We prospectively studied 53 young children (45 less than 4 years old) between 1985 and 1988 with primary vesicoureteral reflux (grades I to V, 74 ureters). All patients had elevated bladder pressures during bladder filling and/or voiding on urodynamic evaluation, which sometimes were associated with abnormal perineal muscle activity. Baclofen, flavoxate, dicyclomine and diazepam were given individually or in combination for each type of dysfunction for 12 to 30 months. Reflux disappeared in 68 ureters (91.8 per cent) and it was downgraded in 6 (8.2 per cent). Urodynamic evaluation at the end of treatment revealed normal bladder pressures in 46 children (83.7 per cent of the ureters in which reflux resolved). Another group of 48 children with primary vesicoureteral reflux (grades I to IV, 67 ureters) seen between 1980 and 1985 was reviewed retrospectively. All patients had been treated with prophylactic antibiotics only. Reflux resolved in 53.7 per cent of the ureters, and it was downgraded in 19.4 per cent, unchanged in 22.4 per cent and upgraded in 4.5 per cent. Urodynamic studies performed in 1985 showed that all persistent cases of reflux in the retrospective group had urodynamic findings similar to those found in the prospective group. These data suggest that vesicoperineal incoordination as well as bladder instability can be important factors in causing and perpetuating reflux, and that medical treatment of these factors individually or in combination may affect therapeutic perspectives of this pathological condition.
Forty-seven trials were identified. Twenty-four, 12, and 11 trials evaluated anticholinergic drugs, drugs with anticholinergic and calcium antagonistic properties, and alternative regimens, respectively. Data regarding treatment effects of anticholinergic drugs are consistent with a high therapeutic efficacy and characteristic side effects. Therapeutic efficacy and side effect patterns of terodiline, an agent with anticholinergic and calcium antagonistic properties, were comparable to those of anticholinergic agents. Terodiline, however, has been withdrawn from the market because of its association with cardiac arrhythmia. Of the investigated alternative drug regimens, the papaverine-like smooth muscle relaxant flavoxate was reported to be ineffective. Studies investigating the dopamine agonist bromocryptine, the alpha-adrenoceptor blocker prazosin, or the gamma-aminobutyric acid receptor agonist baclofen showed subjective and/or objective improvement of symptoms without reaching statistical significance, whereas the tricyclic antidepressant doxepin, the neurotoxin capsaicin, and the prostaglandin synthase inhibitor flurbiprofen led to statistically significant subjective and/or objective improvement of symptoms. No data for subjective and/or objective improvement of symptoms could be extracted from the studies using the anticholinergic and calcium antagonistic agent propiverine and the calcium antagonist thiphenamil.
Only a small proportion of incontinent NH residents with mobility and cognitive function potentially suitable for specific treatment for incontinence receives drug therapy for their condition. Further research is needed to determine whether low drug use reflects an unmet need for treating UI, or appropriate prescribing practices based on the multiple and interacting factors that influence decisions on drug therapy in the NH population.
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K(+) -Krebs'-induced contraction developed more slowly while 64 Hz electrical field stimulation-induced contraction developed faster in flavoxate-treated strips when compared to control. Amplitudes of maximal and steady-state contraction induced by 3 µmol/L carbachol were also larger after flavoxate treatment. Control strips showed an overall greater dependence on stimulus strength in eliciting the responses.
To assess prescription renewal and switch rates in an elderly population receiving oxybutynin or flavoxate for treatment of urinary incontinence in Quebec.
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To assist the clinician in making informed decisions regarding UI, provide information on the wider ramifications of the disease, and provide a comprehensive overview of the condition.
MEDLINE database and abstract books of the major conferences were searched for relevant publications from 1966 to 2011 and using the key words 'overactive bladder', 'detrusor overactivity', 'oxybutynin', 'propiverine', and 'flavoxate'. Two independent reviewers considered publications for inclusion and extracted relevant data, without performing a meta-analysis.
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• The number of patients prescribed each antimuscarinic drug varied from 23 for darifenacin to 1758 for tolterodine ER. • The longest mean persistence was reported for solifenacin (187 days versus 77-157 days for the other treatments). • At 3 months, the proportions of patients still on their original treatment were: solifenacin 58%, darifenacin 52%, tolterodine ER 47%, propiverine 47%, tolterodine IR 46%, oxybutynin ER 44%, trospium 42%, oxybutynin IR 40%, flavoxate 28%. • At 12 months, the proportions of patients still on their original treatment were: solifenacin 35%, tolterodine ER 28%, propiverine 27%, oxybutynin ER 26%, trospium 26%, tolterodine IR 24%, oxybutynin IR 22%, darifenacin 17%, flavoxate 14%. • In a sub-analysis stratified by age, patients aged ≥ 60 years were more likely to persist with prescribed therapy over the 12-month period than those aged <60 years.
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Forty-five men with category IIIa chronic non bacterial protatitis were randomized into three groups as follows: (1) placebo; (2) phenoxybenzamine-hydrochloride:10 mg two times a day for one month; (3) flavoxate HCI-neptumus: 200 mg three times a day for one month. The NIH chronic prostatitis symptom score was used to grade symptoms at the beginning and conclusion of the study.
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A 4-week randomised, double-blind, cross-over study is described which compared the effects of a combination of emepronium bromide and flavoxate hydrochloride with placebo on incontinence and cystometrogram findings in 20 female patients aged 59 to 88 years. All patients initially had detrusor instability demonstrated on cystometrography: 14 patients completed the study; on placebo 10 still had unstable bladders and on active drugs seven were unstable. The number of wettings over a 48-h period before the study commenced and at the end each course of tablets showed no significant differences; also the patients' opinions about the effect on their incontinence indicated that the majority had the same opinion of each course. Active drugs significantly increased residual urine but did not significantly alter the values obtained for maximum cystometric capacity or effective cystometric capacity (the latter volume being maximum cystometric capacity minus the residual urine). No correlation was found, on either course of treatment, between the change to detrusor stability and the amount of improvement in incontinence. Some side effects are described. Despite evidence of a pharmacological effect on the bladder and patients' opinions tending to favour the active combination, nonetheless the main results of this small study do not suggest that the combination of emepronium bromide and flavoxate hydrochloride is an effective treatment of urinary incontinence associated with detrusor instability in elderly women.
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NS-21 is under development for the treatment of urinary frequency and urinary incontinence. The purpose of this study was to investigate the effects of NS-21 and its active metabolite, RCC-36, on lower urinary tract function in an experimental rat model of urinary frequency.
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Multiple Sclerosis (MS) is the commonest physically disabling chronic neurological disease affecting young people. Urinary symptoms are present in about 68% of people with MS but their basis has a number of potential aetiologies that can change with time.
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Review articles, original studies and case reports on MEDLINE, the Cochrane Library, Google Scholar, Scirus, internal repository, etc. were searched using the keyword "flavoxate". For the primary outcome, the comparative data of flavoxate versus comparator was extracted for following parameters - overall efficacy and its side effect profile. Similarly as for secondary outcome, data were extracted for flavoxate per se for overall efficacy, frequency, urinary incontinence, mixed incontinence, nocturia, unpleasant urination, stranguria and its side effect profile and were analyzed using Comprehensive Meta-Analysis (CMA) software version 2.0.
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The effects of flavoxate hydrochloride (Bladderon, piperidinoethyl-3-methylflavone-8-carboxylate; hereafter referred as flavoxate) on voltage-dependent nifedipine-sensitive inward Ba(2+) currents in human detrusor myocytes were investigated using a conventional whole-cell patch-clamp. Tension measurement was also performed to study the effects of flavoxate on K(+)-induced contraction in human urinary bladder. Flavoxate caused a concentration-dependent reduction of the K(+)-induced contraction of human urinary bladder. In human detrusor myocytes, flavoxate inhibited the peak amplitude of voltage-dependent nifedipine-sensitive inward Ba(2+) currents in a voltage- and concentration-dependent manner (K(i) = 10 microM), and shifted the steady-state inactivation curve of Ba(2+) currents to the left at a holding potential of -90 mV. Immunohistochemical studies indicated the presence of the alpha(1C) subunit protein, which is a constituent of human L-type Ca(2+) channels (Ca(V)1.2), in the bundles of human detrusor smooth muscle. These results suggest that flavoxate caused muscle relaxation through the inhibition of L-type Ca(2+) channels in human detrusor.
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Noradrenaline injection in the medial frontal lobe shortened the interval between bladder contractions. In contrast to the bladder contraction interval before and after noradrenaline injection in the medial frontal lobe, the interval was prolonged after noradrenaline injection when glutamate or flavoxate was injected in the rostral pontine reticular formation, or flavoxate was injected intravenously. Noradrenaline injection in the medial frontal lobe plus intravenous propiverine injection also prolonged the interval compared to that after noradrenaline injection alone. However, the interval after noradrenaline injection in the medial frontal lobe plus intravenous injection of propiverine was shorter than that before noradrenaline injection only.
Two years after revision of the practice guideline 'Urinary incontinence' from the Dutch College of General Practitioners, it is time for a summary of the most important changes. The use of a bladder diary is recommended. In primary care, a stress test does not provide more information than history taking. Routine urodynamic testing is not indicated for patients presenting to their general practitioner with urinary incontinence. Treatment of stress, urge and mixed incontinence can usually be commenced in primary care; pelvic floor exercises and bladder training are preferred. If bladder training is not effective for urge incontinence, anticholinergic drugs should be considered. The use of oral and vaginal oestrogens and flavoxate is no longer recommended.
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Following a mandate of the Canadian Urological Association, six Canadian urologists collaborated to produce these guidelines after having extensively reviewed existing foreign guidelines and literature from 1966 to June 2005.
The aim of this paper was to evaluate the efficacy (0= none; 3= fully) of the treatment with nonsteroidal anti-inflammatory (NSAI) drugs on (a) gland post-inflammatory echopattern, by transrectal ultrasound (TRUS); (b) seminal cytologic (WBC concentration and spermiophagies) and (c) >2 physicochemical inflammatory parameters in patients with chronic amicrobial prostato-vesiculitis (PV).
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The effects on urodynamic parameters of i.v. administration of different drugs utilized in the therapy of detrusor instability, have been studied in conscious catheterized rats. Emepronium bromide, oxybutynin and nifedipine affected in a dose-dependent way the micturition pressure (MP), with sporadic changes in bladder volume capacity (BVC). Terodiline induced significant increases in BVC values in a wide range of doses. These changes, however, were always not dose-dependent. The drug significantly reduced MP only at the higher administered dose (10 mg/kg). Flavoxate induced increases of bladder capacity (BVC) not dependent on the administered doses, with no changes in micturition pressure (MP). Indomethacin significantly increased BVC and weakly reduced MP, but the effects were not dose-related. The effects of drugs on BVC were unrelated with the basal value of this parameter, whereas the decrease of MP seems to be related to high basal values before treatment. From a quantitative point of view, cystometrographic recordings in conscious normal rats can provide comparative data among drugs acting on bladder contractility (MP) such as anticholinergics and strong calcium antagonists.
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To evaluate what type of patient received tolterodine compared with the spasmolytic drugs previously marketed (oxybutynin, flavoxate, emepronium).
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An improved HPLC method was developed for the concentration determination of the metabolite of flavoxate, 3-methyl-flavone-8-carboxylic acid (MFCA), in plasma in an attempt to compare two flavoxate tablet formulations. This HPLC method was validated by examining the precision and the accuracy for inter-day and intra-day runs in a linear concentration range of 0.1-24 microg/ml. The coefficients of variation (C.V.) of inter-day and intra-day assays were 0.24-7.18% and 0.06-5.70%, respectively. The standard errors of mean (S.E.M.) were -0.004-8.68% and -2.52-4.86% for inter-day and intra-day assays, respectively. Bioequivalence of the two formulations was determined on 12 normal healthy male volunteers in a single-dose, two-period, two-sequence, two-treatment crossover study. MFCA plasma concentrations were analyzed with this validated HPLC method. The normal pivotal parameters, AUC(0-last), AUC(0-inf) and Cmax, were calculated and compared using the SAS General Linear Model computer program. The two one-sided t distribution test was also performed, as well as the 90% confidence-interval method, for the mean difference of the three pivotal parameters. The results suggest that these two flavoxate tablet formulations are non-bioequivalent when orally administered in a 400-mg dose of two tablets. This result was consistent with the in vitro dissolution of these two formulations.
The effects and the possible mode of action of some drugs were studied in isolated preparations of the human upper urinary tract. Norepinephrine, histamine and serotonin had excitatory effects, whereas isoprenaline had inhibitory effects on smooth muscle activity. Norepinephrine induced different types of mechanical activity in different tissues of the human upper urinary tract suggesting different and separate coupling mechanism between the receptors involved and the calcium pools responsible for initiation of contraction. Acetylcholine had only little effects on smooth muscle activity even in high concentrations. Contractions which were triggered by action potentials or depolarizing extracellular potassium concentrations were highly sensitive to calcium channel blockers. Other drugs with relaxing properties such as papaverine, bencyclane, flavoxate or pitofenone seem to have effects on different calcium activation or calcium storing mechanisms.