Pharmacological Treatment Of Overactive Bladder Research Articles

Inhibition of prejunctional parasympathetic pathways by β3-adrenoceptor agonists in the isolated pig detrusor: comparison with human detrusor studies.

Adrenergic receptors of the β3-subtype (β3-ADRs) seem to represent a new target for a more effective pharmacological treatment of overactive bladder (OAB), a wide spread urinary disorder. A promising opportunity for OAB therapy might rely on the development of selective β3-ADR agonists, but an appropriate preclinical screening, as well as investigation of their pharmacological mechanism(s), is limited by poor availability of human bladder samples and of translational animal models. In this study, we used the porcine urinary bladder as experimental tool to ascertain the functions of β3-ADRs in the control the parasympathetic motor drive. Tritiated acetylcholine ([3H]-ACh), mainly originated from neural stores, was released by electrical field stimulation (EFS) in epithelium-deprived detrusor strips from pigs bred without estrogens. EFS produced simultaneously [3H]-ACh release and smooth muscle contraction allowing to asses neural (pre-junctional) and myogenic (postjunctional) effects in the same experiment. Isoprenaline and mirabegron produced on the EFS-evoked effects a concentration-dependent inhibition antagonized by L-748,337, a high selective β3-ADR antagonist. The analysis of the resultant pharmacodynamic parameters supports the notion that in pig detrusors, as well as in previously described human detrusors, the activation of inhibitory β3-ADRs can modulate neural parasympathetic pathways. In such inhibitory control, the involvement of membrane K+ channels, mainly of the SK type, seems to play a pivotal role similarly to what previously described in humans. Therefore, the isolated porcine detrusor can provide a suitable experimental tool to study the mechanisms underlying the clinical efficacy of selective β3-ADR compounds for human use.

Mirabegron and Physical Exercise Is a Potential Strategical for BAT Activation in Obesity

(1) Background: Obesity is a global epidemic issue that has increased greatly in recent decades. Although interventions such as nutritional approaches and the practice of physical exercise are potential therapies to combat obesity, in some cases they are not sufficient. Therefore, the development of new pharmacological treatments is necessary. Combining these therapies with non-pharmacological alternatives could be an interesting strategy for treating obesity. Considered a pharmacological treatment for overactive bladder (OAB), mirabegron is also categorized as a β(3)-adrenoceptor agonist, and is used in recommended doses of 25 mg and 50 mg. Animal models have shown that the administration of 0.8 mg/kg of mirabegron leads to elevated activation of brown adipose tissue (BAT) and white adipose tissue (WAT) browning. (2) Results: Findings suggest that the pharmacological application of mirabegron has numerous beneficial effects in lipid metabolism, suggesting a potential action against obesity. In this context, physical exercise and mirabegron stimulate browning activation using different mechanisms. (3) Conclusions: According to the results of the studies presented in this review, mirabegron may be a promising pharmacological treatment for obesity due to its significant effects on estimated energy expenditure (EER) through thermogenesis elevation, BAT activation, and WAT browning seen in dosages up to 100 mg. In addition, the administration of mirabegron combined with physical exercise may be a potential alternative for increasing the body’s energy expenditure, with actions in distinct signaling pathways. Thus, physical exercise combined with mirabegron can alleviate some adverse side effects encountered with the use of the medication. Finally, although there have been advances in knowledge, more studies are needed to understand the combined effects of using mirabegron and physical exercise.

Mirabegron, alone and in combination, in the treatment of overactive bladder: real-world evidence and experience.

Overactive bladder (OAB), the syndrome characterized by urgency, with or without urgency incontinence, usually with frequency and nocturia, in the absence of infection or other pathology, is a common, distressing and often debilitating condition with a high prevalence in the general population. For many years, the only available pharmacological treatment for OAB were the antimuscarinic agents. More recently, mirabegron, a selective agonist of the β3 adrenergic receptor, has become available. In this article we review the current evidence and experience of its use.

Choosing oral drug therapy for overactive bladder in older people

ABSTRACTIntroduction: Overactive bladder (OAB) and urgency incontinence are common in older people. Nevertheless, there remains a paucity of prospectively collected data on the efficacy of commonly used drug treatments for the condition. Many trials have included older people, but have seldom reported results stratified by age or reported adverse events of particular relevance to older people in clinical practice. This has partially been rectified with the introduction of more recently introduced antimuscarinic agents, particularly fesoterodine, and the beta-3-agonist, mirabegron.Areas covered: This article discusses evidence from recent trials relevant to robust and medically complex older people including synthesis of evidence on the association of anticholinergic medications and impaired cognition with relevance to OAB medicationsExpert opinion: There are increasing data concerning pharmacological therapy in both robust and medically complex older adults. There is a need to explore the efficacy and tolerability of pharmacological treatment of OAB and UUI (urgency urinary incontinence) in specific subgroups and to produce confirmatory real-world data on efficacy and tolerability. Guidelines which address treatment of older people is currently sparse but, as time progresses and data improve, more specific guidance should become available.

Nerve Stimulation Vs Pharmacological Treatment for Overactive Bladder

Nerve Stimulation Vs Pharmacological Treatment for Overactive Bladder

Pharmacological Characterization of a Novel Beta 3 Adrenergic Agonist, Vibegron: Evaluation of Antimuscarinic Receptor Selectivity for Combination Therapy for Overactive Bladder.

Although the physiologic role of muscarinic receptors in bladder function and the therapeutic efficacy of muscarinic antagonists for the treatment of overactive bladder are well established, the role of β3-adrenergic receptors (β3ARs) and their potential as therapeutics is just emerging. In this manuscript, we characterized the pharmacology of a novel β3AR agonist vibegron (MK-4618, KRP-114V) and explored mechanistic interactions of β3AR agonism and muscarinic antagonism in urinary bladder function. Vibegron is a potent, selective full β3AR agonist across species, and it dose dependently increased bladder capacity, decreased micturition pressure, and increased bladder compliance in rhesus monkeys. The relaxation effect of vibegron was enhanced when combined with muscarinic antagonists, but differentially influenced by muscarinic receptor subtype selectivity. The effect was greater when vibegron was co-administered with tolterodine, a nonselective antagonist, compared with coadministration with darifenacin, a selective M3 antagonist. Furthermore, a synergistic effect for bladder strip relaxation was observed with the combination of a β3AR agonist and tolterodine in contrast to simple additivity with darifenacin. To determine expression in rhesus bladder, we employed a novel β3AR agonist probe, [3H]MRL-037, that selectively labels β3 receptors in both urothelium and detrusor smooth muscle. Vibegron administration caused a dose-dependent increase in circulating glycerol and fatty acid levels in rhesus and rat in vivo, suggesting these circulating lipids can be surrogate biomarkers. The translation of our observation to the clinic has yet to be determined, but the combination of β3AR agonists with M2/M3 antimuscarinics has the potential to redefine the standard of care for the pharmacological treatment of overactive bladder.

Antimuscarinic Medication Use in Elderly Patients with Overactive Bladder.

Antimuscarinic medications are the first-line pharmacological treatment for overactive bladder (OAB); however, little is known about the utilization pattern of antimuscarinic agents in elderly patients with OAB. This study examined the prevalence and predictors of antimuscarinic medication prescribing in elderly patients with OAB, using national ambulatory survey data. This cross-sectional study utilized the 2009-2010 National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Medical Care Survey. The study included patients aged ≥65years diagnosed with OABbased on the International Classification of Diseases. Antimuscarinic medications were operationally defined using the American Hospital Formulary Service classification and identified using Multum Lexicon codes. Descriptive statistics using sampling weights were used to estimate the prevalence of antimuscarinic medication prescription, while multivariable logistic regression within the conceptual framework of the Anderson Behavioral Model was used to identify the factors associated with antimuscarinic medication prescription in elderly patients with OAB. According to the national surveys, 2.18 million (95% confidence interval [CI] 1.62-2.75) elderly outpatient visits were made for OAB, of which 0.90 million (41.43%) visits involved prescribing of antimuscarinic medications. The most frequently prescribed drugs were solifenacin (14.25%), oxybutynin (10.50%), and tolterodine (6.89%). Multivariable analysis revealed that patients ≥85years of age (odds ratio [OR] 3.50, 95% CI 1.23-9.92) were more likely to receive antimuscarinic medications,and the South region (OR 2.78, 95% CI 1.01-7.66) increased the likelihood of receiving antimuscarinic medications in elderly patients with OAB. This study found that antimuscarinic medications are commonly prescribed for elderly patients with OAB and there is variation in antimuscarinic use across age and region.

Estimated Budget Impact of Increased Use of Mirabegron, A Novel Treatment for Overactive Bladder.

BACKGROUND: Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient’s anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient’s ACB. OBJECTIVE: To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model. METHODS: For this budget impact model, 2 analyses were performed. The primary analysis estimated the b...

Persistence and adherence with the new beta-3 receptor agonist, mirabegron, versus antimuscarinics in overactive bladder: Early experience in Canada.

Antimuscarinics are the principal pharmacological treatment for overactive bladder (OAB), but frequently give rise to anticholinergic side effects, such as dry mouth, a factor leading to poor persistence. The β3-adrenoceptor agonist mirabegron is devoid of significant anticholinergic activity, while being effective in OAB. We evaluated persistence and adherence with mirabegron versus antimuscarinics over 12 months. We obtained retrospective claims from a Canadian Private Drug Plan database for patients 18 years old and over, with a first claim for mirabegron or antimuscarinics during a 6-month index period (April-September 2013). A 6-month look-back identified those with no prior claims for OAB medication (treatment-naïve) or ≥1 prior OAB drug (treatment-experienced). Time to end of persistence (≥30 day therapy gap or switch of therapy) was evaluated over 12 months; adherence with medication (medication possession ratio) was also measured. Persistence data from 19 485 patients (74% female, 92% naïve, 19.9% aged ≥65 years) showed that for experienced patients the median number of days on mirabegron was 299 days, compared with a range of 96 to 242 days for the different antimuscarinics; for naïve patients, it was 196 versus 70 to 100 days, respectively. Persistence at 12 months was for mirabegron 39% versus 14% to 35% for antimuscarinics, (experienced) and 30% mirabegron versus 14% to 21% antimuscarinics, (naïve). Patients taking mirabegron demonstrated statistically significantly greater adherence than those taking antimuscarinics. Patients who received mirabegron remained longer on treatment than those treated with antimuscarinics, and had higher 12-month persistence and adherence rates.

The new era in the pharmacological treatment of overactive bladder (OAB): mirabegron--a new selective beta3agonist

Overactive bladder is defined by ICS as urgency frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection, or other obvious causative pathology Lower urinary tract symptoms (LUTS) are highly prevalent, especially in aging populations. Epidemiological studies reported LUTS in 62% of men and 67% of women, rising to 81% and 79%, respectively in adults over 60 years old. However the actual burden of LUTS remains relatively unrecognized. LUTS, mainly due to considerable distress including almost all aspects of social functioning, impact on sleep and mental health, may significantly affect quality of life. Management of LUTS including OAB has undergone dramatic changes since 1972, when the first antimuscarinic drug-oxybutynin, was introduced into clinical practice. In the last two decades, six new antimuscarinic drugs entered OAB field and this was accompanied by introduction of botulinum toxin into clinical practice in patients resistant to or not compliant with antimuscarinics. Nowadays, it is recognized that OAB is progressive, age-related and non sex-specific condition with most patients experiencing a combination of storage, voiding and post-micturition symptoms. In 2013, the next step was taken, with new therapeutic options for OAB, enabling an even more patient-tailored approach. This was possible for both, male and female OAB sufferers with new class of oral 3 adrenoreceptor agonist (mirabegron). This drug, by stimulation of 3-adrenoceptors, couples via Gs proteins to adenylyl cyclase, what results in an increase of intracellular cAMP levels and a subsequent activation of cAMP-dependent protein kinase A, which then phosphorylates myosin light chain kinase responsible for inhibition of calcium-calmodulin dependent interaction of myosin with actin. Moreover the cAMP increase also leads to the reduction of cytoplasmic Ca2+ concentration by removal of calcium ions from cytoplasm. These both actions result in a significant increase in the storage bladder capacity and by this interval between micturitions is prolonged. Mirabegron was evaluated in three 12-week, double blind, randomized, placebo controlled, parallel-group, multicenter clinical trials in OAB patients with symptoms of urge urinary incontinence, urgency and frequency - study 046, 047 and 074. It should be pointed out that efficacy of mirabegron was maintained through the entire 12-month period in phase Ill long-term study Discoveries on the physiology of the normal bladder and on the pathophysiology underlying OAB have led to the development of new treatment options for OAB. Pharmacological management of OAB should be tailored to patient's characteristics. New and recent options of pharmacological treatment have undoubtedly expanded treatment possibilities, what should allow physicians to select the optimal treatment for each patient.

New developments in the management of overactive bladder: focus on mirabegron and onabotulinumtoxinA

In the last few years, much new information has been generated on the pathophysiology, possible therapeutic targets, and pharmacologic treatment of overactive bladder (OAB). Antimuscarinic drugs are still first-line pharmacologic treatment for OAB and often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, prompting a search for new therapeutic alternatives. Mirabegron and onabotulinumtoxinA, two drugs with different mechanisms of action, and with adverse effect profiles different from those of antimuscarinics, were recently approved for treatment of OAB. However, their place in the treatment of this disorder has not yet been established. In this short review, the mechanisms of action, clinical efficacy, and safety profiles of these drugs are discussed and compared with those of the current gold standard, antimuscarinic agents.

Editorial Comment from Dr Kitta to Effect of intrathecal administration of E‐series prostaglandin 1 receptor antagonist in a cyclophosphamide‐induced cystitis rat model

At present, anticholinergic agents are the mainstay of pharmacological treatment of overactive bladder (OAB), and the definitive pharmacological treatment for interstitial cystitis/ painful bladder syndrome (IC/PBS) is limited. The cause of these situations is the poor understanding of disease pathophysiology and insufficient drugs of central action for lower urinary tract dysfunction. This paper throws a new light on the treatment for the pathological condition of lower urinary tract dysfunction. The authors described a study evaluating the possibility that blockade of the spinal E-series prostaglandin 1 (EP1) receptor by ONO-8711 might have a therapeutic potential in the control of urinary frequency. As previous studies reported, systemic administration of EP1 receptor antagonist improved bladder function in some pathological rat models. However, we did not know the effective site of EP1 receptor antagonist. From their result, the authors speculated that EP1 receptor antagonist blocks the afferent signal of spinal prostaglandin E2 (PGE2) through the EP1 receptor. This is a really interesting new concept. In the present study, intracerebral administration of EP1 receptor antagonist was not tested. Therefore, we could not speculate whether the improvement of bladder function after systemic administration of EP1 receptor antagonist was caused partly by suppression of the EP1 receptor in the supraspinal site. Indeed, the tissue PGE2 level at the ventral horn of cyclophosphamide (CYP)-induced cystitis rats was not significantly different from control rats. These data suggest that EP1 antagonist injected intrathecally mainly inhibits the afferent effect of PGE2 through the EP1 receptor. However, the CYP-induced cystitis model was one of the bladder nociceptive cystitis models. We do not really know whether the other bladder dysfunction models, such as the bladder outlet obstruction model or IC/PBS models, have the same expression of the EP1 receptor in the spinal cord. Furthermore, many researchers reported that the EP1 receptor is abundant in the brain. These points should be solved in the future. Time and effort have been invested in the characterization of the central mechanisms controlling the micturition reflexes, and now we move on to find novel drugs for micturition disorders with a central effect.

PUK18 Cost-Effectiveness of Pharmacologic Treatment of Overactive Bladder

PUK18 Cost-Effectiveness of Pharmacologic Treatment of Overactive Bladder

Anticholinergics for Overactive Bladder Therapy: Central Nervous System Effects

The mainstay of pharmacological treatment of overactive bladder (OAB) is anticholinergic therapy using muscarinic receptor antagonists (tertiary or quaternary amines). Muscarinic receptors in the brain play an important role in cognitive function, and there is growing awareness that antimuscarinic OAB drugs may have adverse central nervous system (CNS) effects, ranging from headache to cognitive impairment and episodes of psychosis. This review discusses the physicochemical and pharmacokinetic properties of OAB antimuscarinics that affect their propensity to cause adverse CNS effects, as observed in phase III clinical trials and in specific investigations on cognitive function and sleep architecture. PubMed/MEDLINE was searched for "OAB" plus "muscarinic antagonists" or "anticholinergic drug." Additional relevant literature was identified by examining the reference lists of papers identified through the search. Preclinical and clinical trials in adults were assessed, focusing on the OAB antimuscarinics approved in the United States. The blood-brain barrier (BBB) plays a key role in protecting the CNS, but it is penetrable. The lipophilic tertiary amines, particularly oxybutynin, are more likely to cross the BBB than the hydrophilic quaternary amine trospium chloride, for which there are very few reports of adverse CNS effects. In fact, in 2008 the US product labels for oral oxybutynin were modified to include the potential for anticholinergic CNS events and a warning to monitor patients for adverse CNS effects. Even modest cognitive impairment in the elderly may negatively affect independence; therefore, selection of an antimuscarinic OAB drug with reduced potential for CNS effects is advisable.

IL3 Recent pharmacological treatment for overactive bladder (OAB) and its future perspective

IL3 Recent pharmacological treatment for overactive bladder (OAB) and its future perspective

IJU this issue

This issue contains seven Original Articles, four Editorial Comments, two Short Communications, and one Skills and Pitfalls. In general, chromophobe renal cell carcinomas (chRCC) are believed to have a more favorable prognosis than conventional RCC. Lee et al. (ChunCheon, Korea) analyzed the characteristics and prognostic importance of chRCC based on a large, multicenter experience. Surprisingly, the non-metastatic chRCC showed equivalent oncological outcomes compared to the conventional RCC. It is well recognized that T1 bladder cancer can be life-threatening in some cases. Using the cancer registration database of the Japanese Urological Association, Okajima et al. (Nara, Japan) found that non-papillary tumor appearance, positive urinary cytology and a tumor size greater than 3 cm were independent prognosticators, and claimed that these factors should be included in order to enable the assessment of risk criteria in cancer death from T1 bladder cancer. As not all men necessarily benefit from early secondary treatment for biochemical recurrence (BCR) after radical prostatectomy (RP), it is critical to properly select patients for adjuvant therapies in order to minimize side-effects and maximize their benefits. Moreir et al. (Durham, USA) developed and externally validated a new nomogram incorporating postoperative prostate-specific antigen nadir and other well-established predictors of BCR. Although high-intensity focused ultrasound (HIFU) is a minimally invasive therapy for prostate cancer (CaP), the most common adverse event reported during follow up is the formation of bladder outlet obstruction. Sumitomo et al. (Tokorozawa, Japan) introduced transurethral resection of the prostate immediately after HIFU treatment of CaP, which improved post-treatment urinary status without causing additional morbidity. Antimuscarinic agents have long been the drugs of choice for pharmacological treatment of overactive bladder. Using video urodynamics, Watanabe et al. (Mibu, Japan) demonstrated the efficacy of tolterodine ER for the treatment of neurogenic detrusor overactivity and/or low compliance bladder. Intracytoplasmic sperm injection has allowed patients with very few sperm to achieve fertilization, which leads to the possibility of cryopreservation of semen, even from patients with very low sperm counts. Bak et al. (Seoul, Korea) investigated the fate of patients with severely impaired semen status and warned that patients with severe oligozoospermia are at high risk of becoming azoospermic and hence sperm freezing should be encouraged as early as possible for this population. Electrosurgery is one of the most commonly used energy systems in transurethral prostate and bladder surgery. Chung et al. (Jeonju, Korea) identified several toxic and carcinogenic gases (1,3-butadiene, vinyl acetylene, and acrylonitrile) generated during transurethral resection of the prostate and vaporization. This important finding confirms the need for protective methods to be developed. Okegawa et al. (Tokyo, Japan) reported the usefulness of alternative hormonal therapy for treating resistance to first-line hormonal therapy, adding further evidence to the growing literature in this field. Prepubertal testicular tumors are different from their postpubertal counterparts in histopathological type and clinical behavior. Based on their 20-year experience, Hisamatsu et al. (Kobe, Japan) proposed a treatment algorism for this rare tumor in children. Complete hemostasis after transection of the dorsal vein complex (DVC) is an extremely important step during the course of radical prostatectomy. Sasaki et al. (Tokyo, Japan) found that bleeding from the DVC is easily controlled without suture ligation through a combination of a modest pneumoperitoneum with pinpoint coagulation of one or two small arteries that are found in the superficial layer of the complex. This simple technique can also be applied to the recent robot-assisted radical prostatectomy.

Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats

Impaired melatonin production is involved in disruption of the normal circadian pattern of sleep, which leads to nocturia in older adults. Melatonin improves nocturia. We hypothesized that melatonin could alleviate urinary frequency by suppressing the brain micturition center. We investigated the central contribution of melatonin to bladder function and urine volume. Cystometry was done in conscious female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan). We examined the effect of melatonin alone (4.3 x 10(-1) to 4.3 x 10 pmol intracerebroventricularly) or with the gamma-aminobutyric acid(A) antagonist bicuculline (5.0 x 10(-5) mg/kg intravenously) on bladder function. The influence of melatonin (4.3 x 10 pmol intracerebroventricularly) on urine volume was investigated in water loaded rats. Blood samples were collected to determine antidiuretic hormone, atrial natriuretic peptide and brain natriuretic peptide 4 hours after melatonin administration. Melatonin significantly increased bladder capacity dose dependently by 27.0%, 40.8% and 63.5% at 4.3 x 10(-1), 4.3 and 4.3 x 10 pmol, respectively, but had no significant effect on bladder contraction pressure. Bicuculline inhibited the melatonin induced increases in bladder capacity. Melatonin decreased urine volume in water loaded rats but plasma antidiuretic hormone, atrial natriuretic peptide and bladder contraction pressure were not changed. Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder

In the present review article, we present an overview of beta-adrenoceptor (β-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the β3-AR, the in vivo effect of β3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of β3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of β3-AR mRNA in human bladder, constituting 97% of total β-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the β3-ARs. Moreover, the presence of β1-, β2-, and β3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial β-ARs results in the release of nitric oxide and an unknown substance inhibiting detrusor contractions from the urothelium. Intravenous application of CL316,243, a selective β3-AR agonist, in rats selectively inhibits mechano-sensitive Aδ-fiber activity of the primary bladder afferents. A number of selective β3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the β3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The β3-AR agonists act to facilitate bladder storage function probably through at least two mechanisms: first, direct inhibition of the detrusor, and second, inhibition of bladder afferent neurotransduction.

Medication Nonadherence Secondary to Drug-Induced Memory Loss

Overactive bladder (OAB) is a common condition in the elderly. Treatments for OAB include nonpharmacological or behavioral therapy, pharmacological therapy, and surgical therapy. Antimuscarinic agents are the current pharmacological treatment for OAB and are known to cause memory impairment. A 66-year-old female presented with memory loss secondary to the administration of oxybutynin, which resulted in medication nonadherence. Upon review of her medications, the pharmacist recommended discontinuing the oxybutynin because of the anticholinergic effects on cognition. At a three-week follow-up visit, the patient reported an improvement in memory and medication adherence. Pharmacists can play a vital role in recognizing drug-induced side effects and educating patients in an effort to improve medication adherence.

Pharmacotherapy Update on the Treatment of Overactive Bladder Syndrome: Focus on Fesoterodine

Overactive bladder is a highly prevalent condition that affects both males and females. The risk of developing overactive bladder increases with aging. There appear to be multiple etiologies for overactive bladder. Antimuscarinic agents have been the main-stay for pharmacologic treatment of overactive bladder. Their role is thought to be via antagonism with acetylcholine at the M3 receptor in the detrusor. More recently, the urothelium and suburothelium have been demonstrated to have muscarinic receptors and thus anti-muscarinic agents may affect the afferent pathway component of overactive bladder symptoms. Historically, although effective, the use of antimuscarinic agents has been limited by poor tolerability. The development of once daily formulations and alternative methods of delivery, multiple dose agents and agents with variable muscarinic receptor affinity profiles has resulted in improved tolerability profiles while maintaining efficacy. Although effective, antimuscarinic agents typically improve OAB symptoms and are less likely to lead to complete resolution of symptoms. The success rates of antimuscarinic therapy are improved when used in combination with behavioral therapy. Fesoterodine is one of the most recent OAB agents to be approved by the FDA. It acts as a prodrug and is rapidly and extensively metabolized to 5-hydroxymethyltolterodine, which is also the active metabolite of tolterodine. Fesoterodine is available in two formulations and clinical studies have demonstrated a dose-related response in efficacy with fesoterodine. Fesoterodine is well tolerated, the most common side effects being those of dry mouth and constipation. There were very few discontinuations in the clinical trials due to either dry mouth or constipation. Fesoterodine’s long-term efficacy and tolerability has been demonstrated in the 3-year open label extension trial with fesoterodine. A thorough QT study confirmed the absence of an effect on the QT interval with standard dosing of fesoterodine, 4 mg or a high dose, 28 mg of fesoterodine. Due to multiple metabolic pathways, via the CYP P450 system and excretion by the kidneys, there are limited dosing restrictions with fesoterodine. Fesoterodine is the only antimuscarinic therapy available that comes with the YOURWAY plan, a multidimensional program that brings together pharmacotherapy with education and skills training.