GERD

Gastroesophageal reflux disease (GERD) is a common acid-related disorder presenting with a broad spectrum of symptoms with or without esophageal mucosal damage and/or complications. In general, the frequency and severity of symptoms and esophagitis correlate with the severity and duration of acid exposure, particularly during the nighttime. Acid suppression, with proton pump inhibitors (PPIs), is the mainstay of acute and maintenance treatment of GERD. Optimizing the choice of PPI and dose is essential for controlling GERD symptoms, accelerating healing of esophagitis, and preventing the long-term complications. Postprandial acid control is needed during the day particularly to control the symptoms. Additionally, nocturnal acid control especially in those with nighttime symptoms or severe mucosal injury is important for preventing complicated GERD. However, there is a substantial proportion of patients who do not respond to routine PPI therapy probably because of inadequate acid suppression or nonacid-related problems. Failure to respond to twice daily PPIs can be partly explained by the short half-lives of currently available PPIs that may fail to adequately control acid secretion after midnight, even if given before the evening meal. There has been considerable discussion in recent years over “nocturnal acid breakthrough,” which is really a misnomer, as this represents the pattern of nocturnal acid secretion when there is no drug available to inhibit secretion. Several approaches to properly controlling nocturnal acid secretion have included b.i.d. dosing of PPIs, adding an H2-receptor antagonist at night and the development of an instant release PPI. The former approaches have not been universally effective and clinical studies not yet performed with the latter. There are several new acid suppressing drugs in development and these include PPIs with longer half-lives, which give more prolonged nocturnal acid suppression. In addition, there are drugs which block the potassium channel (potassium competitive acid blockers) of the proton pump and which have a rapid onset of action. These drugs are under investigation and some may require more than 1 dose daily to adequately control acid secretion. In this review, we further explore different aspects of the need for new PPIs for the optimal management of GERD.