Gastroesophageal reflux disease: pathophysiology and pharmacology overview

Gastroesophageal reflux disease (GERD) is one of the most frequently encountered illnesses in the Western Hemisphere. GERD encompasses a spectrum of disorders in which reflux of gastric content into the esophagus causes symptoms and/or damage to the esophagus, oropharynx, or respiratory tract. This article provides a brief update on the pathophysiology and pharmacology of drugs used for the treatment of GERD. The etiology of GERD is multi-factorial and is believed to be principally a consequence of altered motility states in the esophagus and stomach. The drugs used for the treatment of GERD are continuously evolving, but as yet no drug has been shown to cure this chronic, relapsing disease. Antacids, prokinetics, and gastric antisecretory agents are the principal drugs currently used to treat GERD in conjunction with life-style modifications. Due to their ultrashort duration of buffering action, antacids are primarily used as self-medication for temporary relief of mild GERD symptoms. The prokinetic drug cisapride effectively resolves symptoms and heals mild-to-moderate esophagitis, with efficacy similar to that of the histamine H2-receptor antagonists. H2-receptor antagonists exhibit moderate inhibition of gastric acid secretion and are effective for resolving symptoms and healing mild-to-moderate esophagitis. In addition, H2-receptor antagonists slightly augment the therapeutic efficacy of cisapride for healing mild-to-moderate esophagitis. However, use of H2-receptor antagonists at higher doses and higher frequency approaches the efficacy of proton pump inhibitors in healing erosive esophagitis. Given their potent and long-lasting acid-reducing efficacy, proton pump inhibitors have become the drugs of choice for many patients with GERD. Despite progress in the medical treatment of GERD, there are still several unresolved questions relating to cost-effective strategies with specific drugs, how long pharmacologic therapy should be maintained, and when surgical intervention is warranted. Additional studies are clearly needed to address the unresolved treatment issues in GERD.