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Oxybutynin chloride (Ditropan) and placebo were randomized in a double-blind trial to determine the effectiveness of the test agent in controlling post-transurethral pain and spasm. Oxybutynin chloride was found effective in controlling pain and spasm; no significant side effects were noted.
The ability of imipramine, oxybutynin, and flavoxate to antagonize carbamylcholine and barium chloride (BaCl2)-induced contractions of rabbit detrusor, and to block impulse conduction in desheathed frog sciatic nerves has been assessed in vitro. Impiramine exerts noncompetitive carbamylcholine and BaCl2 blockade by 10(-5) M and a local anesthetic effect equipotent with that of tetracaine. Oxybutynin exerts a strong competitive antagonism of carbamylcholine by 10(-8) M, a noncompetitive antagonism of BaCl2 equivalent to that of imipramine, and moderate local anesthetic activity. Flavoxate, under these experimental conditions exerts little anticholinergic, antispasmodis, or local anesthetic activity. Imipramine and oxybutynin thus demonstrate a number of smooth muscle effects by which their therapeutic actions may be exerted. The mechanisms of action of flavoxate remain obscure.
A double-blind study of the short-term effects of oxybutynin chloride versus placebo on bladder spasm after transurethral surgery was done in 106 male patients. No significant difference between the placebo and 10 mg. or 20 mg. of the drug was noted.
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Twenty-four patients with vesicoureteral reflux were studied urodynamically because of a history of dysfunctional voiding. Nine patients eventually had antireflux surgery. The remaining 15 patients were followed from two to six years. These patients were managed conservatively with an emphasis on controlling infection and improving voiding habits. Reflux resolved spontaneously in 12 patients and improved in 1 patient. Dysfunctional voiding is a definite cause of childhood reflux. Treatment should be directed at improving voiding patterns. Coordinated voiding may allow a child to "grow out" of his reflux.
One hundred and fourteen female patients had clinical and urodynamic diagnosis of detrusor instability. They all received oxybutynin chloride (Ditropan) 5 mg t.i.d. for four weeks and evaluation repeated. Sixty-six of the 114 patients (58%) responded favorably to anticholinergic treatment while 48 patients (42%) did not. Based on urethrocystometry, two groups of patients were identified: Group I consisted of 73 women with bladder contraction that preceded any change in urethral pressure. Group II consisted of 41 patients with urethral pressure drop that preceded the detrusor contraction by a few seconds. Sixty-one of the 73 women (84%) in Group I responded favorably to four weeks of anticholinergic therapy while 88 percent (36 of 41) of women in Group II did not (P less than 0.01). Our results suggest that women with bladder contraction that is preceded by urethral relaxation represent a different pathologic entity than women with "classic detrusor instability".
Intermittent catheterization remains the primary method of treatment in the management of patients with neurogenic bladders such as those with meningomyelocele. In a follow-up of a previous study, we re-examined the urologic status of patients with neurogenic bladders continuing on a regimen of clean intermittent catheterization five years after the completion of the first study. Thirty-seven of the original 49 patients were available for follow-up, and no significant differences were found between those lost to follow-up and those included in this study. Among the patients re-evaluated, reflux remained unchanged or improved in most patients, renal function was maintained, and the urinary tract infection rate remained low. Additionally, continuation of an intermittent catheterization program does provide independence and social continence in most young adults with meningomyelocele. We conclude that a long-term intermittent catheterization program is associated with stable reflux status, renal function, and infection rate, and that compliance with a catheterization program can result in improved social continence and independence.
To evaluate the efficacy of intravesical oxybutynin chloride, 42 patients who were incontinent secondary to uninhibited detrusor contractions and had failed oral anticholinergic therapy were begun on intravesical oxybutynin chloride. Indications for intravesical therapy were detrusor hyperreflexia (N = 20), detrusor instability (N = 19), and bowel/bladder overactivity after augmentation cystoplasty (N = 3). A 5-mg tablet dissolved in 30 cc of sterile water was instilled into the bladder two to three times daily via clean self intermittent catheterization. With a mean follow-up of 18.4 months, no patient reported side effects as a result of the intravesical therapy. Nine patients (21%) dropped out of the study due to inability to tolerate the catheterization or difficulty retaining the solution in the bladder. Eighteen of the 33 patients (55%) who followed the protocol experienced elimination or significant improvement of their incontinence. The results of the current study confirm the safety and usefulness of intravesical oxybutynin in treating uninhibited detrusor contractions in a difficult patient population.
In a canine model of the Mainz pouch, intracavitary pressure and compliance were measured during instillation of isosmotic and hyperosmotic (900 mmol/kg water) solutions of saline. Wall properties of small- and large-bowel segments of the pouch were assessed individually by sonomicrometry. Intraluminal pressures increased more steeply during filling with hyperosmotic solution, resulting in reduced distensibility of small- and large-bowel segments. Additionally, instillation of the hyperosmotic solution resulted in increased amplitudes and frequency of intracavitary pressure waves. The results indicate that this was the result of a combination of intensified bowel contractions and an increased mural tension. Topical application of oxybutynin abolished these effects. These findings are reviewed in light of the nocturnal increase in urine osmolality, its correlation with nocturnal incontinence in patients with enterocystoplasty, and possible treatment choices.
Urinary bladder cystometry using urethral catheters is described in vivo in a urethane-anesthetized guinea pig preparation and compared to an awake-animal preparation in which surgically implanted catheters were used. Anticholinergic drugs dose-dependently inhibited the peak intravesical pressure (PvesP) to a maximum of approximately 80% but had no effect on other cystometrogram (CMG) parameters (threshold pressure, bladder capacity). Stereoselectivity was evident; dexetimide but not levetimide potently depressed PvesP. Oxybutynin was equipotent (ID50 approximately 0.15 mg/kg) in both preparations and showed a similar duration of action (t1/2 = 48-53 min). The data suggests that CMG parameters and the effects of oxybutynin were not affected by urethane anesthesia, making the in vivo urethane-anesthetized guinea pig preparation a valuable tool to evaluate both the filling and voiding phases of cystometry.
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Oxybutynin hydrochloride, an anti-cholinergic/anti-spasmodic agent, was examined for its effect on fertility and peri-post natal development in the rat and its embryotoxic potential in the rat and rabbit. In the rat effects on reproductive performance included a slight increase in the incidence of foetal malformations, extended gestation period and impaired post natal performance of offspring. These findings occurred at dosages clearly associated with maternal toxicity. Oxybutynin hydrochloride did not exert an effect on reproductive processes in the rat at lower dosages or on embryonic and foetal development in the rabbit.
The interaction of glyoxal and four other glyoxylic compounds with semiconservative DNA synthesis and with unscheduled DNA synthesis induced by 25-G X-rays on TC-SV40 hamster cells has been studied. Both syntheses were evaluated by measuring the incorporation of [3H-methyl]-thymidine into the newly synthetized DNA. The unscheduled DNA synthesis amounts to 4% of semiconservative synthesis. The modification of both syntheses by the glyoxylic compounds was tested using the products at non-toxic concentrations for the cells. All the glyoxals inhibited semiconservative DNA synthesis and potentiated unscheduled DNA synthesis at rather similar levels. These effects have been compared with the radiosensitizing activity of these glyoxals in the same TC-SV40 cells and no relationship could be established.
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1. The pharmacological properties of an antispasmodic drug, tiropramide, were studied in isolated smooth muscle preparations. 2. Tiropramide at concentrations of 10(-6) to 10(-4) M relaxed various smooth muscles contracted spontaneously and by smooth muscle stimulants or electrical stimulation. Tiropramide did not interact with all drug-receptors examined, suggesting a pure musculotropic smooth muscle relaxant activity. 3. Tiropramide was found to inhibit both Ca uptake and Ca release in the guinea pig urinary bladder. 4. Tiropramide is considered to be useful to inhibit the contractile response of the urinary bladder, as this organ is mainly innervated by noncholinergic excitatory neurons.
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Bedwetting is present in 5 to 7% of children aged 7 to 8 years. The history of the disorder and the examination of the child are of main importance. This is usually the first step to identify nocturnal enuresis, bladder or urethral instability and other voiding dysfunctions. Therapeutic failure is often related to an inadequate analysis of the disorder. For nocturnal enuresis, the best results are obtained with alarms and/or desmopressine; bladder instability usually requires oxybutinine chlorydrate and urethral instability can be treated with biofeedback therapy. The management of other voiding dysfunctions depends on urodynamic assessment.