[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Acid-peptic disease: physiology and treatment strategy # Acid-peptic disease: physiology and treatment strategy How the stomach makes acid and protects itself, and how reflux, ulcers, H. pylori infection and indigestion are treated. Updated Nov 12, 2026 On this page - The basics Key points - Physiology of acid secretion - Mucosal defences - Peptic ulcer and H. pylori eradication - Functional dyspepsia and functional oesophageal disorders - Memory aid - Example drugs - Clinical Gastro-oesophageal reflux disease - Study Test yourself - Connections NSAID-related and stress-related ulcers - Connections Acid-peptic diseases arise when acid and pepsin overwhelm the defences of the oesophagus, stomach or duodenum. This page explains the parietal cell, mucosal defence, and the treatment strategies for reflux disease, peptic ulcer and H. pylori, NSAID and stress ulcers, and functional dyspepsia. The drug classes have their own pages. ## Key points - The parietal cell secretes acid through the H+/K+-ATPase, stimulated by histamine (H2), acetylcholine (M3) and gastrin (CCK2). - Mucus, bicarbonate, mucosal blood flow and prostaglandins protect the stomach; NSAIDs remove the prostaglandin shield. - PPIs are the most effective acid suppressors and heal reflux oesophagitis in most people; they act best taken before the first meal. - H. pylori is eradicated with a PPI plus two or more antibiotics, sometimes with bismuth, chosen with local resistance in mind; cure is confirmed by testing. - Stress ulcers in intensive care are linked to acid and mucosal ischaemia; prophylaxis is targeted at high-risk patients. - Functional dyspepsia has no structural cause; PPIs, prokinetics and low-dose tricyclics are options. ## Physiology of acid secretion Parietal cells in the gastric body pump hydrogen ions into the lumen through the H+/K+-ATPase, the proton pump. Three signals drive them. Histamine from nearby enterochromaffin-like (ECL) cells acts on H2 receptors and raises cyclic AMP. Acetylcholine from vagal and enteric nerves acts on M3 receptors, and gastrin from antral G cells acts on CCK2 receptors, both raising calcium; gastrin works mainly by releasing histamine from ECL cells. Somatostatin from D cells and prostaglandin E2 inhibit secretion. Each drug class blocks one point: H2 antagonists the histamine signal, PPIs and potassium-competitive acid blockers the pump itself. ## Mucosal defences The stomach survives its own acid thanks to a mucus gel that traps secreted bicarbonate at the cell surface, tight epithelial junctions, rapid repair and good mucosal blood flow. Prostaglandins E2 and I2 support all of these and reduce acid secretion. Ulcer disease is best seen as an imbalance between these defences and acid and pepsin: NSAIDs block mucosal prostaglandin synthesis, and H. pylori damages the mucosa and alters gastrin and somatostatin control. ## Gastro-oesophageal reflux disease Reflux ranges from non-erosive disease to erosive oesophagitis, which can lead to strictures and Barrett oesophagus. Lifestyle steps come first: weight loss, raising the head of the bed, avoiding late meals and stopping smoking. Antacids relieve occasional mild heartburn; H2 antagonists are less effective than PPIs; PPIs heal oesophagitis in most people and are used for long-term control in those who need it. A practical strategy is to control symptoms and heal the oesophagus with a PPI, then keep long-term treatment only for those who need it, at the lowest effective intensity. Stopping after prolonged use can cause rebound acid hypersecretion. Fundoplication is an option when symptoms persist or people prefer to stop long-term medicine. ## Peptic ulcer and H. pylori eradication Most peptic ulcers are caused by H. pylori or NSAIDs. H. pylori treatment combines a PPI with two or more antibiotics, with or without bismuth, for a defined course; regimens are chosen to avoid antibiotics the patient has used before and those with high local resistance. A PPI makes the antibiotics more effective. Rising resistance to clarithromycin and metronidazole is a main cause of failure; where it is common, bismuth-based quadruple therapy is preferred. Eradication is confirmed with a test some weeks after treatment, and a different combination is used if infection persists. - Triple therapy: PPI plus clarithromycin plus amoxicillin (or metronidazole). - Bismuth quadruple therapy: PPI plus bismuth plus metronidazole plus tetracycline. - Alternatives: levofloxacin-based or sequential regimens. - Side effects from multi-drug regimens are common and drive poor adherence. ## NSAID-related and stress-related ulcers For NSAID ulcers the first step is to stop the NSAID or switch to a safer analgesic; if an NSAID must continue, a PPI is co-prescribed, and misoprostol is an alternative. Testing for and treating H. pylori before long-term NSAID use lowers risk. Stress ulcers occur in critically ill patients after severe illness or trauma and involve acid plus mucosal ischaemia. Intravenous H2 antagonists or PPIs reduce bleeding in high-risk patients, but raising gastric pH may favour pneumonia from gastric colonisation, so prophylaxis is reserved for those at high risk. Zollinger-Ellison syndrome (a gastrin-secreting tumour) needs high-intensity PPI therapy. ## Functional dyspepsia and functional oesophageal disorders Functional dyspepsia means ulcer-like symptoms (post-meal fullness, early satiety, epigastric pain or burning) with no structural cause. It is divided into postprandial distress syndrome and epigastric pain syndrome. Testing for and treating H. pylori is a first step. PPIs are first-line for the epigastric pain type and prokinetics for the post-meal distress type; H2 antagonists help little and antacids not at all. Because central mechanisms and visceral hypersensitivity contribute, low-dose tricyclic antidepressants and psychological therapies are used when symptoms persist. Functional heartburn, functional chest pain, functional dysphagia and globus are related oesophageal disorders approached in a similar way. ## Memory aid Three keys open the proton pump: Histamine, ACh, Gastrin (HAG); PPIs lock the pump itself. ## Test yourself Think of the answer, then tap the question to see it. ## Which three signals stimulate the parietal cell, and through which receptors? Histamine via H2, acetylcholine via M3 and gastrin via CCK2; gastrin acts largely by releasing histamine from ECL cells. ## Why do NSAIDs cause gastric ulcers? They block mucosal prostaglandin synthesis, reducing mucus, bicarbonate and blood flow that protect the stomach from acid. ## Why does H. pylori treatment fail more often today, and how is that countered? Resistance to clarithromycin and metronidazole; regimens avoid antibiotics with high local resistance, bismuth quadruple therapy is used, and cure is confirmed by testing. ## Why is stress-ulcer prophylaxis not given to every patient in intensive care? Raising gastric pH may increase pneumonia from gastric colonisation, so it is reserved for patients at high risk of bleeding. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/acid-peptic-disease-physiology-and-treatment-strategy/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Example drugs - [Omeprazole](https://durgical.com/en/pharmacology/omeprazole/) - [Esomeprazole](https://durgical.com/en/pharmacology/esomeprazole/) - [Pantoprazole](https://durgical.com/en/pharmacology/pantoprazole/) - [Famotidine](https://durgical.com/en/pharmacology/famotidine/) - [Vonoprazan](https://durgical.com/en/pharmacology/vonoprazan/) - [Misoprostol](https://durgical.com/en/pharmacology/misoprostol/) - [Sucralfate](https://durgical.com/en/pharmacology/sucralfate/) - [Bismuth subsalicylate](https://durgical.com/en/pharmacology/bismuth-subsalicylate/) - [Clarithromycin](https://durgical.com/en/pharmacology/clarithromycin/) - [Amoxicillin](https://durgical.com/en/pharmacology/amoxicillin/) - [Metronidazole](https://durgical.com/en/pharmacology/metronidazole/) - [Tetracycline](https://durgical.com/en/pharmacology/tetracycline/) - [Levofloxacin](https://durgical.com/en/pharmacology/levofloxacin/) - [Amitriptyline](https://durgical.com/en/pharmacology/amitriptyline/) - [Metoclopramide](https://durgical.com/en/pharmacology/metoclopramide/) ## Connections ## Related classes 7 - [Proton pump inhibitors (PPIs)](https://durgical.com/en/pharmacology/classes/proton-pump-inhibitors/) - [H2 receptor antagonists (H2 blockers)](https://durgical.com/en/pharmacology/classes/h2-receptor-antagonists/) - [Potassium-competitive acid blockers (P-CABs)](https://durgical.com/en/pharmacology/classes/potassium-competitive-acid-blockers/) - [Antacids](https://durgical.com/en/pharmacology/classes/antacids/) - [Prostaglandin analogues (obstetric use)](https://durgical.com/en/pharmacology/classes/prostaglandin-analogues/) - [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/) - [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Treatment for Peptic Ulcers (Stomach or Duodenal Ulcers)](https://www.niddk.nih.gov/health-information/digestive-diseases/peptic-ulcers-stomach-ulcers/treatment) (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2026); [Treatment for GER & GERD](https://www.niddk.nih.gov/health-information/digestive-diseases/acid-reflux-ger-gerd-adults/treatment) (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2026); [Treatment of Indigestion](https://www.niddk.nih.gov/health-information/digestive-diseases/indigestion-dyspepsia/treatment) (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/acid-peptic-disease-physiology-and-treatment-strategy/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/acid-peptic-disease-physiology-and-treatment-strategy/