benzofurans and trospium-chloride

Urinary incontinence (UI) in women adversely affects quality of life.. To conduct a systematic literature review of drugs for urgency UI in women.. MEDLINE, the Cochrane Central Register of Controlled Trials, SCIRUS, and Google Scholar were searched for articles published from 1966 to November 2011.. Randomized, controlled trials (RCTs) reported in English.. Rates of outcomes and risk of bias were extracted by using a standardized form to pool absolute risk differences and calculate the number of attributable events per 1000 patients treated, with 95% CIs.. 94 RCTs were eligible. Pooled analyses showed that among drugs for urgency UI, per 1000 treated women, continence was restored in 130 with fesoterodine (CI, 58 to 202), 85 with tolterodine (CI, 40 to 129), 114 with oxybutynin (CI, 64 to 163), 107 with solifenacin (CI, 58 to 156), and 114 with trospium (CI, 83 to 144). Rates of treatment discontinuation due to adverse effects were 31 per 1000 treated with fesoterodine (CI, 10 to 56), 63 with oxybutynin (CI, 12 to 127), 18 with trospium (CI, 4 to 33), and 13 with solifenacin (CI, 1 to 26). The studies' inconsistent definitions of reduction in UI and quality of life hampered synthesis of evidence.. Evidence for quality-of-life improvements and comparative effectiveness with drugs was limited, and evidence for the effects of race, baseline severity of UI, and comorbid conditions on treatment success was insufficient.. Overall, drugs for urgency UI showed similar small benefit. Therapeutic choices should consider the harms profile. Evidence for long-term adherence and safety of treatments is lacking.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Comparative Effectiveness Research; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quality of Life; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

Overactive bladder (OAB) is a chronic syndrome with debilitating symptoms that negatively affect health-related quality of life. Although anticholinergic agents have been first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Anticholinergic agents prevent involuntary contractions of the bladder detrusor muscle by preventing acetylcholine from binding to the M2 and M3 muscarinic receptor subtypes. Anticholinergics are not tissue specific, and their use for treatment of OAB has been associated with side effects such as dry mouth, constipation, and blurred vision. Recent studies with extended-release formulations and newly developed receptor subtype-specific anticholinergic agents demonstrate that side effects are typically mild to moderate and generally tolerable, seldom leading to patient withdrawal. By incorporating patient-initiated dose adjustment into the protocol, the primary care physician can effectively manage adverse events associated with OAB without compromising efficacy. Recent dose-adjustment data with extended-release oxybutynin suggest that, given some control in the process, patients are willing to tolerate certain side effects in exchange for symptom relief.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

Antagonists of muscarinic acetylcholine receptors, such as darifenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium, are the mainstay of the treatment of the overactive bladder syndrome. Fesoterodine is a newer drug awaiting regulatory approval. We briefly review the pharmacological activity of their metabolites and discuss how active metabolites may contribute to their efficacy and tolerability in vivo. Except for trospium, and perhaps solifenacin, all of the above drugs form active metabolites, and their presence and activity need to be taken into consideration when elucidating relationships between pharmacokinetics and pharmacodynamics of these drugs. Moreover, the ratios between parent compounds and metabolites may differ depending on genotype of the metabolizing enzymes, concomitant medication, and/or drug formulation. Differential generation of active metabolites of darifenacin or tolterodine are unlikely to influence the overall clinical profile of these drugs in a major way because the active metabolites exhibit a similar pharmacological profile as the parent compound. In contrast, metabolites of oxybutynin and propiverine may behave quantitatively or even qualitatively differently from their parent compounds and this may have an impact on the overall clinical profile of these drugs. We conclude that more comprehensive studies of drug metabolites are required for an improved understanding of their clinical effects.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive

This year, the US Food and Drug Administration will approve four new drugs indicated for the treatment of lower urinary tract dysfunction. Darifenacin, solifenacin, and trospium are antimuscarinic agents aimed at relieving the symptoms of overactive bladder and urge incontinence in men and women. Duloxetine will be the first drug approved for the treatment of female stress urinary incontinence. This article presents current data on the efficacy and tolerability of these new agents and invites the reader to decide whether they offer any potential advantages over existing therapies.

Topics: Benzilates; Benzofurans; Clinical Trials as Topic; Duloxetine Hydrochloride; Humans; Muscarinic Antagonists; Nortropanes; Pyrrolidines; Quinuclidines; Selective Serotonin Reuptake Inhibitors; Solifenacin Succinate; Tetrahydroisoquinolines; Thiophenes; Urinary Incontinence

Drug therapy for overactive bladder (OAB) most commonly includes antimuscarinic agents, which work by relaxing bladder smooth muscle through inhibition of acetylcholine receptors in the bladder. The major adverse effects with existing antimuscarinic agents are anticholinergic in nature (e.g., dry mouth, constipation, blurred vision). Oxybutynin and tolterodine have been used for several years for treatment of OAB; both are available in immediate- and extended-release formulations. Fewer or less severe adverse effects are reported with the extended- versus the immediate-release formulations, with little or no difference in efficacy. Oxybutynin is also available as a transdermal patch. Trospium, which was recently approved for use in the United States, has efficacy and an incidence of dry mouth similar to existing agents but does not cross the blood-brain barrier. It requires twice-daily dosing. Two new antimuscarinic agents--darifenacin and solifenacin--are in development. Both show significantly better efficacy compared with placebo for key symptoms of OAB, including urgency. The incidence of dry mouth at the lowest effective dose is 19% for darifenacin and 8% and 14% for solifenacin (2 studies).

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Constipation; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Vision Disorders; Xerostomia

Limitations exist with regard to the array of available agents for the pharmacologic therapy of overactive bladder, including issues of efficacy and tolerability. It is clear that the ideal agent for this condition has not been identified. However, several new pharmacologic treatments, including some with novel approaches to drug delivery, have emerged in clinical development over the past few years. These agents include a variety of anticholinergics and others. In initial studies, some of the agents appear to compare favorably with existing therapies. Whether these promising results will hold up when subjected to large-scale, well-controlled clinical trials is unclear.

Topics: Administration, Cutaneous; Administration, Intravesical; Administration, Oral; Adrenergic beta-3 Receptor Antagonists; Benzhydryl Compounds; Benzilates; Benzofurans; Botulinum Toxins; Cresols; Dosage Forms; Dose-Response Relationship, Drug; Drug Compounding; Drug Evaluation; Duloxetine Hydrochloride; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Thiophenes; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urination Disorders

Continued developments in the understanding of lower urinary tract function have led to improvements in the pharmacologic manipulation of bladder dysfunction. Drug delivery changes have produced drugs that provide better efficacy and tolerability, thus improving patient compliance. Improvements in drug delivery systems have altered drug bioavailability and pharmacokinetics. Active current investigation in new agents and delivery systems for intravesical delivery has yielded intriguing early results that may substantially add to the armamentarium for the management of the overactive bladder (urgency, frequency, urge incontinence). New developments in the understanding of the neuropharmacology of the bladder, peripheral pelvic nerves, and sacral cord may provide agents with entirely new drug effects, either as primary agents or agents to be used in combination with currently available drugs. We herein review newer agents and drug delivery systems.

Topics: Adrenergic alpha-Antagonists; Aged; Animals; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Benzilates; Benzofurans; Calcium Channel Blockers; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Drug Administration Routes; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Muscle Relaxants, Central; Nortropanes; Phenylpropanolamine; Pyrrolidines; Tolterodine Tartrate; Urinary Incontinence

To compare the heart rate increase side effect of different antimuscarinic drugs used in overactive bladder (OAB).. Overall 341 patients were consecutively randomized to take seven different antimuscarinic drugs between January 2014 and June 2016 at three institutions, and 250 patients who completed the follow-up visits were accepted into this study. Ninety-one patients who never came to visits were excluded. Drugs were classified into two groups as selective (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride) and non-selective (fesoterodine fumarate, tolterodine tartrate, trospium chloride and propiverine hydrochloride) antimuscarinic drugs. The cardiac pulse rates and the blood pressures were recorded during the baseline, first visit (1 week) and second visit (1 month). Data were compared for drugs and two groups (selective versus non-selective) by using ANOVA test.. Baseline characteristics were similar among the patients using different antimuscarinic drugs. Statistically significant increase in heart rate occurred in patients treated with non-selective antimuscarinic drugs compared to those treated with selective drugs (p < 0.001), and this increase was especially evident in patients treated with trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride (p < 0.001, 0.003, 0.011 and 0.37, respectively). There was no statistical difference for the other side effects.. Our results showed that heart rate significantly increased in OAB patients treated with non-selective antimuscarinic drugs. Trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride seem to have the most unfavorable properties with regard to increased heart rate side effect when compared to the other antimuscarinic drugs (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride).

Topics: Adult; Aged; Benzhydryl Compounds; Benzilates; Benzofurans; Blood Pressure; Female; Heart Rate; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Prospective Studies; Pyrrolidines; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Antidepressive Agents; Benzilates; Benzofurans; Brazil; Clinical Decision-Making; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Pyrrolidines; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Despite enormous progresses in understanding pathophysiology of the lower urinary tract, antimuscarinics remain the chief clinically well-established approach for improving symptoms of overactive bladder (OAB). Dry mouth on the other hand remains one of the most untolerated systemic side effects of these drugs that limits their uses and results in high discontinuation rate. Three novel drugs have been recently approved by US Food and Drug Administration for treatment of OAB: trospium, darifenacin, and solifenacin.. This study has been conducted to provide clear head to head comparative studying of histological and ultrastructural effect of those newly emerging drugs on parotid and submandibular salivary glands and to demonstrate the differential expression of CXCL10 to make a cogent structural and molecular assessment of the relative tolerability of these drugs and the potential mechanisms of occurrence of dry mouth.. Fifty male Sprague Dawley rats were equally divided into five groups: Group I (control), Group II (oxybutynin-treated), Group III (trospium-treated), Group IV (darifenacin-treated) and Group V (solifenacin-treated). Histological and ultrastructural studies were performed on parotid and submandibular glands. Measurement of salivary flow, PCR analysis and immunohistochemical assessment of CXCL10 expression have been carried-out.. Muscarinic receptor antagonists led to various histological, morphometric and ultrastructural changes together with diminished salivary secretion and up-regulation of CXCL10 expression with the mildest alterations observed with solifenacin.. Solifenacin has shown the least adverse effects to salivary glands. CXCL10 is involved in degenerative changes of salivary glands induced by muscarinic antagonists.

Topics: Animals; Benzilates; Benzofurans; Chemokine CXCL10; Immunohistochemistry; Male; Nortropanes; Parotid Gland; Polymerase Chain Reaction; Pyrrolidines; Rats; Rats, Sprague-Dawley; Reference Standards; Salivation; Solifenacin Succinate; Staining and Labeling; Submandibular Gland; Urinary Bladder, Overactive

Incidences of overactive bladder (OAB) and cognitive dysfunction increase with aging. Treatment of OAB with antimuscarinic agents may result in cognitive decline, especially in patients with Alzheimer's disease (AD). The aim of this study is to evaluate the effect of antimuscarinic treatment on cognitive functions, depression, and quality of life (QOL) of patients with OAB.. This non-interventional prospective observational study was conducted in a geriatric medicine outpatient clinic. Overall, 168 OAB patients were enrolled. Patients were followed up in five groups: oxybutynin, darifenacin, tolterodine, trospium, and control groups. Follow-up visits were done at second, third, and sixth months. Comprehensive geriatric assessment, cognitive and mood assessment, QOL scales (IIQ-7, UDI-6) were performed.. Mean age of the patients was 73.5 ± 6.1. Of the 168 patients, 92.3% were female, 83.3% benefited from the treatment, and 37.1% discontinued the medication. Discontinuation rate and frequency of side effects were more frequent in the oxybutynin group. Mini Mental State Examination scores did not decline after treatment, even in AD patients. Geriatric Depression Scale scores, Activities of Daily Living scores, and QOL scores significantly improved after treatment.. Antimuscarinic agents are effective in OAB treatment. They have a positive impact on daily life activities, depression, and QOL indices. Furthermore, they do not have a negative effect on cognitive function in older adults with or without AD.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzilates; Benzofurans; Cognition Disorders; Cresols; Depression; Female; Follow-Up Studies; Geriatric Assessment; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive