Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine.
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• Twelve months after the initial prescription, persistence rates with pharmacotherapy in the context of OAB are generally low. • Solifenacin was associated with higher levels of persistence compared with other prescribed antimuscarinic agents. • Older people are more likely than younger patients to persist with prescribed therapy. Further studies are required to understand this finding and why patients are more likely to persist with one drug rather than another.
The study included 240 children with day-time urinary incontinence. Of these, 45 had faecal problems and 17% obtained urinary continence when these were successfully treated. In total, 126 (55%) became dry on standard urotherapy. Of the 60 children who had a timer-watch in addition to standard urotherapy, 70% became dry. Of the 62 children who had anticholinergics in addition to standard urotherapy, 81% became continent. Fifteen (6%) did not achieve continence and another 11 patients were lost to follow-up. Children who became dry solely on standard urotherapy had a significantly lower voiding frequency (p<0.05), larger voided volumes as a percentage of those expected for age (p<0.01) and fewer incontinence episodes per week (p<0.05) than children needing anticholinergics.
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Seventy two cardiac transplantations have been performed in children under 16 years of age. All recipients who were alive and over 4 years of age at the time of the study received a questionnaire about urinary symptoms; 54 of the 57 eligible children participated.
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The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats.
There are no data from placebo controlled trials regarding the efficacy of naftopidil in men with symptomatic BPH. Limited information suggests that treatment with naftopidil provides short-term improvement in urinary symptom-scale scores (total IPSS/AUA), QoL (quality of life) score, and urinary symptoms from baseline comparable to low-dose tamsulosin. Adverse effects due to naftopidil were few and usually mild.
Anticholinergic agents are used for treatment of overactive bladder syndrome (OAB) by competitive blockade of acetylcholine at the muscarinic receptor. At present five different subtypes of M-receptors can be differentiated. Primary detrusor effects are mediated by M3-receptors as are side effects like dry mouth and constipation. Cardiac and central nervous system side effects appear to be M2 or M1 related. OAB symptom relief by the unselective drugs tolterodine, oxybutynin or trospium chloride and by M3-selective agents like darifenacin or solifenacin seems to be rather similar. Central side effects are different depending on gastrointestinal reabsorption, serum metabolism and penetration of the blood-brain barrier. Slow release formulations may be better tolerated. Anticholinergics that penetrate the blood-brain barrier may cause cognitive imbalance in older patients, as recent studies have shown for oxybutynin. Here M3-selective agents may offer an advantage.
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Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments.
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To assess the effects of ES with non-implanted electrodes for OAB, with or without urgency urinary incontinence, compared with: placebo or any other active treatment; ES added to another intervention compared with the other intervention alone; different methods of ES compared with each other.
Nocturnal enuresis, or bedwetting, is the most common cause of urinary incontinence in children. It is known to have a significant psychosocial impact on the child as well as the family. Nocturnal enuresis typically presents as failure to become dry at night after successful daytime toilet training. It can be primary or secondary (developing after being successfully dry at night for at least 6 months). Children with nocturnal enuresis may have excessive nocturnal urine production, poor sleep arousal and/or reduced bladder capacity. Alarm therapy is the recommended first-line therapy, with treatment choices being influenced by the presence or absence of the abnormalities mentioned above. Children with nocturnal enuresis may also have daytime urinary urgency, frequency or incontinence of urine. This group (non-monosymptomatic nocturnal enuresis) requires a different clinical approach, with a focus on treating daytime bladder symptoms, which commonly involves pharmacotherapy with anticholinergic medications and urotherapy (including addressing bowel problems). This review discusses the current management of nocturnal enuresis using the terminologies recommended by the International Children's Continence Society.
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All children diagnosed with pelvic floor spasms underwent biofeedback pelvic floor relaxation therapy in order to learn them to counteract pelvic pain due to these spasms. In those girls in whom detrusor hyperactivity was seen on urodynamics concomitant anticholinergic treatment was given (oxybutynin).
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Overweight and obese patients with palmar or axillary hyperhidrosis present significant improvement in QOL after treatment with oxybutynin, and the results are comparable to those of normal weight individuals.
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To perform two network meta-analyses summarizing the efficacy and adverse events of antimuscarinics in the treatment of OAB.
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The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.
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The discussion outlines potential mechanisms and management of clozapine-related constipation.
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The medium term efficacy of the treatment of detrusor instability and low compliance is disappointing, and a large part of this failure may be attributable to poor treatment efficacy, side effects of medication, or inadequate follow up following the diagnosis and instigation of therapy.
Tolterodine is the first antimuscarinic agent to specifically developed for the treatment of overactive bladder. The functional selectivity of tolterodine for the bladder translates into good efficacy and tolerability in patients, including the elderly, with overactive bladder. Tolterodine is as effective as oxybutynin in improving micturition diary variables but is associated with a significantly lower incidence and intensity of dry mouth. This favourable tolerability profile, together with sustained clinical efficacy during long term treatment, places tolterodine as valuable treatment for the symptoms of overactive bladder.
To verify whether the combination of transcutaneous electrical neural stimulation (TENS) with oxybutynin in the treatment of women with overactive bladder (OAB) would be more effective than isolated treatments.
We propose a population pharmacokinetic (PK) model with time-dependent covariates measured with errors. This model is used to model S-oxybutynin's kinetics following an oral administration of Ditropan, and allows the distribution rate to depend on time-dependent covariates blood pressure and heart rate, which are measured with errors. We propose two two-step estimation methods: the second-order two-step method with numerical solutions of differential equations (2orderND), and the second-order two-step method with closed form approximate solutions of differential equations (2orderAD). The proposed methods are computationally easy and require fitting a linear mixed model at the first step and a nonlinear mixed model at the second step. We apply the proposed methods to the analysis of the Ditropan data, and evaluate their performance using a simulation study. Our results show that the 2orderND method performs well, while the 2orderAD method can yield PK parameter estimators that are subject to considerable biases.
The incidence of inappropriate prescribing is higher amongst the older age group than the younger population. Inappropriate prescribing potentially leads to drug-related problems such as adverse drug reactions. We aimed to determine the prevalence of inappropriate prescribing in residents of Tasmanian (Australia) residential care homes using Beers and McLeod criteria.
Using standardized protocols, reviewers abstracted cases of continence, improvement of urinary incontinence, and prevalence of urinary incontinence to calculate risk difference.
The subtypes of the muscarinic cholinergic receptor in human detrusor muscle were studied using radioligand binding techniques. It was found that there were significant amount of M1, M2 and M3 receptors labeled by 3H-pirenzepine, 3H-AFDX and 3H-4DAMP, respectively, in human detrusor muscle. The rank order of the amount of these receptors was M3 > M1 > or = M2. The amount of M3 receptors was about 10-fold of M1 or M2. In the inhibition experiment of 3H-QNB binding to human detrusor muscle, the Ki values of pirenzepine or AFDX was 50-100 fold of that of 4DAMP and the rank order of Ki values was pirenzepine > AFDX > 4DAMP. The M3 selective drug, 4DAMP showed smallest Ki value among the three drugs studied, indicating that the affinity of M3 receptor was highest among the three muscarinic subtypes. These data suggest that M3 receptors are predominant in human detrusor muscle biochemically.
Urine from 40 healthy volunteers, half of them male and half female, was collected in the morning, afternoon and evening on 2 occasions 3 months apart. Morning urine samples were collected from 37 female naïve patients with overactive bladder. A total of 24 patients were followed. Urine was collected after a 3-month lifestyle intervention and after 3-month antimuscarinic treatment (oxybutynin 10 mg, extended release). Urinary nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor concentrations were measured by enzyme-linked immunosorbent assay and normalized to creatinine. Patients completed a 7-day bladder diary combined with an urgency severity scale. The number of urgency episodes per week was counted.
When protamine sulfate was infused intravesically, the intercontraction interval (ICI) did not decrease significantly, but intravesical instillation of ATP after protamine sulfate treatment decreased the ICI compared with baseline. Oxybutynin, propiverine, and PPADS given intravenously reversed the ATP-induced ICI reduction in a dose-dependent manner. In contrast, ATP-induced ICI reduction was not reversed by intravenous atropine, 4-DAMP, or methoctramine. Maximum voiding pressure did not change with ATP but decreased with antimuscarinics. Pressure threshold (PT) decreased with ATP and stayed reduced after dose of oxybutynin or propiverine.
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To evaluate the effectiveness and patient satisfaction with the use of oxybutynin at low doses for treating palmar hyperhidrosis in a large series of patients.
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To evaluate Overactive bladder (OAB) with detrusor overactivity (DOA) following oxybutynin or tolterodine treatment in recommended doses at a four-week course. A total of 100 Iranian women 45 years or older with urgency that also showed idiopathic detrusor overactivity (IDO) in the filling phase of their cystometry were included in the current study. In this double-blinded trial two parallel groups were randomized by using two kinds of the antimuscarinic drugs for a four- week course [oxybutinin 5mg, t.d.s. or Tolterodin 2mg, b.i.d.] in the same packages. Data were collected from three-day frequency volume chart (FVC) one month before and after the treatment course. The effectiveness of each drug was compared using the paired, samples t-test. Patients' improvement regarding urinary urgency, frequency and urge incontinence after treatment in both groups was seen, but mean improvements in the terms of urgency and urge incontinence were larger in patients who were treated by oxybutynin. Night-time frequency was shown to be improved by a significantly larger score by tolterodine. Discontinuation of treatment due to adverse events had no significant difference in two groups. Four-week treatment with oxybutynin was better than tolterodine IR in improving urgency and urge incontinence, but there were not statistically significant difference between them. In planning a course of treatment especially in the elderly, the difference in the group of symptoms that reduce patients' quality of life should be considered. Physicians should consider the patient's prominent symptom in selection of anti-muscarinic drugs for the treatment of overactive bladder syndrome especially in elderly patients.
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A literature review.
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Prevalence of xerostomia, dental morbidity, salivary flow, and food avoidances.
Multiple eccrine hidrocystomas are benign cystic skin lesions which originate from the sweat gland ducts and typically affect women's midfacial area. Sweating may lead to an increase in size of the translucent papules. In some cases hidrocystomas are associated with other diseases such as Parkinson's disease. Treatment options include laser, topical and systemic anticholinergic drugs (glycopyrrolate, clonidine, atropine, and oxybutynin), whereby therapeutic success is limited in most cases.
We compared the short-term risk of falls among recipients of oxybutynin or tolterodine to treat urinary incontinence.
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A total of 54 patients with attention deficit hyperactivity disorder and nocturnal enuresis were randomly stratified into 2 groups. Demographic data on patient age and gender were identical in the 2 groups. Functional bladder symptoms were judged using the dysfunctional voiding symptoms survey. The initial dysfunctional voiding symptoms survey score was similar in the 2 groups. The total survey score was compared between the 2 groups in aggregate as well as specifically regarding the incidence of nocturnal enuresis following treatment.
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This review considers intravesical treatment options of neurogenic detrusor overactivity and discusses the underlying mechanism of action, clinical safety and efficacy, and the future trends.