasi-randomised, controlled trials of treatment with anticholinergic drugs for overactive bladder syndrome or urge urinary incontinence in adults, in which at least one management arm involved a non-drug new therapy. Trials amongst patients with neuropathic bladder dysfunction were excluded. DATA COLLECTION AND ANALYSIS: Two authors evaluated the trials for appropriateness for inclusion and methodological quality. Three authors were involved in the data extraction. Data extracted was based on predetermined criteria. Data analysis was based on standard statistical approaches used in Cochrane reviews. MAIN RESULTS: Thirteen trials with 1770 participants were included; all were designed as parallel groups except for one cross-over trial. Trial groups were well matched for baseline characteristics in all trials. Treatment duration was 3 to 12 weeks, with one trial carrying out a follow-up analysis at 24 weeks after starting treatment. During treatment, symptomatic improvement was more common amongst those on anticholinergic drugs compared with bladder training (RR 0.73; 95% CI 0.59 to 0.90). Combination of anticholinergics with bladder training was also associated with more improvement than bladder training alone but with wide confidence intervals (RR 0.55; 95% 0.32 to 0.93). Similarly, the limited data favoured a combination of anticholinergics with bladder training compared with anticholinergics during treatment but the difference was not statistically significant (RR for improvement 0.81; 95% CI 0.61 to 1.06). For all comparisons, there were too few data to compare symptoms after treatment had ended. Adverse effects, such as dry mouth, were reported by around a third of those taking anticholinergics. AUTHORS' CONCLUSIONS: The use of anticholinergic drugs in the management of OAB is well established. During initial treatment there was more symptomatic improvement when (a) anticholinergics were compared with bladder training alone, and (b) anticholinergics combined with bladder training were compared with each modality alone. Anticholinergics have well recognised side effects, such as dry mouth. There were too few data to assess whether or not effects are sustained after stopping treatment.

Adult↗

PubMed2002

State of the science: pathology and management of the patient with overactive bladder.

A relatively new term, overactive bladder is used to describe urinary frequency, urgency, and nocturia with or without urinary incontinence. Normal micturition involves coordination among the nervous system, the bladder, and the sphincter. Theories about pathogenesis include disorders of the central and peripheral nervous system, lowered levels of neurotransmitters, and structural problems of the bladder and sphincter. Assessing the patient with overactive bladder incorporates a thorough history and focused physical exam. Current treatments for this condition include lifestyle changes, behavioral interventions, pharmacologic management, and neuromodulation therapy. Research into different medications and delivery systems proves promising for the patient with overactive bladder.

Aged↗

PubMed2006

The use of the isolated mouse whole bladder for investigating bladder overactivity.

The isolated mouse whole bladder was used to study in vitro bladder overactivity evoked by intramural nerve sensitization with bradykinin, mimicking neurogenic bladder overactivity secondary to bladder inflammation. Intravesical pressure responses to intramural electrical stimulation of intramural nerves were measured under isovolumetric condition. Validation showed that carbachol produced a dose-response curve closely mirroring that observed in the isolated muscle strips and demonstrated the dual nature of electrically evoked neurotransmission, consisting of a cholinergic component largely mediated by M(3) receptors and a purinergic component mediated by P2X receptors. ATP generated a biphasic dose-response curve, suggesting that the P2X receptors may be heterogeneous in distribution. Characterization of bradykinin receptors showed bradykinin to be extremely potent in exciting the bladder, producing a dose-response curve with an EC(50) of 90 nM, and bradykinin also enhanced electrically evoked bladder contractions. These effects were inhibited by the B(2) receptor antagonist HOE 140 (d-Arg(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-Thi(5)-Ser(6)-d-Tic(7)-Oic(8)-Arg(9)) but not the B(1) receptor antagonist desArg(10) HOE 140 (H-d-Arf-Arg-Pro-Hyp-Gly-Thi-Ser-d-Tic-Oic-OH) and were also modulated by alpha,beta,methyleneATP. The isolated mouse whole bladder has proved a viable, robust model in which to demonstrate the pharmacological characteristic of the bladder and adds to the repertoire of in vitro tools for investigating potential therapeutic agents.

Adenosine Triphosphate↗

PubMed2002

Special considerations in premenopausal and postmenopausal women with symptoms of overactive bladder.

The term overactive bladder (OAB) is used to describe the symptoms of urinary frequency and urgency with or without urge incontinence. Commonly reported symptoms are nocturia, urgency, frequency, and urge incontinence. However, some of these symptoms may be because of other lower urinary tract conditions or may simply represent a variant of normal physiologic function. Consequently, special considerations need to be made when diagnosing OAB in women. In women of all ages, lower urinary tract infection is the most common cause of irritative urinary symptoms, and midstream urine microscopy and culture should be performed. A chronic urinary residual secondary to voiding difficulties may also result in symptoms of frequency and overflow incontinence and may be diagnosed using a postmicturition ultrasound scan. In premenopausal women, pregnancy should also be excluded. In postmenopausal women, urogenital atrophy can cause irritative symptoms that may be improved with hormone replacement therapy. Vaginal administration has been shown to be most effective and may be used to supplement systemic replacement therapy. In addition, estrogen replacement may be beneficial in the management of OAB as an adjunct to anticholinergic therapy. When investigating elderly women with OAB, special consideration should be given to comorbidities, such as constipation and fecal impaction, mobility problems, and the loss of independence. Concomitant medication, such as diuretics and alpha-adrenergic blockers, should also be noted and the need for therapy reviewed. In conclusion, OAB is a subjective diagnosis that should only be made when other lower urinary tract conditions have been excluded.

Cholinergic Antagonists↗

PubMed2002

Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: a review.

Overactive bladder (OAB) is a chronic condition that often requires long-term treatment to maintain control of symptoms. A range of therapeutic options are available; however, antimuscarinic agents form the mainstay of treatment. Of these agents, tolterodine and oxybutynin are the most widely used. It is well documented that the immediate-release (IR) formulations of these agents have equivalent efficacy in relieving OAB symptoms. However, tolterodine demonstrates a more favorable tolerability profile, particularly in terms of the frequency and severity of dry mouth. Due to the development of novel drug delivery systems, extended-release (ER) formulations of both oxybutynin and tolterodine are now available, permitting once-daily dosing. The convenience of once-daily dosing of antimuscarinic agents would be expected to improve patient compliance and further relieve the symptoms of OAB. Clinical studies with the ER formulations of tolterodine and oxybutynin demonstrate potential clinical advantages over their respective IR forms in terms of either efficacy or tolerability or both, although the therapeutic index of tolterodine ER appears to show a greater advantage over its IR counterpart compared with oxybutynin ER and its IR form. Importantly, the two ER agents have not been compared directly in a head-to-head clinical study. Overall, available clinical data suggest that the newly developed ER formulation of tolterodine represents a significant therapeutic advancement in the treatment of OAB.

Administration, Oral↗