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PubMed1979

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.

Adult↗
PubMed1983

Placebo--the drug of choice in female motor urge incontinence?

In a randomised double-blind cross-over trial of 19 females with motor urge incontinence but without bladder suspension defect, the effects of 14 days' treatment with emepronium bromide 200 mg qid, flavoxate chloride 200 mg qid or placebo qid were compared by means of micturition charts, the patients' drug preferences and evaluation of side effects. Placebo was the only drug giving rise to a statistically significant decrease in the frequency of voidings, incontinence and nocturia. Forty-seven per cent of the patients preferred placebo and side effects were less frequent during treatment with this medication. No differences could be demonstrated between the effects of emepronium bromide and flavoxate chloride. Perhaps detrusor instability is not always the main reason for the voiding dysfunction in these patients, in whom the effect of placebo was equal or superior to the effect of "active drugs" and superior to no treatment at all.

Adult↗
PubMed1987

Esophageal ulceration due to oral medications.

From 1975 through 1984 at the Department of Otolaryngology, Turku University Central Hospital, a total of 88 patients with esophageal ulceration due to oral medications were diagnosed endoscopically. The frequency of ulcerations increased until 1980 (14 cases) and was then followed by a decline. There were 24 patients (27.3%) under 20 years of age and 67 patients (76.1%) under 40 years of age, the mean age being 30 years 5 months. Emepronium bromide was the cause of esophageal injury in 24 patients (28.9%), doxycycline in 22 patients (26.5%) and analgetics in 11 patients (13.3%). There were three serious complications in the present series: an esophageal perforation due to doxycycline, an acute mediastinitis and a pericarditis due to emepronium bromide. In this material there was only 1 patient needing dilatation because of stricture formation.

Adolescent↗
PubMed1988

Receptor binding studies of the flavone, REC 15/2053, and other bladder spasmolytics.

The new flavone derivative REC 15/2053, a compound with spasmolytic activity on the lower urinary tract, was examined for its in vitro interaction with alpha- and beta-noradrenergic receptors, dopaminergic, muscarinic, serotoninergic, and opiate receptors, and calcium-channel binding sites labeled with 1,4-dihydropyridines from normal rat brain. All the investigated receptors are directly or indirectly involved in the nervous control of the lower urinary tract functions. The activity of REC 15/2053 on these receptors was studied in comparison to the most common drugs used in the management of urinary bladder disorders such as flavoxate, emepronium bromide, oxybutynin, terodiline, and imipramine. REC 15/2053 showed only weak binding to [3H]nitrendipine sites (IC50 = 14 microM) and muscarinic receptors (IC50 = 18 microM), whereas flavoxate was slightly active only at muscarinic receptors (IC50 = 12.2 microM). Emepronium bromide, oxybutynin, and terodiline were active only at muscarinic receptors, with IC50 values of 236, 5.4, and 588 nM, respectively. Oxybutynin showed a weak affinity to [3H]nitrendipine binding sites (IC50 = 44.4 microM). Imipramine was active at alpha 1-adrenergic and muscarinic receptors (IC50 = 248 and 653 nM, respectively). The activity of REC 15/2053 at muscarinic receptors and 1,4-dihydropyridine binding sites seems too low to account for its mechanism of action.

Animals↗
PubMed2000

Selective prescribing of spasmolytics.

BACKGROUND: Daily clinical practice often differs largely from the clinical trial setting, so extrapolation of outcomes from trial data, such as safety, effectiveness, and economic outcomes, can be deceptive. Prescribers may intend to treat a selected group of patients with new drugs; this practice could result in significant bias in assessing outcomes of these agents during their use in daily clinical practice. OBJECTIVE: To evaluate what type of patient received tolterodine compared with the spasmolytic drugs previously marketed (oxybutynin, flavoxate, emepronium). DESIGN: An observational, follow-up study. SETTING: Eighteen collaborating community pharmacies. PATIENTS: Aged > or = 18 years, noninstitutionalized; initial therapy with tolterodine, oxybutynin, flavoxate, or emepronium. RESULTS: Tolterodine was often used as a second-line and even as a third-line treatment, and was prescribed to a "polluted" population in terms of concomitant psychotropic medication. Tolterodine users were 7.5 times more likely to have received another spasmolytic drug (RR 7.5, 95% CI 4.8 to 11.9). In addition, these patients more frequently used antiparkinsonian drugs (RR 4.1, 95% CI 1.6 to 10.4) as well as antipsychotic drugs (RR 2.9, 95% CI 1.4 to 6.2). There was a small difference in concomitant use of antidepressants and benzodiazepines between patients receiving tolterodine versus those taking other spasmolytic drugs. CONCLUSIONS: Tolterodine is prescribed for a population differing from that receiving previously marketed spasmolytic drugs. Selective prescribing should recognized when evaluating new drugs in daily clinical practice. Policy makers, such as pharmacy and therapeutics committees, should consider this aspect in their formulary decisions since selective prescribing can lead to unjustified conclusions about a drug's therapeutic effects (e.g., efficacy, safety, cost-effectiveness).

Aged↗
PubMed1985

Mechanism of flavoxate antispasmodic activity comparative in vitro studies.

In order to clarify the pharmacological activity of flavoxate, its effect on the tone and spontaneous activity of the guinea-pig isolated ureter and of the muscle strip from rat urinary bladder were studied. Flavoxate, as well as papaverine, reduced all three parameters considered on the guinea-pig isolated ureter, namely: peristaltic motility, endoluminal pressure and longitudinal muscle contractility. In the same test, verapamil (a calcium antagonist), emepronium and atropine (both anticholinergic drugs) were used for comparison. Using strips of rat urinary bladder depolarized by KCl, flavoxate, papaverine and verapamil displayed a relaxant activity, while anticholinergic compounds such as atropine, hyoscine and emepronium failed to relax this tissue. In another series of experiments the effects of flavoxate and anticholinergic drugs on the contraction elicited by vagal electrical stimulation of the guinea-pig isolated stomach in toto were assayed. The results obtained suggest that the action of flavoxate is due to direct smooth muscle relaxation and does not involve anticholinergic activity.

Anesthetics, Local↗
PubMed1983

[Drug therapy of detrusor dysfunction].

In a urodynamic study, the effect of carbachol, distigmine and prostaglandin-F2 alpha on neuropathic detrusor areflexia and on the non-contracting detrusor as well as the effect of scopolamine, emepronium bromide and flavoxate on the idiopathic unstable bladder and neuropathic detrusor hyperreflexia were examined. Carbachol and distigmine do not have any effect on detrusor contractility but reduce the bladder capacity by decreasing the detrusor compliance. The instillation therapy by prostaglandin-F2 alpha provokes detrusor contractions in some cases of non-contracting detrusor. Emepronium bromide and flavoxate therapy of the idiopathic unstable bladder and neuropathic detrusor hyperreflexia showed improvement of the subjective symptoms, but not of the urodynamic findings. The oral therapy of scopolamine has no effect on overactive detrusor function. Treatment of the idiopathic unstable bladder by prolonged detrusor distension with the aid of peridural anaesthesia showed satisfactory results in more than 50%.

Adult↗
PubMed1995

Classification of the presynaptic muscarinic receptor subtype that regulates 3H-acetylcholine secretion in the guinea pig urinary bladder in vitro.

The experiments were done to investigate the presence and subtype of functionally presynaptic muscarinic receptors in cholinergic nerves of the guinea pig urinary bladder. Bladder strips were incubated with 3H-choline and superfused with Tyrode's solution containing eserine. Secreted 3H-acetylcholine was separated from 3H-choline. The electrically evoked 3H-acetylcholine secretion increased with the stimulation frequency. 3H-Acetylcholine secretion was enhanced by muscarinic antagonists, was depressed by carbachol and by alpha adrenoceptor agonists but was not influenced by drugs acting at beta adrenoceptors or purinoceptors. The rank order for the enhancing effect of muscarinic antagonist EC50 values was propantheline < atropine < methylatropine < N-desethyloxybutynin < UH-AH 37 < benzhexol < AQ-RA 741 < 4-DAMP < procyclidine < emepronium < secoverine < oxybutynin < tropicamide < promethazine < himbacine < hexahydrosiladifenidol < methoctramine = pirenzepine < dicyclomine < AF-DX 116, and the EC50 values correlated best with constants for the M4/m4 muscarinic receptor subtype. The enhancing effect of atropine was counteracted by carbachol; the effects of atropine and emepronium were not additive. The 3H-acetylcholine secretion was also enhanced by forskolin, 3-isobutyl-1-methylxanthine, 8-bromo cyclic AMP and dibutyryl cyclic AMP. The combined effects of atropine and forskolin were additive. These results suggest that the 3H-acetylcholine secretion in the guinea pig urinary bladder is regulated by a presynaptic muscarinic autoreceptor of the M4 subtype that is not coupled to adenylate cyclase.

Acetylcholine↗
PubMed1988

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.

Administration, Intravesical↗
PubMed1978

Uropharmacology: VII. Ganglionic stimulating and blocking agents.

A classification of the various ganglionic stimulants and blockers is presented, and their pharmacologic effects on the urinary bladder and urethra are discussed. Ganglionic stimulating drugs are of considerable interest in investigational work but are not presently used therapeutically. Ganglionic blockers include hexamethonium, tetraethylammonium, mecamylamine emepronium, pentolinium, chlorisondamine, and pemipidine. Of the numerous ganglionic blocking drugs that have appeared on the therapeutic scene, only mecamylamine, pentolinium, and trimethaphan are currently official.

Animals↗
PubMed1977

Iatrogenic reflux oesophagitis.

A report on two patients with severe reflux oesophagitis caused by Emepronium Bromide ('CETIRPIN') prescribed for the treatment of urinary symptoms.

Emepronium↗
PubMed1978

[Drug-induced oesophageal ulcers (author's transl)].

Within a one-year period seven patients were observed who had developed ulcers of the upper and mid oesophagus after treatment with doxycycline hydrochloride (n = 3), emepronium bromide (n = 3) or Pantogar (n = 1). In each instance the drug had apparently been swallowed dry. The typical symptoms were a sudden onset of retrosternal chest pain and odynophagia during bed rest. Once the drug had been discontinued and treatment with antacid combined with topical anaesthetics and/or alginic acid instituted the symptoms disappeared within a few days. The authors stress that drugs should be swallowed only with good amounts of fluid and generally not immediately before bed rest.

4-Aminobenzoic Acid↗
PubMed1981

Drug-induced esophagitis.

We report two patients with quinidine-induced esophagitis along with a review which reveals drug-induced esophagitis to be uncommon. Certain drugs implicated time and again include tetracycline, doxycycline KCl, quinidine, clindamycin, and a British drug, emepronium. Other drugs are mentioned in isolated case reports. Most patients have a benign course, responding well to antacids and discontinuation of the responsible medication, with the exception of KCl-induced injury, which may be fatal. Taking medication with a drink of water and avoiding medications just before retiring may help prevent drug-induced esophagitis.

Aged↗
PubMed1981

Different cystometric types of deficient micturition reflex control in female urinary incontinence with special reference to the effect of parasympatholytic treatment.

The effect of 4 weeks' treatment with emepronium bromide in 20 incontinent female patients with detrusor hyperreflexia was compared to the effect in 20 patients who did not have uninhibited detrusor contractions during filling cystometry but who were unable to suppress a voluntarily induced detrusor contraction. In both groups, 65% benefited from the drug and no statistically significant differences were seen in the decrease in frequency of voiding and incontinence episodes during treatment. There were no differences between the groups for age, type and degree of urinary incontinence, and radiological findings of bladder suspension defects. In these patients it is important to perform cystometry, including detrusor reflex activation procedures and the testing of their ability to suppress a voluntarily induced detrusor contraction.

Adult↗
PubMed1979

Organic anion and cation transport in vitro by dog choroid plexus: effects of neuroleptics and tricyclic antidepressants.

Dog lateral choroid plexus accumulates the cation 14C-emepronium and the divalent anion 125I-iodipamide in vitro. At 10 micron, high potency neuroleptics with a substituted piperazine side chain and also haloperidol depress only the uptake of the cation and even stimulate the uptake of the anion. In contrast, at 1--10 micron, the accumulation of both test substances is inhibited by neuroleptics and tricyclic antidepressants with an aliphatic side chain. Such unspecific effects on seemingly unrelated transport systems at concentrations reached clinically in the CSF might explain some side actions of low potency neuroleptics and antidepressants.

Animals↗
PubMed1987

Evaluation of the oesophago-irritant potential of terodiline hydrochloride tablets in three animal models.

The oesophago-irritant potential of terodiline hydrochloride 25 mg tablets was evaluated by use of one acute and two recovery animals models, each documented to be sensitive for predicting local irritant and/or ulcerogenic effects of drugs on the human oesophageal mucosa. Both uncoated and coated terodiline hydrochloride tablets produced slight to moderate oesophageal lesions in cats sacrificed after 4 to 8 hours of tablet exposure, whereas emepronium bromide, a drug associated with oesophageal injury in man, showed moderate to severe oesophago-irritant properties when tested in the same model. No significant oesophageal changes were, however, observed with coated terodiline hydrochloride tablets in cats or pigs subjected to five days of recovery after an initial tablet exposure period of eight and five hours, respectively. The results indicate that the oesophago-irritant effect of terodiline hydrochloride 25 mg tablets is very mild and also transient. Thus no or only a minimal risk of oesophageal irritation after accidental lodging of the tablet in the oesophagus is to be anticipated in patients.

Acute-Phase Reaction↗
PubMed1980

Motor urge incontinence: diagnosis and treatment.

A detailed study and analysis of several hundred cases of motor urge incontinence in the female is presented and summarized. This includes the incidence, the history referring to a questionnaire with a new urge and stress score, the symptomatology, possible etiological factors, the cystometric manifestation and the responsiveness to several treatment modalities and medications. A comparison of flavoxate, emepronium, propantheline and a placebo for the treatment of urinary incontinence due to bladder instability is made, the results are discussed and recommendations are made.

Adolescent↗
PubMed1986

Detrusor instability in children with recurrent urinary tract infection and/or enuresis. II. Treatment.

Of 41 children, aged 5-15 years, referred consecutively because of recurrent urinary tract infections (UTIs) and/or enuresis, 18 (44%) showed detrusor instability (DI) in at least 2 of 6 CO2 cystometries. One child was excluded from the study because of lack of follow-up. Four children with less pronounced DI (instability during less than or equal to 50% of the cystometries performed) and frequent UTIs were given antibiotics prophylactically for 3 months. In the remaining 13 children, DI was found during more than half the cystometries performed, and 11 of these children, who also had urge incontinence, were treated with emepronium bromide, 400-600 mg daily (10-12 mg/kg) for 3 months. In 7 of the patients this treatment was supplemented by antibiotics prophylactically because of frequent UTIs. Two children with special problems received other types of treatment. All children were free from symptoms at a clinical check-up 6 months later, 95% confidence limits 0-20%.

Adolescent↗