[Motility disorders of the colon]. / Motilitätsstörungen des Dickdarms.

The motility of the colon is modulated by the enteric nervous system. It is very complex, governing backward and forward movements of the feces. Primary megacolon and megarectum are clinically diverse. Megacolon refractory to laxative treatment may be subject to colectomy, while megarectum should be treated by consistent laxation. Acute colonic pseudo-obstruction may occur with severe systemic diseases and electrolyte disturbances or it may be postoperatively and/or medically induced. A small proportion of chronically constipated patients suffer from slow transit constipation, others from disordered defecation. In the remaining patients no objective cause of the complaints may be found. In slow transit constipation, propulsive colonic motility is disturbed, dietary fiber is ineffective, and the response to bisacodyl is blunted. Pelvic floor dyssynergia is characterized by a voluntary (although unconscious) contraction of the anal sphincter simultaneously with the abdominal muscles. It can be treated by avoiding straining and by sphincter training.

[Pharmacological treatment of constipation]. / Pharmakologische Behandlung der Obstipation.

Chronic constipation is a frequent condition often requiring pharmacological treatment. A number of laxatives that belong to very different pharmacological groups are available. Most relevant are the older representatives osmotic salts, sugars and sugar alcohols, macrogol, anthraquinones, diphenolic laxatives (bisacodyl and sodium picosulphate), and the newer compounds prucalopride and linaclotide. For all of these laxatives, efficacy has been shown in controlled trials. Electrolyte problems do not occur when laxatives are given in therapeutic doses (rare exceptions with salinic laxatives). The older laxatives are also safe regarding teratogenicity, abortion, and lactation; for the newer compounds no respective data are available as yet. It is questionable whether the newer laxatives offer advantages over the older ones. Unfortunately, comparative trials are lacking. Opiate-induced constipation may also be treated with laxatives or certain opiate antagonists.

[Laxative use and satisfaction of chronically constipated women - a survey of female patients and gastroenterologists in Germany]. / Laxanziengebrauch und Zufriedenheit chronisch obstipierter Frauen - eine Umfrage bei Patientinnen und Gastroenterologen in Deutschland.

OBJECTIVE: Data were collected concerning the patient satisfaction in the treatment of chronic constipation with laxatives. METHOD: An internet-based survey of female patients with chronic constipation and an online enquiry addressed to gastroenterologists in Germany were carried out. RESULTS: 492 female patients and 104 physicians participated in the survey. Only 20 % of the patients were currently consuming laxatives. Around one-third of those not using laxatives have had unsatisfactory experiences. Only 32 % of the participants currently taking laxatives were totally satisfied with their drugs. As a general rule several different preparations were tried. The laxatives most closely associated with satisfied patients were bisacodyl and sodium picosulfate, followed by macrogol. The main reasons for dissatisfaction were an insufficient relief of the constipation and a bloated feeling. The majority of the participants expressed an interest in new drugs for the treatment of constipation. The participating physicians stated that they saw several female patients per week who were not satisfied with their constipation treatment, but probably overestimate the proportion. CONCLUSION: The present survey shows that the majority of women suffering from constipation do not take laxatives and also that about half of them were not satisfied with the agents tried. Only about one-third of the chronic users were totally satisfied. Thus, there is a clear need for new laxatives.

[Endoscopic procedures for patients on antithrombotic medication--risks and methods]. / Endoskopische Prozeduren bei Patienten unter antithrombotischer Medikation--Risiken und praktisches Vorgehen.

The decision how to handle an antithrombotic treatment when an intervention during GI endoscopy is planned is influenced both by the risk of bleeding and by the thromboembolic risk when treatment is suspended. The risk of bleeding is negligible even when on oral anticoagulants in diagnostic procedures with standard forceps biopsies. Oral anticoagulation has to be stopped, however, when planning invasive procedures such as polypectomy or EPT. In the case of patients with a high risk of thromboembolic complications such as artificial valves in mitral position or atrial fibrillation with risk factors, one has to temporarily switch to anticoagulants with shorter action ("bridging"). Treatment with inhibitors of platelet function does not preclude procedures with a low risk of bleeding including forceps biopsy. Urgent procedures with a high risk of bleeding should be performed after stopping clopidogrel one week previously but only after consultation with the treating cardiologist. In the case of colonoscopy, in particular as a screening procedure, there are two options: 1) stopping oral anticoagulation (with or without bridging) or clopidogrel, respectively, or 2) continuing antithrombotic treatment and performing a second elective endoscopy for polypectomy with tapered antithrombotic medication if polyps are found which are not amenable to resection by biopsy forceps. The choice between these two options has to be made individually.

Tegaserod is effective in the initial and retreatment of irritable bowel syndrome with constipation.

BACKGROUND: Symptoms of irritable bowel syndrome are often cyclical and thus may require repeated rather than continuous therapy. Tegaserod is effective and well-tolerated for irritable bowel syndrome with constipation but data on retreatment are lacking. AIM: To assess whether tegaserod retreatment is as efficacious and well-tolerated as initial treatment in a primary care setting. METHODS: This open-label trial was designed to evaluate the effectiveness of tegaserod under real-life conditions. Irritable bowel syndrome with constipation patients received tegaserod 6 mg b.d. for 12 weeks; response was assessed at weeks 4 and 12. Responders (those achieving satisfactory relief for at least 2 of the previous 4 weeks) at weeks 4 and/or 12 entered an 8-week withdrawal period where symptom recurrence was assessed. Patients experiencing recurrence could receive tegaserod 6 mg b.d. for another 4 weeks (retreatment phase) and on completion, could choose to continue tegaserod in a 6-month extension study. RESULTS: A total of 513 patients received initial treatment with tegaserod; 85.0% (436 of 513) responded. 403 responders entered the withdrawal period; symptoms recurred in 83.9% (338 of 403) after a mean of 38 days. Of the 307 patients who subsequently entered retreatment 89.3% (274 of 307) responded. Among patients entering the retreatment period, 269 (87.6%) had responded within the first 4 weeks of initial treatment. Of these, 243 (90.3%) responded to tegaserod retreatment. Adverse events were infrequent and similar during 4 weeks of the initial treatment period (11.1%) and on retreatment (10.4%). The extension study, completed by 188 of 232 (81.0%) patients, demonstrated good long-term tolerability of tegaserod. CONCLUSIONS: Irritable bowel syndrome with constipation patients can be successfully treated, and retreated, with tegaserod 6 mg b.d. Tegaserod was well-tolerated during initial and retreatment periods.

Empiric therapy for gastroesophageal reflux disease.

BACKGROUND: In the absence of highly specific symptoms and without esophageal erosions, long-term pH monitoring is necessary for diagnosing gastroesophageal reflux disease. This method, however, is not generally available. OBJECTIVE: To determine whether gastroesophageal reflux disease can be diagnosed empirically by acid suppression in patients with normal results of endoscopy. METHODS: We studied 33 consecutive outpatients with pathologic findings on pH monitoring who had symptoms compatible with gastroesophageal reflux disease and normal results of esophagogastroduodenoscopy, particularly a normal appearance of the esophageal mucosa. The severity of symptoms was graded on a visual analog scale from 1 to 10 by the patient. The patients were treated for at least 7 days with either ranitidine, 150 mg twice daily (patients 1 through 10), omeprazole, 40 mg/d (patients 11 through 21), or omeprazole, 40 mg twice daily (patients 22 through 33). A reassessment of symptoms and second pH monitoring were performed during the last day of treatment. RESULTS: Omeprazole, 40 mg/d, significantly reduced the severity of symptoms from 7.1 (range, 4 to 9) to 3.7 (0 to 8) and the reflux measure mean acidity from 0.98 mmol/L (0.21 to 76 mmol/L) to 0.02 mmol/L (0 to 0.47 mmol/L). Omeprazole, 40 mg twice daily, significantly reduced the severity of symptoms from 6.8 (3 to 10) to 0.6 (0 to 2) and the mean acidity from 0.38 mmol/L (0.13 to 8.5 mmol/L) to 0.01 mmol/L (0 to 0.14 mmol/L). Both doses of omeprazole were superior to ranitidine, 150 mg twice daily. When a 75% reduction of symptoms was defined as positive, the "omeprazole test" with 40 mg twice daily had a sensitivity of 83.3%, whereas the sensitivity with 40 mg/d was only 27.2%. CONCLUSION: In practice, the diagnosis of gastroesophageal reflux disease can be ruled out if symptoms do not improve with a limited course of high-dose proton pump inhibitors.

Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome.

Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.

Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation.

AIM: To investigate the efficacy and safety of tegaserod, a novel 5-HT(4) receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. METHODS: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. RESULTS: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo. CONCLUSIONS: Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.

Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) and constipation have a major impact on public health; however, the wide variety of treatment options presents difficulties for recommending therapy. Lack of definitive guidelines in pharmacy and general practice medicine further exacerbates the decision dilemma. AIMS: To address these issues, a panel of experts discussed the principles and practice of treating GERD and constipation in the general population and in pregnancy, with the aim of developing respective treatment guidelines. RESULTS: The panel recommended antacids 'on-demand' as the first-line over-the-counter treatment in reflux, and as rescue medication for immediate relief when reflux breaks through with proton pump inhibitors. Calcium/magnesium-based antacids were recommended as the treatment of choice for pregnant women because of their good safety profile. In constipation, current data do not distinguish a hierarchy between polyethylene glycol (PEG)-based laxatives and other first-line treatments, although limitations are associated with stimulant- and bulk-forming laxatives. Where data are available, PEG is superior to lactulose in terms of efficacy. In pregnancy, PEG-based laxatives meet the criteria for the ideal treatment. CONCLUSIONS: The experts developed algorithms that present healthcare professionals with clear treatment options and management strategies for GERD and constipation in pharmacy and general practice medicine.

The effect of hormones and peptides involved in water balance on rat colonic motility in vitro.

We have previously shown that restriction of water intake decreased stool frequency and stool weight in volunteers. The aim of this study was to investigate whether these effects of thirst could be mediated by an action of systematically released hormones on colonic smooth muscle. Using isolated colonic smooth muscle strips the effect of arginine-vasopressin (AVP), angiotensin II (ANG II) and aldosterone on rat colonic motility in vitro was investigated. AVP (10(-12)-10(-10) mol/l) and aldosterone (3 x 10(-10)-3 x 10(-8) mol/l) and physiological hormonal concentrations of ANG II (10(-13)-10(-10) mol/l) had no effect on either basal activity, direct stimulation of colonic smooth muscle or neurally stimulated contractions using carbachol 10(-7)-3 x 10(-5) mol/l or neurally stimulated contractions using electrical field stimulation at various stimulation frequencies (1-10 pps, 1 ms, 40 V). ANG II in higher concentrations (10(-7)-10(-6) mol/l) increased basal activity and neurally mediated contractions. Accordingly, ANG II (10(-6) mol/l) caused a prestimulation but did not increase the maximum contractile effect of carbachol. The response to ANG II was not affected by atropine (10(-6) mol/l). TTX (10(-6) mol/l) and N-nitro-L8-arginine (L-NNA) (3 x 10(-4) mol/l) stimulated basal muscular activity but did not affect the maximum contractile effect of ANG II. Systemic serum concentrations of AVP, aldosterone and ANG II are presumably not involved in thirst-induced colonic motility changes. The ANG II effect in higher concentrations is mediated by a direct stimulatory smooth muscle effect and/or by facilitating neuronal liberation of acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)