This article highlights current and emerging pharmacological treatments for gastroesophageal reflux disease (GERD), opportunities for improving medical treatment, the extent to which improvements may be achieved with current therapy, and where new therapies may be required. These issues are discussed in the context of current thinking on the pathogenesis of GERD and its various manifestations and on the pharmacologic basis of current treatments.
Gastroesophageal reflux disease (GERD) has come to be regarded as a simple condition that is easy to treat; proton pump inhibitors (PPIs) are generally considered the most effective medical treatment of GERD. Patients with mild or infrequent symptoms often do not require PPI therapy but those with more severe or frequent symptoms may benefit significantly from regular PPI therapy.
One of the major challenges in GERD management is the persistence of symptoms despite regular, once-daily therapy, considered by some as PPI failure. However, this is not necessarily a failure of acid suppression therapy. Current, first-generation PPIs have a short plasma half-life and cannot provide day-long acid suppression; thus, there are opportunities for improved outcomes with (1) more frequent dosing using current PPIs, (2) longer-acting PPIs or potassium-competitive acid blockers (P-CABs), (3) antireflux agents, (4) visceral pain modulators, or (5) mucosal protectants. In the short-term, improved outcomes can be achieved by fine-tuning treatment using currently available medications, based on their pharmacology and the patient’s disease manifestations; a careful consideration of the choice of drug, dose, and treatment regimen is crucial in the day-to-day management of GERD. For the future, an improved understanding of GERD and the pharmacology of available medications is essential for improving symptoms and quality of life.
Background
The prevalence of GERD is increasing worldwide and it has become the most prevalent gastrointestinal disorder. It is responsible for a substantial proportion of health care expenditure in the developed world. In the last 3 decades, the development of increasingly potent acid suppressants has revolutionized the medical management of GERD. Initially, histamine H 2 -receptor antagonists (H 2 -RAs) supplanted antacids for the healing of erosive esophagitis (EE); H 2 -RAs were, in turn, supplanted, to a large extent, by PPIs, which provided healing and symptom relief in a significantly greater proportion of patients than H 2 -RAs. Despite the success of acid suppression, GERD is not primarily a disorder of acid secretion and there have been many attempts to develop pharmacologic, endoscopic, and surgical treatments to increase basal lower esophageal sphincter (LES) pressure, reduce the frequency and duration of inappropriate transient LES relaxations (TLESRs), improve esophageal clearance, and accelerate gastric emptying. The attractions of targeting the pathophysiologic basis of GERD rather than acid suppression have not yielded new medications that produce healing and symptom relief comparable with those reported for PPIs.
Documented costs for managing GERD are attributable predominantly to the costs of pharmacotherapy, although surgical therapy is also associated with substantial costs, as are over-the-counter remedies. The costs of treating GERD and its complications have prompted close scrutiny of prescribing habits with the expectation that management guidelines and consequent constraints on pharmacotherapy will reduce expenditure. Reports that antireflux therapy may be provided without documentation of a diagnostic indication, in up to one-third of patients, suggest a significant opportunity to reduce the costs of GERD treatments. However, GERD is associated with an increased risk of esophageal adenocarcinoma and other complications and with substantial impairment of patients’ sleep, work productivity, and quality of life that warrant therapy. Furthermore, despite apparently optimal therapy, many patients continue to experience symptoms attributable to GERD, suggesting that there are still unmet needs.
The aim of this article to is to highlight current and emerging treatments for GERD, opportunities for improving medical treatment, the extent to which improvements may be achieved with current therapy, and where new therapies may be required. These issues are discussed in the context of current thinking on the pathogenesis of GERD and its various manifestations and on the pharmacologic basis of current treatments.
Related posts:
Nonsteroidal Antiinflammatory Drug-Related Injury to the Gastrointestinal Tract: Clinical Picture, Pathogenesis, and Prevention
Clinical Pharmacology of 5-ASA Compounds in Inflammatory Bowel Disease
Therapeutic Potential of Peroxisome Proliferator-Activated Receptors in Chronic Inflammation and Colorectal Cancer
Current Medical Treatments of Dyspepsia and Irritable Bowel Syndrome
Clinical Pharmacology of 5-ASA Compounds in Inflammatory Bowel Disease
New Pharmacologic Therapies in Gastrointestinal Disease
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
