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A review of flavoxate hydrochloride in the treatment of urge incontinence.

This article provides a review of the use of flavoxate hydrochloride in the treatment of urge incontinence. It outlines the pharmacology, mode of action, toxicology and pharmacokinetic studies which have been carried out, and then reviews the clinical studies, including those involving patients with benign prostatic hypertrophy. The effects of dosages of 600-1200 mg/day are compared, particularly regarding safety and tolerability factors. Finally, alternative therapies to flavoxate hydrochloride (alpha-adrenergic receptor blockers, oxybutinin chloride, terodiline hydrochloride, emepronium bromide and imipramine) are summarized. The article is written in the knowledge of recent evidence which indicates that flavoxate hydrochloride exhibits only weak anticholinergic activity on receptors involved in the control of the lower urinary tract.

Flavonoids↗

Terodiline. A review of its pharmacological properties, and therapeutic use in the treatment of urinary incontinence.

Terodiline has both anticholinergic and calcium antagonist properties and, as a result, effectively reduces abnormal bladder contractions caused by detrusor instability. When administered to adult patients with urge incontinence (generally as a 25mg twice-daily dose) terodiline reduces diurnal and nocturnal micturition frequency and incontinence episodes. In studies also assessing cystometric parameters, bladder volume at first urge and bladder capacity are increased. Children with diurnal enuresis respond similarly to a daily 25mg dose. Several studies have shown that terodiline 50 mg/day is preferred by patients when compared with emepronium 600 mg/day or flavoxate 600 mg/day, and tends to reduce voluntary micturition frequency and episodes of incontinence more effectively than these drugs. Terodiline is well tolerated in short and long term (up to 3.5 years) studies. Anticholinergic effects are most commonly reported; other adverse effects occur equally during terodiline and placebo treatment. Thus, terodiline is effective and well tolerated in patients with urge incontinence or neurogenic bladder dysfunction, and will claim an important place in the treatment of such patients in light of the limitations of alternative therapies.

Animals↗

Carcinoma of the prostate. Treatment of pain.

Treatment of different types of pain Type A: 1. Diflunisal 500 mg b.i.d./naproxen 500 mg b.i.d. or another NSAID. Satisfactory effect: Continue Partial effect: Continue, but add step 2 No effect: Proceed to step 2 2. Morphine. Conventional tablets/mixture or slow release morphine. Dosage as described above. Nausea is treated with haloperidol 1-5 mg at night. Some patients do better t.i.d. 3. Glucocorticosteroid, as described above 4. Epidural morphine/local anaesthetic Type B: 1. Amitriptyline. Starting dose: 10 mg at night. Increase by 10 mg every other night until the patient has pain relief or experiences unacceptable side effects 2. Nerve blocks, if possible 3. Glucocorticosteroids 4. Strong opioids 5. Epidural opioids/local anaesthetics Type C: 1. Carbamazepine in increasing doses to 200-400 mg t.i.d. 2. Proceed as described for type B Type D: 1. Urinary colic: flavoxolate (Urispadol) 200-400 mg t.i.d. or emepronium bromide (Cetiprin) 200-400 mg t.i.d. 2. Opioids perorally 3. Epidural local anaesthetic (sympathetic block)/opioids.

Analgesics↗

Drug-induced esophagitis.

Drug-induced esophagitis is being recognized increasingly in the past few years. We have reviewed 175 cases with a view to classifying this disease based on pathology. Drug-induced esophageal injury tends to occur at the anatomical site of narrowing, with the middle third behind the left atrium predominating. The disease is classified broadly into two groups. The first group is transient and self-limiting, as exemplified by tetracycline- and emepronium-induced injury (57.3%). The second is the persistent esophagitis group, often with stricture with two distinct entities: 1) patients on nonsteroidal antiinflammatory agents whose injury is aggravated by gastroesophageal reflux (26.2%) (reflux aggravated), and 2) patients with potassium chloride and quinidine sulfate-induced injury (16.2%) (persisting drug injury). We report a case that highlights the pathophysiology (delayed transit, persisting potassium within the stricture) of this type of injury which is not reflux aggravated.

Delayed-Action Preparations↗

Medication-induced esophagitis in children.

Clinical and endoscopic features of two pediatric cases of esophageal ulcers caused by capsules of oxytetracycline and doxycycline are described. Several cases of medication-induced esophageal injury in children have been reported until now, all of which were in association with tablets or capsules. Antibiotics are known to be responsible for medication-induced esophagitis in adults. In this study, 4 cases were caused by emepronium bromide and 3 cases, including the present patients, by antibiotics. All cases but one complained of chest pain and/or dysphagia. Although the interval between the onset of the symptoms and the diagnosis varied among cases, the clinical courses were relatively uneventful, without any long-term sequelae. This clinical entity seems to be unfamiliar to pediatricians and is omitted from the differential diagnosis.

Child↗

Pharmacological studies on the mode of action of flavoxate.

Previous studies on the mode of action of flavoxate have shown that the drug exerts a selective and direct muscle relaxant activity. In order to study the mode of action of flavoxate, the following activities were investigated: calcium blocking, inhibition of cyclic AMP phosphodiesterase (PDE), local anaesthetic activity, the effects on the synthesis and release of prostaglandins. In the K+-depolarized guinea-pig taenia coli, contracted by CaCl2, flavoxate and papaverine showed a moderate calcium antagonistic activity. Anticholinergic drugs, such as atropine and emepronium, did not exert a similar action. The antispasmodic activity of a drug can be correlated with inhibition of cyclic AMP phosphodiesterase, and since papaverine is a potent PDE inhibitor, we tested flavoxate for this activity. Flavoxate exerted a PDE inhibitory activity about three and five times greater than that of aminophylline in tissues homogenates of guinea-pig ureter and urinary bladder, respectively. It also showed the same local anaesthetic activity of lidocaine. Finally, the synthesis and release of prostaglandins by urinary bladder muscle in vitro have been investigated before and after treatment with flavoxate. Myolytic activity of papaverine and flavoxate do not involve inhibition of prostaglandins synthesis in rat urinary bladder in vitro. Therefore, the mode of action of flavoxate can be related to a superimposition of myotropic, calcium antagonistic and local anaesthetic activity.

3',5'-Cyclic-AMP Phosphodiesterases↗

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.

Adolescent↗

Urinary incontinence in the female. The value of detrusor reflex activation procedures.

One hundred consecutive female patients with urinary incontinence were investigated with CO2 cystometry including detrusor reflex activation procedures such as postural change and ability to suppress self-induced detrusor contractions. Detrusor hyperreflexia was seen in 20 patients during bladder filling in the supine position, and in an additional 35 patients after detrusor reflex activation procedures. Four different types of detrusor hyperreflexia are described based on the cystometric findings. In 38 patients treated with parasympatholytics, 66% showed a good result independent of the type of detrusor hyperreflexia.

Carbon Dioxide↗