Antacids neutralize acids in the stomach, and are the drugs of choice for mild GERD symptoms. They may also stimulate the defensive systems in the stomach by increasing bicarbonate and mucus secretion. They are best used alone for relief of occasional and unpredictable episodes of heartburn. Many antacids are available without a prescription. The different brands all rely on various combinations of 3 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. It can cause constipation. There have been rare cases of elevated levels of calcium in the blood (hypercalcemia) in people taking large doses of calcium carbonate for long periods of time. This condition can lead to kidney failure and is very dangerous. None of the other antacids has this potential 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 that leads to bone density loss, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Getting regular exercise and taking vitamin D and calcium supplements can reduce and even reverse bone density loss.
Although all antacids work equally well, it is generally believed that liquid antacids work faster and are more potent than tablets. 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 1 hour before, or 3 hours after taking the antacid. Long-term use of nearly any antacid increases the risk for kidney stones.
Proton Pump Inhibitors
Proton pump inhibitors suppress the production of stomach acid and work by inhibiting the molecule in the stomach glands that is responsible for acid secretion (the gastric acid pump). Recent guidelines indicate that PPIs should be the first drug treatment, because they are more effective than H2 blockers. Once symptoms are controlled, patients should receive the lowest effective dose of PPIs.
The standard PPI 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). In February 2009, the FDA approved the long-acting PPI dexlansoprazole (Kapidex), which is taken once a day.
Studies report significant heartburn relief in most patients taking PPIs. PPIs are effective for healing erosive esophagitis.
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 the acid reflux that typically occurs during strenuous exercise.
Patients with impaired esophageal muscle action are still likely to have acid breakthrough and reflux, especially at night. PPIs also may have little or no effect on regurgitation or asthma symptoms.
Currently, these drugs are recommended for patients with:
- Moderate symptoms that do not respond to H2 blockers
- Severe symptoms
- Respiratory complications
- Persistent nausea
- Esophageal injury
These medications have no effect on non-acid reflux, such as bile backup.
Adverse Effects. Proton-pump inhibitors may pose the following risks:
- Side effects are uncommon but may include headache, diarrhea, constipation, nausea, and itching.
- Long-term use of these drugs has been linked to an increased risk of hip, wrist, and spine fractures, possibly because stomach acid may be needed to absorb calcium from the diet. Patients who are on long-term PPI therapy may need to take a calcium supplement or the osteoporosis drugs, bisphosphonates to reduce their fracture risks.
- There is some evidence that PPIs increase the risk for community-acquired pneumonia, especially within the first 2 weeks of starting the medication. Researchers do not know the reason for this possible association. Newer research indicates that PPIs may also increase the risk for hospital-acquired pneumonia.
- Pregnant women and nursing mothers should discuss the use of proton pump inhibitors with their health care provider, although recent studies suggest that PPIs do not pose an increased risk of birth defects.
- PPIs may interact with certain drugs, including anti-seizure medications (such as phenytoin), anti-anxiety drugs (such as diazepam), and blood thinners (such as warfarin). Studies have found that taking PPIs with the blood thinner clopidogrel (Plavix) reduces the effectiveness of this blood thinner by nearly 50%.
- Long-term use of high-dose PPIs may produce vitamin B12 deficiencies, but more studies are needed to confirm whether this risk is significant.
- A new warning added in May 2012 cautions that using certain PPIs with methotrexate, a drug commonly used to treat certain cancers and autoimmune disorders, can lead to elevated levels of methotrexate in the blood, causing toxic side effects.
Some evidence suggests that acid reflux may contribute to the higher risk of cancer in Barrett's esophagus, but it is not yet confirmed whether acid blockers have any protective effects against cancer in these patients. Moreover, long-term use of proton pump inhibitors by people with H. pylori may reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach). This condition is a risk factor for stomach cancer. To compound concerns, long-term use of PPIs may mask symptoms of stomach cancer and thus delay diagnosis. To date, however, there have been no reports of an increased risk of stomach cancer with the long-term use of these drugs.
There had been concerns that the PPIs Prilosec and Nexium might lead to heart attacks or cardiovascular problems. However, after a careful review, the FDA found no evidence of increased cardiovascular risk.
H2 blockers interfere with acid production by blocking or antagonizing the actions of histamine, a chemical found in the body. Histamine encourages acid secretion in the stomach. H2 blockers are available over the counter and relieve symptoms in about half of GERD patients. It takes 30 to 90 minutes for them to work, but the benefits last for hours. People usually take the drugs at bedtime. Some people may need to take them twice a day.
H2 blockers inhibit acid secretion for 6 to 24 hours and are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes. In some studies, H2 blockers improved asthma symptoms in people with both asthma and GERD. However, they rarely provide complete symptom relief for chronic heartburn and dyspepsia, and they have done little to reduce physician office visits for GERD.
Brands. Four H2 blockers are available in the U.S.:
- Famotidine (Pepcid AC, Pepcid Oral). Famotidine 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 Food and Drug Administration (FDA) has issued a warning on its use in patients with kidney problems.
- Cimetidine (Tagamet, Tagamet HB). Cimetidine is the oldest H2 blocker. It has few side effects, although about 1% of people taking it will have 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 get better after the drug is stopped.
- Ranitidine (Zantac, Zantac 75, Zantac EFFERdose, Zantac injection, and Zantac Syrup). Ranitidine may provide better pain relief and heal ulcers more quickly than cimetidine in people younger than age 60, but there appears to be no difference in older patients. A common side effect associated with ranitidine is headache, occurring in about 3% of people who take it. Ranitidine interacts with very few drugs.
- Nizatidine Capsules (Axid AR, Axid Capsules, Nizatidine Capsules). Nizatidine is nearly free from side effects and drug interactions. A controlled-release form can help alleviate nighttime GERD symptoms.
- Over-the-counter antacids and H2 blockers. This combination may be the best approach for many people who get heartburn after eating. Both classes of drugs are effective in relieving GERD, but they have different timing. Antacids work within a few minutes but are short-acting, while H2 blockers take longer but have long-lasting benefits. Pepcid AC combined with an antacid (calcium carbonate and magnesium) is available as Pepcid Complete.
- Proton pump inhibitors and H2 blockers. Doctors sometimes recommend a nighttime dose of an H2 blocker for people who are taking PPIs twice a day. This is based on the belief that adding the H2 blocker will prevent a rise in acid reflux at night. Some experts recommended that patients who are on PPIs take an H2 blocker only to prevent breakthrough symptoms, such as before a heavy meal.
Long-Term Complications. In most cases, these medications have good safety profiles and few side effects. H2 blockers can interact with other drugs, although some less so than others. In all cases, the physician should be made aware of any other drugs a patient is taking. Anyone with kidney problems should use famotidine only under a doctor's direction. More research is needed into the effects of long-term use of these medications.
Concerns and Limitations. Some experts are concerned that the use of acid-blocking drugs in people with peptic ulcers may mask ulcer symptoms and increase the risk for serious complications.
These drugs do not protect against Barrett's esophagus. Also 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 ongoing.
FDA Precautions for Famotidine (Pepcid AC)
Famotidine is removed primarily by the kidney. This can pose a danger to people with kidney problems. The FDA and Health Canada are advising physicians to reduce the dose and increase the time between doses in patients with kidney failure. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances.
Caution is warranted in pregnant and nursing mothers as the effects are unknown.
Medications 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 the damaging effects of stomach acid and pepsin. Sucralfate may be helpful for maintenance therapy in people with mild-to-moderate GERD. Other than constipation, the drug has few side effects. Sucralfate interacts with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.
Prokinetic drugs help the stomach empty more quickly and strengthen the esophageal sphincter. These are considered second-line access drugs due to side effects. The currently available prokinetic is Metoclopramide (Reglan).