Medical management of patients with esophageal or supraesophageal gastroesophageal reflux disease
Section snippets
Nonresponders to proton pump inhibitor therapy
For the purpose of this article, nonresponders are defined as those patients who have persistent symptoms and abnormal reflux, as demonstrated by 24-hour ambulatory pH monitoring, despite twice-daily treatment with a PPI. Physiologically, several factors may contribute to this phenomenon, including the considerable variation in oral bioavailability of PPIs, the need for the ATPase pumps to be activated by meals, the influence of Helicobacter pylori–associated gastritis, and genetic variation in
Improved pharmacokinetic parameters
The development of newer PPIs has resulted in improved outcomes in some groups of nonresponders. The first available PPI, omeprazole, along with other subsequently developed PPIs, is a racemic mixture of R- and S-isomers. Recent studies suggest that the S-isomer of omeprazole (esomeprazole) is subject to less first-pass metabolism and lower plasma clearance than is omeprazole, thereby offering higher systemic bioavailability, less intersubject variability, and more prolonged acid suppression.
Relation to meals
PPIs bind to H+K+ ATPase molecules that have been recruited to the surface of the parietal cell by the intake of a meal. Because of their short half-lives (0.6 to 3.0 hours) after absorption, the optimal administration of a PPI is 15 to 30 minutes before a meal (usually breakfast) and ideally after a period of fasting. Nevertheless, as shown in Figure 1, from a study of physicians and their prescription patterns, much confusion exists about the optimal time to take a PPI in relation to meals.6
Helicobacter pylori gastritis
The effect of H pylori infection on the prevalence of GERD remains controversial. However, many studies with older PPIs have found that patients who test negative for H pylori have poorer gastric acid control on standard doses of PPIs than their positive counterparts. This phenomenon appears to be due to the acid-suppressive effects of chronic corpus gastritis associated with H pylori infection in positive subjects, whereas H pylori–negative subjects have high volumes of gastric acid. Recent
Nocturnal gastric acid breakthrough
The phenomenon of increasing gastric acidity at night in individuals receiving twice-daily treatment with a PPI was recently described.8 This event has been called nocturnal acid breakthrough and is arbitrarily defined as the appearance of gastric acid, marked by a pH <4 in the fundus, for a period >1 hour overnight during twice-daily PPI therapy. The prevalence of nocturnal acid breakthrough ranges from 69% to 79% in normal volunteers and patients with GERD, and typically appears in the second
Treatment failure in gastroesophageal reflux disease
Table 1 summarizes the most common reasons that patients with GERD symptoms do not improve, or even worsen, on aggressive PPI therapy. In fact, clinical experience suggests that all patients with GERD can now be treated adequately in an acute situation with these highly effective drugs.
The most common reason that patients with heartburn and regurgitation do not improve is an inaccurate diagnosis. Symptoms may be functional in origin, secondary to delayed gastric emptying or even achalasia.
Elderly patients
Older patients with GERD often complain of less severe reflux symptoms than do younger individuals, possibly due to decreased pain sensitivity. However, because of prolonged acid exposure over years, the elderly may have more complicated forms of the disease.14 Treatment of the older GERD patient follows the same principles as treatment of other adults, although it may require more aggressive acid-suppression therapy.15 Pill-induced esophagitis may complicate treatment in this group.
Supraesophageal presentations
A number of supraesophageal complaints have been associated conclusively with GERD, including chest pain; pulmonary diseases such as asthma, bronchitis, microaspiration, and pulmonary fibrosis; and ear, nose, and throat symptoms, including hoarseness, cough, laryngitis, subglottic stenosis, and cancer. The mechanisms by which acid reflux causes or aggravates these diseases is multifactorial, including microaspiration of gastric contents or a vagally mediated reflex triggered by intraesophageal
Barrett esophagus
Symptomatic patients with Barrett esophagus can be easily managed with PPI therapy. Furthermore, their esophagitis, strictures, and ulcers can be healed, and relapse can be prevented, enabling this group to have an enhanced quality of life. As shown in Table 5, 29, 30, 31, 32, 33 however, there is little evidence that PPI therapy promotes predictable regression of Barrett epithelium. Theoretically, the elimination of pulses of acid reflux could reduce proliferation of Barrett epithelium based
The choice of medical or surgical treatment for gastroesophageal reflux disease: personal philosophy
At the Cleveland Clinic Foundation, all patients being considered for antireflux surgery are jointly evaluated by the gastroenterology and surgery teams. When GERD is causing the patient’s symptoms, both groups are convinced that these patients can achieve symptomatic relief and healing of esophagitis, especially with the use of PPI therapy. True “intractable” GERD cases are rare in our collective experience; PPI failure suggests that GERD may be the wrong diagnosis. Noncompliance with drug
References (40)
- et al.
Medical therapymanagement of the refractory patients
Gastroenterol Clin North Am
(1999) - et al.
Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitisa randomized controlled trial
Am J Gastroenterol
(2001) - et al.
Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis
Am J Gastroenterol
(2002) - et al.
Oral pantoprazole for erosive esophagitisa placebo-controlled, randomized clinical trial
Am J Gastroenterol
(2000) - et al.
Patterns of proton pump inhibitor use in clinical practice
Am J Med
(2001) - et al.
Nocturnal recovery of gastric acid secretion with twice-daily dosing of PPIs
Am J Gastroenterol
(1998) - et al.
Ranitidine controls nocturnal gastric acid breakthrough on omeprazolea controlled study in normal subjects
Gastroenterology
(1998) - et al.
Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough
Gastroenterology
(2002) - et al.
Duodenogastroesophageal refluxrelationship to pH and importance in Barrett’s esophagus
Gastroenterology
(1994) Gastroesophageal reflux disease in the older patientpresentation, treatment and complications
Am J Gastroenterol
(2000)
Double-blind, placebo-controlled study of ranitidine for gastroesophageal symptoms during pregnancy
Obstet Gynecol
Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease
Am J Gastroenterol
Approach to the patient with unexplained chest pain
Am J Gastroenterol
Asthma and gastroesophageal reflux
Am J Gastroenterol
ENT manifestations of gastroesophageal reflux
Am J Gastroenterol
Lansoprazole treatment of patients with chronic idiopathic laryngitisa placebo controlled trial
Am J Gastroenterol
A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough
Am J Gastroenterol
Outcome of atypical symptoms attributed to gastresophageal reflux disease treated by laparoscopic fundoplication
Surgery
Partial regression of Barrett’s esophagus by long-term therapy with high-dose omeprazole
Gastrointest Endosc
Differentiation and proliferation in Barrett’s esophagus and the effect of acid suppression
Gastroenterology
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