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PubMed1999

Pharmacological management of incontinence.

Many patients with incontinence do not need surgery - for these patients symptoms can often be considerably improved by conservative measures, including drugs. Several different pharmacological actions are potentially useful depending on the underlying cause of the incontinence: a) Detrusor instability (DI) responds to drugs reducing bladder contractility: Anticholinergic agents, e.g. oxybutynin and tolterodine, act at postganglionic parasympathetic cholinergic receptor sites on the detrusor muscle, reducing the strength of the detrusor contraction. Tricyclic antidepressants, e.g. imipramine, have anticholinergic effects, block presynaptic uptake of amine neurotransmitters and directly inhibit detrusor muscle. Alpha-adrenergic antagonists may have a role to play by dual actions on bladder overactivity (due to altered receptor function) and by reducing outlet resistance. b) Genuine stress incontinence (GSI) may be treated using alpha-adrenergic agonists, e.g. phenylpropanolamine, to increase outlet resistance by stimulating smooth muscle of the urethra and bladder neck. c) In nocturnal enuresis reduction of nocturnal urine output with the anti-diuretic hormone (ADH) analogue DDAVP (1-deamino, 8-arginine vasopressin) is beneficial. d) Bladder emptying may be facilitated in patients with retention and 'overflow' incontinence by alpha-adrenergic antagonists, which reduce outlet resistance, and perhaps by parasympathomimetics, e.g. bethanecol. e) In postmenopausal women, systemic oestrogen replacement reduces filling symptoms including urge incontinence. Evidence for oestrogen replacement alone in GSI is lacking, but combination with alpha-agonists is beneficial in milder GSI. For the future, tolterodine and other new anticholinergics offer the hope of treatment for DI with fewer of the side effects that limit the use of established drugs. Better understanding of the pathophysiology of DI may provide new targets for drug therapy, such as hyperpolarisation of detrusor muscle membrane. Alpha-agonists may find a greater role in the future, as may ADH analogues for noctural symptoms.

Adrenergic alpha-Agonists↗

PubMed2002

Tolterodine: selectivity for the urinary bladder over the eye (as measured by visual accommodation) in healthy volunteers.

OBJECTIVE: Tolterodine exhibits a favourable selectivity for the urinary bladder over salivary glands in vivo, in the anaesthetised cat, whereas oxybutynin shows the opposite selectivity profile in this model. This study further evaluated the selectivity profiles of tolterodine and oxybutynin by comparing the effects on bladder function and visual accommodation in the same individuals. METHODS: In a double-blind, randomised, four-way crossover study, 16 healthy volunteers received single oral doses of tolterodine 5 mg and oxybutynin 2.5, 5 and 7.5 mg. Voiding parameters were assessed for 12 hours post-dose, along with visual accommodation (near point of vision) at regular intervals. RESULTS: A dose-dependent increase in maximum bladder capacity was observed for oxybutynin [2.5 mg (+35%), 5 mg (+45%) and 7.5 mg (%)]. The effect of tolterodine 5 mg on bladder capacity was approximately twice (+93%) that seen after oxybutynin 5 mg and the onset of the effect was more rapid with tolterodine. Effects on visual accommodation were also dose-dependent for oxybutynin (maximum changes in near point of vision were 13%, 20% and 29%, respectively). The maximum change observed after tolterodine 5 mg was the same as after oxybutynin 5 mg (i.e. 20%). CONCLUSIONS: Tolterodine seems to exhibit selectivity for the bladder over the eye. Therefore, these results suggest that the normal dosage of tolterodine (2 mg twice daily) may have less effect on visual accommodation than the equivalent dosage of oxybutynin (5 mg three times daily) in patients with an overactive bladder.

Adult↗

PubMed2005

Combined radical prostatectomy and bladder augmentation for concomitant prostate cancer and detrusor instability.

OBJECTIVES: To determine the outcomes of a select cohort of patients with severe voiding dysfunction, refractory to medical management, and a concomitant diagnosis of prostate cancer, who were treated with radical prostatectomy and augmentation enterocystoplasty. METHODS: Four men with biopsy-proven prostatic adenocarcinoma, as well as a diagnosis of severe overactive bladder, underwent combined radical retropubic prostatectomy and augmentation enterocystoplasty. All patients underwent fluorourodynamic testing confirming nonobstructive detrusor instability or hyperreflexia. Three patients underwent nerve-sparing radical retropubic prostatectomy with a clamshell ileocystoplasty, and one with neurogenic hyperreflexia underwent sigmoid cystoplasty with a continent catheterizable stoma at radical retropubic prostatectomy. RESULTS: The mean follow-up was 21.5 months (range 8 to 48). All patients had an undetectable prostate-specific antigen level postoperatively. The average hospitalization was 8 days. Perioperative complications occurred in 2 patients, including a prolonged urine leak managed with catheter drainage and postoperative hematuria requiring cystoscopic clot evacuation. Erectile function was preserved in 2 patients with good preoperative erections. At last follow-up, the 3 patients who voided per urethra had minimal postvoid residual urine volumes and maintained good continence, with only 1 patient describing occasional mild stress incontinence. At last follow-up, the patient with the sigmoid cystoplasty catheterized every 4 hours with volumes of about 300 mL and complete stomal continence. No patient required anticholinergic medications postoperatively. CONCLUSIONS: The concomitant diagnosis of prostate cancer and severe detrusor instability may be difficult to treat. The results of our study have shown that for those desiring surgical management for their prostate cancer, a combined bladder augmentation and radical prostatectomy may be performed with minimal added morbidity and significantly improved voiding function in the properly selected individual.

Adenocarcinoma↗

PubMed1997

Effects of the K+ channel opener, ZD6169, on volume and PGE2-stimulated bladder activity in conscious rats.

PURPOSE: To investigate the effects of the new K(ATP) channel opener, ZD6169, shown to have an in vivo selectivity for the bladder, on bladder activity in rats. MATERIALS AND METHODS: ZD6169 was given intra-arterially (i.a., 0.1 and 1 mg./kg.) or orally (3 mg./kg.) to conscious Sprague-Dawley rats undergoing continuous cystometry. Investigations were also performed before and after stimulation of bladder activity by intravesical prostaglandin (PG) E2. RESULTS: Intra-arterial ZD6169 increased residual volume, but caused no changes in other cystometric parameters. In rats receiving oral ZD6169, cystometric parameters were compared (every hour up to five hours) to those recorded in rats receiving oral vehicle. No differences were found, except in threshold pressure, which was significantly increased. Intravesical PGE2 20 microM increased micturition and basal pressures, and decreased bladder capacity and micturition volume. ZD6169 1 mg./kg., given i.a., reduced or completely prevented the activity induced by intravesical PGE2. Three hours after orally administered ZD6169 (3 mg./kg.), intravesical PGE2 20 microM had no effect. Three hours after oral administration of vehicle, the effects of PGE2 were attenuated, but still statistically significant. CONCLUSIONS: ZD6169, given i.a. or orally, increased threshold pressure, but had otherwise little effect on volume-induced micturition. However, the drug markedly reduced or prevented PGE2-induced bladder activity when given i.a.; it was also effective when given orally. If ZD6169 has inhibiting effects on bladder contraction in man without any cardiovascular actions, the drug may represent a novel, promising way of treating bladder overactivity.

Administration, Intravesical↗

PubMed2004

Bladder training for urinary incontinence in adults.

BACKGROUND: Urinary incontinence is a common and distressing problem. Bladder training aims to increase the interval between voids and is widely used for the treatment of urinary incontinence. OBJECTIVES: To assess the effects of bladder training for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register (January 2003). The reference lists of relevant articles were searched, and trialists contacted for details of other trials. Date of the most recent search: January 2003. SELECTION CRITERIA: Randomised or quasi-randomised trials of bladder training for the treatment of any type of urinary incontinence. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and independently extracted data. Five primary outcomes were prespecified: participant's perception of cure of urinary incontinence; participant's perception of improvement of urinary incontinence; number of incontinent episodes; number of micturitions; and quality of life. Adverse events were also noted. Three hypotheses were tested: bladder training is better than no bladder training; bladder training is better than other treatments; and combining bladder training with another treatment is better than that other treatment alone. MAIN RESULTS: We assessed 73 reports of 36 potentially relevant trials; 28 reports of ten trials were eligible for inclusion with a total of 1366, predominantly female, participants. Not all participants' with overactive bladder, in five trials had urinary incontinence. Data from five trials with 467 participants, all female, are therefore included in the review. The quality of trials was variable. Few data describing long term follow up are available.Is bladder training better than no bladder training? Data were available for 149 women from two trials comparing bladder training with no bladder training. These described only a limited number of prespecified outcomes, which varied across the two trials. Point estimates of effect favoured bladder training however confidence intervals were wide and no statistically significant differences were found for primary outcome variables.Is bladder training better than other treatments? Only two trials including 125 women compared bladder training with drugs: one with oxybutynin and one with imipramine plus flavoxate. In the former trial the only outcomes demonstrating a statistically significant difference were participant's perception of cure at six months (RR 1.69; 95% CI 1.21 to 2.34) and adverse events (RR 0.03; 95% CI 0.00 to 0.44), both favouring bladder training. In the latter trial participant's perception of cure immediately after treatment just achieved statistical significance (RR 1.50; 95% CI 1.02 to 2.21) favouring bladder training, and this difference was maintained at approximately two months post treatment. One comparison of bladder training with pelvic floor muscle training plus biofeedback included 132 women: none of the differences in the primary outcomes achieved statistical significance.Is combining bladder training with another treatment better than that other treatment alone? One trial compared pelvic floor muscle training plus biofeedback supplemented with bladder training versus pelvic floor muscle training plus biofeedback alone and included 125 women. Of the primary outcomes both participants' perception of improvement and quality of life, both immediately after treatment, achieved statistical significance, favouring the bladder training combined with pelvic floor muscle training and biofeedback group (perception of improvement: RR 1.18; 95% CI 1.01 to 1.39; quality of life: MD -47.20; 95% CI -87.03 to -7.37), this was not sustained at three months. REVIEWER'S CONCLUSIONS: The limited evidence available suggests that bladder training may be helpful for the treatment of urinary incontinence, but this conclusion can only be tentative as the trials were of variable quality and of small size with wide confidence intervals around the point estimates of effect. There was also not enough evidence to determine w evidence to determine whether bladder training was useful as a supplement to another therapy. Definitive research has yet to be conducted: more research is required.

Adult↗

PubMed2000

Treatment of urinary incontinence.

The treatment of urinary incontinence is a dynamic and evolving field. New therapies, techniques, and procedures, as well as some subtle refinements in treatments currently used, offer hope for the millions of people suffering from this condition. Recent attention has been directed toward reevaluating the efficacy and durability of some standard treatments for stress urinary incontinence, including pelvic floor exercise, bladder neck suspensions, and pubovaginal slings. Occlusive or supportive devices have evolved into a suitable alternative in some patients. Extracorporeal magnetic therapy and alternative periurethral injectable agents may offer additional treatment strategies for the relief of symptomatic stress urinary incontinence. New drugs for the treatment of overactive bladder and urge urinary incontinence have been introduced recently and, in combination with neuromodulation, offer the first new treatments for this condition in over 25 years. Yet, as rapidly as new therapies become available for the treatment of urinary incontinence, problems have become evident with some that were introduced just a short time ago. Thus, cautious skepticism regarding these "new and improved" treatments should be maintained until long-term data become available with respect to safety, efficacy, and durability.

Humans↗

PubMed2006

Design of the Behavior Enhances Drug Reduction of Incontinence (BE-DRI) study.

PURPOSE: To describe the design of a multi-center randomized clinical trial of behavioral training combined with drug therapy for the treatment of urge incontinence. The study aims are to determine whether adding behavioral training will increase the number of women who can discontinue drug therapy and sustain a significant reduction of incontinence; to test whether the short-term effectiveness of drug therapy can be enhanced by combining it with behavioral training; and to determine the cost-effectiveness of combined therapy. DESIGN: Two-stage randomized clinical trial currently being conducted by the Urinary Incontinence Treatment Network, a clinical trials network established by the National Institutes of Health. METHODS: Participants are 307 community-dwelling women with pure or predominant urge incontinence. Stage 1 consists of 10 weeks of drug therapy with sustained-release tolterodine alone or combined with behavioral training (pelvic floor muscle exercise training, bladder control techniques, fluid management). In stage 2, drug is withdrawn and behavioral training stopped. The primary outcome, measured at 8 months, is a composite of two endpoints (1) successful drug withdrawal (i.e. not requesting any other treatment for incontinence) and (2) achieving and maintaining > or =70% reduction in the frequency of incontinence episodes on bladder diary. The effects of treatment and drug withdrawal are measured at week 10 and months 4, 6, 8, 14, 20, and 26. Assessments include: the Medical Epidemiological and Social Aspects of Aging (MESA) incontinence questionnaire, pelvic floor muscle strength assessment, Incontinence Impact Questionnaire, Urogenital Distress Inventory, Overactive Bladder Questionnaire, Short-Form Health Survey (SF-12), costs associated with incontinence care, Health Utility Index Mark 3, Willingness to Pay Scale, and Patient Satisfaction Questionnaire. SIGNIFICANCE: The BE-DRI study is the first clinical trial to investigate the use of drug therapy combined with behavioral therapy with the pre-established goal of discontinuing the medication. The concept of drug cessation represents a new paradigm in this field of research and has important implications for future treatment approaches to urge incontinence.

Adult↗

PubMed2004

Delayed treatment of bladder outlet obstruction after sling surgery: association with irreversible bladder dysfunction.

PURPOSE: Our urethrolysis cohort demonstrated an unusual delay time to surgical treatment of bladder outlet obstruction. We determined whether urethrolysis outcomes, ie persistent bladder symptoms, were associated with time between sling and urethrolysis surgeries. MATERIALS AND METHODS: Retrospective analysis of all patients who underwent urethrolysis for post-sling voiding dysfunction between June 1997 and June 2002 was performed. We excluded from study 6 patients with a known history of overactive bladder symptoms, neurogenic bladder dysfunction and use of anticholinergic pharmacotherapy before stress incontinence surgery. The remaining 15 patients were stratified into 2 outcomes groups based upon the absence or presence of post-urethrolysis bladder storage symptoms. Patients (7) in group 1 have no current bladder symptoms. Patients (8) in group 2 still require anticholinergic drug therapy for significant bladder symptoms of frequency and urgency. Data collected for the 2 groups included mean age, existence of urinary retention before urethrolysis, mean time to urethrolysis in months, urethrolysis outcome based upon subjective bladder symptoms and followup duration. For comparison of mean age between groups the standard t test was used. Fisher's exact test was used to compare frequency of urinary retention before urethrolysis between groups. Lastly the Mann-Whitney U test was conducted to compare time to urethrolysis between groups. All statistical analyses were conducted using the SPSS software package (SPSS, Inc., Chicago, Illinois). RESULTS: There was no statistically significant difference between the groups with respect to age or frequency of urinary retention before urethrolysis. Time to urethrolysis for the whole cohort ranged from 2 to 66 months. Mean followup after urethrolysis was 17.3 +/- 22.9 months. Comparison of mean time between incontinence and urethrolysis surgeries between group 1 (9.0 +/- 10.1 months) and group 2 (31.25 +/- 21.9 months) demonstrated a statistically significant difference (p = 0.01). CONCLUSIONS: This urethrolysis population demonstrated an unusual delay time to surgical treatment of bladder outlet obstruction. We categorized the cohort according to absence or presence of persistent bladder storage symptoms, and found a strong association between persistent bladder symptoms and greater delay to urethrolysis.

Aged↗

PubMed2026

A prospective crossover study comparing ICCS-recommended and Palmer-adjusted filling rates in children with spina bifida.

OBJECTIVE: This study aimed to investigate whether the maximal cystometric capacity (MCC) in children with spina bifida (SB) is indeed lower, as predicted by the Palmer formula, and to evaluate the impact of different bladder filling rates on urodynamic parameters. MATERIALS AND METHODS: This prospective, randomized, two-sequence crossover-controlled study included 70 children aged 3-18 years with spina bifida under regular follow-up. In Group 1, the first two bladder fillings were performed at the ICCS-recommended rate, and the third at 75% of that rate (Palmer formula). In Group 2, the sequence was reversed. Urodynamic parameters, including maximal cystometric capacity (MCC), bladder compliance, detrusor activity, filling pressures, and detrusor leak point pressure (DLPP), were analyzed across fillings. RESULTS: Cystometric bladder capacity was lower during fillings performed at the Palmer-adjusted rate compared with those at the ICCS-recommended rate. The proportion of reduced compliance significantly decreased in Group 1 (p = 0.046) but remained unchanged in Group 2. A significant positive correlation was observed between expected bladder capacity (EBC) and measured MCC in both groups (ρ ≈ 0.5-0.6). The highest correlation and agreement were found in Group 1 during the third filling at the Palmer rate (ICC = 0.606). No significant intra- or intergroup differences were observed in detrusor pressure, end-filling pressure, DLPP, or overactive bladder prevalence. CONCLUSION: Bladder filling rate was associated with differences in both cystometric capacity and bladder compliance in children with spina bifida. Fillings performed according to the Palmer formula (approximately 75% of the ICCS-recommended rate) were associated with capacities that more closely approximated age-expected values and with modest differences in bladder compliance. Conversely, faster filling rates did not produce similar benefits. These findings suggest that slower filling strategies may improve measurement consistency and agreement with expected bladder capacity estimates. However, the magnitude and direct clinical impact of these differences should be interpreted cautiously, particularly in light of the potential influence of sequence-related effects.

Humans↗

PubMed2002

Electrical stimulation for the treatment of bladder dysfunction: current status and future possibilities.

Electrical stimulation of peripheral nerves can be used to cause muscle contraction, to activate reflexes, and to modulate some functions of the central nervous system (neuromodulation). If applied to the spinal cord or nerves controlling the lower urinary tract, electrical stimulation can produce bladder or sphincter contraction, produce micturition, and can be applied as a medical treatment in cases of incontinence and urinary retention. This article first reviews the history of electrical stimulation applied for treatment of bladder dysfunction and then focuses on the implantable Finetech-Brindley stimulator to produce bladder emptying, and on external and implantable neuromodulation systems for treatment of incontinence. We conclude by summarizing some recent research efforts including: (a) combined sacral posterior and anterior sacral root stimulator implant (SPARSI), (b) selective stimulation of nerve fibers for selective detrusor activation by sacral ventral root stimulation, (c) microstimulation of the spinal cord, and (d) a newly proposed closed-loop bladder neuroprosthesis to treat incontinence caused by bladder overactivity.

Animals↗

PubMed1996

Micturition in conscious rats with and without bladder outlet obstruction: role of spinal alpha 1-adrenoceptors.

1. In normal rats and rats with bladder hypertrophy secondary to outflow obstruction, undergoing continuous cytometry, we examined the responses to the selective alpha 1-adrenoceptor antagonist doxazosin given intrathecally (i.t.) and intra-arterially (i.a.). In addition, we investigated the effects of the drug on L-dopa-induced bladder hyperactivity in normal, unobstructed rats. 2. Doxazosin 50 nmol (approximately 60 micrograms kg-1), given i.t., decreased micturition pressure in normal rats and in animals with post-obstruction bladder hypertrophy. The effect was much more pronounced in the animals with hypertrophied/overactive bladders. Doxazosin did not markedly affect the frequency or amplitude of the unstable contractions observed in obstructed rats. In contrast, however, doxazosin reduced L-dopa-induced bladder overactivity. When tested, the enantiomers of doxazosin produced qualitatively similar effects to doxazosin, but there was no evidence of stereoselectivity. 3. The results suggest that in addition to the well documented action on prostatic and lower urinary tract smooth muscle, and an effect on the sympathetic outflow to the bladder, bladder neck, prostate, and external urethral sphincter, doxazosin may have an action at the level of the spinal cord and ganglia, thereby reducing activity in the parasympathetic nerves to the bladder. This effect is more pronounced in rats with bladder hypertrophy than in normal rats.

Adrenergic alpha-Antagonists↗

PubMed2005

Practice patterns of Japanese physicians in urologic surveillance and management of spinal cord injury patients.

STUDY DESIGN: Analysis of answers to a new questionnaire. OBJECTIVE: To examine current practice patterns of physicians in the urological surveillance and management of spinal cord injury (SCI) patients in Japan. SETTING: Nationwide questionnaire survey to physicians in Japan. METHODS: A Japanese version of the 14-item questionnaire survey carried out in US was mailed to 770 members of the Japanese Neurogenic Bladder Society (JNBS). RESULTS: We received answers to our questionnaire from 333 (43.2%) members of JNBS. The responders were all urologists. For surveillance of the upper urinary tract (UUT), 239 (71.8%) respondents preferred abdominal ultrasound. Cystometry was performed routinely by 174 (52.3%) respondents for the evaluation of vesicourethral function. Cystoscopy was carried out in cases of hematuria (88.0%) and bladder stone (55.3%). Surveillance of the urinary tract was performed every year in 154 (46.2%). For detection of bladder cancer, which 119 (37.9%) respondents have experienced, 94.9% physicians perform cystoscopy, 76.3% urinary cytology, and 60.4% ultrasound. For initial treatment of detrusor-sphincter dyssynergia (DSD), 225 (69.2%) respondents chose alpha-blocker, and 94 (28.9%) chose clean intermittent catheterization (CIC) with/without anticholinergic agent(s). For initial treatment of overactive bladder, 245 (74.7%) chose anticholinergic agent(s) only and 63 (19.2%) chose anticholinergic agent(s) with CIC. For initial treatment of areflexic bladder, 233 (73.7%) chose CIC and 63 (19.9%) chose Credé maneuver or tapping. CONCLUSIONS: This survey shows that there are some differences in urological surveillance and management of SCI patients between Japan and the US. Reasons for the discrepancy should be examined.

Comorbidity↗

PubMed2006

Effects of imatinib mesylate (Glivec) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder.

AIMS: In the gastrointestinal tract, slow wave activity in smooth muscle is generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips of most species show spontaneous contractions which are triggered by action potential bursts, however, the pacemaker mechanisms for the detrusor are still unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c-kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig detrusor and intravesical pressure of isolated guinea-pig bladders. METHODS: Changes in the membrane potential were measured in guinea-pig detrusor smooth muscle using conventional microelectrode techniques. Pressure changes in the bladder were recorded using whole organ bath techniques. RESULTS: Smooth muscle cells in detrusor muscle bundles exhibited spontaneous action potentials, and spontaneous pressure rises occurred in isolated bladders. Glivec (10 microM) converted action potential bursts into continuous firing with no effects on the shape of individual action potentials. Glivec (>50 microM) reduced the amplitude of spontaneous pressure rises in the whole bladder in a dose dependent manner and abolished spontaneous action potentials in detrusor smooth muscle cells. CONCLUSIONS: The results suggest that ICC-like cells may be responsible for generating bursts of action potentials and contractions in detrusor smooth muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the overactive bladder.

Animals↗

PubMed2004

[Mechanical changes of the detrusor after antiincontinence surgery].

BACKGROUND: Stress urinary incontinence is secondary to an intrinsic defect in the closure or a lack of urethral support; the treatment is surgical and this may affect vesical voiding by creating an obstruction, modifying the contraction power at opening and the mechanical properties of the detrusor. OBJECTIVES: To know if there are changes in the contractile characteristics of the detrusor in order to maintain an efficient voiding after surgical correction of the urinary incontinence. MATERIAL AND METHODS: This was a cohort study of the urodynamic variables, mechanical work and energy of the detrusor, during cystometric and pressure-flow analysis, before and after antiincontinence surgery. Forty-five patients were included with urodynamic study before surgery and another one between 6 weeks and 6 months. We analyzed these data using student T test and ANOVA. RESULTS: The average and maximum flow rates, voiding efficient and velocity of the detrusor decreased. The pressures of the detrusor, the opening power and energy increased significantly after the surgery. These changes were more important in the Burch group. The 24.4% of the patients presented de novo hyperactive bladder; before surgery these patients had detrusor's pressures, voiding power and energy significantly greater. CONCLUSION: There are changes in the mechanical properties of the detrusor after antiincontinence surgery; the detrusor needs a greater energy output to defeat urethral resistance and to maintain the vesical voiding, these were better in patients with Burch procedure and with overactive bladder.

Adult↗

PubMedDate not supplied

[Urinary incontinence: anticholinergic treatment].

The bladder and urethra are a functional unit controlled and coordinated by the central and peripheral nervous systems. Voluntary or involuntary contraction of the Detrusor muscle depends mainly on muscarinic receptor stimulation by Acetylcholine, which is released from parasympathetic terminals. This receptors are the antimuscarinic (anticholinergic) drug target. Anticholinergic drugs are the first line of treatment for overactive bladder. They have been widely investigated and have shown superior efficacy to placebo in numerous studies. Their effects on bladder function result in an increase of the capacity at which involuntary detrusor contractions are produced, a decrease in its amplitude and an increase in bladder capacity. The purpose of this Literature Review is to provide an up-to-date overview of the current situation of this form of treatment (Oxybutinin, Long Acting Tolterodine, Trospium Chloride) and the main developments in this area. Some of these drugs are already commercially available in Spain (Long Acting Tolterodine), some may appear soon (Extended Release Oxybutinin, Transdermal Oxybutinin), and others are available for specific cases (Intravesical Oxybutinin). Other drugs, which are theoretically more uroselective (Darifenacin or Solifenacin), are not yet freely available on the open market, while yet others are already in use in other countries (Propioverine). Finally I would like to mention the increasing use of Botulinum Toxin detrusor injection for bladder hyperactivity that fails to respond to conservative treatments.

Cholinergic Antagonists↗

PubMed2006

Perceptions and behaviours of women with bladder control problems.

OBJECTIVES: To evaluate women's perceptions about bladder control problems. METHODS: 757 Women with one or more bladder control symptoms (frequency, urgency, stress or urge urinary incontinence and nocturia) participated in an Internet-based survey. A separate study involved 12 focus groups including a total of 180 women with bladder control problems. RESULTS: Respondents in the survey reported multiple symptoms, e.g. stress urinary incontinence (72%), frequency (56%), nocturia (45%), urge urinary incontinence (43%) and urgency (33%). Women in both the survey and the focus groups revealed extensive use of coping mechanisms to manage their symptoms. The focus groups revealed that many women were not aware that overactive bladder (OAB) is a pathophysiological condition. Approximately 30% of respondents in the survey felt uncomfortable talking to their doctor about their condition. Among women who did speak with their doctor, stress-related symptoms were described more readily than urge-related symptoms. In the survey, only about half (56%) of the women felt their OAB medication was effective, and half (50%) stopped taking their medication at some point. Information from the focus groups suggested that some women may have unrealistic expectations of onset of efficacy or extent of benefit and may be unprepared for managing side effects. CONCLUSIONS: Feelings of embarrassment and limited understanding of the pathophysiology of OAB can contribute to miscommunication between a woman and her doctor. Patient education regarding reasonable expectations coupled with suggestions for coping with unwanted side effects will likely result in better management.

Adaptation, Psychological↗

PubMed2001

Relaxant effects of isoproterenol and selective beta3-adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders.

PURPOSE: We compared the relaxant effects of the stimulation of beta-adrenoceptors with isoproterenol and of drugs selective for beta-adrenoceptor subtypes in detrusor preparations from patients with normal and neurogenic bladder, respectively. MATERIALS AND METHODS: We studied in vitro preparations of a cystometrically normal, low compliant and hyperreflexic bladder from 45, 26 and 7 patients, respectively. RESULTS: Isoproterenol relaxed concentration dependently and with the same potency as detrusor preparations obtained from normal and neurogenic bladders. In 37 normal detrusor, 25 low compliant and 7 hyperreflexic cases pD2 values were 6.36, 6. 25 and 6.38, respectively. Maximal relaxation did not differ significantly among the 3 groups (about 80% of 10-5 M. forskolin induced relaxation). Neither the beta1-/beta2-adrenoceptor agonist dobutamine nor the beta2-adrenoceptor agonist procaterol produced any significant relaxation of preparations from the 3 groups at a concentration of up to 10-5 M. At a concentration of 10-4 M. the preparations were relaxed but neither of these effects reached a maximum. BRL37344A and CL316243, selective beta3-adrenoceptor agonists and CGP-12177A (a selective beta3-adrenoceptor partial agonist and beta1-/beta2-adrenoceptor antagonist) relaxed detrusor preparations from the normal, low compliant and hyperreflexic groups when applied at concentrations greater than 10-6 M. For each agonist the pD2 value did not differ significantly among the 3 groups. CONCLUSIONS: beta-adrenoceptor stimulation is an effective way of relaxing the human detrusor and the effect is similar in normal and neurogenic bladders. A major portion of the relaxant effect of isoproterenol is mediated via beta3-adrenoceptor stimulation. Clinical trials may reveal whether this method is useful for treating bladder overactivity.

Adrenergic beta-Agonists↗

PubMed1985

Urethral and perineal instability.

50 out of 271 female patients showed urethral pressure variations of at least 15 cm H2O during bladder filling. These pressure fluctuations were accompanied by variations in the EMG activity of the anal and periurethral striated musculature. Urethral instability is frequently associated with bladder overactivity and occurs in younger people. Possible pathophysiological mechanisms and implications for therapy are discussed.

Adult↗