Ege Altan

Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: postprandial distress syndrome

Functional dyspepsia (FD) is a highly prevalent condition with major socioeconomic and healthcare impact. To date, no pharmacological treatment for FD has been approved. The Rome consensus proposed to subdivide FD into postprandial distress syndrome (PDS), characterized by meal-related symptoms and epigastric pain syndrome, characterized by pain and burning. Acotiamide (Z-338 or YM443) is a new drug, developed for the treatment of FD. Acotiamide enhances acetylcholine release from enteric neurons through muscarinic receptor antagonism and acetycholinesterase inhibition, thereby enhancing gastric emptying and gastric accommodation. Acotiamide was evaluated in FD in clinical studies in Europe, Japan and the USA, beneficial effects were observed for the PDS symptoms of postprandial fullness and early satiation, with a dose of 100 mg three-times a day. A 4-week placebo-controlled Phase III study in PDS patients in Japan confirmed efficacy of acotiamide in relieving postprandial fullness, early satiation and upper abdominal bloating.

Evolving pharmacological approaches in gastroesophageal reflux disease

Introduction: Proton pump inhibitors (PPIs) have considerably improved quality of life in patients with gastroesophageal reflux disease (GERD). However, many patients remain symptomatic despite standard PPI therapy. Areas covered: This review focuses on evolving therapeutic strategies related to the pathophysiological processes of GERD and insufficient response to PPIs. Several clinical trials evaluated new PPI formulations and newer types of acid-suppressive drugs. These studies have evaluated traditional end points in GERD, but have not shown clinical superiority to current PPIs. Novel therapeutic strategies targeting underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxations (TLESRs) and esophageal hypersensitivity, are being developed for add-on therapy to PPIs. Prokinetic drugs may also have some potential in the add-on treatment of GERD with insufficient response to PPIs. Add-on studies are hampered by insufficient information on optimal patient selection and lack of established end points. Expert opinion: Newer drugs for symptomatic control in GERD have largely focused on improved acid suppression, without evidence of clinical superiority. Drugs targeting esophageal motility and sensitivity to be used as add-onc therapy in PPI insufficient responders have not reached Phase III trials to date, due to difficulties with patient selection, tolerability and end points.

137c Globus Patients are Characterized by Abnormal Sensitization of the Esophageal Body Upon Repeated Balloon Distensions

participating 15 refused, 10 were deceased secondary to unrelated conditions, 5 were medically incapacitated for unrelated reasons, and 2 could not be reached. Of the 94 participants, 68% were female with a mean age of 53 years old. Manometric findings were normal in 63 (67%), weak peristalsis in 23 (25%), frequent failed peristalsis in 2 (2%), and hypertensive peristalsis in 6 (6%). No patients with normal studies or borderline manometric abnormalities had undergone myotomy or dilation. Further, PPI use and fundoplication rates were similar in patients with borderline manometric abnormalities when compared to those with normal esophageal manometry. Significant dysphagia at follow up (IDQ>8) was rare, seen in only 9 patients. The main indications for HRM were dysphagia (46%) and gastroesophageal reflux (35%), with no association between these indications and peristaltic abnormalities or persistence of dysphagia at follow up. (Table) Conclusion: Patients defined as normal or having borderline esophageal motor function using the Chicago classification appear to have minimal symptoms or medical interventions related to esophageal dysfunction during a 5 year follow-up.Only 14% of patients had significant dysphagia. Thus, identification of normal and borderline motor function is a good prognostic indicator as these patterns are associated with minimal long term consequences. Natural history of peristalsis patterns on HRM

Esophageal food impaction with an unexpected meal in an elderly woman: Letters to the Editor

ener because of dysphagia resulting from a previous cerebral infarction. She was served easy-to-swallow food and drugs including MgO tablets (500 mg/day) for constipation. Two weeks after admission, follow-up plain computed tomography incidentally showed a tablet-shaped foreign body in the colon, while the size of the aortic dissection had not significantly changed (Fig. 1a). We recovered an undisintegrated, ocher-colored tablet approximately 7 mm in length in the stool (Fig. 1b). Elemental analysis under scanning electron microscopy with energy-dispersive X-ray spectrometry identified a MgO tablet (Fig. 1c–e). Food thickeners have been reported to decrease the dissolution rate and affect the laxative activity of MgO tablets in mice. Food thickeners have also been shown to potentially inhibit MgO disintegration in vitro. As the patient had no obvious gastrointestinal problems, we assume that the food thickener was responsible for the lack of disintegration of the MgO tablet. Food thickeners have been shown to delay the rate of disintegration of various other drugs, including acetaminophen, valproic acid, carbamazepine and voglibose, affecting drug pharmacokinetics in both rodents and humans. However, to the best of our knowledge, this is the first report beyond a small number of abstracts to describe precise identification of an undistintegrated tablet in a patient taking a food thickener. Such effects of food thickeners are partly attributable to the structure of the polymer matrix in polysaccharide thickeners, and also depend on the concentrations of the specific components (e.g. polysaccharide or gum). The present case, together with previous reports, suggests that clinicians should be aware that food thickeners can impede the disintegration of some drug formulations.

232 Another Extraesophageal Reflux Syndrome: Ventilator Associated Pneumonia and Deteriorating Respiratory Function in ICU Patients

Background: Gastroesophageal reflux (GER) and microaspiration of gastric contents has been proposed as an important mechanism in the pathogenesis of ventilator associated pneumonia (VAP) but properties of GER in patients receiving acid suppresive therapy in intensive care unit (ICU) and its effect on VAP and respiratory function in these patients is not elucidated. Aim: This study aims to assess the association between GER and VAP by defining the differences between VAP and non-VAP patients in ICU in terms of proximal extension and chemical properties of GER assessed by 24 hour combined esophageal intraluminal electrical impedance/pH measurements. We also aimed to study the association of impedance/pH values with respiratory function (PaO2/FiO2 ratio) and gastropulmonary microaspiration assessed by pepsin measurements in deep tracheal aspirates(DTA). Methods: 20 intubated patients on acid suppressive medication for stress ulcer prophylaxis in a neurological and medical ICU were included in this study. Patients who had pneumonia at the time of intubation or who were diagnosed with pneumonia during the first 48 hours after intubation were excluded. Pepsinmeasurements weremade onDTA samples on the third day. Afterwards esophageal impedance/pHmetry catheters were placed and 24 hour recordings were analyzed. Patients were followed throughout their stay in ICU for VAP and daily PaO2/FiO2 ratios were recorded for one week. Impedance/pH values and pepsin levels were compared between VAP and nonVAP patients. Results: 8 patients were diagnosed with VAP. VAP patients had more proximal reflux compared to non-VAP patients (7(2-14) vs. 3,5(0-8))(p=0,003). Proximal weakly acidic reflux was again more common in VAP patients (4,5(2-9) vs 2(04)(p=0,006). Pepsin levels in DTA samples were correlated with the number of weakly acidic reflux episodes(r=0,615;p=0,004). Pepsin levels were also correlated with the number of proximal reflux episodes, especially with proximal weakly acidic reflux(r=0,489;p=0,029 ; r=0,651,p=0,002 ). PaO2/FiO2 ratios were negatively correlated with both pepsin levels and proximal weakly acidic reflux (r=-0,585,p=0,007 ; r=-0,620;p=0,004). Conclusion: Proximal extension of GER, especially proximal weakly acidic reflux is associated with microaspiration, VAP and worsening of respiratory function in intubated ICU patients on acid suppressive therapy.