[Intravesical drug therapy in women with severe urge incontinence. Clinical experiences from a department of gynecology]. / Intravesikal medicinsk behandling af kvinder med svaer urgeinkontinens. Kliniske erfaringer fra en gynaekologisk afdeling.

Conventional oral pharmacotherapy for urge incontinence remains problematic because of limited efficacy and systemic side effects. In this study 27 patients with severe urge incontinence were treated with intravesical drugs (emepron 200 mg or oxybutynin 5 mg) twice a day. They had previously on average undergone 3.3 other treatment options without satisfactory effect. The average age was 62 years, and their incontinence had on average lasted for 15 years. Seven percent were cured and 41% were improved. Fifty-two percent had no satisfactory effect of the treatment. The number of side effects was low, and none left the study for this reason. Intravesical anticholinergic pharmacotherapy can be a treatment option in women with severe urge incontinence.

[Comparison of emepronium bromide with intravesical administration of lidocaine gel in women with urge incontinence]. / Vergleich von Emeproniumbromid mit intravesikal appliziertem Lidocain-Gel bei Frauen mit Urge-Inkontinenz.

In the treatment of urge incontinence, drug therapy predominates. In a prospective randomised study on treatment of females with motor urge incontinence, intravesically administered lidocaine-gel and oral emepronium bromide were compared using clinical and urodynamic parameters. From 30 patients, 15 women were treated for 3 weeks with repeated intravesical lidocaine gel instillations whilst the other 15 had a peroral emepronium bromide medication. The intravesical lidocaine gel installation proved more efficient compared with peroral emepronium bromide therapy with regard to the parameters of imperative micturition, occurrence of detrusor contractions as well as number of urinary frequencies per diem. Intravesical application of lidocaine-gel is particularly indicated in patients with increased sensitivity against parasympathicolytics and anticholinergics.

Vesical instillation of emepronium bromide in defunctionalized postobstructive noncompliant bladder: an alternative to intestinal augmentation surgery?

A contracted noncompliant bladder is an infrequent but severe complication of cutaneous ureterostomy. Recently, we effected a significant increase in bladder capacity by long-term, gentle hydraulic dilation with saline solution plus an anticholinergic drug (emepronium bromide). Based on this experience, we suggest a conservative approach like this before electing a patient for bladder augmentation or permanent diversion for any child with vesical contracture.

The effect of intravesically administered Cetiprin on bladder spasms after transurethral resection of the prostate. A double-blind randomized study.

A double-blind study of the short-term effects of intravesically administered emepronium bromide (Cetiprin) versus placebo on bladder spasms after transurethral prostatectomy was done in 40 male patients. In the Cetiprin group there was a significant decline in the need for analgesia, and significantly fewer catheter problems. The use of intravesically instilled Cetiprin is recommended only in cases of severe postoperative bladder spasms.

Dose titration in clinical trials. An example using emepronium carrageenate in detrusor instability.

Seventy-two women with proven detrusor instability completed a novel clinical trial of the new anticholinergic emepronium carrageenate (Cetiprin novum), which allowed for dose titration. The tolerated dose has been shown to correlate with the severity of symptoms. Statistically significant improvement was achieved in symptomatic and urodynamic parameters without serious side effects.

Pharmacokinetics and pharmacodynamics of emepronium bromide (Cetiprin) after intravenous administration in man.

Intravenous doses of 1, 5, 10 and 15 mg of emepronium bromide were given to three healthy volunteers. Emepronium serum concentration declined in a triexponential manner with half-lives between 2.2-3.0 min., 1.0-1.6 hours and 5.1-13 hours, respectively. The initial dilution space (volume of the central compartment) varied between 4.1-7.5 l. The area under the serum concentration time curve increased linearly with dose, indicating constancy of total serum clearance (range: 24-38 l/hr) with dose. The renal clearance of emepronium varied with serum concentration; secretion in addition to glomerular filtration was evident. Tubular secretion of emepronium was half-saturated at serum concentrations of approximately 50 nmol/l. No obvious drug-related effect on blood pressure was noted, whereas salivary secretion decreased and heart rate increased with 10-15% at emepronium serum concentrations of about 200 nmol/l. ECG recordings were without abnormalities after slow intravenous injections of emepronium bromide in doses of up to 15 mg. Since no adverse effects were noted, intravenous administration of emepronium bromide may be an alternative in situations where the drug is now used intramuscularly e.g. severe tenesmus in the urinary bladder.

A comparison between the combination emepronium bromide/flavoxate and emepronium bromide in the treatment of detrusor instability.

Emepronium bromide and flavoxate have both and separately been used with success in the treatment of detrusor instability. In this study we have combined the two drugs emepronium bromide and flavoxate and compared the results with emepronium bromide. 20 consecutive patients with an uninhibited bladder, 12 men and 8 women, were randomly allocated to treatment with either emepronium bromide/flavoxate or emepronium bromide. In this trial we found that treatment with the combination is significantly better than treatment with emepronium bromide only.

The lack of effect of intramuscular emepronium bromide for urinary incontinence.

Six elderly volunteers (4 men and 2 women), suffering from urinary incontinence due to small capacity, hyper-reflexic bladders, were assessed cystometrically 1/2 h, 1 h and 4 h after an intramuscular injection of emepronium bromide (Cetiprin). The dose given was sufficient to raise serum levels of emepronium to approximately 10 times those that could be reached with an oral dose. Analysis of the results showed that there was no significant difference in the state of the bladder at any time. The study confirms that emepronium bromide is ineffective in increasing bladder capacity in subjects with small, hyper-reflexic bladders. It has no value, therefore, in the management of urinary incontinence in elderly patients with this condition.

[Ulcer of the esophagus after intake of emeproniumbromide (author's transl)]. / Osophagusulkus nach Einnahme von Emeproniumbromid.

Two female patients were treated because of pollakiuria with emeproniumbromide tablets. They developed extended ulcers of the esophageal mucosa. The tablets had been taken late in the evening with only little fluid. Ulcer formation is thought to be due to prolonged passage time and to a locally damaging effect of the hygroscopic compound. There may be lesions of the esophageal musculature as well, as demonstrated by considerable disturbance of esophageal motility. Ulcers tend to be painfull; they heel fast without formation of scars.

An objective comparison of the effects of parenterally administered drugs in patients suffering from detrusor instability.

Cystometric changes produced by 3 parenterally administered drugs, flavoxate hydrochloride, emepronium bromide and imipramine hydrochloride, have been evaluated in 15 female patients with detrusor instability. Each patient was given 2 of the 3 drugs and cystometric recordings were done 10 and 30 minutes after the administration of each drug. Emepronium bromide was found to be the only drug to cause a significant improvement in bladder capacity and reduction in detrusor pressure.

Drug-induced corrosive injury of the oesophagus.

Five patients are described who had retrosternal pains following the consumption of CetiprinR tablets. The pains increased so markedly within a few days that, initially, solid foods and, subsequently liquid foods also were impossible to swallow. Typically the history was of the comsumption of a tablet in the evening or night without fluids and the pains lasted 2--3 weeks. A marked corrosive injury of the middle third of the oesophagus was shown at oesophagoscopy in each case, but the mucosa of the lower one-third of the oseophagus was normal. Gastro-oesophageal reflux was not demonstrated radiologically in any of the patients. None of the patients developed a stricture of the oesophagus. The most likely alternative in the differential diagnosis was a foreign body. Oesophagoscopy should be performed on any patient in whom such pains persist for more than 4--5 days, even if the X-rays are normal. The physician should advise his patients to take tablets or capsules with fluids. This is especially important if the drug is taken in the evening or at night. CetiprinR tablets should be taken in the evening while the patient is still upright, and should be taken with fluids. If a corrosive injury does develop, we suggest that treatment should be with cortisone and with agents which protect the oesophageal mucous membranes.

Treatment of urgency by instillation of emepronium bromide in the urinary bladder.

The possibility of a purely local action of intravesically instilled emepronium bromide (Cetiprin) was investigated. Subjective reports and simultaneous urethrocystometry were used to assess such effect. In order to ascertain the purely local nature of effect, the serum was analyzed for freely circulating emepronium ion at increasing intravesical concentrations. No adverse effects were found at the highest dosage (100 mg in 100 ml saline solution), and the concentrations in serum were very low or were not detectable. The seemingly promising influence on micturition frequency and urge prompted a double-blind study of 20 patients with chronic urgency. In ten of them 100 mg emepronium bromide in 100 ml saline solution was instilled intravesically, while the other ten received only the same volume of saline solution. The symptoms were relieved in eight of the ten patients given emepronium bromide. The observation time was one week. The therapeutic possibilities were further evaluated in 24 women with frequency and urgency with or without urge incontinence. Emepronium bromide was intravesically instilled in the mentioned concentration and, if the symptoms were not totally relieved, this was repeated at weekly intervals. The maximum number of instillations was four and the observation time after the final treatment was at least three weeks. Frequency and urgency disappeared in approximately 70% of the affected women, nocturia in 60%, but urge incontinence in only 30%. Both frequency and urgency therefore were therapeutically influenced by intravesical instillation of emepronium bromide.

A second look at emepronium bromide in urinary incontinence.

Response to oral and intramuscular emepronium bromide was assessed cystometrically in nine patients with urinary incontinence caused by an uninhibited bladder. Oral therapy had no effect, whereas intramuscular administration increased bladder capacity and significantly delayed the onset of bladder spasm and the desire to void. Plasma-propranolol response was delayed and concentrations were reduced after an oral 40 mg dose of propranolol in 3 patients who had received oral emepronium bromide. These results indicate that although oral emepronium bromide had some anticholinergic effect--i.e., in reducing gastrointestinal motility--absorption of an oral dose was not sufficient for the bladder to be affected.