(Taken from application) The most commonly used therapy for reflux disease is based on neutralization of acid either with the help of antacids, H2 receptor antagonists and proton pump inhibitors in spite of the fact that acid secretion in the majority of patients with GER disease is normal. However, there are a number of problems with the acid neutralization therapy in reflux disease: (1) it is unphysiologic; (2) effective therapy requires acid suppression of the magnitude of 80-90% of the normally secreted acid, such severe acid suppression raises issues regarding side effects, i.e., bacterial overgrowth and proliferation of the enterochromoffin cells; and (3) reflux of neutral contents can still occur after acid neutralization and can cause a number of symptoms related to bile reflux, chronic regurgitation and pulmonary symptoms as a result of chronic aspiration. For many years, traditional views held that gastroesophageal reflux (GER) was the consequence of a weak basal LES pressure. However, a large number of studies conducted during last 10 years consistently show that in both, normal subjects and patients with GER disease, intermittent transient lower esophageal sphincter relaxations (TLESR), rather than a persistently defective LES tone is the mechanism of GER. Anticholinergic drugs reduce basal LES pressure, and based on conventional thinking that a low LES pressure is the mechanism of GER they have been contraindicated in GER disease. Fortuitously, we found that atropine reduces the frequency of postprandial physiologic reflux through it's inhibitory effect on the frequency of TLESR. Since the major mechanism of GER in patients, just like normal subjects, is TLESR we propose that anticholinergics may be useful in the treatment of GER disease.
THE SPECIFIC AIMS OF OUR PROPOSAL ARE TO STUDY THE: 1. Effects of atropine on the frequency of GER in patients with reflux esophagitis. 2. Effect of oral anticholinergic drugs on the frequency of GER. 3. Effect of oral anticholinergic drugs in combination with proton pump inhibitors in the treatment of resistant reflux esophagitis. 4. Effects of central vs peripheral anticholinergic agents on TLESR and GER in patients with reflux disease.
| Pehlivanov, N; Liu, J; Mittal, R K (2001) Sustained esophageal contraction: a motor correlate of heartburn symptom. Am J Physiol Gastrointest Liver Physiol 281:G743-51 |
