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Pharmacology of antiulcer medications

Andrew H Soll, MD
Section Editor
Mark Feldman, MD, MACP, AGAF, FACG
Deputy Editor
Shilpa Grover, MD, MPH


The treatment of peptic ulcers has changed dramatically in the past two decades, mirroring the revolution in understanding of the etiologies of peptic ulcers. Principles of treatment include:

  • Antibiotic therapy is indicated for ulcer disease associated with Helicobacter pylori (H. pylori) infection.
  • Anti-secretory drugs (H2 receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]) are the mainstays of treatment for ulcer healing.
  • Maintenance therapy, once a mainstay of treatment for peptic ulcer disease, is no longer indicated after successful eradication of H. pylori [1].
  • Antacids, bismuth, and protective agents (eg, sucralfate) were shown to heal peptic ulcers in an era before the role of H. pylori was recognized, and, in retrospect, studies were performed on largely H. pylori-positive peptic ulcer patients. The efficacy of these agents for nonsteroidal antiinflammatory drug (NSAID) ulcers or for non-NSAID, non-H. pylori ulcers has not been established, and, thus, they have no role in the current treatment of peptic ulcers. The only exception is the use of bismuth as part of antibiotic regimens to cure H. pylori infection.
  • Prostaglandin analogues (eg, misoprostol) are effective for preventing NSAID-induced ulcers, but they have no established role for healing ulcers.

The pharmacology of antiulcer drugs, excluding the antibiotics used to treat H. pylori, will be reviewed here. The treatment of H. pylori as well as an overview of the natural history and treatment of peptic ulcer disease are discussed elsewhere. (See "Treatment regimens for Helicobacter pylori" and "Overview of the natural history and treatment of peptic ulcer disease".)


H2 receptor antagonists (H2RAs) inhibit acid secretion by blocking histamine H2 receptors on the parietal cell (figure 1). H2RAs (eg, cimetidine, ranitidine, famotidine, and nizatidine) are still used for treatment and maintenance therapy of peptic ulcer disease, treatment of gastroesophageal reflux disease, and management of dyspepsia. However, they achieve less acid suppression than proton pump inhibitors.

H2RAs have efficacy for inhibiting acid secretion, preventing NSAID-induced ulcers, and in healing peptic ulcers when used at appropriate doses [2]. However, proton pump inhibitors have been shown to have superior healing rates for both duodenal and gastric ulcers [3]. In patients with NSAID-induced ulcers who require continued NSAID therapy while receiving treatment for ulcer disease, proton pump inhibitors are also superior to H2RAs [4].


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Literature review current through: Jan 2015. | This topic last updated: May 11, 2013.
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  1. Liu CC, Lee CL, Chan CC, et al. Maintenance treatment is not necessary after Helicobacter pylori eradication and healing of bleeding peptic ulcer: a 5-year prospective, randomized, controlled study. Arch Intern Med 2003; 163:2020.
  2. Laine L, Kivitz AJ, Bello AE, et al. Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers. Am J Gastroenterol 2012; 107:379.
  3. Walan A, Bader JP, Classen M, et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med 1989; 320:69.
  4. Agrawal NM, Campbell DR, Safdi MA, et al. Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti-inflammatory drug-associated gastric ulcers: results of a double-blind, randomized, multicenter study. NSAID-Associated Gastric Ulcer Study Group. Arch Intern Med 2000; 160:1455.
  5. Feldman M, Burton ME. Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases. 1. N Engl J Med 1990; 323:1672.
  6. Lewis JH. Hepatic effects of drugs used in the treatment of peptic ulcer disease. Am J Gastroenterol 1987; 82:987.
  7. Manlucu J, Tonelli M, Ray JG, et al. Dose-reducing H2 receptor antagonists in the presence of low glomerular filtration rate: a systematic review of the evidence. Nephrol Dial Transplant 2005; 20:2376.
  8. Gladziwa U, Koltz U. Pharmacokinetic optimisation of the treatment of peptic ulcer in patients with renal failure. Clin Pharmacokinet 1994; 27:393.
  9. Reynolds JC. The clinical importance of drug interactions with antiulcer therapy. J Clin Gastroenterol 1990; 12 Suppl 2:S54.
  10. Smallwood RA, Berlin RG, Castagnoli N, et al. Safety of acid-suppressing drugs. Dig Dis Sci 1995; 40:63S.
  11. McCarthy DM. Ranitidine or cimetidine. Ann Intern Med 1983; 99:551.
  12. Jensen RT, Collen MJ, Pandol SJ, et al. Cimetidine-induced impotence and breast changes in patients with gastric hypersecretory states. N Engl J Med 1983; 308:883.
  13. Potter HP Jr, Byrne EB, Lebovitz S. Fever after cimetidine and ranitidine. J Clin Gastroenterol 1986; 8:275.
  14. Nakano T, Kuroiwa T, Tsumita Y, et al. Aplastic anemia associated with initiation of nizatidine therapy in a hemodialysis patient. Clin Exp Nephrol 2004; 8:160.
  15. Takami N, Yamamoto Y, Matsuo H, et al. Agranulocytosis possibly caused by ranitidine in a patient with renal failure. Int J Clin Pharmacol Ther 2002; 40:520.
  16. Ecker RD, Wijdicks EF, Wix K, McClelland R. Does famotidine induce thrombocytopenia in neurosurgical patients? J Neurosurg Anesthesiol 2004; 16:291.
  17. Feldman M, Burton ME. Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases (2). N Engl J Med 1990; 323:1749.
  18. Kumar A. Cimetidine: an immunomodulator. DICP 1990; 24:289.
  19. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol 2004; 57:422.
  20. Cantú TG, Korek JS. Central nervous system reactions to histamine-2 receptor blockers. Ann Intern Med 1991; 114:1027.
  21. von Einsiedel RW, Roesch-Ely D, Diebold K, et al. H(2)-histamine antagonist (famotidine) induced adverse CNS reactions with long-standing secondary mania and epileptic seizures. Pharmacopsychiatry 2002; 35:152.
  22. Hanlon JT, Landerman LR, Artz MB, et al. Histamine2 receptor antagonist use and decline in cognitive function among community dwelling elderly. Pharmacoepidemiol Drug Saf 2004; 13:781.
  23. Black M. Hepatotoxic and hepatoprotective potential of histamine (H2)-receptor antagonists. Am J Med 1987; 83:68.
  24. Fisher AA, Le Couteur DG. Nephrotoxicity and hepatotoxicity of histamine H2 receptor antagonists. Drug Saf 2001; 24:39.
  25. Hinrichsen H, Halabi A, Kirch W. Clinical aspects of cardiovascular effects of H2-receptor antagonists. Eur J Clin Invest 1995; 25 Suppl 1:47.
  26. Lee KW, Kayser SR, Hongo RH, et al. Famotidine and long QT syndrome. Am J Cardiol 2004; 93:1325.
  27. Garbis H, Elefant E, Diav-Citrin O, et al. Pregnancy outcome after exposure to ranitidine and other H2-blockers. A collaborative study of the European Network of Teratology Information Services. Reprod Toxicol 2005; 19:453.
  28. Howden CW, Ballard ED, Koch FK, et al. Control of 24-hour intragastric acidity with morning dosing of immediate-release and delayed-release proton pump inhibitors in patients with GERD. J Clin Gastroenterol 2009; 43:323.
  29. Goldstein JL, Hochberg MC, Fort JG, et al. Clinical trial: the incidence of NSAID-associated endoscopic gastric ulcers in patients treated with PN 400 (naproxen plus esomeprazole magnesium) vs. enteric-coated naproxen alone. Aliment Pharmacol Ther 2010; 32:401.
  30. Katz PO, Koch FK, Ballard ED, et al. Comparison of the effects of immediate-release omeprazole oral suspension, delayed-release lansoprazole capsules and delayed-release esomeprazole capsules on nocturnal gastric acidity after bedtime dosing in patients with night-time GERD symptoms. Aliment Pharmacol Ther 2007; 25:197.
  31. Burget DW, Chiverton SG, Hunt RH. Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression. Gastroenterology 1990; 99:345.
  32. Howden CW, Hunt RH. The relationship between suppression of acidity and gastric ulcer healing rates. Aliment Pharmacol Ther 1990; 4:25.
  33. Tarnawski A, Tanoue K, Santos AM, Sarfeh IJ. Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of mucosal scar affected by treatment? Scand J Gastroenterol Suppl 1995; 210:9.
  34. Konturek SJ. New aspects of clinical pharmacology of antacids. J Physiol Pharmacol 1993; 44:5.
  35. Tarnawski A, Hollander D, Gergely H. Antacids: new perspectives in cytoprotection. Scand J Gastroenterol Suppl 1990; 174:9.
  36. Weberg R, Berstad K, Berstad A. Acute effects of antacids on gastric juice components in duodenal ulcer patients. Eur J Clin Invest 1990; 20:511.
  37. Orwoll ES. The milk-alkali syndrome: current concepts. Ann Intern Med 1982; 97:242.
  38. Soll AH, Weinstein WM, Kurata J, McCarthy D. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med 1991; 114:307.
  39. Banerjee S, El-Omar E, Mowat A, et al. Sucralfate suppresses Helicobacter pylori infection and reduces gastric acid secretion by 50% in patients with duodenal ulcer. Gastroenterology 1996; 110:717.
  40. Kaehny WD, Hegg AP, Alfrey AC. Gastrointestinal absorption of aluminum from aluminum-containing antacids. N Engl J Med 1977; 296:1389.
  41. Berstad A, Weberg R. Antacids for peptic ulcer: Do we have anything better. Scand J Gastroenterol 1986; 21(Suppl 125):32.
  42. Haram EM, Weberg R, Berstad A. Urinary excretion of aluminium after ingestion of sucralfate and an aluminium-containing antacid in man. Scand J Gastroenterol 1987; 22:615.
  43. Allain P, Mauras Y, Krari N, et al. Plasma and urine aluminium concentrations in healthy subjects after administration of sucralfate. Br J Clin Pharmacol 1990; 29:391.
  44. Robertson JA, Salusky IB, Goodman WG, et al. Sucralfate, intestinal aluminum absorption, and aluminum toxicity in a patient on dialysis. Ann Intern Med 1989; 111:179.
  45. Chines A, Pacifici R. Antacid and sucralfate-induced hypophosphatemic osteomalacia: a case report and review of the literature. Calcif Tissue Int 1990; 47:291.
  46. Arieff AI, Cooper JD, Armstrong D, Lazarowitz VC. Dementia, renal failure, and brain aluminum. Ann Intern Med 1979; 90:741.
  47. Walker JA, Sherman RA, Cody RP. The effect of oral bases on enteral aluminum absorption. Arch Intern Med 1990; 150:2037.
  48. Katzman R. Alzheimer's disease. N Engl J Med 1986; 314:964.
  49. Sherrard DJ. Aluminum--much ado about something. N Engl J Med 1991; 324:558.
  50. Flaten TP, Glattre E, Viste A, Søoreide O. Mortality from dementia among gastroduodenal ulcer patients. J Epidemiol Community Health 1991; 45:203.
  51. Shields HM. Rapid fall of serum phosphorus secondary to antacid therapy. Gastroenterology 1978; 75:1137.
  52. Malfertheiner P, Bazzoli F, Delchier JC, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet 2011; 377:905.
  53. Gorbach SL. Bismuth therapy in gastrointestinal diseases. Gastroenterology 1990; 99:863.
  54. Baron JH, Barr J, Batten J, et al. Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate (De-Nol). Gut 1986; 27:486.
  55. Koo J, Ho J, Lam SK, et al. Selective coating of gastric ulcer by tripotassium dicitrato bismuthate in the rat. Gastroenterology 1982; 82:864.
  56. Elder JB. Recent experimental and clinical studies on the pharmacology of colloidal bismuth subcitrate. Scand J Gastroenterol Suppl 1986; 122:14.
  57. Graham DY, Lew GM, Malaty HM, et al. Factors influencing the eradication of Helicobacter pylori with triple therapy. Gastroenterology 1992; 102:493.
  58. Nwokolo CU, Gavey CJ, Smith JT, Pounder RE. The absorption of bismuth from oral doses of tripotassium dicitrato bismuthate. Aliment Pharmacol Ther 1989; 3:29.
  59. Nwokolo CU, Prewett EJ, Sawyer AM, et al. Lack of bismuth absorption from bismuth subnitrate (Roter) tablets. Eur J Gastroenterol Hepatol 1990; 2:433.
  60. Nwokolo CU, Prewett EJ, Sawyerr AM, et al. The effect of histamine H2-receptor blockade on bismuth absorption from three ulcer-healing compounds. Gastroenterology 1991; 101:889.
  61. Wagstaff AJ, Benfield P, Monk JP. Colloidal bismuth subcitrate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease. Drugs 1988; 36:132.
  62. Sweeney JD, Hoernig LA. Hemostatic effects of salsalate in normal subjects and patients with hemophilia A. Thromb Res 1991; 61:23.
  63. Danesh BJ, McLaren M, Russell RI, et al. Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety. Haemostasis 1989; 19:169.
  64. Cohen A. Fecal blood loss and plasma salicylate study of salicylsalicylic acid and aspirin. J Clin Pharmacol 1979; 19:242.
  65. Torgyán S, Ady E, Wagner L, et al. Reduction of indomethacin-induced gastrointestinal blood loss by sodium salicylate in man. Int J Clin Pharmacol Biopharm 1978; 16:610.
  66. Chen MC, Amirian DA, Toomey M, et al. Prostanoid inhibition of canine parietal cells: mediation by the inhibitory guanosine triphosphate-binding protein of adenylate cyclase. Gastroenterology 1988; 94:1121.
  67. Feldman M. Prostaglandins and gastric ulcers: from seminal vesicle to misoprostol (Cytotec). Am J Med Sci 1990; 300:116.
  68. Bianchi Porro G, Parente F. Side effects of anti-ulcer prostaglandins: an overview of the worldwide clinical experience. Scand J Gastroenterol Suppl 1989; 164:224.
  69. Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet 1988; 2:1277.
  70. Raskin JB, White RH, Jackson JE, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med 1995; 123:344.
  71. Kulier R, Kapp N, Gülmezoglu AM, et al. Medical methods for first trimester abortion. Cochrane Database Syst Rev 2011; :CD002855.