Antacids

Despite the development of potent medications for the treatment of GERD, antacids remain a mainstay of treatment. Antacids neutralize the acid in the stomach so that there is no acid to reflux. The problem with antacids is that their action is brief. They are emptied from the empty stomach quickly, in less than an hour, and the acid then re-accumulates. The best way to take antacids, therefore, is approximately one hour after meals or just before the symptoms of reflux begin after a meal. Since the food from meals slows the emptying from the stomach, an antacid taken after a meal stays in the stomach longer and is effective longer. For the same reason, a second dose of antacids approximately two hours after a meal takes advantage of the continuing post-meal slower emptying of the stomach and replenishes the acid-neutralizing capacity within the stomach.

Antacids may be aluminum, magnesium, or calcium based. Calcium-based antacids (usually calcium carbonate), unlike other antacids, stimulate the release of gastrin from the stomach and duodenum. Gastrin is the hormone that is primarily responsible for the stimulation of acid secretion by the stomach. Therefore, after the direct acid-neutralizing effect of the calcium carbonate is exhausted, the secretion of acid rebounds. The rebound is due to the release of gastrin, which results in an overproduction of acid. Theoretically at least, this increased acid is not good for GERD.

Acid rebound, however, has not been shown to be clinically important. That is, treatment with calcium carbonate has not been shown to be less effective or safe than treatment with antacids not containing calcium carbonate. Nevertheless, the phenomenon of acid rebound is theoretically harmful. In practice, therefore, calcium-containing antacids such as Tums and Rolaids are not recommended. The occasional use of these calcium carbonate-containing antacids, however, is not believed to be harmful. The advantages of calcium carbonate-containing antacids are their low cost and the calcium they add to the diet.

Aluminum-containing antacids have a tendency to cause constipation, while magnesium-containing antacids tend to cause diarrhea. If diarrhea or constipation becomes a problem, it may be necessary to switch antacids or alternately use antacids containing aluminum and magnesium.

Histamine antagonists

Although antacids can neutralize acid, they do so for only a short period of time. For substantial neutralization of acid throughout the day, antacids would need to be given frequently, at least every hour.

The first medication developed for more effective and convenient treatment of acid-related diseases, including GERD, was a histamine antagonist, specifically cimetidine (Tagamet). Histamine is an important chemical because it stimulates acid production. Released within the wall of the stomach, histamine attaches to receptors (binders) on the stomach's acid-producing cells and stimulates the cells to produce acid. Histamine antagonists work by blocking the receptor for histamine and thereby preventing histamine from stimulating the acid-producing cells. (Histamine antagonists are referred to as H2 antagonists because the specific receptor they block is the histamine type 2 receptor.)

Because histamine is particularly important for the stimulation of acid after meals, H2 antagonists are best taken 30 minutes before meals. The reason for this timing is so that the H2 antagonists will be at peak levels in the body after the meal when the stomach is actively producing acid. H2 antagonists also can be taken at bedtime to suppress nighttime production of acid.

H2 antagonists are very good for relieving the symptoms of GERD, particularly heartburn. However, they are not very good for healing the inflammation (esophagitis) that may accompany GERD. In fact, they are used primarily for the treatment of heartburn in GERD that is not associated with inflammation or complications, such as erosions or ulcers, strictures, or Barrett's esophagus.

Four different H2 antagonists are available by prescription, including cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine, (Pepcid). All four are also available over-the-counter (OTC), without the need for a prescription. However, the OTC dosages are lower than those available by prescription.

Proton pump inhibitors

The second type of drug developed specifically for acid-related diseases, such as GERD, was a proton pump inhibitor (PPI), specifically, omeprazole (Prilosec). A PPI blocks the secretion of acid into the stomach by the acid-secreting cells. The advantage of a PPI over an H2 antagonist is that the PPI shuts off acid production more completely and for a longer period of time. Not only is the PPI good for treating the symptom of heartburn, but it also is good for protecting the esophagus from acid so that esophageal inflammation can heal.

PPIs are used when H2 antagonists do not relieve symptoms adequately or when complications of GERD such as erosions or ulcers, strictures, or Barrett's esophagus exist. Five different PPIs are approved for the treatment of GERD, including omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium). PPIs are best taken an hour before meals. The reason for this timing is that the PPIs work best when the stomach is most actively producing acid, which occurs after meals. If the PPI is taken before the meal, it is at peak levels in the body after the meal when the acid is being made.

Pro-motility drugs

Pro-motility drugs work by stimulating the muscles of the gastrointestinal tract, including the esophagus, stomach, small intestine, and/or colon. One pro-motility drug, metoclopramide (Reglan), is approved for GERD. Pro-motility drugs increase the pressure in the lower esophageal sphincter and strengthen the contractions (peristalsis) of the esophagus. Both effects would be expected to reduce reflux of acid. However, these effects on the sphincter and esophagus are small. Therefore, it is believed that the primary effect of metoclopramide may be to speed up emptying of the stomach, which also would be expected to reduce reflux.

Pro-motility drugs are most effective when taken 30 minutes before meals and again at bedtime. They are not very effective for treating either the symptoms or complications of GERD. Therefore, the pro-motility agents are reserved either for patients who do not respond to other treatments or are added to enhance other treatments for GERD.

Foam barriers

Foam barriers provide a unique form of treatment for GERD. Foam barriers are tablets that are composed of an antacid and a foaming agent. As the tablet disintegrates and reaches the stomach, it turns into foam that floats on the top of the liquid contents of the stomach. The foam forms a physical barrier to the reflux of liquid. At the same time, the antacid bound to the foam neutralizes acid that comes in contact with the foam. The tablets are best taken after meals (when the stomach is distended) and when lying down, both times when reflux is more likely to occur. Foam barriers are not often used as the first or only treatment for GERD. Rather, they are added to other drugs for GERD when the other drugs are not adequately effective in relieving symptoms. There is only one foam barrier, which is a combination of aluminum hydroxide gel, magnesium trisilicate, and alginate (Gaviscon).

Surgery

The drugs described above usually are effective in treating the symptoms and complications of GERD. Nevertheless, sometimes they are not. For example, despite adequate suppression of acid and relief from heartburn, regurgitation, with its potential for complications in the lungs, may still occur. Moreover, the amounts and/or numbers of drugs that are required for satisfactory treatment are sometimes so great that drug treatment is unreasonable. In such situations, surgery can effectively stop reflux.

The surgical procedure that is done to prevent reflux is technically known as fundoplication and is called reflux surgery or anti-reflux surgery. During fundoplication, any hiatal hernial sac is pulled below the diaphragm and stitched there. In addition, the opening in the diaphragm through which the esophagus passes is tightened around the esophagus. Finally, the upper part of the stomach next to the opening of the esophagus into the stomach is wrapped around the lower esophagus to make an artificial lower esophageal sphincter. All of this surgery can be done through an incision in the abdomen (laparotomy) or using a technique called laparoscopy. During laparoscopy, a small viewing device and surgical instruments are passed through several small puncture sites in the abdomen. This procedure avoids the need for a major abdominal incision.

Surgery is very effective at relieving symptoms and treating the complications of GERD. Approximately 80% of patients will have good or excellent relief of their symptoms for at least 5 to 10 years. Nevertheless, many patients who have had surgery--perhaps as many as half--will continue to take drugs for reflux. It is not clear whether they take the drugs because they continue to have reflux and symptoms or if they take them for symptoms that are being caused by problems other than GERD. The most common complication of fundoplication is swallowed food that sticks at the artificial sphincter. Fortunately, the sticking usually is temporary. If it is not transient, endoscopic treatment to stretch (dilate) the artificial sphincter usually will relieve the problem. Only occasionally is it necessary to re-operate to revise the prior surgery.

Endoscopy

Very recently, endoscopic techniques for the treatment of GERD have been developed. One type of endoscopic treatment involves suturing (stitching) the area of the lower esophageal sphincter, which essentially tightens the sphincter. A second type involves the application of radio-frequency waves to the lower part of the esophagus just above the sphincter. The waves cause damage to the tissue beneath the esophageal lining and a scar (fibrosis) forms. The scar shrinks and pulling on the surrounding tissue, thereby tightening the sphincter and the area above it.a third type of endoscopic treatment involves the injection of material into the esophageal wall in the area of the LES. This increases the pressure in the LES and prevents reflux.

Endoscopic treatment has the advantage of not requiring surgery. It can be performed without hospitalization. Since these endoscopic techniques are new, however, it is not yet clear how effective they are or for how long they will be effective. More studies with endoscopic treatments are necessary.

Prevention of transient LES relaxation

Transient LES relaxations appear to be the most common way in which acid reflux occurs. Although there are available drugs that prevent relaxations, they have too many side effects to be useful. Much attention is being directed at the development of drugs that prevent these relaxations without accompanying side effects.