Antireflux Drug Therapy - Gastroesophageal Reflux Disease: Digestive Disorders

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Antireflux drug therapy

How do you spell relief? Nonstop advertisement has acquainted most people with antacids, the least expensive treatment for heartburn. These work by reducing the acidity of refluxed material. Almost as well known are H₂-receptor antagonists (H₂ blockers) and proton pump inhibitors (PPIs). The former cost a little more than antacids, but are generally more convenient, and some can be purchased over the counter. PPIs are more effective than either antacids or H₂ blockers, but tend to be costly. In severe cases, physicians may favor combining various antireflux drugs, such as over-the-counter antacids and H₂ blockers or PPIs and prokinetic drugs. However, PPIs without additional medications are generally preferable to combinations.

Let's look at them in the order in which physicians typically recommend or prescribe their use.

Proton pump inhibitors

PPIs are more effective than H₂ blockers at lowering the production of gastric acid. PPIs, also known as acid pump inhibitors, work by inactivating a specific enzyme responsible for the final step of acid release in the stomach. They can reduce gastric acid secretion by more than 95% without causing systemic side effects.

Initially, PPIs were only available by prescription. In 2003, omeprazole (Prilosec) became the first to become available without a prescription, and it also is the only one approved by the FDA for repeated courses of treatment for erosive esophagitis. PPIs available by prescription include lansoprazole (Prevacid), rabeprazole (AcipHex), pantoprazole (Protonix), omeprazole (Zegerid), and esomeprazole (Nexium). Zegerid is an immediate-release medication in contrast to all others which are delayed-release.

PPIs are the drugs of choice for erosive esophagitis. This condition usually recurs when the drug is stopped, so long-term treatment is usually necessary. All these medications are impressive in their ability to heal esophagitis and alleviate heartburn.

Although they have numerous advantages, PPIs are expensive. In addition, they may make the GI tract more susceptible to bacterial infections. Despite these concerns, however, PPIs have become the preferred medication for reflux esophagitis and for patients with unremitting GERD-derived respiratory symptoms. They are often tried first for frequent, uncomplicated heartburn, but once symptoms are controlled, a less expensive medication such as an H₂-receptor antagonist can be tried.

Histamine H₂-receptor antagonists

For chronic reflux, histamine H₂-receptor antagonists (H₂ blockers) are now widely available either by prescription or, in smaller doses, over the counter. They are often effective for GERD symptoms that don't respond to antacids or changes in eating habits.

H₂ blockers work by countering the effect of histamine (which stimulates gastric acid), thereby decreasing the amount of acid that the stomach produces. They act directly on the stomach's acid-secreting cells to stop them from making hydrochloric acid, particularly at night when acid gathers in the stomach and can wash back into the esophagus. Cimetidine (Tagamet) was the first H₂ blocker on the market. Others available in the United States include ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid).

For people whose heartburn is troublesome only at night, a single dose taken in the evening may suffice, but if symptoms occur during the day and night, more frequent treatments will be needed. The H₂ blockers are equally effective, so switching to another if one fails to work is likely to be fruitless. Increasing the dose, however, may be helpful.

While considered relatively safe, H₂ blockers can have side effects (see Table 2). Treating with over-the-counter H₂ blockers may cause sufferers to mistake serious conditions for heartburn, delaying diagnosis and proper treatment.

Antacids

These inexpensive over-the-counter remedies neutralize digestive acids in the stomach and esophagus, at least in mild cases of heartburn. While many people find tablets more convenient, liquids provide faster relief. Tablets must be chewed thoroughly in order to be effective. The best time to take an antacid is after a meal or when symptoms occur. The usual recommended dosage is one to two tablespoons each time.

There are three basic salts used in antacids: magnesium, aluminum, and calcium. Some consider magnesium- and aluminum-based antacids (including Di-Gel, Maalox, and Mylanta) to be the most cost-effective heartburn drugs. A major side effect of magnesium hydroxide is diarrhea, while the most common side effect of antacids containing aluminum hydroxide is constipation.

Antacids high in calcium (Tums, Rolaids, Titralac, and Alka-2) are probably the strongest. Calcium carbonate products have been used for centuries in the form of chalk powder and oyster shell. They, too, can be constipating if consumed in sufficient quantities.

Sodium bicarbonate, or baking soda, which is less powerful than other antacids, is the active ingredient in many seltzer antacids (Alka-Seltzer, Bromo-Seltzer) and is present in mineral water.

Because no single agent is perfect, many antacids combine several ingredients that are designed to balance their respective side effects. Maalox, for example, combines magnesium and aluminum. Gaviscon combines antacids with alginic acid, a substance derived from marine algae. It creates a "raft" that floats on the gastric "sea" and helps block reflux.

Prokinetic agents

Prokinetics — or gastrokinetics, as they're occasionally called — are a wide-ranging group of drugs that help empty the stomach of acids and fluids. They can also improve LES muscle tone. These medications are used only for occasional cases of GERD, either with or in place of H₂ blockers, particularly when the stomach appears to empty slowly.

Cisapride (Propulsid) was pulled from the U.S. market in 2000 after it was linked to more than 300 reports of heart rhythm abnormalities, including more than 80 deaths. Its predecessors, metoclopramide (Reglan) and bethanechol (Urecholine), are available by prescription, but have a variety of side effects (see Table 2).

Last updated:	August 21, 2007