Säurehemmende Pharmaka (in erster Linie Protonenpumpeninhibitoren, PPI) gehören zu den Medikamenten, die bei älteren Patienten am häufigsten verordnet werden, allerdings nicht immer indikationsgerecht. Sie dienen in erster Linie der Prävention und Therapie von peptischen Ulzera unter der Gabe von ulzerogenen Substanzen und der Therapie der Refluxkrankheit. Trotz ihres hohen Sicherheitsprofils werden derzeit mehrere Risiken in der PPI-Langzeittherapie diskutiert (Frakturgefahr, Begünstigung einer pseudomembranösen Kolitis, Entwicklung eines Vitamin-B12-Mangels), aber keines dieser potenziellen Risiken ist bisher auch nur annähernd gut belegt. Dennoch gilt: PPI nur bei korrekter Indikation einsetzen, Notwendigkeit in der Dauertherapie kritisch überprüfen (aber nicht leichtfertig absetzen, wenn indiziert), Dosierung so niedrig wie erforderlich wählen.

Thrombozytenaggregationshemmer wie Protonenpumpeninhibitoren (PPIs) gehören zu den am weitesten verbreiteten Medikamenten. Die Therapie der koronaren Herzkrankheit (KHK) basiert neben interventionellen und chirurgischen Maßnahmen wesentlich auf der medikamentösen Hemmung der Plättchenaggregation mittels ASS und P2Y12-Inhibitoren. Dem positiven Nutzen dieser Medikamente stehen ihre gastrointestinalen Risiken gegenüber, die im Wesentlichen in gastroduodenalen Ulzera und möglichen Blutungskomplikationen bestehen. PPIs können diese signifikant reduzieren und wurden bei der dualen Plättchenhemmung als Begleitmedikation empfohlen. In den letzten beiden Jahren wurde indessen über eine mögliche Interaktion von Clopidogrel und PPIs berichtet, die zu intensiven Diskussionen geführt hat. Angesichts der Heterogenität der Studienergebnisse und der großen klinischen Bedeutung dieses Themas haben die Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten und die Deutsche Gesellschaft für Kardiologie ein Positionspapier verabschiedet, das klare Empfehlungen zum Umgang mit diesen Substanzen ausspricht. Sie basieren auf dem individuellen kardiovaskulären und gastrointestinalen Risiko.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Four years after mastectomy for a scirrhous carcinoma a 71-year-old woman developed diarrhoea. Crohn's disease was suspected. At endoscopy a stenosis of the sigmoid colon was found which could not be passed: the mucosa was normal looking. Gastrointestinal radiography revealed segmental subtotal stenoses of the colon with linitis plastica, typical for tumour-caused infiltration, as well as indentations in the small intestine by mesenteric metastases. The diagnosis was confirmed by computed tomography and, finally, operation. Chemotherapy failed to produce any regression of the colon stenoses, and the patient died from mechanical ileus. In case of a similar history and colon stenoses of uncertain aetiology the possibility of intestinal metastases should be considered in the differential diagnosis.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

: The current guidelines of the German Society for Digestive Diseases (DGVS) endoscopy recommends for patients representing with reflux symptoms. In daily routine as well as in Guidelines from other countries and international guidelines, however, a symptom-based strategy for the management of patients with reflux disease is favoured. Since either strategies is dependent on specific clinical findings, neither can be recommended. The preference for one or the other strategy depends on the prevalence of so-called alarm symptoms, risk factors for a reflux carcinoma or Barrett's metaplasia, demographic factors, e. g., age and gender, patient's wish and initial response to empirical therapy with proton pump inhibitors (PPI). However, most patients with characteristic reflux symptoms without any alarm symptoms and/or other risk factors can be safely managed with a symptom-based strategy in acute and long-term care.

The gold standard for the diagnosis of Helicobacter infection is the analysis of endoscopic biopsies. The C13-urea breath test allows a diagnosis of the infection reliably and with non invasive means. Serology can not differentiate between active and healed infection. In patients with ulcer disease and low grade MALT-lymphoma there is an absolute indication for Helicobacter treatment. In other cases such as functional dyspepsia, NSAID-gastropathy, reflux esophagitis, gastric carcinoma etc., it is not possible to give simple recommendations. The prophylactic treatment of healthy carriers is, at present, not recommended. Optimal treatment consists of omeprazole 2 x 20 mg, amoxicillin 2 x 1000 mg and clarithromycin 2 x 500 mg or of omeprazole 2 x 20 mg, metronidazole 2 x 400-500 mg and clarithromycin 2 x 250 mg, given for 7 days. These combinations have been registered by the German Drug Registration Agency (BfArM).

BACKGROUND:Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+. K+-ATPase necessary for the final step in gastric acid secretion.AIM:To investigate the tolerability and the prophylactic effect of pantoprazole 40 mg once daily on relapse in patients whose reflux oesophagitis had been healed.METHODS:The safety of pantoprazole 40 mg once daily was assessed in an open 1-year trial on 222 patients whose reflux oesophagitis had been healed with omeprazole or pantoprazole. Relapse was defined as endoscopically-confirmed reflux oesophagitis (at least Grade I), with endoscopies being performed for patients experiencing 3 consecutive days of disease-specific symptoms.RESULTS:Kaplan-Meier survival analysis at 6 and 12 months gave estimated treatment failure rates of 2% and 6% from confirmed relapses (per-protocol), and of 9% and 30% for a worst-case group (all withdrawals counted as failures). The only population shift in laboratory variables was a doubling of the median serum gastrin level over the first 6 months; thereafter it stabilized. Fifty-four (24%) patients experienced adverse events; 15 of these withdrew. Serious adverse events were reported for 12 patients.CONCLUSIONS:Pantoprazole appears to be highly effective and to have a good safety profile for long-term prophylaxis of reflux oesophagitis.

H. pylori defies the physicochemical defence of gastric mucosa mechanisms using his mobility, his adapted acid metabolism and his adherence to the gastric epithelium, The immune-biological defence of the host is unable to eliminate the infection Helicobacter infection always leads to gastritis. Progression to more serious disorders depends on the Helicobacter strain, on host factors and on the environment. Helicobacter plays an essential role in the pathogenesis of gastric and duodenal ulcers and of MALT-lymphoma. H. pylori contributes to the development of gastric carcinoma. Its role in functional dyspepsia is controversial; its role in extra-gastroduodenal diseases such as myocardial infarction is highly controversial.

BACKGROUND:The physiological relevance of duodenal bile acids in the control of cholecystokinin release and pancreatic enzyme secretion is still unknown.AIMS:To provide a near physiological situation by perfusing a bile acid mixture mimicking the individual endogenous bile acid composition of the person under investigation. For maximal reduction of endogenous bile output the CCK-A receptor antagonist loxiglumide was infused intravenously.SUBJECTS AND METHODS:Seven healthy volunteers were studied on four different days by a duodenal marker perfusion technique. The individual bile acid composition in duodenal juice and test meal stimulated bile acid output was assessed on day 1. Bile acids were perfused at an amount of 30 or 100% as determined on day 1 in combination with the test meal in the presence or absence of loxiglumide. Pancreatic enzymes, bilirubin, and bile acid output were determined in duodenal juice. Plasma cholecystokinin (CCK) and plasma pancreatic polypeptide (PP) were measured radioimmunologically.RESULTS:Bile acid perfusion did not significantly alter stimulated pancreatic enzyme, bilirubin or bile acid output or plasma CCK. Loxiglumide did not alter basal CCK release but increased test meal stimulated CCK output fourfold (p < 0.05). The addition of bile acids to the test meal at a dose resembling 30% of bile acid output as determined on day 1 prevented this increase. Plasma PP concentration remained unchanged by bile acids and were mostly undetectable during loxiglumide infusion.CONCLUSIONS:The CCK producing cell is under constant suppression by intraduodenal bile acids which cannot be further enhanced by a physiological bile acid mixture. However, removal of duodenal bile acids by inhibition of gall bladder contraction unmasks this suppression leading to a dramatic increase in plasma CCK levels. As little as one third of postprandially released bile acids completely reverse this effect. Bile acids are the most important luminal regulator of CCK release in humans.

In 249 patients with acute symptomatic reflux esophagitis grade II and III (Savary-Miller classification), we compared the efficacy and safety of pantoprazole, a newly developed proton pump inhibitor given at a once-daily dose of 40 mg, with a standard dose of the H2 receptor antagonist ranitidine (150 mg b.i.d.) in a randomized, double-blind, multicenter study. Complete healing was achieved after 4 and 8 weeks of therapy (protocol-correct) in 69 and 82% (pantoprazole) and 57 and 67% (ranitidine), respectively (p = 0.054 at 4 weeks and p < 0.01 at 8 weeks). The predominant symptoms of gastroesophageal reflux, i.e., heartburn and acid eructation, were more effectively reduced in pantoprazole- than in ranitidine-treated patients. The frequency of adverse events was low and did not differ between the two treatment groups. We conclude that pantoprazole is superior to ranitidine in the acute treatment of reflux esophagitis.

The effect of exendin-4, a peptide of the secretin-glucagon family with high homology of amino acid sequence with glucagon-like peptide-1 (GLP-1), on gastric hormone release was investigated in the isolated perfused rat stomach. Exendin-4 dose dependently stimulated somatostatin release up to 9-fold at a concentration of 10(-7) M whereas gastrin release was inversely inhibited by up to 63%. These effects could partially be reduced by concomitant perfusion of truncated exendin-4, exendin(9-39)amide. Similarly, stimulation of somatostatin secretion and inhibition of gastrin release induced by GLP-1(7-36)amide was partially reversed by exendin-4 (9-39)amide. These data are consistent with the assumption that exendin-4 and truncated GLP-1 amide exert their effects on gastric D and G cell by interaction with the same receptor.