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PubMedDate not supplied

The overactive bladder: an overview for primary care health providers.

The overactive bladder, with symptoms of frequency, urgency and urge incontinence, substantially affects the life styles of millions of people throughout the world. The symptoms are associated with significant social, psychological, occupational, domestic, physical, and sexual problems. Despite the considerable impact of the condition on quality of life, sufferers are often reluctant to discuss their problem with family members or health care professionals. This state of affairs is unfortunate, for much can be done to alleviate the symptoms of this distressing condition. It is therefore of utmost importance that medical education about symptoms of the overactive bladder and other related problems be improved, to help health care professionals identify and treat patients who will benefit from therapy. This article reviews current thinking regarding definition, epidemiology, quality of life effects, evaluation and management. Emphasis is placed on knowledge particularly useful in primary care, especially, noninvasive modalities of therapy.

Behavior Therapy↗
PubMed2005

Decrease in bladder overactivity with REN1820 in rats with cyclophosphamide induced cystitis.

PURPOSE: Studies suggest that nerve growth factor (NGF) contributes to bladder overactivity stemming from bladder inflammation. Studies were performed to determine the NGF dependence of cyclophosphamide (CYP) induced changes in bladder function using the recombinant NGF sequestering protein REN1820. MATERIALS AND METHODS: Urodynamic testing and behavioral observations were made in female rats treated with CYP (4 or 48 hours) and REN1820 or vehicle. RESULTS: Rats examined 4 or 48 hours after CYP treatment plus REN1820 showed significantly fewer nonvoiding contractions with smaller amplitude (p </=0.01). Rats examined 48 hours after CYP treatment plus REN1820 showed decreased voiding frequency (p </=0.01). No changes in filling, threshold or micturition pressure were observed with REN1820 treatment. Rats treated with CYP plus REN1820 showed greater mobility and normal resting postures compared with rats treated with CYP plus vehicle. CONCLUSIONS: These studies demonstrate that the use of the NGF sequestering protein REN1820 in rats with CYP induced cystitis decreases bladder overactivity. This is characterized by 1) a decrease in the number and amplitude of nonvoiding contractions and 2) decreased voiding frequency. Rats treated with REN1820 showed greater mobility and normal resting postures, which may reflect improved overall health or well-being. REN1820 may prove to be a novel therapeutic in individuals with the chronic inflammatory bladder syndrome interstitial cystitis.

Animals↗
PubMed2004

Oxybutynin for treatment of urge urinary incontinence and overactive bladder: an updated review.

Urge urinary incontinence (UUI) and overactive bladder are common conditions often associated with profound impairment of the health and quality of life of the patient. Antimuscarinic medications have been the mainstay of treatment for these disorders. Oxybutynin hydrochloride, one of the most widely used antimuscarinic agents, has attracted considerable interest from both clinicians and pharmacologists over the last three decades. Although efficacy of this drug has been proven to be high, its use is limited by antimuscarinic adverse effects, possibly related to its active metabolite N-desethyloxybutynin (N-DEO). The extended-release form of oxybutynin uses a push-pull osmotic release system which has significantly improved its tolerability and safety profile. A transdermal transport system has also been developed, bypassing the first-pass metabolism in the liver and gut. This system is associated with significant reduction in the production of the primary metabolite and additional improvement in the tolerability profile of the drug. Intravesical instillation of oxybutynin has been reported although the efficacy and safety of this delivery system has yet to be determined. This article comprehensively reviews the contemporary literature on the pharmacology, clinical efficacy and adverse reactions of oxybutynin in its various delivery forms, and compares them to other frequently used medications for UUI and overactive bladder.

Adult↗
PubMed2000

Treatment of overactive bladder with modified intravesical oxybutynin chloride.

Intravesical oxybutynin chloride has been reported to be effective for overactive bladder, although sometimes the efficacy does not last long enough. To improve this deficiency, we report the effects of intravesical oxybutynin chloride with hydroxypropylcellulose (modified intravesical oxybutynin). Modified intravesical oxybutynin (5 mg/10 mL, twice a day) was administered to six overactive bladder patients for more than 1 year (two men and four women; average age, 56.5 years) who did not respond to oral anticholinergic agents and electric stimulation. Cystometography (CMG) was performed before, 2 hours, and 1 week after the start of modified intravesical oxybutynin. In addition, plasma levels of oxybutynin and its active metabolite, N-desethyl-oxybutynin (DEOB), were measured by high-performance liquid chromatography before, 1, 2, and 4 hours after the initial treatment of modified intravesical oxybutynin. CMG studies revealed that two of the six patients did not demonstrate uninhibited contractions 1 week after the treatment and that cystocapacity of before, 2 hours, and 1 week after the initial modified intravesical oxybutynin was 141.8+/-15.3, 210.0+/-35.5, and 305.0+/-21.3 mL, respectively. Plasma levels of oxybutynin and DEOB before, 1, 2, and 4 hours after the first instillation of modified intravesical oxybutynin were oxybutynin; not detected, 8.8+/-2.5, 6.8+/-1.1, 3.0+/- 1.0 ng/ml, and DEOB; not detected, 4.2+/-1.3, 6.4+/-1.7, 5.1+/- 1.4 ng/ml, respectively. No side effects were observed in any of the patients. Modified intravesical oxybutynin is an effective and safe therapy option for overactive bladder patients who do not respond to other treatments such as oral anticholinergic agents and electric stimulation.

Administration, Intravesical↗
PubMed2003

Overactive bladder symptoms: do we need urodynamics?

AIMS: The aim of our study was to determine whether the urodynamic diagnosis is useful in the management of women with symptoms of an overactive bladder (OAB). METHODS: Women with lower urinary tract symptoms, attending a tertiary referral urogynaecology clinic were studied. All women were fully evaluated, with history, urinary symptoms questionnaire, frequency-volume chart, vaginal examination, and videocystourethrography. Women with symptoms consistent with an overactive bladder (urinary frequency, urgency, and/or urge incontinence) were selected. Women with neurological disorders were excluded. Finally, urinary symptoms and urodynamic diagnosis were correlated. All terms and definitions are in accordance with the International Continence Society [Abrams et al., 1988, Scand J Urol Nephrol 114(Suppl):5-19.]. RESULTS: A total of 4,500 women 22-73 years of age were studied. Only 843 women (18.7%) could be classified as having an OAB. Of these, 457 women (54.2%) had urodynamically proven detrusor instability, whereas 386 women (45.8%) had a stable urodynamic trace. Sixty-eight (8.1%) of the women studied had postvoid residual greater than 100 mL. Of the 4,500 women studied, 1,641 (36.5%) had detrusor instability on laboratory urodynamics. Only 27.5% of these women (457 of 1,641) had OAB symptoms. CONCLUSIONS: Symptomatic diagnosis of OAB does not correlate with a urodynamic diagnosis of detrusor instability. The diagnosis of overactive bladder based on urinary symptoms underdiagnoses the condition of detrusor instability in a population of women suffering from lower urinary tract symptoms. Therefore, symptomatic diagnosis of OAB alone is not recommended. Our study suggested that urodynamic evaluation is mandatory in the management of the women with symptoms of an overactive bladder.

Adult↗
PubMed1999

Tolterodine use for symptoms of overactive bladder.

OBJECTIVE: To describe the pharmacology, pharmacokinetics, clinical efficacy, and safety of tolterodine for the treatment of overactive bladder. DATA SOURCES: Published articles and abstracts were identified from a MEDLINE search (January 1980-October 1998) using the terms tolterodine, PNU-200583E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English were considered for review. Additional articles were identified from the bibliographies of retrieved articles. Data from the Food and Drug Administration-approved product labeling and the manufacturer were also used in the absence of published data. STUDY SELECTION AND DATA EXTRACTION: Clinical studies of tolterodine involving human subjects were evaluated. DATA SYNTHESIS: Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), which is partially responsible for its pharmacologic activity. Those who are genetically devoid of CYP2D6 will have higher concentrations of the parent compound and virtually undetectable concentrations of DD 01; however, the clinical efficacy does not appear to be altered. In dosages of 2 mg twice daily, tolterodine has shown consistent reductions in the number of micturitions per 24 hours and less consistently decreased incontinence episodes in patients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects, such as dry mouth, than occur with comparable nonselective antimuscarinic agents. CONCLUSIONS: Clinical studies have shown that the effectiveness of tolterodine for symptoms of overactive bladder is similar to that of oxybutynin. The adverse effect profiles of tolterodine and oxybutynin are similar; however, comparative clinical trials have shown significantly fewer patients taking tolterodine require dosage reductions or discontinue therapy due to antimuscarinic adverse effects such as dry mouth. Although more costly than oxybutynin, tolterodine represents a modest improvement over oxybutynin with respect to adverse effect profile, which may allow more patients with incontinence to tolerate therapeutic doses. Further research is necessary to determine whether tolterodine has clinical advantages over similar agents in patients with other muscarinic adverse effects, such as constipation or cognitive impairment.

Benzhydryl Compounds↗
PubMed2006

The overactive bladder: Epidemiology and morbidity.

The International Continence Society recognizes the overactive bladder (OAB) as a "symptom syndrome suggestive of lower urinary tract dysfunction" that is defined as "urgency, with or without urge incontinence, usually with frequency and nocturia." Patients who have OAB are often sleep deprived and their sexual life is hindered. These patients have a restricted social life and an increased risk for depression. Accurate prevalence figures are difficult to obtain because most patients consider OAB an inevitable part of aging and some patients are too embarrassed to seek diagnosis. Primary care physicians need to be educated about the importance of identifying this clinical problem and managing it in a way that will minimize morbidity and maximize quality-of-life improvement. This article describes the various aspects of OAB, with special emphasis on epidemiology and morbidity.

Humans↗
PubMedDate not supplied

The challenge of overactive bladder therapy: alternative to antimuscarinic agents.

Contemporary, the management of overactive bladder (OAB), a medical condition characterized by urgency, with or without urge urinary incontinence, frequency and nocturia, in absence of genitourinary pathologies or metabolic factors that could explain these symptoms, is complex, and a wide range of conservative treatments has been offered, including bladder training, biofeedback, behavioral changes, oral or intravesical anticholinergic agents, S3 sacral neuromodulation and peripheral electrical stimulation. Clinical efficacy of these treatments remains an open issue and several experimental and clinical studies were carried out in the last years improving the results of medical treatment. Here we review the pathophysiology of micturition reflex, the current therapies for OAB and the rationale for alternative treatments. Furthermore we critically address the potential use of medications targeting the central nervous system (CNS) and the primary sensory nerves of the bladder wall, we review the use of agonists of nociceptin/orphanin protein (NOP) receptor and finally we report the results obtained by intradetrusor injection of botulinum toxin.

Botulinum Toxins↗
PubMed2004

Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder.

PURPOSE: The current study was done to elucidate the in vivo mechanism of action of intravesical instillation of oxybutynin to treat overactive bladder. MATERIALS AND METHODS: In rats receiving oral and intravesical oxybutynin we measured muscarinic receptors in the bladder and other tissues by radioligand binding assay using [3H]NMS ([N-methyl-3H] scopolamine methyl chloride) with the simultaneous measurement of plasma concentrations of oxybutynin and its active metabolite N-desethyl-oxybutynin. Pilocarpine induced salivary secretion was also measured. RESULTS: Following oral administration of oxybutynin there was a significant increase in the apparent dissociation constant (Kd) for specific [3H]NMS binding in the bladder, submaxillary gland, heart and colon of rats at 1 and 3 hours with a consistent decrease in the maximal number of binding sites (Bmax) in the submaxillary gland. Furthermore, a marked and prolonged decrease in pilocarpine induced salivary secretion in rats was observed by oral oxybutynin. In contrast, intravesical instillation of oxybutynin produced a significant increase in Kd for specific [3H]NMS binding in the bladder of rats at 0.5 to 4 hours later and also in the submaxillary gland only at 0.5 hours later. The enhancement in Kd was much larger and longer lasting in the bladder than in the submaxillary gland. Moreover, intravesical oxybutynin had little muscarinic receptor binding activity in the heart and colon, and little significant suppression of pilocarpine induced salivation in rats. The plasma concentrations of oxybutynin and N-desethyl-oxybutynin were much higher in rats receiving oxybutynin orally than intravesically. CONCLUSIONS: Intravesical oxybutynin in rats may cause selective binding of bladder muscarinic receptors via a direct local effect, while oral oxybutynin may exert predominant binding of salivary gland receptors.

Administration, Intravesical↗
PubMed2003

Urodynamic effect of acute transcutaneous posterior tibial nerve stimulation in overactive bladder.

PURPOSE: Of the various treatments proposed for urge incontinence, frequency and urgency electrostimulation has been widely tested. Different techniques have been used with the necessity of surgical implantation (S3 neuromodulation or sacral root stimulation) or without requiring surgery (perineal transcutaneous electrostimulation). Recently peripheral electrical stimulation of the posterior tibial nerve was proposed for irritative symptoms in first intention or for intractable incontinence. Clinical studies have demonstrated good results and urodynamic parameters were improved after chronic treatment. However, to our knowledge no data concerning acute stimulation and immediate cystometry modifications have been reported. We verified urodynamic changes during acute posterior tibial nerve stimulation. MATERIALS AND METHODS: A total of 44 consecutive patients with urge incontinence, frequency and urgency secondary to overactive bladder were studied. There were 29 women and 15 men with a mean age +/-SD of 53.3 +/- 18.2 years. Of the patients 37 had detrusor hyperreflexia due to multiple sclerosis (13), spinal cord injury (15) or Parkinson's disease (9), and 7 had idiopathic detrusor instability. Routine cystometry at 50 ml. per minute was done to select the patients with involuntary detrusor contractions appearing before 400 ml. maximum filling volume. Repeat cystometry was performed immediately after the first study during left posterior tibial nerve stimulation using a surface self-adhesive electrode on the ankle skin behind the internal malleolus with shocks in continuous mode at 10 Hz. frequency and 200 milliseconds wide. Volume comparison was done at the first involuntary detrusor contraction and at maximum cystometric capacity. The test was considered positive if volume at the first involuntary detrusor contraction and/or at maximum cystometric capacity increased 100 ml. or 50% during stimulation in compared with standard cystometry volumes. RESULTS: Mean first involuntary detrusor contraction volume on standard cystometry was 162.9 +/- 96.4 ml. and it was 232.1 +/- 115.3 ml. during posterior tibial nerve stimulation. Mean maximum cystometric capacity on standard cystometry was 221 +/- 129.5 ml. and it was 277.4 +/- 117.9 ml. during stimulation. Posterior tibial nerve stimulation was associated with significant improvement in first involuntary detrusor contraction volume (p <0.0001) and significant improvement in maximum cystometric capacity (p <0.0001). The test was considered positive in 22 of the 44 patients. CONCLUSIONS: These results suggest an objective acute effect of posterior tibial nerve stimulation on urodynamic parameters. Improved bladder overactivity is an encouraging argument to propose posterior tibial nerve stimulation as a noninvasive treatment modality in clinical practice.

Female↗
PubMed2003

The acute effect of magnetic stimulation of the pelvic floor on involuntary detrusor activity during natural filling and overactive bladder symptoms.

OBJECTIVE: To evaluate the effect of magnetic stimulation of the pelvic floor (MSPF) on involuntary detrusor activity observed during natural filling, and on the overactive bladder symptom complex. PATIENTS AND METHODS: Eighteen women with detrusor overactivity on conventional cystometry underwent ambulatory urodynamic monitoring over two filling cycles. Fluid intake was standardized, provocative manoeuvres applied at regular intervals and symptoms documented contemporaneously. During the second filling cycle MSPF was delivered whenever the detrusor pressure increased by > 5 cmH2O. The women were subsequently treated with MSPF for 6 weeks; their lower urinary tract symptoms were assessed before and after treatment. RESULTS: Comparing the second (stimulated) cycle with the first (unstimulated) cycle, cystometric capacity was higher (373 vs 224 mL, P < 0.03). and involuntary detrusor activity of shorter duration (370 vs 427 s, P < 0.82) and lower amplitude (53 vs 63 cmH2O, P < or = 0.05). All women tolerated the procedure comfortably, but nine found it too time-consuming and withdrew. In the nine women who completed treatment there was no consistent change in overactive bladder symptoms. CONCLUSIONS: In this pilot study, MSPF during natural filling was associated with a decrease in the amplitude of involuntary detrusor contractions and a significant increase in cystometric capacity. However, MSPF had a variable effect on sensations of urgency, both acutely and after treatment, and currently there is no evidence to suggest that MSPF has an enduring effect on symptoms of the overactive bladder.

Electric Stimulation Therapy↗
PubMed2006

[Results of sacral nerve modulation for treatment of overactive bladder].

Currently, sacral nerve modulation (SNM) is an effective treatment for overactive bladder symptoms which are refractory to anticholinergic or muscarinergic treatment. However, SNM requires the implantation of stimulation electrodes at the sacral nerves and a subcutaneous impulse generator. The SNM procedure can be divided into three phases: the acute phase comprising the implantation of the test stimulation electrodes, the subchronic stimulation phase over a period of 7-14 days during which neurostimulation takes place by means of an external impulse generator, and finally chronic SNM after implantation of the final impulse generator. In 1981 the SNM technique for treatment of bladder dysfunctions was first developed by Tanagho and Schmidt and has since been refined, while the range of indications has been extended continuously. It has been shown that patients with neurogenic bladder dysfunctions are able to gain the greatest benefit from SNM. The long-term results of SNM are very encouraging so far. In addition, a highly innovative and promising technique is the implantation of a miniaturized impulse generator with integrated stimulation electrode at the n. pudendus. However, the outcome of these trials has not fully been capable of living up to the expectations so far.

Clinical Trials as Topic↗
PubMed2006

The economic costs of overactive bladder in Germany.

OBJECTIVE: To estimate the annual direct costs of overactive bladder (OAB) in Germany from a societal perspective. METHODS: Direct costs were calculated based on prevalence figures and medical resource utilisation due to hospitalisation, office-based physician visits, visits to other health care professionals, medication, medical aids and devices, and nursing care. RESULTS: A total of 6.48 million adults>or=40 yr of age in Germany are affected by OAB, and 2.18 million of these individuals experience incontinence. The annual incidence of comorbidities attributable to OAB is 310,000 for skin infections, 40,000 for falls, 12,000 for fractures, and 26,000 for depression (based on 2004 census data). Direct OAB-related costs per year are euro3.98 billion, with euro1.76 billion covered by statutory health insurance, euro1.80 billion by nursing care insurance, and euro0.41 billion by the patients. Nursing care accounts for euro1.80 billion of total costs (45%), devices account for euro0.68 billion (17%), physician visits account for euro0.65 billion (16%), complications account for euro0.75 billion (19%), and medication accounts for euro0.08 billion (2%). CONCLUSION: OAB imposes a substantial economic burden on German health and nursing care, insurance, and on patients with OAB. Direct annual costs are comparable to those of other chronic diseases such as dementia or diabetes mellitus.

Comorbidity↗
PubMed2004

The association between overactive bladder symptoms and objective parameters from bladder diary and filling cystometry.

AIMS: To investigate the association between overactive bladder symptoms and objective parameters from the bladder diary and conventional filling cystometry. METHODS: We reviewed the records of the 95 consecutive patients presenting at our center for urodynamic investigation. These women were asked to self-complete a questionnaire and a bladder diary for 48 hr. Urogenital symptoms and disease-specific quality of life were assessed with standardized questionnaire, namely the Dutch version of the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ). RESULTS: The frequency symptom as well as the urge incontinence symptom is significantly associated with the presence of detrusor overactivity. In univariate analysis both frequency and urgency symptoms are associated with lower micturition and bladder sensation volumes. In multivariate (ANOVA) analysis, the frequency symptom is associated with a higher 24-hr frequency, lower maximum volume voided, and mean volume voided per micturition on the bladder diary. It is also associated with lower sensation volumes on the filling cystometry. CONCLUSIONS: Of the four symptoms that are currently considered to be part of the overactive bladder syndrome, the frequency symptom is the best associated with objective parameters from the bladder diary, filling cystometry, and with the occurrence of detrusor overactivity. Therefore, we would like to suggest that reporting subjective symptoms frequency is obligatory for considering one to have an overactive bladder.

Adult↗
PubMed2002

Bladder afferents and their role in the overactive bladder.

The role of afferent innervation of the bladder in the pathophysiology of urinary incontinence has become the focus of intense interest. In normal health, the afferent pathway is mediated largely by Adelta-fibers, which ultimately send information about the state of bladder fullness to the pontine micturition center via the periaqueductal gray matter. However, after spinal disruption, a different type of afferent pathway emerges, mediated by capsaicin-sensitive C-fibers that drive a spinal segmental reflex pathway, causing neurogenic detrusor overactivity. The common sources of afferent information for either pathway are likely to be afferents from the urothelium, lamina propria, and afferents that originate in the bladder wall. Ultrastructural investigations of the constituent neural elements of these structures contribute to our knowledge of their role in both health and disease and help provide a rational approach to treatment strategies. Evidence of the involvement of capsaicin-sensitive C-fibers in the spinal reflex pathway has been supported by the successful treatment of patients with neurogenic incontinence with intravesical capsaicin or its ultrapotent nonpungent analog, resiniferatoxin. On the other hand, capsaicin has not been shown to be clearly effective in treatment of overactive bladder caused by detrusor overactivity or suprapontine pathology without the emergent C-fiber-mediated reflex. It is hoped that continued investigation of neurotoxins that have the potential to act on afferent innervation will lead to other treatment strategies for bladder disorders and other disorders involving afferent dysfunction.

Afferent Pathways↗
PubMed2004

Diagnosis and management of patients with overactive bladder syndrome and abnormal detrusor activity.

Overactive bladder syndrome (OABS) is a widely recognized syndrome with symptoms that can include urinary urgency, frequency, nocturia, and incontinence. Although there may be several causative factors for OABS, detrusor overactivity is the most common. In addition, urinary incontinence can also be due to a distinct but equally bothersome condition underactive bladder syndrome, or detrusor underactivity. The incomplete bladder emptying that characterizes detrusor underactivity often arises from impaired contractile function of the detrusor muscle. The variations in etiologies of the two syndromes necessitate patient evaluations tailored to individual symptom presentation. Increased awareness of the differences between the manifestations of OABS and underactive bladder syndrome call for specific approaches to the management of bladder dysfunction.

Humans↗