Drug-induced esophagitis.

Drug-induced esophagitis is being recognized increasingly in the past few years. Since 1970 more than 650 cases have been reported worldwide caused by 30 or more medications. We have reviewed these cases with a view to classifying this disease based on underlying pathological mechanism. Drug-induced esophageal injury tends to occur at the anatomical site of narrowing, with the middle third behind the left atrium predominating (75.6%). The disease is broadly classified into two groups. The first group being transient and self-limiting as exemplified by the tetracycline group induced injury (65.8%). The second is the persistent esophagitis group, often with stricture, with two distinct entities: (i) patients on nonsteroidal anti-inflammatory agents whose injury is aggravated by gastroesophageal reflux (21.8%) (reflux aggravated); and (ii) patients with potasium chloride and quinidine sulphate induced injury (12.4%) (persistent drug injury). Severe esophageal injury has been reported in some women taking biphosphonates as treatment for postmenopausal osteoporosis. Endoscopic findings in such patients with esophageal injury generally suggested a chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Most cases of medication-induced esophageal injury heal without intervention within a few days. Thus, the most important aspect of therapy is to make the correct diagnosis and then to avoid reinjury with the drug. When possible, potentially caustic oral medications should be discontinued.

[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.

Estudio comparativo entre el test de Salbutamol en relación al test de Salbutamol más bromuro de ipratropio en la intercrisis del asma

Es una práctica que cada día se hace más frecuente el administrar bromuro de ipratropio en combinación con agonistas B como salbutamol, a los pacientes que acuden a los servicios hospitalarios por consultorios externos, con el diagnóstico de asma en periodo intercrítico. La fisiopatología del árbol bronquial y el mecanismo de acción a diferente nivel del bromuro de ipratropio apoyan esta combinación de drogas, más diversos estudios desbaratan esta tesis; también existen algunos que la corroboran. Con la finalidad de dilucidar en forma definitiva la participación de todo el árbol bronquial en la patología asmática y establecer un estándar de tratamiento es que se realizó este trabajo. Se tomó un total de 30 pacientes captados de consultorios externos y hospitalización del Servicio de Neumología del Hospital Regional Honorio Delgado de Arequipa con el diagnóstico clínico y laboratorial de asma en intercrisis. Previa toma de espirometría (control) se les aplicó dos inhalaciones de salbutamol (100 mcg/inhalación) y luego de 15 minutos se les realizó la segunda espirometría, por último se les aplicó dos inhalaciones de bromuro de ipratropio (20 mcg/inhalación) y una tercera espirometría. Se empleó pruebas de estadística descriptiva (frecuencia, media aritmética, desviación estándar y porcentajes) además de pruebas de estadística (T de Student) para establecer el nivel de significancia P<0.05, y se obtuvieron los siguientes resultados: - Dentro de todas las variables tomadas en cuenta en la espirometría, la FEVI fue la única en la que se encontró diferencia estadísticamente significativa entre los valores obtenidos al aplicar el test de salbutamol y los obtenidos con el test de salbutamol + bromuro de ipratropio. Por tanto se concluye que la adición rutinaria de bromuro de ipratropio al salbutamol es de mayor utilidad en el tratamiento de la intercrisis del asma que el uso aislado del salbutamol.

Lesiones esofágicas medicamentosas / Drug-induced esophageal lesions

Las lesiones agudas erosivas o ulceraciones del esófago provocadas por medicamentos, son poco frecuentes pero no excepcionales. Sus principales causantes son algunos antibióticos y el cloruro de potasio. En su fisiopatología intervienen la naturaleza del medicamento y la lentificación del tránsito esofágico (ingestión con poco líquido, en posición de decúbito; disminución o pérdida del peristaltismo y en especial de las ondas de barrido, administración de antiespasmódicos y anticolinérgicos que reducen la producción de saliva, disminuyen el peristaltismo del cuerpo esofágico y alteranla continencia del esfínter esofágico inferior, permitiendo el reflujo gastroesofágico

Incontinencia urinaria de esforco: conceito, diagnostico e tratamento / Urinary incontinence stress: concept, diagnosis and treatment

Os autores revisaram os aspectos etiologicos, fisiologicos, diagnostico e tratamento da incontinencia urinaria de esforco discutindo os recursos diagnosticos e inovacoes do tratamento.

[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.

[Drug-induced esophagitis and its complications. Retrospective study of 30 case reports and review of 650 published cases (1970-1987)]. / L'oesophagite médicamenteuse et ses complications. Etude rétrospective de 30 observations et revue de 650 cas publiés (1970-1987).

Prevalence and incidence of drug-related esophagitis are probably underestimated. The condition can often be diagnosed on the basis of history alone. Tetracyclines and emepronium bromide were implicated in most published cases. Endoscopy usually shows erosions in the upper two thirds of the esophagus. These esophageal lesions generally heal after the medication has been stopped. Complications such as stricture, hemorrhage or perforation are very rare.

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.

Drug induced esophageal lesions studied in vitro.

This paper describes an in vitro method of studying the esophago-irritant potential of oral formulations of drugs. Porcine esophagus was used. The method offers the possibility of studying muscle activity and enzyme leakage (e.g. LDH) and of performing histomorphology of the exposed preparations. Examples of drugs which were tested are alprenolol (Aptin), propranolol (Inderal), doxycycline (Idocyklin) and (Vibramycin) and emepronium bromide (Cetiprin). Concerning effects on muscle activity, Aptic caused a marginal contraction while Cetiprin caused a relaxation of the esophagus preparation. Increased LDH-leakage was noted during exposure with the above mentioned pills in comparison with concurrent control preparations. Histopathological examination disclosed morphological changes such as softening and necrosis of the squamous epithelium of the esophageal mucosa after exposure to drugs like Idocyklin and Aptin.

Relationship between gastric emptying and serum concentrations of emepronium in dogs and human volunteers.

Clinical trials with increased dosages, relative to the standard regimen, of the anticholinergic drug emepronium (Cetiprin Novum) resulted in a clear improvement in micturition- and urodynamic parameters in urinary incontinent patients. In the present study possible effects on the gastric emptying were tested in dogs and in human volunteers. In dogs a wide dose range of emepronium (5-100 mg/kg p.o.) was used to establish a relationship between serum concentration and effect on the gastric emptying. Gastric emptying was slightly decreased after 25 mg/kg (peak conc. of emepronium about 100 micrograms/l) and markedly decreased after 50 mg/kg (500 micrograms/l) and 100 mg/kg (5000 micrograms/l). In the volunteers no effect of emepronium on gastric emptying was observed, either after 200 mg q.i.d. or after 400 mg q.i.d. (about 3 and 6 mg/kg q.i.d.), which resulted in peak serum concentrations of 100-300 micrograms/l).

Terodiline, emepronium bromide or placebo for treatment of female detrusor overactivity? A randomised, double-blind, cross-over study.

In a randomised, double-blind study, 20 women with idiopathic detrusor instability and associated symptoms were treated with terodiline 25 mg bd, placebo, and emepronium bromide 200 mg tds--each drug being given for 3 weeks with placebo as wash-out period before cross-over. The results were evaluated according to drug preference, frequency charts and elimination of detrusor instability on cystometry. Serum levels of both drugs were monitored as control of tablet intake. The preference for terodiline to placebo was statistically significant: 14/3 women (P less than 0.05), and the majority of women (12/4) preferred terodiline to emepronium. Terodiline also gave a small but significant reduction in 24 h micturition frequency and eliminated detrusor instability in almost 50% of the patients (P less than 0.05). Side effects were frequent but mild in all three treatment periods. It was concluded that terodiline offers an alternative in the treatment of female detrusor instability.

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.

Species differences in the intestinal excretion of emepronium.

A substantial proportion of a parenteral dose of emepronium given to dogs is excreted via the gastrointestinal tract by biliary excretion and by excretion through the intestinal mucosa (Hallén et al. 1979). In the present paper the different routes of elimination were further investigated in mouse and man and compared to the dog. The disposition of emepronium-derived radioactivity (14C) in the three species showed that about 45% was excreted via urine and 55% via faeces. The proportion of the faecal excretion of 14C that could be referred to the intestinal route differed between the species and was about 20% in man, 60% in the mouse and most pronounced, 80%, in the dog.

Medication-induced esophageal injury: survey of the literature.

A review of the 127 cases of drug-induced esophagitis reported since 1970 indicates that commonly used medications may be a source of esophageal injury. Retrosternal pain, odynophagia, and dysphagia were the most commonly reported symptoms and most cases were self-limited with 7 to 10 days of symptomatic therapy. Occasionally, severe odynophagia or dysphagia necessitated hospitalization. Emepronium bromide, tetracycline, and its derivatives, potassium chloride, and quinidine accounted for 89% of the reported cases; the remaining 11% were caused by 14 other medications. Serious sequelae, including death, have been linked to potassium-induced esophageal injury. With other medications, however, serious complications were rare. The diagnostic study of choice for suspected medication-induced esophageal injury is endoscopy, although air contrast barium swallow may often detect subtle mucosal abnormalities. In uncomplicated cases the history alone may be sufficient to make the diagnosis. Concurrent ingestion of adequate amounts of fluid and avoidance of unnecessary bedtime medications may help to prevent medication-induced esophageal injury.

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.