Medical Therapy for GERD

Pharmacologic therapy of GERD with antise-cretory agents originated in the mid-1970s when histamine-2-receptor antagonists first became available.2,3 However, healing of esophagitis was obtained in only 40-50% of patients and a similar number of patients continued to have symptoms of reflux. Omeprazole was released in 1989 as the first proton pump inhibitor (PPI) for clinical use. Three other firstgeneration PPIs subsequently became available but all were similar in efficacy, healing esophagi-tis in approximately 80% of GERD patients with a similar number achieving acceptable symptom relief.2-4 When a more potent PPI, esomeprazole, was introduced, its use was associated with healing of esophagitis and symptom relief in nearly 90% of patients with GERD.5 Physicians recently have come to realize that many patients require more frequent dosing (twice daily) or higher doses to achieve and maintain healing and symptomatic remission.6

MANAGING FAILED ANTI-REFLUX THERAPY

Most importantly, we have learned that these potent antisecretory agents often do not eliminate all symptoms of GERD, especially regurgitation. Thus, medical therapy as it currently stands is not an ideal treatment for GERD in all patients with this disorder and has not proven to be superior to surgery for this condition, having been outperformed by anti-reflux surgery in several studies.7-10

What does the future hold for pharmacologic anti-reflux therapy? In the antisecretory arena, longer-acting (e.g., tenatoprazole) and more rapid-acting (i.e., the newly launched immediate release omeprazole and the forthcoming acid pump antagonists) all appear pro-mising.11,12 Longer-acting agents may prevent breakthrough symptoms with once-a-day dosing and rapid onset agents may allow PPIs to be effective in on-demand situations. It is clear that antisecretory agents are treating the effects of reflux, not the underlying mechanism of reflux.13 Prokinetic agents that increase gastric emptying (i.e., tegaserod) may be valuable adjuncts to PPI therapy or effective in managing regurgitation or other symptoms that PPIs are relatively ineffective in controlling. Gamma-aminobutyric acid agonists (e.g., baclofen) or other neuromodulators may become useful in treating GERD via their inhibition of transient lower esophageal sphincter relaxations, the primary mechanism for a reflux event. Agents that improve tissue resistance by affecting the "tight-junctions" between cells are being developed and may prove to be very effective in symptom control and healing when reflux cannot be eliminated surgically.

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