Appropriate Acid Suppression for the Management of Gastro-Oesophageal Reflux Disease

Abstract

Gastro-oesophageal reflux disease (GORD) results from an abnormally prolonged dwell time of acidic gastric contents in the oesophagus. Although GORD is primarily a motor disorder, the injurious effects of gastric acid are central to the pathogenic process of oesophagitis, and the severity of disease correlates with the degree and duration of oesophageal acid exposure. In the majority of patients with mild disease, oesophageal acid exposure occurs predominantly during post-prandial periods. Conventional doses of H²-receptor antagonists cannot overcome the integrated stimulus to acid secretion resulting from a meal, and are thus relatively ineffective in preventing daytime, post-prandial oesophageal acid exposure. In patients with more severe grades of oesophagitis, there are abnormally high levels of nocturnal acid exposure, with the intra-oesophageal pH being less than 4.0 for 36% of the time, compared with 5% of the time in patients with mild GORD. Control of nocturnal acid secretion thus becomes increasingly important. This may be made worse by relative gastric acid hypersecretion in some patients with severe GORD. The long duration of action and effective inhibition of meal-stimulated acid secretion probably explains the superiority of omeprazole in treating GORD. Preliminary meta-analysis shows that the healing rate of erosive oesophagitis at 8 weeks by antisecretory agents is directly related to the duration of suppression of gastric acid secretion achieved over a 24-hour period (r = 0.87; p < 0.05).

European College of Equine Internal Medicine Consensus Statement—Equine Gastric Ulcer Syndrome in Adult Horses

“…In human, maintenance of a pH above 3 and 4 for a minimum of 16 hours is required for healing of gastric ulceration and reflux esophagitis, respectively 78. Initial studies suggested that once daily administration of omeprazole results in 24 hours of acid suppression,79, 80 however, the duration of acid suppression after PO dosing at 4 mg/kg might be as short as 12 hours in some animals 66.…”

Review article: the pharmacological inhibition of gastric acid secretion—tolerance and rebound

“…In this condition, the clinical effect of treatment is clearly proportional to the degree and duration of acid suppression. 47 The effect of histamine H 2 -receptor antagonists in long-term treatment of GERD has generally been disappointing, at least in patients with high-grade oesophagitis. 48 This has led to a widespread use of proton pump inhibitors in the treatment of GERD, and the long duration of effect of the proton pump inhibitors has led to the use of these drugs even in patients with low-grade in¯ammation.…”

Cisapride inhibits meal‐stimulated gastric acid secretion and post‐prandial gastric acidity in subjects with gastro‐oesophageal reflux disease

“…It is also well established that other inhibitors of gastric acid secretion, such as histamine H 2 -receptor antagonists and proton pump inhibitors, reduce oesophageal acidity in subjects with GERD. 8,[36][37][38] When the results from the present study were analysed using conventional methods, such as the number and duration of oesophageal reflux episodes or the percentage of time the oesophageal pH < 4, there was no detectable effect of cisapride on oesophageal acid exposure. On the other hand, using integrated acidity, a more sensitive analytical approach, to assess oesophageal acidity demonstrated a clear statistically significant effect of cisapride.…”

“…Indeed, the small cisapride-induced increase in gastric emptying will tend to increase the values calculated for gastric acid secretion, because cisapride will cause the meal to empty more rapidly, reduce the meal buffer capacity in the stomach and, thereby, shorten the titration time (and increase the calculated gastric acid secretion). Although the inhibition of gastric acid secretion is known to decrease the time that the oesophageal pH < 4, 8,[36][37][38] gastric acidity has received limited attention with respect to its potential underlying role in oesophageal acid exposure in GERD. [39][40][41][42][43][44][45] The present finding that cisapride decreases post-prandial oesophageal acid exposure in subjects with GERD agrees with previous findings by others, [11][12][13][14][15] who have attributed this action of cisapride to its motility effects on the lower oesophageal sphincter pressure, oesophageal peristalsis and gastric emptying.…”