An in-depth report on the causes, diagnosis, treatment, and prevention of stomach and gastrointestinal (GI) ulcers.
Duodenal ulcers; Gastric ulcers; Helicobacter pylori; H. pylori
The following drugs are sometimes used to treat peptic ulcers caused by either NSAIDs or H. pylori.
Many antacids are available without a prescription, and they are the first drugs recommended to relieve heartburn and mild dyspepsia. Antacids are not effective for preventing or healing ulcers, but they can help in the following ways:
It is generally believed that liquid antacids work faster and are more potent than tablets, although some evidence suggests that both forms work equally well.
Basic Salts Used in Antacids. There are three basic salts used in antacids:
Interactions with Other Drugs. Antacids can reduce the absorption of a number of drugs. Conversely, some antacids increase the potency of certain drugs. The interactions can be avoided by taking other drugs 1 hour before or 3 hours after taking the antacid.
Drug Interactions with Antacids (such as Maalox, Mylanta)
Drugs that are not absorbed as well if taken with antacids
Drugs that are made more potent by antacids
Famotidine (Pepcid AC)
H. pylori is usually highly sensitive to certain antibiotics, particularly amoxicillin, and to antibiotics in the macrolide class, such as clarithromycin. Either class of antibiotics is an effective second antibiotic in a three-drug regimen. Other antibiotics that are sometimes used include tetracycline, metronidazole, and ciprofloxacin.
Side Effects of Antibiotics.
Compounds that contain bismuth are often used in the three-drug treatment programs. They destroy the cell walls of H. pylori bacteria. The only bismuth compound available in the U.S. has been bismuth subsalicylate (Pepto-Bismol), although a drug combination of the H2 blocker ranitidine and bismuth citrate (Tritec) has been released. High doses can cause vomiting and depression of the central nervous system, but the doses given for ulcer patients rarely cause side effects.
Actions against ulcers. PPIs are the drugs of choice for managing patients with peptic ulcers, regardless of the cause. They suppress the production of stomach acid by blocking the gastric acid pump -- the molecule in the stomach glands that is responsible for acid secretion.
PPIs can be used either as part of a multidrug regimen for H. pylori, or alone for preventing and healing NSAID-caused ulcers. They are also useful for treating ulcers caused by Zollinger-Ellison syndrome. They are considered to be more effective than H2 blockers.
Some people carry a gene that reduces the effectiveness of PPIs. This gene is present in 18 - 20% of people of Asian descent.
Standard Brands. Most PPIs are available by prescription as oral drugs. There is no evidence that one brand of PPI works better than another. Brands approved for ulcer prevention and treatment include:
Possible Adverse Effects.
In theory, long-term use of PPIs by people with H. pylori may reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach), a risk factor for stomach cancer. Long-term use of PPIs may also mask the symptoms of stomach cancer and delay diagnosis. At this time, however, there have been no reports of an increase in the incidence of stomach cancer with long-term use of these drugs.
H2 blockers interfere with acid production by blocking histamine, a substance produced by the body that encourages acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until proton pump inhibitors and antibiotic regimens against H. pylori were developed. These drugs cannot cure ulcers, but they are useful in certain cases. They are effective only for duodenal ulcers, however.
Four H2 blockers are currently available over-the-counter in the U.S.: famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac), and nizatidine (Axid). All have good safety profiles and few side effects. There are some differences between these drugs:
PPIs are more effective than H2 blockers at healing ulcers in people who take NSAIDs. Treatment effectiveness for PPIs is between 65 and 100%, versus 50 and 85% for H2 blockers, depending on which specific drugs are being used.
Nizatidine (Axid). Nizatidine is nearly free from side effects and drug interactions.
Long-Term Concerns. In most cases, H2 blockers have good safety profiles and few side effects. Because H2 blockers can interact with other drugs, be sure to tell your doctor about any other drugs you are taking. There are also some concerns about possible long-term effects -- for example, that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who also have untreated H. pylori infection. More research is needed. However, the following concerns are well documented:
Famotidine is removed from the body primarily by the kidney. This can pose a danger to people with kidney problems. The U.S. Food and Drug Administration (FDA) and Health Canada are now advising physicians to reduce the dose and increase the time between doses in patients with kidney failure. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances.
Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major gastrointestinal side effects of NSAIDs.
Actions against ulcers. Misoprostol can reduce the risk of NSAID-induced ulcers in the upper small intestine by two-thirds, and in the stomach by three-fourths. It does not neutralize or reduce acid, so although the drug is helpful for preventing NSAID-induced ulcers, it is not useful for healing existing ulcers.
Sucralfate (Carafate) seems to work by adhering to the ulcer crater and protecting it from further damage by stomach acid and pepsin. It also promotes the defensive processes of the stomach. Sucralfate has an ulcer-healing rate similar to that of H2 blockers. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate does interact with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.
Bertleff M, Helm JA, Bemelman WA, van der Ham AC, van der Harst E, Oei HI, et al. Randomized clinical trial of laparoscopic versus open repair of the perforated peptic ulcer: The LAMA Trial. World J Surg. 2009;33(7):1368-1373.
Chey WD, Wong BC. Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808-1825.
Grainek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med. 2008;359(9):928-937.
Kim JI, Cheung DY, Cho SH, et al. Oral proton pump inhibitors are as effective as endoscopic treatment for bleeding peptic ulcer: a prospective, randomized, controlled trial. Dig Dis Sci. 2007;52(12):3371-3376.
Lanza FL, Chan FK, Quigley EM. Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728-738.
Luo J, Nordenvall C, Nyren O, et al. The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer. 2007;120(2):368-372.
Malagelada J-R, KuipersMartin EJ, Blaser J. Acid Peptic Disease: Clinical manifestations, Diagnosis, Treatment, and Prognosis. In: Goldman: Cecil Medicine, 23rd ed. Philadelphia, PA: WB Saunders, 2007.
Mercer DW, Robinson EK. Stomach. In: Townsend: Sabiston Textbook of Surgery, 18th ed. Philadelphia, PA: WB Saunders, 2007.
Pietroiusti A, Forlini A, Magrini A, et al. Shift work increases the frequency of duodenal ulcer in H. pylori infected workers. Occup Environ Med. 2006;63(11):773-775.
Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician. 2007;76(7):1005-1012.
Saif MW, Elfiky A, Salem RR. Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol. 2007;14(6):1860-1869.
Taha AS, McCloakwy C, Prasad R, Bezlyak V. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): A phase III, randomized, double-blind, placebo-controlled trial. Lancet. 2009:doi: 10.1016/S0140-6736(09)61246-0.
Take S, Mizuno M, Ishiki K, et al. Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer disease. J Gastroenterol. 2007;42(suppl 17):21-27.
© 2011 University of Maryland Medical Center (UMMC). All rights reserved.
UMMC is a member of the University of Maryland Medical System,
22 S. Greene Street, Baltimore, MD 21201. TDD: 1-800-735-2258 or 1.866.408.6885