Peptic Ulcers

Description

Alternative Names

Medications

The following drugs are sometimes used in the treatments of peptic ulcers caused by either NSAIDs or H. pylori. They are described in alphabetical order.

Antacids

Many antacids are available without prescription and are the first drugs recommended to relieve heartburn and mild dyspepsia. They play no major role in either prevention or healing of ulcers but help in the following ways:

• All of the many brands available rely on various combinations of three basic compounds, magnesium, calcium, or aluminum, which neutralize the acid in the stomach.
• They may also defend the stomach by increasing acid-buffering bicarbonate and mucus secretion.

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 various 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. 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. This can lead to kidney failure and is very dangerous. None of the other antacids have this side effect.
• Aluminum. The most common side effect of antacids containing aluminum compounds (Amphogel, 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 that contain aluminum may also be at risk for calcium loss and osteoporosis. Long-term use also increases the risk for kidney stones. People who have recently experienced GI bleeding should not use aluminum compounds, if possible.

Interactions with Other Drugs. Antacids can interact with a number of drugs in the intestines and reduce their absorption. Conversely, some antacids increase the potency of certain drugs. The interactions can be avoided by taking these other drugs one hour before or three hours after the antacid.

Antibiotics

H. pylori is usually highly sensitive to certain antibiotics, particularly amoxicillin or antibiotics such as clarithromycin that belong to the drug class known macrolides. Either type of agent serves effectively as a second antibiotic in a three-drug regimen. Others being used are tetracycline, metronidazole, and ciprofloxacin.

• Amoxicillin is the most common form of penicillin. It is inexpensive, but many people are allergic to it.
• Clarithromycin (Biaxin) is a macrolide and is the most expensive of the antibiotics used against H. pylori. It is also 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 the drug is used more and more against H. pylori.
• Tetracycline is effective, but tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration. Pregnant women cannot take it.
• Ciprofloxacin (Cipro), known as a fluoroquinolone, is also sometimes used in ulcer regimens.
• Metronidazole (Flagyl) was the mainstay in initial combination regimens for H. pylori. As with clarithromycin, however, there continues to be growing bacterial resistance to the drug (about 25% to 35% of H. pylori bacteria).

Side Effects of Antibiotics.

• The most common side effects of nearly all antibiotics are gastrointestinal problems, including 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, even life-threatening anaphylactic shock.
• Some drugs, including certain over-the-counter medications, interact with antibiotics; patients should report to the physician all medications they are taking.
• They double the risk for vaginal infections in women.

Bismuth

Compounds that contain bismuth are often used in the three-drug antibiotic regimens. They destroy the cell walls of the H. pylori bacteria. The only bismuth compound available in the US 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.

H2 Blockers

H2 blockers impede acid production by blocking the actions of histamine, a substance produced by the body that encourages acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until the development of antibiotic regimens against H. pylori. These drugs cannot cure ulcers, but in certain cases they are useful. They are effective only for duodenal ulcers, however, and have little effect on stomach (gastric) ulcers. Four H2 blockers are currently available over the counter in the US: famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac), and nizatidine (Axid). All have good safety profiles and few side effects. Each is discussed below. H2 blockers can interact with other drugs, so the physician should be made aware of any other drugs a patient is taking. There are some differences among these drugs.

Famotidine (Pepcid AC). Famotidine (Pepcid AC) is the most potent H2 blocker. The most common side effect of famotidine is headache, which occurs in 4. 7% of people who take it. Famotidine is virtually free of drug interactions but it may have significant adverse effects in patients with kidney problems.

Cimetidine. Cimetidine (Tagamet) has few side effects; approximately 1% of people taking cimetidine will experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, such as phenytoin, theophylline, and warfarin. Long term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men; these problems resolve after the drug is discontinued.

Ranitidine. Ranitidine (Zantac) interacts with very few drugs. In one study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people younger than 60, but there was no difference in older patients. A common side effect of ranitidine is headache, which occurs in about 3% of the people who take it.

Nizatidine. Nizatidine (Axid) is a new H2 blocker. It is nearly free of side effects and drug interactions.

Long-Term Concerns. In most cases, these agents have good safety profiles and few side effects. H2 blockers can interact with other drugs, although some less so than other. In all cases, however, the physician should be made aware of any other drugs a patient is taking. There are also some concerns about possible long-term effects.

Also of concern are reports that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who also have untreated H. pylori infections. More research is needed.

• Liver damage. (This is more likely with ranitidine than other H2 blockers, but is rare in any event.)
• Kidney-related complications. Adverse effects on the central nervous system in patients with even moderate renal (kidney) insufficiency have been reported with famotidine and may result in anxiety, depression, and mental disturbances.
• Increased risk for pneumonia in hospitalized patients.
• Ulcer complications (perforation, bleeding). Some experts are concerned that the use of acid-blocking drugs may actually increase the risk for serious complications from ulcers by masking their symptoms.

Misoprostol

Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major intestinal toxicity of NSAIDs.

Actions Against Ulcers. Misoprostol can reduce formation of ulcers in the upper small intestine by two-thirds and in the stomach by three quarters. It does not neutralize or reduce acid, so although the drug is helpful for preventing NSAID-induced ulcers, it is not useful in healing existing ulcers.

Side Effects.

• 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. One study indicated that taking the drug two or three times a day instead of the standard regimen of four times may prove to be just as effective and cause fewer side effects.
• Misoprostol can induce abortion or cause birth defects and should not be taken by pregnant women. If pregnancy occurs during treatment, the drug should be discontinued at once and the physician contacted immediately.

Proton-Pump Inhibitors (PPIs)

Actions Against Ulcers. Proton-pump inhibitors (PPIs) are the drugs of choice for managing patients with peptic ulcers from any cause. They suppress the production of stomach acid. These agents work by inhibiting the molecule in the stomach glands that is responsible for acid secretion, which is called the gastric acid pump.

PPIs can be used as part of a multi-drug regimen for H. pylori or used alone for preventing and healing NSAID-related ulcers. They are even useful in the treatment of ulcers caused by Zollinger-Ellison syndrome. (Of note, certain individuals carry a gene that regulates an enzyme called CYP2C19 that reduces the effectiveness of proton-pump inhibitors. This gene may be present in between 18% and 20% of Asians, who may not respond as well to these agents.)

Standard Brands. The standard PPI for ulcers has been omeprazole (Prilosec). In fact, it has been recommended for over-the-counter use. Other newer agents include lansoprazole (Prevacid), rabeprazole (Aciphex), esomeprazole (Nexium), and pantoprazole (Protonix). All are available orally. Pantoprazole is also available as an injection and lansoprazole as a suspension, which may be useful for patients who cannot take oral medications. In a comparison study of these agents, esomeprazole was superior in treating healing injuries in the esophagus that caused gastroesophageal reflux disease (GERD). It is not known yet, however, whether any individual PPI has superior advantages for treating ulcers.

Adverse Effects. Proton-pump inhibitors may pose the following concerns:

Side effects are uncommon but may include headache, diarrhea, constipation, nausea, and itching.

• Proton-pump inhibitors should be avoided by pregnant women and nursing mothers, although recent studies suggest that they do not pose an increased risk of birth defects.
• They may interact with certain drugs, such as antiseizure agents (e.g., phenytoin), anti-anxiety drugs (e.g., diazepam), and blood thinners (e.g., warfarin).
• Long-term use of high-dose PPIs may produce vitamin B12 deficiencies, but studies are needed to confirm any significance of this risk.
• The long-term use of proton-pump inhibitors by people with H. pylori may, in theory at least, reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach). This condition, in turn, is a risk factor for stomach cancer. To compound concerns, long-term use of PPIs may mask symptoms of stomach cancer and so delay a diagnosis. To date, however, there have been no reports of an increased risk of stomach cancer with long-term use of these drugs.

Sucralfate

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, including warfarin, phenytoin, and tetracycline.

Experimental Agents

Ecabet is a unique anti-ulcer agent that is showing promise in early studies. It acts on the mucus lining of the stomach and has anti-bacterial activity.