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At least 613 records · Page 34Linked to original sources
PubMed2005

Newer pharmacologic options in management of overactive bladder syndrome.

PURPOSE OF REVIEW: Urinary incontinence is an under-reported epidemic that currently affects an estimated 13 million people in the United States, of whom about 11 million are women, according to the National Institute of Diabetes and Digestive and Kidney Diseases (Publication No. 02-4132). Because many patients are unaware of curative options and perceive it to be an inevitable outcome of advancing age, they fail to report their symptoms and increase their risk of developing associated co-morbid disease. Failure to diagnose and treat this condition increases financial burdens on individuals, their families and health care organizations. RECENT FINDINGS: Pharmacologic therapy of urge incontinence previously had limited treatment success because efficacious drugs were poorly tolerated, resulting in low patient compliance. Tolerance and effectiveness continue to be improved due to innovative new drugs and alternative delivery systems. SUMMARY: The goal of this review is to update the clinician on the efficacy and the tolerability of established and investigational pharmacologic modalities of therapy.

Animals↗
PubMed2005

Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats.

PURPOSE: We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically. MATERIALS AND METHODS: To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated. RESULTS: Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats. CONCLUSIONS: These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.

Administration, Intravesical↗
PubMed2006

Clinical efficacy of an alpha1A/D-adrenoceptor blocker (naftopidil) on overactive bladder symptoms in patients with benign prostatic hyperplasia.

AIM: We evaluated the efficacy of an alpha1a/d blocker, naftopidil, on storage symptoms in patients with benign prostatic hyperplasia (BPH), using frequency/volume charts (FVC). METHODS: A total of 81 patients with BPH (52-91 years, mean age 69.0 years) were studied. The inclusion criteria were: (i) one or more episode(s) of urinary urgency/day; (ii) a score of eight or more points on the International Prostate Symptom Score (I-PSS); and (iii) three or more points in any of the scores for three items (frequency, nocturia, and urgency) of the I-PSS. The patients received 50-75 mg/day of naftopidil for 6 weeks. All the patients were examined for 2-day FVC before and after the administration of naftopidil. I-PSS, quality of life index, and uroflowmetry were also evaluated. RESULTS: Total I-PSS decreased from 19.1 to 10.5 points (P < 0.0001), with significant improvement of both storage and voiding symptom scores (P < 0.0001, both). The score for urgency decreased from 3.1 to 1.4 (P < 0.0001). Daytime and night-time frequency decreased from 9.3 to 8.0 (P < 0.0001) and from 2.7 to 2.0 (P = 0.0009), respectively. Mean volume/void increased from 174.0 to 188.6 mL (P = 0.0453). Nocturia decreased from 3.2 to 2.3 (P < 0.0001) in 40 patients who suffered from nocturia two times or more. Notably, significant improvement of nocturia was observed in the patients both with and without nocturnal polyuria (P = 0.0006 and 0.0135, respectively). CONCLUSION: The alpha1a/d blocker naftopidil improves not only voiding symptoms but also storage symptoms, and is effective for nocturia in patients with BPH regardless of the existence of nocturnal polyuria.

Adrenergic alpha-Antagonists↗
PubMed1994

Clam cystoplasty for the overactive bladder: a review of 23 cases.

A clam enterocystoplasty was performed for refractory urge incontinence due to either idiopathic instability (13 patients) or neuropathic hyperreflexia (10 patients). Twelve patients became dry and appliance free. Of the remaining 11 wet patients, seven developed low pressure reservoirs, of whom five had stress incontinence and two had overflow incontinence. The other four patients had persistent symptomatic involuntary phasic contractions and ongoing urge incontinence. The magnitude of the surgery and the voiding dysfunction associated with the relative lack of motivation of elderly patients made the operation less successful and more hazardous in those over the age of 65. Successful outcome could be improved by careful patient selection and by performing an antistress incontinence procedure, such as implantation of an artificial urinary sphincter cuff or a cystourethropexy, where there is associated bladder outlet incompetence.

Adolescent↗
PubMed2004

Effect of controlled-release delivery on the pharmacokinetics of oxybutynin at different dosages: severity-dependent treatment of the overactive bladder.

OBJECTIVE: To assess the pharmacokinetics of a controlled-release formulation of oxybutynin (OROS-O, ALZA Corp., Mountain View, CA) at different dosages, compared with immediate-release oxybutynin (IR-O), and to determine the pharmacodynamic properties in the severity-dependent reduction of urge urinary incontinence (UUI). PATIENTS AND METHODS: In all, 105 patients were enrolled in this multicentre, randomized, double-blind study. Individual dose titration was used to assess the minimum effective, maximum tolerated or maximum allowed dose of either OROS-O or IR-O. Blood samples were collected during maintenance therapy with frequent sampling to analyse for R-oxybutynin and R-desethyloxybutynin concentrations. Pre-dose plasma levels before dosing were obtained as the minimum concentrations achieved at steady state during the dosing regimen. In parallel, UUI episodes were assessed at baseline and during maintenance therapy at the final dose level. RESULTS: For both IR-O and OROS-O, initial R-oxybutynin plasma concentrations increased in a dose-dependent fashion. For comparable dosages pre-dose plasma levels were higher for OROS-O than IR-O. After one dose of IR-O plasma concentrations peaked at approximately 27-fold after 1 h and decreased to baseline levels within 4-8 h. In contrast, plasma concentrations of R-oxybutynin remained constant for up to 24 h after taking OROS-O at all doses. The overall percentage reduction in weekly UUI episodes was 84% (to 4.8 episodes) and 88% (to 3.1 episodes) for OROS-O and IR-O, respectively (P < 0.05). Patients who titrated to final dose levels of 10, 15 and 20 mg OROS-O differed in their weekly UUI episodes at baseline (14.5, 30.3 and 42.0). Because of individual dose titration, UUI episodes/week were profoundly reduced at all applied doses (1.9-2.0, respectively). Fewer patients reported moderate to severe dry mouth with OROS-O than with IR-O (25% vs 46%, P < 0.05). CONCLUSION: The pharmacokinetics of OROS-O are proportional to dose, with minimal fluctuations between peak and trough concentrations, as associated with IR-O. In clinical practice OROS-O may thus facilitate the highly effective severity-dependent treatment of UUI with flexible dose adaptations based on the patients' needs.

Cholinesterase Inhibitors↗