Functional dyspepsia: modern pathogenetic aspects and therapeutic approaches

Abstract

Functional  dyspepsia, affecting  up to 20% of individuals worldwide, remains  both a cause  of decreased activity of patients’ daily life and an obvious economic burden  due to healthcare costs. Despite extensive research, the etiology of dyspepsia  is unknown  in most  patients. Intestinal motility dysfunction  has long been  considered the  major culprit, but recent  studies suggest  that  immune  pathophysiological and molecular  effects  in the  duodenum are far more likely predisposing factors. Eosinophilia  and an increase  in mast  cells in both  the  duodenum and gastric mucosa  are identified  in most patients with this disease. More and more data  on the significant  role of impaired  paracellular permeability of the intestinal mucosa are now available. It is associated with subclinical  inflammation in the submucosal layer in patients with functional  dyspepsia. This explains  the  poor effectiveness of the  treatments taken. The evidence  from practice  suggests that  symptoms  persist or return  after  eradication therapy  in most patients. Proton  pump inhibitors  and antidepressants do not ease  postprandial distress  syndrome.  Montelukast  and  cromolyn  therapy  has  been  proposed,  but  this  approach  is not  yet  widely popular. Therefore, there  is an obvious need  in finding other  therapeutic approaches. One of them  is the increased use of prokinetics, the most recent  of which is acotiamide.  Its mechanism  of action  is similar to that  of prior generation prokinetics  (inhibition of acetylcholinesterase activity), but is distinguished by the absence of impact on dopaminergy, due to which the drug has  far fewer  side  effects. In addition,  its effect  on the  production  of ghrelin, which physiological  role  is being  actively studied, is discussed.