From the Guidelines
Gastric acid secretion should be managed with a personalized approach, focusing on lifestyle modifications and a stepwise diagnostic approach to identify the underlying mechanisms driving symptoms, as recommended by the 2022 AGA clinical practice update 1. The process of gastric acid secretion involves a complex system of neural, hormonal, and paracrine pathways, with parietal cells in the stomach playing a crucial role through the H+/K+ ATPase pumps (proton pumps) that actively secrete hydrogen ions into the stomach lumen. Key factors that stimulate acid secretion include:
- Histamine (acting on H2 receptors)
- Acetylcholine (muscarinic receptors)
- Gastrin (CCK-B receptors) These stimulants increase intracellular calcium and cAMP, activating the proton pumps. Conversely, acid secretion is inhibited by:
- Somatostatin
- Secretin
- Prostaglandins Medications targeting this process include:
- Proton pump inhibitors (like omeprazole 20-40mg daily) which irreversibly block the H+/K+ ATPase pump
- H2 receptor antagonists (like ranitidine 150mg twice daily) which block histamine's stimulatory effect, as part of a precision management approach for patients with GERD symptoms, as outlined in the 2022 AGA clinical practice update 1. A 4- to 8-week trial of single-dose PPI is considered safe and appropriate for patients with typical reflux symptoms and no alarm symptoms, with escalation to twice-a-day dosing or switching to a more potent acid suppressive agent if symptoms persist, as recommended by the 2022 AGA clinical practice update 1.
From the FDA Drug Label
Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days. Inhibition of secretion is about 50% of maximum at 24 hours and the duration of inhibition lasts up to 72 hours The “max” value represents determinations at a time of maximum effect (2 to 6 hours after dosing), while “min” values are those 24 hours after the last dose of omeprazole % Decrease in Basal Acid Output 78-80 % Decrease in Peak Acid Output 79-88 % Decrease in 24-hr Intragastric Acidity 80 to 97
Gastric Acid Secretion Inhibition:
- Omeprazole inhibits gastric acid secretion by 78-80% in basal acid output and 79-88% in peak acid output.
- The duration of inhibition lasts up to 72 hours.
- The inhibitory effect increases with repeated once-daily dosing, reaching a plateau after four days 2.
Ranitidine inhibits both daytime and nocturnal basal gastric acid secretions as well as gastric acid secretion stimulated by food, betazole, and pentagastrin Time After Dose, hours % Inhibition of Gastric Acid Output by Dose, mg 75 - 80 100 150 200 Basal Up to 4 99 95 Nocturnal Up to 13 95 96 92 Betazole Up to 3 97 99 Pentagastrin Up to 5 58 72 72 80 Meal Up to 3 73 79 95
Gastric Acid Secretion Inhibition:
- Ranitidine inhibits gastric acid secretion, with basal and nocturnal secretions being most sensitive to inhibition.
- Doses of 100 mg or less can almost completely suppress basal-, nocturnal-, and betazole-stimulated secretions.
- Pentagastrin- and food-stimulated secretions are more difficult to suppress 3.
From the Research
Gastric Acid Secretion Mechanism
- Gastric acid secretion is stimulated by gastrin, histamine, and acetylcholine, and inhibited by somatostatin and glucagon-like peptide-1 4
- Proton pump inhibitors (PPIs) reduce acid secretion by inhibiting the gastric hydrogen/potassium adenosine triphosphatase (H+,K(+)-ATPase) enzyme, which is part of the proton pump in gastric parietal cells 5
Regulation of Gastric Acid Secretion
- The main stimulants of acid secretion are gastrin, released from antral G cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons 4
- Other stimulants include ghrelin, motilin, and hydrogen sulfide, while somatostatin and glucagon-like peptide-1 inhibit acid secretion 4
Proton Pump Inhibitors and Gastric Acid Secretion
- PPIs, such as omeprazole and lansoprazole, are effective in reducing gastric acid secretion and are used to treat acid-related disorders 6, 5
- However, nocturnal acid breakthrough can occur in patients taking PPIs twice daily, resulting in the recovery of gastric acid secretion during the night 6
- The level of gastric acid suppression during PPI treatment does not differ between patients with and without persistent gastroesophageal reflux disease (GERD) symptoms 7
Clinical Implications
- PPIs are more effective than histamine-2 receptor antagonists (H2RAs) in healing ulcers and bringing pain relief, and are the mainstay of treatment for peptic ulcer disease 8
- However, long-term use of PPIs can have adverse effects, such as diarrhea, constipation, headaches, and gastrointestinal infections, and may require calcium supplements to prevent the risk of fractures in older adults 8