Abstract

Treatment modalities for gastro-oesophageal reflux disease (GORD) mirror the pathophysiology of the disease. Since acid plays a key role in GORD-associated mucosal lesions, proton pump inhibitors (PPIs) are the dominant GORD treatment, being the most potent inhibitors of acid secretion available. However, the clinical effectiveness of PPIs varies with the specific symptoms being treated; they are more effective for heartburn than for regurgitation than for extra-oesophageal symptoms. An alternative therapeutic approach to GORD is to prevent the most fundamental cause of reflux symptoms, reflux itself, which most commonly occurs by transient lower oesophageal sphincter relaxation (TLOSR). Among potential pharmaceutical agents developed to target TLOSRs, the most advanced are GABA(B) (γ-aminobutyric acid) agonists, which experimentally reduce the occurrence of TLOSRs by about 40% in both animal and human studies. However, the effectiveness of GABA(B) agonists in clinical trials of patients with GORD with an incomplete response to PPI treatment has been modest. In part, this is probably attributable to the difficult problem of patient selection in these trials. Identifying patients by partial response to PPI treatment results in a heterogeneous population, including those with persistent weakly acidic reflux, patients with visceral hypersensitivity and those with functional heartburn, dyspepsia, or chest pain. From the clinical data available, the best treatment results and, hence, the patients most likely to benefit from reflux inhibitors, are those with persistent reflux, most commonly manifest as persistent regurgitation despite PPI treatment.

Links

Publisher Full Text

Authors

Kahrilas PJ, Boeckxstaens G

Institution

Northwestern University, Feinberg School of Medicine, Division of Gastroenterology and Hepatology, Department of Medicine, 676 N St Clair Street, Chicago, IL 60611, USA. p-kahrilas@northwestern.edu

Source

Gut 61:10 2012 Oct pg 1501-9

MeSH

GABA-B Receptor Agonists
Gastroesophageal Reflux
Gastrointestinal Agents
Humans
Patient Selection
Proton Pump Inhibitors
Receptors, Metabotropic Glutamate
Treatment Failure

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

22684485