Use Of Antimuscarinic Drugs Research Articles

Short version of the S2k guideline on drug therapy of neurogenic lower urinary tract dysfunction (NLUTD)

In Germany about one million patients suffer from neurogenic lower urinary tract dysfunction (NLUTD). If left untreated, various forms of NLUTD can lead to secondary damage of the lower and upper urinary tract. Thus, the guideline was developed for the drug therapy of patients with NLUTD, who frequently require lifelong care and aftercare. The guideline was developed in aconsensus process with several meetings and online reviews, and final recommendations were decided on in online consensus meetings. Ballots were sent to elected officials of the contributing professional societies. Level of consensus was given for each coordinated recommendation ( https://www.awmf.org/leitlinien/detail/ll/043-053.html ). RESULTS/MOST IMPORTANT RECOMMENDATIONS: (Video)urodynamic classification of the NLUTD should be conducted before the use of antimuscarinic drugs (84.2%). Approved oral antimuscarinics should be used as first choice. Contraindications must be respected (100%). If oral treatment is ineffective or in the case of adverse drug reaction (ADRs) alternatively instillation of oxybutynin solution intravesically (83%) or onabotulinumneurotoxine (OBoNT) injection should be offered (89.5%). In case of failure or ADRs of antimuscarinics, β3 sympathomimetic mirabegron can be used to treat neurogenic detrusor overactivity (NDO) (off-label use) (100%). In case of paraplegia below C8 or multiple sclerosis with an expanded disability status scale (EDSS) of ≤ 6.5, OBoNT injection can be offered as an alternative (89.5%). Drug therapy for NDO should be started early in newborns/young children (84.2%). Conservative, nondrug therapy should be considered in frail elderly (94.7%). No parasympathomimetic therapy should be used to treat neurogenic detrusor underactivity (94.7%). Precise knowledge of the neurological underlying disease/sequence of trauma and the exact classification of the NLUTD are required for development of individualized therapy.

β3-Adrenoceptor Agonist for the Treatment of Bladder Dysfunction in Children: A Systematic Review and Meta-Analysis.

ß3-adrenergic receptor agonists (ß3 agonists) have been used in treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) in adults. However, their use in children has only recently been approved by the U.S. Food and Drug Administration for patients with NDO. As in adults, the role of ß3 agonists in children may include conditions such as OAB. This systematic review and meta-analysis aims to understand the intended use, efficacy and safety of ß3 agonists in the pediatric population. A literature search was performed in February 2021 across MEDLINE®, Embase®, Scopus®, the Cochrane Library and ClinicalTrials.gov. No language restrictions were placed. All records describing the clinical use of ß3 agonists in pediatric patients (<18 years of age) were included, regardless of the methodological design or outcomes assessed. The identified records were screened by 2 independent authors. The reporting was compliant with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Data extraction was performed by 2 independent reviewers, blinded to each other's extractions. The data were pooled using the fixed effects model. Of 367 records identified, 8 studies were included in the review (3 prospective and 5 retrospective). ß3 agonists led to improvements in both urodynamics parameters and self-reported outcomes such as incontinence. Commonly reported side effects were headaches (3%‒5.9%), constipation (3.5%‒5.7%), rhinitis/nasopharyngitis (1.7%‒5.8%) and blurred vision (1.7%‒2.9%). Clinically meaningful changes in safety outcomes (blood pressure, heart rate, electrocardiogram-related changes, liver function) were rare. Before and after ß3 agonist use, pooled effect estimates for maximum cystometric capacity for 171 patients were mean difference of +98.84 ml (95% CI 74.72, 122.96); for complete dryness, assessment of 235 patients showed a Peto odds ratio of 8.68 (95% CI 5.22, 14.45). ß3 agonists appear to be a promising, effective and safe alternative/adjunctive therapy in management of pediatric NDO or OAB, with improvements in both objective urodynamics parameters and subjective patient-reported outcomes following their use.

Antimuscarinic drug therapy for overactive bladder syndrome in the elderly – are the concerns justified?

ABSTRACTIntroduction: The use of antimuscarinic drugs is common in the management of the overactive bladder (OAB). Concerns have been raised over their use in the elderly population in whom the use of these drugs is highly prevalent, consequent to the reported link between these drugs and cognitive impairment and dementia.Areas covered: Recent publications have heightened concerns regarding antimuscarinic drug use in the elderly. In this review, the author discusses the available evidence upon which conclusions have been based and has presented the need for cortical review and need for caution in interpreting the data. The available evidence is inconsistent, differences in pharmacokinetics have not been widely recognized in clinical trials, clinical estimation of antimuscarinic activity has not been standardized, and serum antimuscarinic activity has not been found to correlate with cognitive impairment. Furthermore, the significant heterogeneity within cognitive aging processes raises questions regarding the extent to which various factors, including medication, influences this process.Expert opinion: Whilst caution should indeed be exercised in the use of antimuscarinic medication in the elderly, advocacy of discontinuation of their use may deprive patients of the benefits of improved quality of life from treatment where currently alternative management remain limited or invasive.

Effets cardio-vasculaires des traitements anticholinergiques à visée vésicale chez la personne âgée : une revue

The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly. A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French. In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Geriatric population has a high prevalence of cardiovascular diseases (24.4% of heart diseases on 65-74years and 36.9% on ≥75years). More than 20% of the geriatric population has overactive bladder history and 41.43% of them use of antimuscarinic drugs. Evaluating the cardiovascular adverse effects of antimusarinics in the geriatric population is not easy because of exclusion of high-risk patients in trials. However, serious cardiovascular adverse effects were reported like atrial fibrillation, atrioventricular block or torsade de pointe. Further studies are needed especially in the "real life" in order to precise the exact prevalence of such cardiovascular alterations. Without conclusive evidence, potential cardiovascular adverse effects of anticholinergic agents used in overactive bladder must lead to a cautious prescription.

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Anticholinergic use in children: Persistence and patterns of therapy.

Overactive bladder (OAB) symptoms are complex and generally require long-term therapy. Nevertheless, it has been demonstrated that persistence rates of antimuscarinic drug use are low in adults. Better understanding of the treatment patterns of children treated with antimuscarinics could help to improve drug management. Our objective was to evaluate persistence rates of patients under 20 years of age on antimuscarinic therapy over a four-year period. Patients having received a first-ever antimuscarinic drug prescription between April 2007 and March 2008 were identified using IMS Brogan's Public and Private Drug Plans database. Canadian drug claims data from Private Drug Plans, Régie de l'Assurance Maladie du Québec, and Ontario Public Drug Plans were analyzed retrospectively. Patients were followed for four years to assess the prescribed drugs, the lines of treatment, and the duration of each treatment. Data were available for 374 patients. The most prescribed drug as a first-line therapy was oxybutynin (87.2%), followed by tolterodine LA (5.9%). Patients refilled their index prescriptions for an average of 429 days. Solifenacin had the highest mean duration of index therapy (765 days). The median number of antimuscarinics prescribed was one. At the end of the followup, 44 patients were still on therapy. Reasons for discontinuation of treatment were not available. Overall discontinuation rate of antimuscarinic therapy in children is comparable to what has been reported in adult patients with OAB. However, children seem to persist on the medication for a longer duration before adherence rates start declining. The low rate of persistence highlights the need to identify the reasons for discontinuation of therapy in children in order to obtain better persistence rates.

Factors Associated With Continuing Medical Therapy After Transurethral Resection of Prostate

To report the clinical characteristics of patients who have persistent lower urinary tract symptoms (LUTS) after surgery for benign prostatic hyperplasia (BPH) and continue their medical therapy postoperatively. We retrospectively studied 372 patients who underwent transurethral resection of prostate for LUTS/BPH in 8 institutions to determine the differences between patients who continued LUTS/BPH medications for >3 months after surgery and those who did not. Preoperative, intraoperative, and postoperative clinical parameters were assessed. The Student t test and chi square test were used to compare each parameter between patient groups. Multivariate logistic regression analysis was performed to identify risk factors for persistent LUTS and continuing medical therapy after surgery. There were 205 patients (55.1%) who continued their LUTS/BPH medications for >3 months postoperatively. They reported poorer International Prostate Symptom Scores and uroflowmetry results after surgery. Multivariate analysis showed that age >70 years (odds ratio [OR], 2.474; P = .001), history of diabetes (OR, 1.949; P = .040), history of cerebrovascular accident (OR, 5.932; P = .001), any previous LUTS/BPH medication use (OR, 5.384; P = <0.001), and previous antimuscarinic drug use (OR, 2.962; P = .016) were significantly associated with symptom persistency and continuing medical therapy. Many patients have persistent voiding dysfunction after surgical treatment for LUTS/BPH. Older age, history of diabetes, history of cerebrovascular accidents, and preoperative antimuscarinic drug uses are possible risk factors.

Use of symptom-relieving drugs before and after surgery for urinary incontinence in women: a cohort study

ObjectiveTo describe the use of symptom-relieving drugs (antimuscarinic drugs or duloxetine) before and after surgery for urinary incontinence (UI); and for those with use of antimuscarinic drugs or duloxetine before...

Long-Term Adherence to Antimuscarinic Therapy in Everyday Practice: A Systematic Review

Antimuscarinic drug treatment is known to have side effects and, consequently, poor adherence in therapeutic regimens. In this systematic review we study the long-term (greater than 6 months) adherence to antimuscarinic drugs in daily clinical practice, and identify factors contributing to poor adherence and persistence. This systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed using PubMed® and Embase™ using synonyms for incontinence, overactive bladder and antimuscarinics combined with synonyms for medication adherence. We chose to include only pharmaceutical database studies (using prescription/insurance claim data) and patient self-report studies, using established pharmacoepidemiological parameters such as persistence rate and medication possession rate. A total of 1,245 titles were screened, of which 102 abstracts were assessed. Fourteen studies were ultimately included, comprising 190,279 unique patients (mean age 69.5 years). Regardless of which specific antimuscarinic drug is studied, persistence rates are usually poor. Considering all drugs together, median persistence rates were 12.0% to 39.4% (with an outlier of 75.5%) at 12 months, 8.0% to 15.0% at 18 months and 6.0% to 12.0% at 24 months. At 36 months persistence rates ranged from 0.0% (darifenacin) to 16.0% (trospium). Mean reported medication possession rates were also low, with a mean of 0.37 at 12 months. Risk factors for discontinuation were identified, with the most important being younger age group, use of oxybutynin and use of immediate release formulations. Improvement in adherence and persistence with antimuscarinic medication should be an important goal in the development of new drugs for overactive bladder and urinary incontinence.

Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone

The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate. A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis. Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis. The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.

Spinal cord transection before scoliosis correction in myelomeningocele may improve bladder function

In patients with myelomeningocele (MMC) and coexistent scoliosis, a spinal cord transection (SC-transection) is sometimes performed before scoliosis correction to prevent traction on the myelum after stretching the spinal column. Performing a SC-transection may have positive effects on bladder function, especially in case of refractory detrusor-sphincter dyssynergia. This study investigates the effects of SC-transection on lower and upper urinary tract outcomes. All children with MMC who underwent scoliosis correction (1989-2009) were retrospectively reviewed. Cases were defined as those who underwent a SC-transection before scoliosis correction, whereas the control group comprised children who had a scoliosis correction alone. Urodynamic and clinical outcomes were examined. A total of 7 cases and 13 controls were identified. Postoperatively, compared to the control group, cases had relatively more often improvement of compliance (improvement in 6/7 vs. 9/13) and bladder capacity (improvement in 6/7 vs. 8/13). No effect of SC-transection was found on incontinence severity, clean intermittent catheterization frequency, use of antimuscarinic drugs, or signs of renal damage on ultrasound. SC-transection before scoliosis correction in children with MMC without lower extremity function, may improve bladder function with respect to bladder compliance and bladder capacity. Changes in symptoms or renal ultrasound were not found. No harmful effects of SC-transection were found, indicating that this procedure can be performed safely with respect to bladder function in these patients. Whether or not SC-transection should be recommended during scoliosis correction in patients with MMC to improve bladder function requires further study.

Results of a Randomized Phase III Trial of Mirabegron in Patients with Overactive Bladder

Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects. Mirabegron, a β3-adrenoceptor agonist, may offer an effective and well tolerated alternative treatment for overactive bladder. A randomized, double-blind, placebo controlled trial was conducted in the United States and Canada. After a 2-week placebo run-in period, adults with overactive bladder symptoms for 3 or more months were randomized 1:1:1 to receive placebo, 50 or 100 mg mirabegron once daily for 12 weeks. Efficacy data were collected via patient completed diaries and quality of life assessments. Co-primary efficacy end points were changes from baseline to final visit in mean number of incontinence episodes per 24 hours and micturitions per 24 hours. Key secondary micturition and incontinence end points were also evaluated. Safety assessments included treatment emergent adverse events, laboratory assessments, vital signs, electrocardiograms and post-void residual volume. Compared to placebo, 50 and 100 mg mirabegron groups demonstrated statistically significantly greater mean decreases (95% CI) from baseline for incontinence episodes (-1.13 [-1.35, -0.91], -1.47 [-1.69, -1.25] and -1.63 [-1.86, -1.40]) and micturitions (-1.05 [-1.31, -0.79], -1.66 [-1.92, -1.40] and -1.75 [-2.01, -1.48]) per 24 hours (p <0.05). Significant improvements in all key secondary end points were observed for both mirabegron doses vs placebo. The incidence of frequently reported treatment emergent adverse events (hypertension, urinary tract infection, headache, nasopharyngitis) was similar in the mirabegron and placebo groups. Dry mouth was reported for 1.5%, 0.5% and 2.1% of patients in the placebo, 50 and 100 mg mirabegron groups, respectively. Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects.

Acetylcholine Induces Human Detrusor Muscle Cell Proliferation: Molecular and Pharmacological Characterization

The purpose of the study is to understand whether the cholinergic stimulation is important, not only in inducing contraction of the detrusor muscle, but also in modulating the proliferation of smooth muscle cells. These results could help to better understand the role of antimuscarinic drugs, which are currently used for the treatment of many urological diseases. Primary cultures were prepared from biopsies of human detrusor muscle of subjects >65 years. From the cell culture set-up for each patient, mRNA was extracted and both the gene expression and the influence of increasing passages on the expression of muscarinic receptor subtypes were evaluated by semi-quantitative and quantitative PCR (RT-PCR and Q-RT-PCR). The rate of cell proliferation induced by cholinergic drugs was assessed by the evaluation of the [3H]-thymidine incorporation. The gene expression analysis demonstrated that the range of expression of muscarinic subtypes in human detrusor smooth muscle cells (HDSMCs) is M2 > M3 > M1 > M4 >> M5. The exposure to the cholinergic agonist carbachol induced a concentration-dependent increase in cell proliferation rate. The pharmacological characterization indicated that this effect was mainly mediated by the receptor subtypes M3 and M2. The cholinergic stimulation led to an increase in HDSMC proliferation, suggesting that this phenomenon might be involved in the pathogenic mechanism through which the cervico-urethral obstruction causes a detrusor hypertrophy, followed by a loss of function. These results could then provide an indication of the use of antimuscarinic drugs in the treatment of lower urinary tract disorders.

Repeated Botulinum Toxin Type A Injections for Refractory Overactive Bladder: Medium-Term Outcomes, Safety Profile, and Discontinuation Rates

BackgroundEfficacy and safety of botulinum toxin type A (BoNTA) injection is supported by level 1 evidence, but data regarding repeated injections are limited in patients with refractory overactive bladder (OAB) and idiopathic detrusor overactivity (IDO). ObjectivesDescribe medium-term outcomes and discontinuation rates for patients adopting repeated BoNTA as a management strategy for IDO. Design, setting, and participantsProspective data from a single centre were collected from the first 100 patients. InterventionBladder injection of BoNTA (predominantly 200 U onabotulinumtoxinA; Allergan Ltd., Marlow, Buckinghamshire, UK) in an outpatient setting. MeasurementsOAB symptoms, quality of life, discontinuation rates, interinjection interval, and adverse events were recorded. Data comparisons were performed using a generalised linear model or a chi-square test where appropriate. Results and limitationsTwo hundred seven injections were performed in 100 patients. All patients had 1 injection, 53 had a total of 2, 20 had 3, 13 had 4, 10 had 5, 5 had 6, 3 had 7, 1 had 8, 1 had 9, and 1 had 10 injections. Statistics were applied up to five repeated injections. A statistically significant reduction in frequency, urgency, and urge urinary incontinence were seen following the first BoNTA injection compared to baseline. This improvement was maintained after repeated injections and was not statistically different when comparing differences between injections. Thirty-seven patients stopped treatment after the first two injections; thereafter, dropouts were rare. The most common reasons for discontinuing treatment were poor efficacy (13%) and clean intermittent self-catheterisation (CISC)–related issues (11%). The incidence of CISC after the first injection was 35%. Bacteriuria was detected in 21% of patients. The mean interinjection interval was 322 d. Limitations included the concurrent use of antimuscarinic drugs in some patients. ConclusionsBoNTA can provide a safe and effective medium-term management option for patients with refractory IDO. The most common reasons cited for stopping treatment were poor efficacy and CISC-related issues.

Long-Term Outcome of Transobturator Tension-Free Vaginal Tape: Efficacy and Risk Factors for Surgical Failure

To assess the 5-year efficacy of the inside-out transobturator tension-free vaginal tape (TVT-O) for the treatment of stress urinary incontinence (SUI) and to explore possible predictors for long-term failure. Sixty-five consecutive patients who underwent TVT-O were prospectively enrolled. Patients who required concomitant anterior or apical pelvic organ prolapse repair or both and those with urodynamic occult SUI were excluded. Postoperatively, patients were scheduled for evaluation at 1, 3, 6, and 12 months and annually thereafter. Surgical failure was defined as positive stress test, daily episodes of SUI, and negative global satisfaction. Preoperative and interim clinical and urodynamic predictors for long-term failure were analyzed from a computerized database. Sixty-one patients (mean age at surgery 56.6±10.2 years) completed 5 years of follow-up. Of these, 11 (18%) patients were classified as surgical failure, 5 (8%) as improved, and 45 (74%) as cured. Any SUI (100% vs. 10%, p=0.001), daily SUI (100% vs. 0%, p=0.001), overactive bladder (OAB) (100% vs. 48%, p=0.001), and the use of antimuscarinic drugs (64% vs. 26%, p=0.03) were found to be significantly more common among failure cases. Preoperative detrusor overactivity (odds ratio [OR] 7.6, 95% confidence interval [CI] 1.7-32.9), interim 1-year OAB (OR 20.5, 95% CI 1.9-215.4), and interim 1-year SUI (OR 26.4, 95% CI 1.5-475.2) were found to be significant independent risk factors for long-term surgical failure. An 18% rate of surgical failure was observed 5 years after TVT-O. Larger studies with longer follow-up periods may facilitate the identification of risk factors for failure and, thus, enable better preoperative consultation.

1351 A SIMPLE TOOL FOR PREDICTING REMISSION OF URINARY INCONTINENCE IN PATIENTS UNDERGOING GASTRIC BYPASS

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence—Evaluation & Therapy1 Apr 20111351 A SIMPLE TOOL FOR PREDICTING REMISSION OF URINARY INCONTINENCE IN PATIENTS UNDERGOING GASTRIC BYPASS Emil Kheterpal, Michael Jurewicz, Matt Osher, and Arthur M. Carlin Emil KheterpalEmil Kheterpal Detroit, MI More articles by this author , Michael JurewiczMichael Jurewicz Detroit, MI More articles by this author , Matt OsherMatt Osher Detroit, MI More articles by this author , and Arthur M. CarlinArthur M. Carlin Detroit, MI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1172AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Morbid obesity is an independent risk factor of urinary incontinence and weight loss has been associated with improvement in urinary symptoms. We prospectively evaluated morbidly obese women with urinary incontinence to assess factors that would be predictive of resolution of symptoms after laparoscopic gastric bypass surgery. METHODS The International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) was given to morbidly obese women preoperatively and at 3 and 12 months following lap RYGB. The ICIQ-SF is a validated, reliable, self-administered, easy-to-use, one page questionnaire. Our prospectively maintained bariatric database was utilized to examine preoperative characteristics, ICIQ-SF scores and postoperative weight loss measures for potential predictive value in determining UI remission. Data are expressed as mean ± standard deviation. RESULTS A total of 177 women with UI completed preoperative and 3 and/or 12 month postoperative ICIQ-SF. Mean age, preoperative weight, and BMI were 47 years, 300 lbs and 52 kg/m2 respectively. Preoperative prevalence of UI included 37% stress, 15% urge, and 48% mixed. Complete remission of UI was demonstrated in 71% at 3 months and 80% at 12 months postoperatively. Preoperative age, weight, BMI, use of antimuscarinic drugs, type of UI, presence of comorbidities (diabetes, hypertension, sleep apnea) and postoperative weight loss measures were not predictive of UI remission at either time point. Preoperative ICIQ-SF was significantly lower in those with UI remission both at 3 months (8 ± 5 vs. 10 ± 4; p = 0.014) and at 12 months (8 ± 4 vs. 12 ±4; p <0.001) postoperatively as compared to those without UI remission. If the preoperative ICIQ-SF was < 13, remission of UI 12 months postoperatively was 88% as compared to only 50% in those with a preoperative ICIQ-SF of ≥13 (p <0.001). CONCLUSIONS The ICIQ-SF is a simple tool for predicting UI remission in morbidly obese women undergoing lap RYGB. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e539-e540 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Emil Kheterpal Detroit, MI More articles by this author Michael Jurewicz Detroit, MI More articles by this author Matt Osher Detroit, MI More articles by this author Arthur M. Carlin Detroit, MI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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 β3-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, α-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.

Preventive therapy in perforated colonic diverticular disease? Calcium channel blockers may hold the key

Preventive therapy in perforated colonic diverticular disease? Calcium channel blockers may hold the key

Drug therapy for urinary incontinence

Drugs used for treatment of urinary incontinence may act on the central nervous system (CNS) or peripherally. Few drugs with a defined CNS site of action are available for treatment of urine storage disorders; most of those currently used have a peripheral site of action. To treat bladder overactivity associated with urgency and urge incontinence, antimuscarinic drugs, α-adrenoceptor antagonists, β-adrenoceptor agonists, prostaglandin synthesis inhibitors, and several other agents most often developed for non-urological indications, are employed. Current treatment is based on the use of antimuscarinic drugs, and oxybutynin is, despite a high incidence of side-effects, the gold standard. Pharmacological treatment of stress incontinence has had limited success, and only α-adrenoceptor agonists, with and without combination with oestrogens have had a documented effect. New drugs, specifically directed at treatment of urine storage disorders, are desirable.

An audit of anti-muscarinic drug use at the State Hospital

Aims and MethodThis paper is based on two audits carried out in 1996 and 1998 atThe State Hospital, Carstairs. Each audit looked at anti-muscarinic drug use within the hospital, in relation to approved prescribing standards issued in 1996. All patients within the hospital on anti-muscarinic drugs were identified at the timeof each audit. These prescriptions were compared with the approved prescribing standards. In the 1998 audit additional information was obtained from the case notes and the consultants, when the approved standards were not met.ResultsThe percentage of patients on regular anti-muscarinic drugs, falling outwith the prescribing standards, reduced between the two audits. However, in 1998 a small number of patients were still outwith the approved prescribing standards set in 1996.ConclusionsAn improvement in the prescribing practice of anti-muscarinics occurred following the introduction of prescribing guidelines. However, the guidelines were not fully met in the 1998 audit. This demonstrates the need for further audit and continued monitoring of anti-muscarinic prescription at the State Hospital.