These agents competitively and reversibly inhibit gastric acid secretion by blocking the histamine receptor on the parietal cell and perhaps other effector cells as well. There are four available agents—cimetidine, ranitidine, famotidine, and nizatidine. These compounds have been shown to be effective in relieving mild-to-moderate GERD symptoms as well as preventing postprandial GERD symptoms. A review of 20 randomized controlled trials, however, showed only five studies that demonstrated a significant improvement in symptom control over placebo.14 These agents have also been shown to be effective in controlled clinical trials assessing the healing erosive esophagitis. The efficacy for healing, however, has been particularly poor for severe esophagitis. All comparative trials to date have shown that H2RAs are substantially inferior to proton pump inhibitor (PPI) therapy for healing of erosive esophagitis or in controlling GERD symptoms. This is in part related to the diminished effect versus the PPIs that H2RAs have on gastric acid secretion as well as the tachyphylaxis, or pharmacological tolerance, that has been reported as a consequence of continued administration of these agents. It is likely that tolerance develops as a down-regulation of the H2 receptors.
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