Category:Anti-ulcer agents

An anti-ulcer agent is a medicine used to treat or prevent the gastric and duodenal ulcers of peptic ulcer disease, the related erosive disease of gastroesophageal reflux disease (GERD), and the rare gastrin-secreting tumours of the Zollinger-Ellison syndrome. The category overlaps substantially with the antisecretory agents (the medicines that reduce gastric acid secretion: proton pump inhibitors, H2-receptor antagonists, potassium-competitive acid blockers); it adds the mucosal protectants that coat the ulcer base rather than reducing acid (sucralfate, bismuth compounds), the prostaglandin analogues (misoprostol) used for prevention of NSAID-induced ulcers, and the antibacterial regimens used to eradicate Helicobacter pylori.

The clinical practice of anti-ulcer therapy has been reshaped twice in the modern era. The first reshaping was the introduction of effective acid suppression in the 1970s and 1980s (cimetidine 1976, then ranitidine and famotidine; then omeprazole 1988 and the proton pump inhibitor class), described in detail under antisecretory agents; before then, elective surgery (vagotomy, partial gastrectomy) was a common treatment for medically refractory ulcer disease. The second reshaping was the demonstration by Barry Marshall and Robin Warren that most peptic ulcer disease was caused by H. pylori infection and was curable rather than just suppressible; the antibacterial eradication of H. pylori combined with a course of acid suppression replaced the chronic acid-suppression-only paradigm for most ulcer patients.

The contemporary anti-ulcer pharmacopoeia is organised by clinical use into four broad strategies. The first is acid suppression, covered in detail under antisecretory agents and including the proton pump inhibitors (the foundational class; omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole), the H2 receptor antagonists (famotidine, the largely-retired cimetidine, the withdrawn ranitidine and nizatidine), and the newer potassium-competitive acid blockers (vonoprazan).

The second strategy is mucosal protection. Sucralfate, an aluminium-sucrose octasulfate complex, polymerises in the acidic gastric environment to a viscous paste that adheres to the ulcer base and forms a physical barrier against further acid attack; it is also a binder of pepsin and bile salts. It is most useful where acid suppression is undesirable (some critically ill patients) or where acid suppression is incomplete in spite of PPI therapy. The bismuth-containing preparations (bismuth subsalicylate as Pepto-Bismol; bismuth subcitrate as Pepto-Bismol Plus; bismuth subnitrate in selected European formulations) coat the gastric mucosa, have direct antibacterial action against H. pylori, and are component agents in some quadruple-therapy eradication regimens.

The third strategy is prostaglandin analogue therapy for prevention of NSAID-induced gastric ulcer in patients who must continue chronic NSAID use (rheumatic disease, low-dose-aspirin cardiovascular indications combined with another NSAID). Misoprostol (Searle, 1985), a synthetic prostaglandin E1 analogue, replaces the gastric-mucosal prostaglandin lost to COX-1 inhibition by the NSAID; the MUCOSA trial in 1995 demonstrated its prevention of NSAID-induced ulcer complication. Its diarrhoea and abdominal-cramping adverse-effect profile, and its concurrent off-label use for cervical ripening and medical abortion, have limited its routine NSAID-prophylaxis use; combined PPI co-prescription with the NSAID is now the more common approach. Misoprostol remains in active use as a uterotonic in obstetrics.

The fourth strategy is H. pylori eradication, the antibacterial-and-PPI combination regimens that cure ulcer disease rather than just suppress its symptoms. Standard first-line therapy in regions of low clarithromycin resistance is "triple therapy" with a PPI, clarithromycin, and amoxicillin for 14 days; "quadruple therapy" with a PPI, bismuth subcitrate, metronidazole, and tetracycline for 14 days is preferred in regions of clarithromycin resistance or as second-line. The fluoroquinolone-containing levofloxacin-based regimens are an alternative; the high-dose dual-therapy of high-dose PPI plus amoxicillin is being increasingly studied. Eradication success rates are 85 to 90 percent on first-line and somewhat lower on second-line, with continuing pressure on the choice of regimens from changing local resistance patterns.

The acute gastric stress ulcer of intensive care is a separate clinical entity, prevented by stress-ulcer prophylaxis with a PPI or H2 antagonist in ventilated and otherwise high-risk ICU patients. The need for routine prophylaxis is a matter of ongoing trial evidence; the PEPTIC and REVISE trials of the 2020s have refined the indications and have shown smaller benefit than was previously assumed, with corresponding emphasis on selective rather than universal prophylaxis.

By mechanism:

• Antisecretory agents (cross-indexed; the foundational ulcer treatment):
  • Proton pump inhibitors: omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole
  • H2 receptor antagonists: famotidine (the survivor), cimetidine, nizatidine
  • Potassium-competitive acid blockers: vonoprazan (Japan, U.S., other jurisdictions)
• Mucosal protectants:
  • Sucralfate
  • Bismuth compounds (bismuth subsalicylate, bismuth subcitrate, bismuth subnitrate)
  • Carbenoxolone (largely retired)
• Prostaglandin analogues:
  • Misoprostol (NSAID-ulcer prophylaxis; also obstetric use)
• Antibacterial components of H. pylori eradication regimens (cross-indexed under antibacterials):
  • Clarithromycin (macrolide), amoxicillin (penicillin), metronidazole (nitroimidazole), tetracycline, levofloxacin, rifabutin (in selected refractory regimens)
• Antacids (over-the-counter symptomatic relief): aluminium hydroxide, magnesium hydroxide, calcium carbonate, sodium bicarbonate, the combination products Maalox, Mylanta, Tums, Rolaids

The boundary of this category is "medicine prescribed primarily to treat or prevent peptic ulcer disease, related acid-peptic disease, or H. pylori infection." The medicines used for inflammatory bowel disease (the 5-aminosalicylates, the immunosuppressants, the anti-TNF and anti-integrin and anti-IL-12/23 biologics) are not anti-ulcer agents in this category sense, although they treat related inflammatory gastrointestinal pathology, and are collected under IBD medications when that page is built. The prokinetics used in gastroparesis (metoclopramide, domperidone, prucalopride, erythromycin in its prokinetic use) are not anti-ulcer agents. The antiemetics used for the nausea of acid-peptic disease are listed separately. Bariatric medicine, although it has gastrointestinal effects, is not an anti-ulcer pharmacology.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.