Novel therapeutic strategies in acid-related disorders

Abstract

Acid-related disorders of the upper gut encompass diseases of the oesophagus, stomach and duodenum, such as gastro-oesophageal reflux disease (GORD), gastric and duodenal (peptic) ulcers, Zollinger–Ellison syndrome and iatrogenic ulcers and gastrointestinal bleeding mostly induced by non-steroidal anti-inflammatory drugs (NSAIDs). Gastric acid and pepsin are largely involved in their pathophysiology, both factors acting with Helicobacter pylori (especially in peptic ulcers) or with either NSAIDs, stress or smoking. All these diseases can benefit from agents that neutralise gastric acid or inhibit its secretion. Neutralising acid with antacids or decreasing acid secretion with histamine H₂-receptor antagonists (H₂-RAs) was the standard of care before the introduction of proton pump inhibitors (PPIs), which have been one of the major advances in the field of gastrointestinal pharmacology. Their superior efficacy in acid-related disorders with respect to other acid reducing drugs is now widely recognised. PPIs are also used to control atypical GORD symptoms, such as laryngitis, asthma and cough associated with reflux. In spite of their clinical efficacy in a number of conditions, the emerging need for new therapeutic approaches, such as ‘on-demand’ treatment for GORD symptoms, requires some features (e.g., fast onset of action at day 1 with an acid suppressant effect throughout the day and night, to avoid the nocturnal acid breakthrough) that currently available PPIs only partially achieve. Moreover, a subset of patients with GORD still do not respond to the available therapeutic regimens. Novel agents (or novel formulations of available PPIs) have recently been patented to try to overcome these problems.

• acid-related disorder
• antisecretory drug
• gastric acid secretion
• novel therapeutic
• proton pump inhibitor (PPI)