Oxybutynin transdermal gel has been shown to have significant advantages over placebo, in terms of urgency incontinence episodes, urinary frequency and voided volume in a Phase III study. Application site effects were higher in the gel group, but the incidence of antimuscarinic side effects were lower than those seen with oral preparations. The lower incidence of skin side effects, as compared with the transdermal patch, may confer a theoretical advantage toward the gel product. While promising, unanswered questions remain regarding persistence with treatment after this mode of therapy, and head-to-head comparisons with other antimuscarinics are absent.
In the HCl-treated rats, the micturition interval and micturition volume were significantly (48% and 55%, respectively, P <.05) decreased and the number of micturitions was significantly (3.2-fold, P <.05) increased compared with those of the control rats. The maximal number of binding sites for [³H]NMS and [³H]αβ-MeATP was significantly (55% and 72%, respectively, P <.001) decreased in the bladder of HCl-treated rats, suggesting downregulation of both muscarinic and purinergic receptors. In the HCl-treated rats, the inhibition constant, K(i), values for oxybutynin, solifenacin, and darifenacin were significantly (1.3-1.4-fold, P <.05) increased, but those for tolterodine and AF-DX116 were unchanged. Similarly, the inhibition constant for A-317491, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium, and MRS2273 was significantly (5.5, 11, and 7.6-fold, respectively, P <.001) increased. Furthermore, the in vivo release of ATP was significantly (P <.05) enhanced in the HCl-treated rat bladder.
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To investigate the place of urodynamics in the evaluation of patients with symptoms of the overactive bladder by comparing the response to antimuscarinic therapy in those with and with no urodynamically verified symptoms.
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For equivalent doses for each drug, the longer acting preparation of risperidone, but not oxybutynin, is pharmacokinetically more forgiving of noncompliance than the shorter acting counterparts. Further analysis is required to confirm whether these observations are valid clinically.
The objective of this study is to evaluate the cost effectiveness of two new treatments for overactive bladder: once-daily controlled-release oxybutynin, and twice-daily tolterodine, with a comparison with oxybutynin immediate release. Also estimated are the potential cost savings to a health plan budget resulting from increased utilization of the most cost-effective treatment. The design is a decision-tree model based on clinical trial data and expert panel estimates with a six-month time horizon conducted from a payer perspective. The primary outcome measure used in the analysis was treatment success, with success defined as zero incontinence episodes per week. A secondary outcome measure was the expected number of continent days. As first-line therapy, controlled-release oxybutynin is the most cost-effective treatment as measured by expected cost per success and expected cost per continent days. Controlled-release, once-daily oxybutynin yielded the highest expected success rate and the highest number of expected continent days. The expected cost of treatment with controlled-release oxybutynin was lower than tolterodine and equivalent to immediate-release oxybutynin. Increased utilization of controlled-release oxybutynin results in an estimated saving of $0.007 to $0.026 per member per month for a hypothetical HMO. The model was robust, incorporating all assumptions based on univariate and multivariate sensitivity analysis. Initiating treatment with controlled-release oxybutynin is the most cost-effective approach to treatment for overactive bladder.
Primary nocturnal enuresis is one of the most frequent complaints in paediatric and urologic practice. Physicians face the dilemma of whether or not to treat primary nocturnal enuresis since the trend towards spontaneous remission is countered by social disadvantages and reduced self esteem of the children affected and their families. We reviewed randomised, controlled trials investigating efficacy and adverse effects of current medical treatment for primary nocturnal enuresis. Only desmopressin and imipramine displayed significant effects in reducing wet nights: when compared with baseline bedwetting or placebo controls, 30-70% of the studied children achieved therapeutic success. For drugs such as indometacin or oxybutynin, convincing studies displaying a significant positive effect are still needed. However, considering the adverse effects profiles of desmopressin and imipramine it can be seen that imipramine is associated with about twice as many unwanted reactions. More importantly, a serious adverse effect of imipramine is sudden cardiac arrest. In general, adverse effects with desmopressin are rare and mild, but there have been a number of case reports of hyponatraemic hypervolaemia associated with coma and seizures. Of these, many cases were attributed to excess water intake before taking the drug and all children recovered fully. In summary, if medical treatment is considered, preference should be given to desmopressin.
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In all, 127 patients given propiverine and 128 given oxybutynin were enrolled. The primary efficacy outcome, i.e. reductions in urodynamically assessed individual maximum detrusor pressure (P(detmax)), was assumed to indicate success in 74.2% of those on propiverine vs 49.6% on oxybutynin. The mean P(detmax) was significantly reduced during treatment, from 59.8 to 36.7 cmH(2)O in the propiverine and from 65.2 to 54.9 cmH(2)O in the oxybutynin groups. The mean maximum cystometric bladder capacity increased from 146 to 242 mL in the propiverine and from 222 to 310 mL in the oxybutynin group. Propiverine was better tolerated than oxybutynin, having fewer adverse drug reactions (9.4% vs 17.2%, odds ratio 2.04), and for its severity grades and premature treatment termination (none vs 11 cases).
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Oral administration of oxybutynin chloride is effective in increasing bladder capacity in patients with neurogenic bladder dysfunction who are practising clean intermittent catheterisation, but it is often associated with systemic side effects. The effect of intravesical instillation of oxybutynin chloride was studied in 14 patients who were practising clean intermittent catheterisation and in whom the maximum cystometric capacity was < 250 ml and/or vesical compliance < 5. A 5-mg tablet of oxybutynin chloride was crushed and suspended in 10 ml of boiled and cooled water and instilled into the bladder after emptying it completely; this was carried out thrice daily either by the patient or by his carer. During follow-up (6-12 months) no local or systemic side effects were observed and patient compliance was excellent in 12 patients, who showed an increase in maximum cystometric capacity and vesical compliance. One patient could not retain the drug intravesically because of reflex detrusor contraction and he was excluded from the study. One patient was lost to follow-up. The results suggest that the intravesical instillation of oxybutynin chloride is safe and effective in the treatment of selected patients with neurogenic bladder dysfunction whose bladder capacity is small and who are practising clean intermittent catheterisation.
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Bladder compliance was decreased in 14 (28%) patients and normal in 36 (72%) patients. There was a significantly long time interval between the onset of injury and the initiation of rehabilitative treatment in the neurogenic bladder group with low compliance when compared to those of the normal compliance group (P < 0.05). Clean intermittent catheterization was used as the voiding method, significantly less than the normal compliance group (P < 0.05). ADC was observed in six out of fourteen patients with low compliance neurogenic bladder, but none in the normal compliance group. Upon the completion of conservative treatment, ADC disappeared in four patients whose compliance and capacity of the bladder were normalized on follow-up urodynamic studies.
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Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years.
The potency and selectivity of (-)cis-2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5 benzothiazepin-4-(5H)one HCl (BTM-1086) for muscarinic receptor subtypes was compared in functional assay systems, in guinea pig peripheral tissues, to known reference drugs: atropine (nonselective), pirenzepine (M1), AF-DX 116 (M2) and HHSiD (M3). Like atropine, BTM-1086 was a potent, nonselective, competitive muscarinic antagonist with no detectable antispasmodic activity in urinary bladder or ileal muscle. In vivo, in the guinea pig cystometrogram, BTM-1086 depressed intravesical bladder pressure (PvesP) with the same efficacy and potency as oxybutynin, a drug used clinically for the treatment of urinary incontinence. The pharmacological profile of BTM-1086, however, suggests that it may not be suitable for development for bladder dysfunction disorders.
The data were too few and of insufficient quality to provide empirical support for or against the intervention of timed voiding.
Forty-seven males referred due to postprostatectomy urinary incontinence (34 after transurethral resection of prostatic adenoma and 13 after open suprapubic adenomectomy) were retrospectively studied. Urodynamic evaluation identified 19 (40.4%) men with incontinence due solely to sphincter incompetence, and 19 (40.4%) men, in addition to sphincter incompetence, had urinary bladder dysfunction (unstable detrusor and/or reduced bladder compliance). Seven (14.8%) men had pure bladder dysfunction as the only cause of urinary incontinence. Two patients had normal urodynamic findings (N = 2; 4.2%). Men with urinary incontinence due only to sphincter incompetence were treated by insertion of artificial sphincter devices or condom catheter drainage (lack of artificial sphincters), while others were treated pharmacologically (imipramine, propantheline, oxybutynin or their combinations ... N = 25), or by augmentation cystoplasty using ileum after unsuccessful pharmacological treatment (N = 3). Out of 25 patients with pharmacological treatment, 21 were available for the final assessment of the treatment efficacy. Eleven (52.3%) patients were "socially continent" after the treatment. It is concluded that in the assessment of the cause of postprostatectomy urinary incontinence urodynamic evaluation is mandatory, and that the treatment should be based on the results of such studies. The role of bladder dysfunction as a cause of postsurgical urinary incontinence is again strongly emphasized.
Desmopressin is more effective and has lower rate of side effects in comparison to oxybutynin for treatment of nocturnal enuresis. We recommend using Desmopressin for treatment of nocturnal enuresis in children. More studies are needed to achieve the best pharmacological treatment option for treatment of nocturnal enuresis.
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This randomized, open-label, community-based study enrolled 2878 participants aged >/=18 years who had been given a diagnosis of OAB. The 327 study sites were representative of various practice types. All participants were treated with OXY-TDS 3.9 mg/day for =6 months. HRQoL was assessed using the King's Health Questionnaire (KHQ); the primary endpoint was the change in KHQ scores from baseline to study end.
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Cross-sectional study of a stratified, representative sample of 193 facilities in four states.
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The oxybutynin solution remained stable up to 24 months. In 13 of the 15 children therapeutic compliance was excellent. Detrusor hyperactivity decreased and systemic side effects were absent or minimal. After 4 and 24 months mean cystometric bladder capacity plus or minus standard error of mean increased from 114+/-15.2 to 161+/-26.6 and 214+/-21.7 ml. (p <0.01), mean ratio of cystometric-to-expected bladder capacity increased from 0.88+/-0.12 to 1.18+/-0.14 and 1.24+/-0.16 (p <0.01), and end filling bladder pressure decreased from 57.0+/-7.1 to 25.6+/-4.4 and 30.8+/-4.4 cm. water (p <0.01), respectively.
To examine the response to conversion from regular oxybutynin (Ditropan) to an extended-release form (Ditropan XL) in children with persistent daytime urinary incontinence.
Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date.
The stiffness characteristics of the empty and filling bladder and the modulating influence of oxybutynin were investigated using a new biosensor system. Studies were done comparing the stiffness measured using the pressure/volume relationship with direct biosensor monitoring on male and female rats during isovolumetric contractions elicited during the cystometrogram (CMG). Bladder stiffness at zero volume, measured in vitro using the biosensor, was evaluated and compared with the stiffness of the prostate, seminal vesicles, testicles, and uterus. In 5 small anesthetized male rats, in vivo isovolumetric studies were performed and bladder stiffness was measured during the storage and contraction phase of the CMG. In 6 mature female rats, change in bladder stiffness during isovolumetric contractions was investigated following intraarterial (i.a.) administration of 0.1 and 1.0 mg/kg of oxybutynin. After the in vivo CMG was completed, an in vitro CMG was done measuring bladder stiffness. The results show that bladder stiffness, measured during the storage phase of the CMG, increased in accordance with the stretched length of bladder wall. During the in vivo CMG, bladder stiffness increased consequent to a spontaneous contraction from 10.0 +/- 1.9 g/cm to 29.9 +/- 3.0 g/cm (P < 0.005). Oxybutynin produced a significant decrease in bladder stiffness during the storage phase of the CMG, as measured using the biosensor, which was concomitant with an increase in bladder compliance derived from pressure/volume data. The incremental change in stiffness, delta K, during isovolumetric contraction decreased due to i.a. oxybutynin in accordance with a decrease of maximum detrusor pressure. These results indicate that delta K is related to the active change of viscoelastic properties of bladder smooth muscle. These findings imply that direct measurement of the stiffness of the bladder wall possesses the potential to be an objective assessment of bladder biomechanical properties and of their functional response to obstruction and pharmacological intervention.
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A literature search was conducted from 1966 to May 2011. Meta-analysis of all published randomised controlled trials (RCTs) comparing anticholinergic drugs with placebo and comparing different types, doses, and routes of administration of anticholinergic drugs, in adults with NDO, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The primary outcome was patient-reported cure/improvement of overactive bladder symptoms. Secondary outcomes were quality of life (QoL) changes, bladder diary events, urodynamic outcomes, adverse events, and costs to health services.
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We investigated the effects of the novel gastroprokinetic agent Z-338 (N-(N-N'-diisopropylaminoethyl)-[2-(2-hydroxy-4,5-dimethoxybenzoylamino)-1,3-thiazole-4-yl] carboxyamide monohydrochloride trihydrate) on L-type voltage-dependent Ca2+ currents (ICa) in guinea pig gastric myocytes by using the whole-cell patch clamp technique. Bath-applied acetylcholine (ACh) produced biphasic effects on ICa, i.e., enhancement (1-100 nM) and inhibition (1-100 microM), both of which were abolished by pretreatment with atropine (10 microM) or intracellular perfusion of GDPbetaS (500 microM). Z-338 (> or = 1 nM, ED50: 120 nM) mimicked the enhancing effects of ACh, but did not inhibit ICa. The effects of Z-338 and ACh were non-additive and blocked by atropine and GDPbetaS, but not by pertussis toxin (PTX) pretreatment (500 ng/ml). ACh (> or = 1 microM) induced slow inward currents via activation of the muscarinic receptor/PTX-sensitive G-protein pathway, but Z-338 was devoid of these effects. Neither pirenzepine (1 microM), AF-DX116 (1 microM), nor oxybutynin (100 nM) could prevent Z-338 (1 microM) and ACh (10 nM) from enhancing ICa, whilst 4-DAMP (100 nM) blocked the effects of Z-338 and ACh. Bath-application of protein kinase C (PKC) activator PDBu (phorbol-12,13-dibutyrate) (250 nM) enhanced ICa, and conversely, pipette inclusion of PKC inhibitor peptide (150 microM) abolished the effects of ACh and Z-338 on ICa. These results collectively suggest that although contribution of the M3 receptor is not excluded, the major actions of Z-338 on gastric myocytes are potentiation of ICa through activation of M5-like receptor.
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Two newer antimuscarinic anticholinergic drugs--tolterodine and extended-release oxybutynin--are approximately as effective in treating overactive bladder as immediate-release oxybutynin, but are more tolerable. I review clinical trial data on the newer agents.
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We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis.
This review summarizes the pharmacological properties and the clinical efficacy and safety profile of OTG based on the published literature and unpublished data provided by the manufacturer upon request.
To evaluate the effects of tolterodine and oxybutynin on visual accommodation, pupillary diameter, intraocular pressure and tear secretion in women with overactive bladder.
The GABAB receptor agonist baclofen reduces urethral resistance and detrusor overactivity in patients with spasticity. However, baclofen's side effects limit its use for the treatment of overactive bladder (OAB). Here, we tested a novel GABAB positive allosteric modulator (PAM) ADX71441 in models of OAB in mice and guinea pigs.