Trospium chloride (Sanctura): another anticholinergic for overactive bladder.
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Patients with human T-cell lymphotropic virus type 1 associated myelopathy (HAM) have complaints of urinary disturbance frequently. Symptoms and urodynamic examinations were evaluated in untreated twenty-one patients with HAM. Although two cases (11%) had no urinary symptom, nineteen cases (89%) suffered from dysuria, pollakisuria, incontinence or urgency. The combination of irritative and obstructive urinary disturbance was a characteristic symptom in the HAM patients. In three cases the urinary symptoms preceded the gait disturbance which is a main symptom of HAM. In urodynamic study overactive bladder was found in fourteen cases (66%), although three cases (15%) showed underactive or acontractile bladder with disturbance of urinary sensation. There was no abnormal finding by urethral pressure profile (UPP), but detrusor sphincter dyssynergia (DSD) was revealed frequently by EMG. This typical dysfunction of the HAM patients was thought to be caused by destruction of the lateral column of the spinal cord.
OBJECTIVES: To review the available evidence concerning the use of anticholinergic drugs, alone or in combination with alpha-blockers, in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and concomitant overactive bladder syndrome, to assess whether the currently available evidence suggests a role for antimuscarinic drugs in patients with BPH. METHODS: A systematic review of the literature was performed using Embase, MEDLINE, and Web of Science through a complex search strategy including "free text" and "MeSH" protocols. Moreover, the Cochrane database of systematic review was browsed for records regarding BPH and the abstract books of the American Urological Association, European Association of Urology, and International Continence Society annual meetings from 2000 to 2005 were hand-searched for studies concerning the topic of the review. RESULTS: From the literature search, we identified four randomised controlled trials (RCTs), two prospective case series, and a few congress abstracts. For methodologic issues, the best RCT was based on urodynamic data, but did not provide any clinical insight on the patients' symptoms. The other papers were affected by significant methodologic or clinical drawbacks. CONCLUSION: The available data may be considered promising in terms of safety and efficacy. The evidence of the limited number of RCTs available, considering their methodologic or clinical shortcomings, is not sufficient to support the clinical use of combination therapy with alpha-blockers and anticholinergic drugs in patients with associated storage and voiding symptoms. Well-designed, large, double-blind, placebo-controlled, long-term RCTs are needed to assess the long-term safety and efficacy of antimuscarinic drugs, alone or in combination with alpha-blockers, in this category of patients.
PURPOSE OF REVIEW: A substantial proportion of men with lower urinary tract symptoms have a combination of both 'storage' and 'voiding' symptoms, suggesting possible coexisting bladder outlet obstruction and bladder overactivity. Bladder overactivity is traditionally treated with anticholinergic drugs. However, guidelines from the European Association of Urologists make no mention of the possible therapeutic role of anticholinergic drugs for treating storage symptoms in such patients. It is a common perception that using an anticholinergic drug in men with bladder outlet obstruction runs the risk of inducing acute urinary retention, because of the inhibitory effect of anticholinergics on bladder contraction in the presence of outlet obstruction. This review focuses on recent data determining the efficacy of anticholinergic medication in men with lower urinary tract symptoms/benign prostatic hyperplasia and the associated risk of acute urinary retention. RECENT FINDINGS: One recent study in men with urodynamically confirmed obstruction supports the assertion that anticholinergic drugs are safe in men with bladder outlet obstruction. Safety data from larger studies using anticholinergics in patients with overactive bladders supports these findings. SUMMARY: Efficacy and safety studies of anticholinergic medication in men with lower urinary tract symptoms/benign prostatic hyperplasia are few and far between, but preliminary data suggests they are not associated with a substantial risk of urinary retention nor with a substantial increase in residual urine volume.
OBJECTIVE: Our purpose was to compare the diagnostic efficacy of observing urine loss during simple bladder filling (without pressure measurement) and a cough stress test, with multichannel subtracted cystometry. STUDY DESIGN: The urodynamic records of 77 women complaining of urinary incontinence were reviewed. All women had undergone a full evaluation that included a standardized history and physical examination, urinalysis and urine culture, uroflowmetry with measurement of postvoid residual urine, a cough stress test performed during and after simple retrograde bladder filling, and multichannel subtracted cystometry. The results of simple bladder filling and the cough stress test were recorded as "urge incontinence," "stress incontinence,"mixed incontinence," or "incontinence not demonstrated." The subtracted cystometrogram was then performed, and the urodynamic diagnoses were recorded as "detrusor instability," "genuine stress incontinence," "mixed incontinence," or "incontinence not demonstrated." The records were reviewed, and the results of simple bladder filling with a cough stress test were compared with those obtained by subtracted multichannel provocative cystometry. RESULTS: With the subtracted multichannel cystometrogram used as the "gold standard" for diagnosis, the demonstration of "urge incontinence" during simple bladder filling had a sensitivity of 64% and a specificity of 86.8% for the demonstration of detrusor instability during cystometry, with a positive predictive value of 83.3% and a negative predictive value of 70.2%. The demonstration of "stress incontinence" during simple bladder filling had a sensitivity of 88.1% and a specificity of 77.1% for the demonstration of "genuine" stress incontinence during cystometry, with a positive predictive value of 82% and a negative predictive value of 84.4%. CONCLUSIONS: The demonstration of urge incontinence during simple bladder filling is a reliable predictor of detrusor instability, but its absence is less reliable in excluding detrusor overactivity as a cause of urinary incontinence. Similarly, the clinical demonstration of stress incontinence during simple bladder filling is predictive of the presence of "genuine" stress incontinence during subtracted multichannel provocative cystometry. The inability to demonstrate stress incontinence during simple bladder filling is highly correlated with the absence of "genuine" stress incontinence during complex urodynamic testing. Simple bladder filling is a reliable method of diagnosing urinary incontinence. In many cases it can replace complex urodynamic testing, particularly if the proposed treatment for the condition carries a low level of risk, and is helpful in selecting patients who need more extensive evaluation.
Generations of urologists have presumed that the cause of lower urinary tract symptoms (LUTS) in men is infravesical (prostatic) obstruction. When symptoms such as urinary urgency and frequency can't easily be explained directly by obstruction, secondary effects of obstruction on the bladder are identified as causative factors. Although to some extent this explanation may still be accurate, emerging concepts in the pathophysiology of LUTS in men may be at odds with these traditional explanations. The idea that primary bladder pathology may explain the symptom complex in at least one subset of men with LUTS has both experimental and clinical support. This review discusses the physiologic and clinical observations used to explain the mechanisms underlying LUTS. Specifically, this review focuses on two data sets: one supporting infravesical obstruction as the causative factor for LUTS, and another positing that a primary bladder abnormality is responsible.
Solifenacin succinate [YM905, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a novel muscarinic receptor antagonist. We examined the effects of solifenacin and two other muscarinic receptor antagonists, tolterodine and propiverine, on detrusor overactivity in cerebral infarcted rats. Evaluation was done under conscious conditions using cystometry 1 day after middle cerebral artery occlusion. The cerebral infarcted rats showed decreases in bladder capacity and voided volume and an increase in residual volume, but no change in micturition pressure. Solifenacin increased bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more. Tolterodine increased bladder capacity and voided volume at 0.03 and 0.1 mg/kg i.v., while propiverine increased bladder capacity and voided volume at 1 mg/kg i.v. and at 0.3 and 1 mg/kg i.v., respectively. In contrast, none of the three drugs affected residual volume or micturition pressure. These results suggest that solifenacin may improve detrusor overactivity without causing urinary retention and may be a promising drug in the treatment of patients with overactive bladder syndrome.
To investigate the role of nitric oxide (NO) in spinal regulation of lower urinary tract function and bladder nociceptive behaviour, cystometry was performed in conscious rats. The effects of intra-arterial and intrathecal administration of the NO synthase (NOS)-inhibitor, L-NG-nitroarginine methyl ester (L-NAME), were studied on volume- and capsaicin-induced micturitions. The incidence of nociceptive behaviour after intravesical capsaicin was investigated in the absence and presence of L-NAME. Intrathecal L-NAME (0.5 mg) had no effect on the normal, volume-induced micturition. Intravesical capsaicin (30 microM) increased the micturition pressure (p < 0.01), the basal pressure (p < 0.01) and decreased the bladder capacity (p < 0.01) and the micturition volume (p < 0.01). Administration of L-NAME intrathecally (0.5 mg) or intra-arterially (25 mg/kg) had no effects on the capsaicin-induced bladder activity. During capsaicin-infusion, the rats showed signs of distress such as licking and head-turning directed toward the abdomen. This nociceptive behaviour was shown during 31 +/- 3% (n = 6) of the observation period. The capsaicin-induced nociceptive behaviour was markedly reduced by intrathecal and to a less extent by intra-arterial, administration of L-NAME. The percentage time spent licking and head-turning was reduced to 11 +/- 2%, n = 6 (p < 0.001) and 18 +/- 3%, n = 6 (p < 0.05) in rats treated with intrathecal and intra-arterial L-NAME, respectively. The results suggest that NO is not involved in the spinal regulation of the volume- or capsaicin-induced micturition. In contrast, the nociceptive behaviour evoked by intravesical capsaicin seems to involve spinal NO.
Overactive bladder (OAB) is a condition defined by its symptoms--urinary urgency with or without urgency urinary incontinence and often with frequency and nocturia. As such, determining the efficacy of OAB treatments using objective measures, such as urodynamic testing, can be difficult. A better means of gauging treatment efficacy for symptom-based conditions is through the use of patient-reported outcomes (PROs). With PROs, clinicians can gain insight into how a treatment affects a patient's symptoms and whether improvement in symptoms has a positive effect from the patient's perspective. PROs are increasingly being included as end points in clinical trials, including those of antimuscarinic drugs for OAB. Consequently, clinicians should become familiar with the most commonly used instruments. We provide an overview of instruments used to assess symptoms, health-related quality of life, and treatment satisfaction in patients with OAB and discuss how PROs can be incorporated into clinical trial protocols.
The Standardisation Subcommittee of the International Continence Society (ICS) now recognizes overactive bladder (OAB) as a "symptom syndrome suggestive of lower urinary tract dysfunction." It is specifically defined as "urgency, with or without urge incontinence, usually with frequency and nocturia." The ICS definition was not formulated until January 2001 and was not formally approved until September 2001. Therefore, collection and discussion of the epidemiologic characteristics of OAB are somewhat hampered by the different definitions of this condition used by different investigators. Most communications that appeared before 2000 more often described characteristics of incontinence rather than OAB, and the estimates of OAB prevalence within those studies varied significantly. Until recently, little definite epidemiologic information was available on the prevalence and comorbidities of OAB. An important challenge in treating OAB is to increase awareness of this significant problem worldwide and to impress on other specialists and primary care physicians the importance of identifying this clinical problem and managing it in a way that will maximize quality-of-life improvement while minimizing morbidity.
The term overactive bladder (OAB) is used to describe the symptoms of urinary frequency and urgency with or without urge incontinence. Commonly reported symptoms are nocturia, urgency, frequency, and urge incontinence. However, some of these symptoms may be because of other lower urinary tract conditions or may simply represent a variant of normal physiologic function. Consequently, special considerations need to be made when diagnosing OAB in women. In women of all ages, lower urinary tract infection is the most common cause of irritative urinary symptoms, and midstream urine microscopy and culture should be performed. A chronic urinary residual secondary to voiding difficulties may also result in symptoms of frequency and overflow incontinence and may be diagnosed using a postmicturition ultrasound scan. In premenopausal women, pregnancy should also be excluded. In postmenopausal women, urogenital atrophy can cause irritative symptoms that may be improved with hormone replacement therapy. Vaginal administration has been shown to be most effective and may be used to supplement systemic replacement therapy. In addition, estrogen replacement may be beneficial in the management of OAB as an adjunct to anticholinergic therapy. When investigating elderly women with OAB, special consideration should be given to comorbidities, such as constipation and fecal impaction, mobility problems, and the loss of independence. Concomitant medication, such as diuretics and alpha-adrenergic blockers, should also be noted and the need for therapy reviewed. In conclusion, OAB is a subjective diagnosis that should only be made when other lower urinary tract conditions have been excluded.
Overactive bladder (OAB) is a syndrome characterized by symptoms of urinary urgency with or without urgency urinary incontinence (UUI), usually with frequency and nocturia. OAB affects approximately 17% of women in the United States and Europe. The causes of OAB, as with many bladder disorders, are multifactorial and are not completely understood. The primary functions of the lower urinary tract (bladder and bladder outlet mechanism) are storage and evacuation of urine. The bladder and the micturition cycle are under complex neural control involving both the sympathetic and parasympathetic nervous systems. Micturition may occur in response to the activation of receptors in the bladder muscle and detection of chemical stimuli by receptors within the bladder lining. Neurogenic or myogenic bladder dysfunction can lead to the symptoms of urgency, frequency, and UUI that characterize OAB. The consequences of this condition are far-reaching and include direct medical consequences and coping strategies that adversely affect quality of life. Although the prevalence of OAB increases with age, it is not a normal consequence of aging. Antimuscarinic agents (e.g., oxybutynin, tolterodine, trospium, solifenacin, and darifenacin) have demonstrated efficacy for the treatment of OAB symptoms in multiple clinical trials. This review explores the physiological basis for OAB, the effects of OAB on health-related quality of life, and the pharmacotherapies that may provide relief to patients with this distressing condition.
AIMS: To investigate the prevalence and characteristics of nocturnal enuresis (NE) and to examine the prevalence of overactive bladder (OAB) symptoms in primary schoolchildren. METHODS: After conducting an anonymous questionnaire survey about voiding habits and bowel habits in primary schoolchildren, a total of 6917 schoolchildren belonging to 11 primary schools were randomly enrolled in the survey. According to the International Continence Society, we defined NE as any involuntary loss of urine during sleep, occurring more frequently than once per month. Children with NE were subdivided into two groups, monosymptomatic NE (MNE) and enuretic syndrome (ES). To evaluate the characteristic differences of MNE and ES, we assessed the relationships between NE and voiding habits, and episodes of cystitis and constipation. Overactive bladder was defined as increased daytime frequency and/or urge urinary incontinence, and its prevalence was investigated. RESULTS: The response rate to the questionnaire was 76.4%. The prevalence of NE was 5.9% and was inversely related to increasing age. Monosymptomatic NE comprised 59.4% of NE cases. The annual spontaneous resolution rate of MNE was higher than that of ES. Increased daytime frequency, a history of cystitis and infrequent bowel habits were not related to MNE, but were significantly related to ES. The prevalence of OAB was 17.8%. Children with a history of cystitis had a significantly higher rate of OAB than children without it. CONCLUSIONS: Overall, NE and OAB were detected in 5.9% and 17.8% of primary schoolchildren, respectively. The link between NE and OAB symptoms, urinary tract infections and constipation deserves more attention.
This article summarizes the quality of life (QOL), cost of illness, and cost-effectiveness considerations in the treatment and management of patients with overactive bladder (OAB). Most cost studies have focused primarily on urinary incontinence, which is only one possible symptom of OAB. Prevalence rates of urge and mixed incontinence in the United States ranged from 3% to 8% and 5% to 37%, respectively. The highest prevalence was found in geriatric and psychogeriatric populations, where 40% and 90%, respectively, were classified as incontinent. In patients with OAB, all aspects of QOL can be compromised including physical, social, occupational, domestic, and sexual activities, and associated costs can be substantial. Oxybutynin has been the mainstay of pharmacotherapy for OAB but its more frequent side effects (including dry mouth) may deter patients from full compliance with treatment. Tolterodine, a newer antimuscarinic drug, has proven safe and effective in the treatment of OAB, with fewer side effects and better tolerability than existing agents. Cost effectiveness reports are reviewed. Further research on OAB is needed to characterize the disease process and identify risk factors.
Tolterodine is a new muscarinic receptor antagonist intended for the treatment of urinary urge incontinence and other symptoms associated with an overactive bladder. The in vivo metabolism of 14C-labeled tolterodine was investigated in rats, mice, and dogs by analysis of blood and urine samples, whereas in vitro metabolism studies were performed by incubation of [14C]tolterodine with mouse, rat, dog, and human liver microsomes in the presence of NADPH. Tolterodine was extensively metabolized in vivo. Mice and dogs showed similar metabolite patterns, which correlated well with that observed in humans. In these species, tolterodine was metabolized along two different pathways, with the more important being the stepwise oxidation of the 5-methyl group to yield the 5-hydroxymethyl metabolite of tolterodine and then, via the aldehyde, the 5-carboxylic acid metabolite. The other pathway involved dealkylation of the nitrogen. In the subsequent phase II metabolism, tolterodine and the metabolites were conjugated with glucuronic acid to various degrees. Rats exhibited more extensive metabolism and a markedly different metabolite pattern, with metabolites also being formed by hydroxylation of the unsubstituted benzene ring. In addition, a gender difference was observed, with male rats showing more extensive metabolism than females. Incubation of [14C]tolterodine with liver microsomes yielded a total of five metabolites with rat liver microsomes and three with mouse, dog, and human liver microsomes. The 5-hydroxymethyl metabolite of tolterodine and N-dealkylated tolterodine were major metabolites in all incubations, representing 83-99% of total metabolism. Although the extent of metabolism varied among species, the metabolic profiles were similar. However, rat liver microsomes also formed metabolites hydroxylated in the unsubstituted benzene ring. These results show that the metabolism of tolterodine in mice and dogs corresponds to that observed in humans, whereas rats exhibit a different metabolite pattern.
PURPOSE: Antimuscarinic therapy for men with OAB and BOO is perceived as a potential risk for urinary retention. Using pressure flow urodynamics, we evaluated the safety of tolterodine vs placebo in men with OAB and BOO. MATERIALS AND METHODS: Men (older than 40 years) with BOO and confirmed detrusor overactivity were randomized to tolterodine (2 mg twice daily in 149) or placebo (in 72) for 12 weeks. Primary end points were Qmax and pdetQmax. RESULTS: Median treatment differences in Qmax (-0.7 ml per second, 95% CI -1.6 to 0.4) and pdetQmax (-7 cm H2O, 95% CI -3 to 11) were comparable. Tolterodine significantly reduced the BOOI vs placebo (-9 vs 0, p < 0.02). There were significant treatment differences in volume to first detrusor contraction (+59 ml, 95% CI 19-100) and maximum cystometric capacity (+67 ml, 95% CI 35-103), favoring tolterodine over placebo (p < 0.003). Change in PVR was significantly greater among patients treated with tolterodine (+25 ml) than placebo (0 ml, p < 0.004). There were no significant between-group differences in the incidence of adverse events. Urinary retention was reported by 1 patient treated with placebo. CONCLUSIONS: Tolterodine did not adversely affect urinary function in men with OAB and BOO. Urinary flow rate was unaltered, and there was no evidence of clinically meaningful changes in voiding pressure and PVR or urinary retention. Tolterodine was well tolerated. These results suggest that antimuscarinics can be safely administered in men with BOO.
AIM: The aim of this study was to report the changes in prevalences of urogenital symptoms during pregnancy and to evaluate the amount of bother nulliparous pregnant women experience from these symptoms. METHODS: We have used a prospective longitudinal cohort study design. Five hundred fifteen nulliparous women with a singleton pregnancy were recruited from 10 midwifery practices between January 2002 and July 2003. The women received postal questionnaires. Urogenital symptoms were assessed with the Dutch version of the standardized and validated Urogenital Distress Inventory (UDI). We analyzed our data on item level and on the clustering of items. RESULTS: The prevalences of the frequency and urgency symptoms are high at 12 weeks (74% and 63%) and remain stable during pregnancy. The prevalences of urinary incontinence and voiding difficulties increase with gestational age. Frequency disappears in 12% in late pregnancy, urgency in 22%, and stress incontinence in 23%. The prevalence of bothersome frequency symptoms is much higher than of urinary incontinence (21% compared to 6%). All UDI subscales increase significantly during pregnancy. CONCLUSIONS: Urogenital symptoms occur in almost all women during pregnancy. Whereas the prevalence of overactive bladder symptoms is high and remains stable from early pregnancy on, the prevalences of urinary incontinence symptoms increase with gestational age. Despite the high prevalences of symptoms, the majority of women report not to be bothered by it.