Gastroesophageal Reflux Disease and Heartburn

Description

Alternative Names

Medications

Antacids neutralize digestive acids and are the primary drugs for mild symptoms. They are best used alone for relief of occasional and unpredictable episodes of heartburn. They all work by neutralizing the acid in the stomach. They may also stimulate the defensive systems in the stomach by increasing bicarbonate and mucous secretion. Many antacids are available without prescription and are the first drugs recommended to relieve heartburn and mild symptoms. Despite the many brands, they all rely on various combinations of three basic ingredients: magnesium, calcium, or aluminum.

Magnesium. Magnesium salts are available in the form of magnesium carbonate, magnesium trisilicate, and most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of magnesium salts is diarrhea. Magnesium salts offered in combination products with aluminum (Mylanta and Maalox) balance the side effects of diarrhea and constipation.

Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid acting antacid that can cause constipation. These antacids are actually sources of calcium. 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 has this side effect.

Aluminum. Aluminum salts (Amphogel, Alternagel) are also available. The most common side effect of antacids containing aluminum salts is constipation. People who take large amounts of antacids that contain aluminum may also be at risk for calcium loss, which can lead to osteoporosis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

It is generally believed that liquid antacids work faster and are more potent than tablets, although evidence suggests that they all work equally well. Antacids can interact with a number of drugs in the intestines by reducing their absorption. These drugs include tetracycline, ciprofloxacin (Cipro), propranolol (Inderal), captopril (Capoten), and H2 blockers. Interactions can be avoided by taking the drugs one hour before or three hours after taking the antacid. Long-term use of nearly any antacid increases the risk for kidney stones.

H2 Blockers

H2 blockers impede acid production by blocking or antagonizing the actions of histamine, a chemical found in the body that encourages acid secretion in the stomach. They are available over the counter and provide symptom relief in about half of GERD patients. It takes between a half hour to 90 minutes for them to work, but benefits last for hours. The drugs are usually taken at bedtime. Some people may need to take them twice a day.

H2 blockers inhibit acid secretion for six to 24 hours and are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes in people who are able to predict its occurrence. In some studies, H2 blockers improved asthmatic symptoms in people who suffer from both conditions. A 2001 study suggested, however, that they rarely provide complete symptoms relief for chronic heartburn and dyspepsia and they have done little to reduce office visits to physicians for GERD.

Brands. Four H2 blockers are currently available in the U.S.:

• 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 the FDA has issued a warning on its use in patients with kidney problems.
• Cimetidine (Tagamet). Cimetidine (Tagamet) is the oldest H2 blocker. It has few side effects; approximately 1% of people taking it 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 (Zantac). Ranitidine (Zantac) interacts with very few drugs. In a recent study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people less than 60 years old, but there was no difference in older patients. A common side effect associated with ranitidine is headache, which occurs in about 3% of the people who take it.
• Nizatidine (Axid) Nizatidine (Axid) is a new H2 blocker. It is nearly free of side effects and drug interactions. A controlled release form is proving to help alleviate nighttime GERD symptoms.

Drug Combinations.

• Over-the-counter antacids and H2 blockers: This combination may be the best approach for many people who experience heartburn after eating. Both classes of drugs are effective in relieving GERD, but have different timing. Antacids work within a few minutes but are short-acting, while H2 blockers take longer but benefits are long lasting. Pepcid AC combined with an antacid (calcium carbonate and magnesium) is now available as Pepcid Complete.
• Proton pump inhibitors and H2 blockers: Physicians sometimes recommend a nighttime dose of an H2 blocker for people who are taking proton-pump inhibitors twice a day. This is based on the belief that adding the H2 blocker will prevent a rise in acid reflux at night. An important 2002 study, however, reported no additional benefits from the nighttime H2 blocker. Some experts recommended an H2 blocker in these patients only to prevent breakthrough symptoms, such as before a heavy meal.

Long Term Complications. 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. More research is needed. Anyone with kidney problems should use famotidine only under the direction of a physician.

Concerns and Limitations. Some experts are concerned that the use of acid-blocking drugs in people with peptic ulcers may mask ulcer symptoms of ulcers and increase the risk for serious complications.

These agents provide no protection against Barrett's esophagus. In fact, of concern are reports that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who are infected with H. pylori. Research on this question is still on-going.

Proton-Pump Inhibitors

Proton-pump inhibitors (PPIs) suppress the production of stomach acid and work by inhibiting the molecule in the stomach glands that is responsible for acid secretion, which is called the gastric acid pump.

The standard agent has been omeprazole (Prilosec) which is now available over-the-counter without a prescription. Newer prescription oral PPIs include esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).

Studies report significant relief from PPIs in most patients with heartburn. PPIs are effective for healing erosive esophagitis and may also be helpful in patients with chronic laryngitis that is suspected to be caused by GERD. The newer agents provide quicker symptom relief compared to omeprazole. However, a 2002 comparison study suggested that to date esomeprazole (Nexium) is the only newer oral PPI to show any significant advantage over omeprazole (Prilosec). In any case all PPIs are more effective than the H2 blockers.

In addition to relieving most common symptoms, including heartburn, proton-pump inhibitors also have the following advantages:

• They are effective in relieving chest pain and laryngitis caused by GERD.
• They may also reduce acid reflux that typically occurs during strenuous exercise.

Patients with impaired esophageal muscular action are still likely to experience acid breakthrough and reflux at night. Proton-pump inhibitors also may have little or no effect on regurgitation or asthmatic symptoms. Some experts believe, however, that they should be the first drugs of choice even for patients with milder symptoms. At this time, these drugs are recommended for the following patients:

• Those with moderate symptoms that do not respond to H2 blockers.
• Those with severe symptoms.
• Those who have respiratory complications.
• Those who have persistent nausea.
• Those who have esophageal injury.

These agents have no affect against non-acid reflux, such as bile back-up.

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.

There is some evidence that acid reflux may contribute to the higher risk of cancer in BE, but it is not known yet if acid-blockers have any protective effects against cancer in these patients. In fact, 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.

Agents that Protect the Mucus Lining (Sucralfate)

Sucralfate (Carafate) protects the mucus lining in the gastrointestinal tract. It seems to work by sticking to an ulcer crater and protecting it from damage due to stomach acid and pepsin. It may be helpful for maintenance therapy in people with mild to moderate GERD. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate interacts with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.

Anti-Spasm Drugs to Prevent Acid and Non-Acid Reflux

Most drugs used for GERD have no effect on non-acid reflux, such as back-up of bile. Baclofen, known as a gamma-amino butyric acid agonist, is commonly used to reduce muscle spasms. Investigators are now showing that is can reduce both acid and non-acid reflux episodes (as much as 70% in one study) and to increase LES pressure, an important factor for preventing back up.