Acetylcholine and the overactive bladder.
Explore the source record for details and available documents.
Acetylcholine↗
SEARCH · PubMed Health
Results for “Urinary Bladder, Overactive”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Transdermal drug delivery treatment for overactive bladder.
Overactive bladder is commonly treated with oral anticholinergic drugs such as oxybutynin chloride. Although oral anticholinergic agents have been effective in controlling urinary urgency and incontinence, adverse events, particularly dry mouth, often cause patients to discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered transcutaneously, maintaining the efficacy of oral oxybutynin while significantly minimizing side effects (e.g., dry mouth) that may complicate therapy. By avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N-desethyloxybutynin (N-DEO) is produced and this compound is deemed to be responsible for anticholinergic side effects such as dry mouth. This novel oxybutynin formulation offers patients with OAB and urge urinary incontinence a well-tolerated option for managing the symptoms of overactive bladder.
Administration, Cutaneous↗
Which factors predict upper urinary tract deterioration in overactive neurogenic bladder dysfunction?
OBJECTIVES: To determine whether bladder histopathologic changes, detrusor leak point pressure (DLPP), disease duration, and preoperative catheterization time can predict for upper urinary tract (UUT) deterioration in patients with overactive neurogenic bladder dysfunction (ONBD). METHODS: A total of 39 patients (7 women and 32 men) with ONBD who were treated with augmentation cystoplasty were included in the study. The patients had undergone perioperative full-thickness bladder biopsies during augmentation cystoplasty. Routine evaluation using light microscopy to investigate for inflammation, fibrosis, and mast cell count was done. Statistical analysis was done using the chi-square and Mann-Whitney U tests. RESULTS: The mean duration of the disease was 8.7 years. Of the 39 patients, 18 (46%) had had indwelling catheters preoperatively. UUT deterioration was found in 16 (41%) of 39 patients. The mean DLPP was 105 cm H2O. The severity of detrusor fibrosis was a significant risk factor for UUT deterioration (P = 0.036). However, the degree of inflammation and the severity of fibrosis did not affect UUT deterioration. A DLPP of more than 75 cm H2O was a statistically significant risk factor (P = 0.04), but the disease duration and preoperative catheterization time were not. CONCLUSIONS: The results of our study have shown that moderate to severe fibrosis in the detrusor and a DLPP of more than 75 cm H2O are the risk factors for UUT deterioration in patients with ONBD. However, additional studies, including ones with more patients, are needed to determine the relationship between the histopathologic changes and UUT deterioration in ONBD.
Adolescent↗
Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?
OBJECTIVE: To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. PATIENTS AND METHODS: Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. RESULTS: Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. CONCLUSION: Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.
Administration, Oral↗
Parity, mode of delivery, and pelvic floor disorders.
OBJECTIVE: This study aimed to assess the associations between parity, mode of delivery, and pelvic floor disorders. METHODS: The prevalence of pelvic organ prolapse, stress urinary incontinence, overactive bladder, and anal incontinence was assessed in a random sample of women aged 25-84 years by using the validated Epidemiology of Prolapse and Incontinence Questionnaire. Women were categorized as nulliparous, vaginally parous, or only delivered by cesarean. Adjusted odds ratios and 95% confidence intervals (CIs) for each disorder were calculated with logistic regression, controlling for age, body mass index, and parity. RESULTS: In the 4,458 respondents the prevalence of each disorder was as follows: 7% prolapse, 15% stress urinary incontinence, 13% overactive bladder, 25% anal incontinence, and 37% for any one or more pelvic floor disorders. There were no significant differences in the prevalence of disorders between the cesarean delivery and nulliparous groups. The adjusted odds of each disorder increased with vaginal parity compared with cesarean delivery: prolapse = 1.82 (95% CI 1.04-3.19), stress urinary incontinence = 1.81 (95% CI 1.25-2.61), overactive bladder = 1.53 (95% CI 1.02-2.29), anal incontinence = 1.72 (95% CI 1.27-2.35), and any one or more pelvic floor disorders = 1.85 (95% CI 1.42-2.41). Number-needed-to-treat analysis revealed that 7 women would have to deliver only by cesarean delivery to prevent one woman from having a pelvic floor disorder. CONCLUSION: The risk of pelvic floor disorders is independently associated with vaginal delivery but not with parity alone. Cesarean delivery has a protective effect, similar to nulliparity, on the development of pelvic floor disorders when compared with vaginal delivery. LEVEL OF EVIDENCE: II-2.
Adult↗
Effects of potassium channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets for overactive bladder.
OBJECTIVES: Increased urinary bladder detrusor smooth muscle phasic contractility has been suggested to be associated with idiopathic bladder overactivity (OAB). We examined the role of voltage-dependent L-type calcium channels, adenosine triphosphate-sensitive potassium (K(ATP)) channels, and calcium-activated potassium (BK(Ca) and SK(Ca)) channels in the regulation of human detrusor phasic contractile activity. METHODS: Isolated human bladder strip phasic contractions were measured and quantified as the mean area under the force-time curve, amplitude, and frequency of phasic contractions in 22 bladder samples. RESULTS: Human detrusor strips displayed myogenic phasic contractions in the presence of atropine (10(-6) M), phentolamine (10(-6) M), propranolol (10(-6) M), suramin (10(-5) M), and tetrodotoxin (10(-6) M). The L-type calcium channel inhibitor nifedipine (300 nM) abolished the contractile activity. Blockade of K(ATP) channels by glibenclamide (1 and 10 microM) did not alter myogenic contractions. In contrast, the K(ATP) channel opener pinacidil (10 microM) markedly inhibited phasic contractility. Iberiotoxin (100 nM) and apamin (100 nM), potent and selective inhibitors of BK(Ca) and SK(Ca) channels, respectively, significantly increased the area under the force-time curve and the amplitude of contractions. CONCLUSIONS: Phasic contractions of human detrusor are dependent on calcium entry through L-type calcium channels. BK(Ca) and SK(Ca) channels play a key role in the modulation of human detrusor smooth muscle phasic contractility. Furthermore, these observations support the concept that increasing conductance through K(ATP), BK(Ca), and SK(Ca) channels may represent attractive pharmacologic targets for decreasing phasic contractions of detrusor smooth muscle in OAB.
Calcium Channels, L-Type↗
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↗
The overactive bladder: Epidemiology and morbidity.
The International Continence Society recognizes the overactive bladder (OAB) as a "symptom syndrome suggestive of lower urinary tract dysfunction" that is defined as "urgency, with or without urge incontinence, usually with frequency and nocturia." Patients who have OAB are often sleep deprived and their sexual life is hindered. These patients have a restricted social life and an increased risk for depression. Accurate prevalence figures are difficult to obtain because most patients consider OAB an inevitable part of aging and some patients are too embarrassed to seek diagnosis. Primary care physicians need to be educated about the importance of identifying this clinical problem and managing it in a way that will minimize morbidity and maximize quality-of-life improvement. This article describes the various aspects of OAB, with special emphasis on epidemiology and morbidity.
Humans↗
Functional constipation in children.
PURPOSE: Constipation in children increases the likelihood of urinary incontinence, bladder overactivity, dyscoordinated voiding, a large capacity, poorly emptying bladder, recurrent urinary tract infection and deterioration of vesicoureteral reflux. We present a consensus related to the assessment, diagnosis and treatment of children with bowel dysfunction coexisting with a known disorder of urinary continence or voiding coordination. MATERIALS AND METHODS: A panel of international multidisciplinary clinicians working on pediatric continence care was invited to participate in the First International Children's Continence Society Bowel Dysfunction Workshop. The seminar sought to address the interrelationship of bowel dysfunction with disorders of urinary continence or voiding mechanics. RESULTS: Constipation is an end point defined by a constellation of symptoms, including infrequent passage of stool, difficulty passing stool, feces that are either large and hard or in small pieces, abdominal pain, palpable stool in the abdomen, stool in the rectal vault, loading on x-ray or fecal soiling. Assessment was done to identify potential organic causes of constipation, clarify symptoms, and identify altered motor behavior and abdomino/pelvic floor muscle incoordination. Whether the underlying problem was one of stool consistency, poor cognition, motivation or fear on the part of the child, or whether it related to gut motility, rectal sensation, stool retention or disordered emptying mechanics, the definitive therapy begins with rectal emptying of impacted stool followed by maintenance of regular soft stools to eliminate fear of pain with defecation. CONCLUSIONS: Constipation is a challenge to the clinician but with comprehensive assessment and systematic intervention children can achieve independent bowel emptying, which positively impacts bladder function.
Child↗
Current and emerging investigational medical therapies for the treatment of overactive bladder.
Overactive bladder (OAB) is a chronic distressing condition characterised by urinary urgency with or without urge incontinence, usually with frequency (voiding at least eight times daily) and nocturia. It affects millions of people worldwide independent of age, sex and race. The prevalence increases with age and is relatively higher in women compared with men. The treatment of OAB is aimed at reducing the debilitating symptoms so as to improve the overall quality of life for patients. Anticholinergic agents targeting the muscarinic receptors in the bladder represent the mainstay of pharmacotherapy for the treatment of OAB. Besides their status as the current standard of care, use of antimuscarinic drugs is limited by certain side effects, particularly dry mouth and constipation; therefore, various attempts have been made to improve the organ selectivity of these drugs to overcome the side effects. These include the development of new antimuscarinic agents with structural modifications and the use of innovative drug delivery methods. The advancement in the drug delivery systems extends to the long-term therapeutic efficacy with improved tolerability and patient compliance; however, future prospective therapies are aimed at novel targets with novel mechanisms of action, including beta3-adrenoceptor agonists, K+ channel openers, 5-HT modulators and botulinum toxin, which are currently under different stages of clinical development. Among other investigational therapies, neurokinin receptor antagonists, alpha-adrenoceptor antagonists, nerve growth factor inhibitors, gene therapy and stem cell-based therapies are of considerable interest. The future for the development of new modalities for the treatment of OAB looks promising.
Animals↗
Trospium chloride: the European experience.
The primary pharmacological therapy for overactive bladder syndrome is muscarinic receptor antagonists. Muscarinic receptor blockade is effective in decreasing the symptoms of urinary urgency and urgency incontinence, but can be associated with troublesome complications, such as dry mouth, blurred vision, constipation and CNS side effects. Trospium chloride, an antimuscarinic medication, has been available in Europe for > 20 years and has recently been approved by the FDA for the treatment of overactive bladder. Trospium chloride is a quaternary amine that is minimally metabolised, not highly protein bound and, importantly, has not been demonstrated to cross the unaltered blood-brain barrier in healthy volunteers. Some characteristics of this unique antimuscarinic agent and the European experience with trospium chloride are reviewed in this article.
Administration, Oral↗
Electrical pelvic floor stimulation in the management of urinary incontinence due to neuropathic overactive bladder.
Electrical pelvic floor stimulation employing a portable functional electrical stimulation system with percutaneously indwelling electrodes was carried out to improve detrusor urinary incontinence. Cyclic stimulation using negative going pulse trains of 20 Hz was applied 3 to 6 times daily to the bilateral pudendal nerves distributing to the pelvic floor muscles for the purpose of strengthening these muscles, including the urethral sphincter, and simultaneously, suppressing detrusor overactivity and increasing cystometric capacity. Electrical training for 4-8 weeks resulted in an improvement of urinary incontinence in five of six patients. In two of six cases incontinence had subjectively disappeared. Urodynamic investigations demonstrated an increase in detrusor reflex threshold and less tendency for abortive detrusor contraction. No apparent complications were encountered during these periods. This procedure appears to be efficient for the management of patients with detrusor incontinence who respond poorly to conservative therapies.
Adult↗
[Overactive bladder--new definition, more patients!?].
Explore the source record for details and available documents.
Humans↗
Overactive bladder made ridiculously simple?
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents.
Solifenacin succinate [YM905; (3R)-1-azabicyclo[2.2.2]oct-3-yl(1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the antimuscarinic properties of solifenacin and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin, propiverine and atropine. In radioligand receptor binding assay, Ki values of solifenacin for human muscarinic M1, M2, M3, M4 and M5 receptors were 26, 170, 12, 110 and 31 nM, respectively. In isolated rat urinary bladder, solifenacin competitively antagonized carbachol-induced contractions, with a pA2 value of 7.44+/-0.09. In these in vitro studies, the antimuscarinic action of solifenacin was more potent than that of propiverine and less potent than those of tolterodine, oxybutynin, darifenacin and atropine. In anesthetized rats, solifenacin and oxybutynin increased the maximum bladder capacity in a dose-dependent manner and also decreased the maximum intravesical pressure. The dosages required to produce a 30% increase in maximum bladder capacity (ED30 values) of solifenacin and oxybutynin were 0.35 and 0.30 mg/kg i.v., respectively, indicating approximately equal efficacies. These results support the fact that solifenacin, similarly to currently used antimuscarinic agents, is an effective agent in the treatment of overactive bladder symptoms such as urinary frequency and urge incontinence.
Animals↗
The case for bladder botulinum toxin application.
Botulinum toxin (BoNT) has been shown to be and effective agent in suppressing detrusor overactivity due to neurogenic causes. Recently, BoNT has been extended to patients who have idiopathic detrusor overactivity. This article reviews the use of BoNT to treat disorders of neurogenic detrusor overactivity and establishes BoNT as a therapeutic modality to treat idiopathic bladder overactivity. It is important to remember that the application of BoNT in the lower urinary tract is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.
Administration, Intravesical↗
The challenge of overactive bladder therapy: alternative to antimuscarinic agents.
Contemporary, the management of overactive bladder (OAB), a medical condition characterized by urgency, with or without urge urinary incontinence, frequency and nocturia, in absence of genitourinary pathologies or metabolic factors that could explain these symptoms, is complex, and a wide range of conservative treatments has been offered, including bladder training, biofeedback, behavioral changes, oral or intravesical anticholinergic agents, S3 sacral neuromodulation and peripheral electrical stimulation. Clinical efficacy of these treatments remains an open issue and several experimental and clinical studies were carried out in the last years improving the results of medical treatment. Here we review the pathophysiology of micturition reflex, the current therapies for OAB and the rationale for alternative treatments. Furthermore we critically address the potential use of medications targeting the central nervous system (CNS) and the primary sensory nerves of the bladder wall, we review the use of agonists of nociceptin/orphanin protein (NOP) receptor and finally we report the results obtained by intradetrusor injection of botulinum toxin.
Botulinum Toxins↗
Re: safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction.
Explore the source record for details and available documents.
Benzhydryl Compounds↗