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:
- They neutralize stomach acid with various combinations of three basic compounds -- magnesium, calcium, or aluminum.
- They may protect the stomach by increasing bicarbonate and mucus secretion.
Liquid antacids are thought to work faster and more effectively 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:
- Magnesium. Magnesium compounds are available in the form of magnesium carbonate, magnesium trisilicate, and, most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of these magnesium compounds is diarrhea.
- Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid-acting antacid, but it can cause constipation. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. Hypercalcemia can lead to kidney failure.
- Aluminum. The most common side effect of antacids containing aluminum compounds (Amphojel, ALternaGEL) is constipation. Maalox and Mylanta are combinations of aluminum and magnesium, which balance the side effects of diarrhea and constipation. People who take large amounts of antacids containing aluminum may be at risk for calcium loss and osteoporosis. Long-term use also increases the risk of kidney stones. People who have recently experienced GI bleeding should not use aluminum compounds.
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 may be treated with the following antibiotics:
- Amoxicillin is a part of the penicillin class of antibiotics. It is very effective against H pylori and is inexpensive, but some people are allergic to it.
- Clarithromycin (Biaxin) is part of the macrolide class of antibiotics. It is the most expensive antibiotic used against H pylori. It is very effective, but there is growing bacterial resistance to this drug. Resistance rates tend to be higher in women and increase with age. Researchers fear that resistance will increase as more people use the drug.
- Tetracycline is effective, but this medicine has unique side effects, including tooth discoloration in children. Pregnant women cannot take tetracycline.
- Ciprofloxacin (Cipro, generic) or levofloxacin (Levaquin), fluoroquinolone, is also sometimes used in H pylori regimens.
- Metronidazole (Flagyl, generic) was the mainstay in initial combination regimens for H pylori. As with clarithromycin, however, there continues to be growing bacterial resistance to the drug.
Side Effects of Antibiotics
- The most common side effects of nearly all antibiotics are gastrointestinal problems such as cramps, nausea, vomiting, and diarrhea.
- Allergic reactions can also occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare, but severe and even life-threatening anaphylactic shock.
- Some drugs, including certain over-the-counter medications, interact with antibiotics. Patients should report all medications they are taking to their doctor.
- Antibiotics double the risk of vaginal yeast infections.
- Use of antibiotics like amoxicillin increases the risk of developing Clostridium difficile colitis, a potentially serious infection.
Probiotics and yeasts can help minimize gastrointestinal side effects.
Compounds that contain bismuth inhibit the growth of H pylori bacteria by complex mechanisms. The most common bismuth compound available in the United States has been bismuth subsalicylate (Pepto-Bismol). High doses of bismuth can cause vomiting and depression of the central nervous system, but the doses given for ulcer patients rarely cause side effects.
Proton Pump Inhibitors (PPIs)
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. Additionally, they have direct effects on H pylori urease production. They are well tolerated during short term use.
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% to 20% of people who are of Asian descent.
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:
- Omeprazole (Prilosec, generic, Prilosec OTC, Zegerid)
- Esomeprazole (Nexium)
- Lansoprazole (Prevacid)
- Rabeprazole (AcipHex)
- Dexlansoprazole (Dexilant)
- Pantoprazole (Protonix)
Possible Adverse Effects
Side effects of PPIs are uncommon, but may include headache, diarrhea, constipation, abdominal pain, nausea, and itching.
- PPIs may interact with certain drugs, including antiseizure medications (such as phenytoin), anti-anxiety drugs (such as diazepam), and blood thinners (such as warfarin and clopidogrel). Studies have found that taking PPIs with the blood thinner clopidogrel (Plavix) reduces the effectiveness of this blood thinner by nearly 50%. Always talk to your doctor before stopping any of these medications.
- A warning added in May 2012 cautions that using certain PPIs with methotrexate, a drug commonly used to treat certain cancers, types of arthritis, and autoimmune conditions, can lead to elevated levels of methotrexate in the blood, causing toxic side effects.
- If possible, patients should avoid long term use of PPIs. Long term use may be associated with several adverse effects including Clostridium difficile intestinal infection, low magnesium levels, pneumonia, fractures, cardiac events, iron deficiency and rebound reflux symptoms. Older adults and those in long-term care facilities are at highest risk.
- Pregnant women and nursing mothers should avoid taking PPIs. Although recent studies suggest that these drugs do not increase the risk of birth defects, their safety during pregnancy is not yet proven.
- Long-term use of high-dose PPIs can cause vitamin B12 deficiency.
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 (histamine receptor-2 blockers) interfere with acid production by blocking histamine, a substance produced by the body that stimulates acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until PPIs and antibiotic regimens against H pylori were developed. H2 blockers cannot cure H pylori related ulcers, but they are useful in certain cases.
Four H2 blockers are currently available over-the-counter in the United States:
- Famotidine (Pepcid AC)
- Cimetidine (Tagamet)
- Ranitidine (Zantac)
- Nizatidine (Axid)
All 4 drugs have good safety profiles, similar effectiveness and few side effects. There are some differences in side effects between these drugs:
- Famotidine (Pepcid AC) is the most potent H2 blocker. The most common side effect is headache, which occurs in 4.7% of people who take it. Famotidine is virtually free from drug interactions, but it may have significant adverse effects in patients with kidney problems.
- Cimetidine (Tagamet) has few side effects. However, about 1% of people taking it experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, including phenytoin, theophylline, and warfarin. Long-term use of excessive doses (more than 3 grams a day) may cause erectile dysfunction or breast enlargement in men. These problems go away after the drug is stopped.
- Ranitidine (Zantac) interacts with very few drugs. Ranitidine may provide more pain relief than cimetidine in people younger than age 60, but there doesn't seem to be a difference in older patients. A common side effect of ranitidine is headache, which occurs in about 3% of people who take it.
- Nizatidine (Axid) has few drug interactions. Side effects of nizatidine include headache and dizziness.
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 drugs are used.
In most cases, H2 blockers have good safety profiles and few side effects. Because H2 blockers can interact with other drugs (such as theophylline, warfarin, phenytoin and lidocaine), be sure to tell your doctor about any other medications 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 to prove this risk.
However, the following concerns are well documented:
- Liver damage. This is more likely with ranitidine than with the other H2 blockers, but it is rare with any of these drugs.
- Kidney-related central nervous system complications. Famotidine is removed by the body primarily by the kidney. This can pose a danger in people with kidney problems. Use of the drug in people with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances. As a result, people with kidney failure should reduce the dose and increase the time between doses.
- Increased risk for pneumonia in hospitalized patients, as well as in the community.
- Ulcer perforation and bleeding. Some experts are concerned that the use of acid-blocking drugs may increase the risk for serious complications by masking ulcer symptoms.
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 66%, and in the stomach by 75%. 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.
- Because misoprostol can induce abortion or cause birth defects, pregnant women should not take it. If pregnancy occurs during treatment, the drug should be stopped at once and the doctor contacted immediately.
- Diarrhea and other gastrointestinal problems are severe enough to cause 20% of patients to stop taking the drug. Taking misoprostol after meals should minimize these effects.
Sucralfate (Carafate) seems to work by adhering to the ulcer and protecting it from further damage by stomach acid and pepsin. It also promotes the defensive processes of the stomach. 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, ketoconazole, fluoroquinolones, and tetracycline.