Drugs for GERD and Peptic Ulcer Disease

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is the most common GI condition encountered in the outpatient setting; it affects about 20% of people.

Diagnosis

Heartburn and regurgitation are the clas sic symptoms of GERD. Other symptoms include dyspepsia, chest pain, belching, and chronic cough. Endoscopy is recommended to evaluate alarm signs and symptoms such as dysphagia, GI bleeding, anemia, weight loss, and persistent vomiting. It is also recommended for patients at high risk for complications, including those whose symptoms do not respond adequately to acid suppression, and for those with multiple risk factors for Barrett’s esophagus.1,2

Lifestyle Modification

Lifestyle modifications, such as tobacco cessation, not lying down for at least 2 hours after eating or drinking, and elevating the head of the bed, should be a component of GERD management.3 Weight loss can improve symptoms in patients who are overweight or have recently gained weight.4,5 Routine avoidance of foods that have been associated with reflux, such as chocolate, caffeine, alcohol, and spicy foods, may be helpful, especially for nocturnal symptoms, but is generally not necessary.2

Choice Of Drugs

Drugs that suppress gastric acid are the standard treatment for GERD (see Table 2). The choice of drug depends on the frequency and severity of symptoms and the presence or absence of erosive esophagitis. Patients with infrequent or mild symptoms can be treated with an antacid or H2-receptor antagonist (H2RA) as needed. For patients whose symptoms are inadequately controlled on these agents and those with more frequent or severe symptoms or erosive esophagitis, a proton pump inhibitor (PPI) is recommended.

Key points: drugs for GERD and PUD

GERD

• Lifestyle modifications, such as not lying down for at least 2 hours after eating or drinking, elevating the head of the bed, and weight loss in patients who are overweight or have recently gained weight, should be a component of management.

• As-needed use of an antacid or H2-receptor antagonist (H2RA) is recommended for patients with infrequent or mild symptoms.

• Daily use of a proton pump inhibitor (PPI) is recommended for patients with more frequent or severe symptoms or erosive esophagitis.

• PPIs are more effective than H2RAs in relieving chronic heartburn and regurgitation and in healing erosive esophagitis.

• Addition of an H2RA as needed may be beneficial for patients who have symptoms despite twice-daily PPI treatment.

PUD

• Helicobacter pylori infection and use of nonsteroidal antiinflammatory drugs cause most cases of PUD.

• All patients with PUD should be tested for H. pylori.

• All patients with PUD should be treated with a PPI.

• If the underlying cause of PUD can be identified and eliminated, long-term PPI therapy may not be needed.

• Bismuth quadruple therapy is recommended for first-line treatment of H. pylori infection; rifabutin triple therapy is an alternative.

• Clarithromycin-based therapy should only be used when antimicrobial susceptibility tests have shown that H. pylori is susceptible to clarithromycin or in areas where H. pylori resistance to clarithromycin is known to be <15%.

• All patients should be tested for eradication of H. pylori ≥4 weeks after completion of therapy.

PPIs decrease GERD symptoms and heal esophagitis more effectively than H2RAs and are generally preferred.

Antacids

Antacids containing aluminum, magnesium, and/or calcium carbonate can provide rapid but transient relief of GERD symptoms.

Adverse Effects

Aluminum and calcium carbonate can cause constipation, and magnesium-based antacids can cause diarrhea.

Drug Interactions

Antacids can decrease the absorption of some other drugs (e.g., tetracyclines, levofloxacin) by altering gastric acidity or by binding to other drugs in the GI tract.

Pregnancy

Heartburn occurs commonly during pregnancy; it is largely attributed to a progesterone-mediated decrease in lower esophageal sphincter tone. Antacids can be tried for symptomatic relief, but products containing sodium bicarbonate (may cause metabolic alkalosis and fluid overload) or magnesium trisilicate (long-term use of high doses has been associated with nephrolithiasis, hypotonia, and respiratory distress in the fetus) should be avoided.6

H2-RECEPTOR ANTAGONISTS

H2RAs inhibit the action of histamine at H2 receptors on parietal cells, decreasing basal acid secretion and, to a much lesser extent, food-stimulated acid secretion. H2RAs have a faster onset of action than PPIs, but they are less effective in relieving chronic heartburn and regurgitation and in healing erosive esophagitis,2 and tolerance can develop quickly with continuous use.

Drugs In Practice

Drugs for GERD and Peptic Ulcer Disease

Adverse Effects

Severe adverse effects are uncommon with H2RAs. Hepatic enzyme elevations, hematologic toxicity, and CNS effects such as headache, lethargy, depression, and cognitive impairment have occurred. Cimetidine is weakly antiandrogenic; chronic use may rarely cause reversible impotence and gynecomastia. The FDA has withdrawn all prescription and OTC formulations of ranitidine because they may contain the carcinogen N-nitrosodimethylamine (NDMA).

Drug Omeprazole Equivalent

Pantoprazole 20 mg 4.5 mg

Lansoprazole 15 mg 13.5 mg

Omeprazole 20 mg 20 mg

Esomeprazole 20 mg 32 mg

Rabeprazole 20 mg 36 mg

Dexlansoprazole 30 mg2 50-60 mg

1. Based on the percentage time gastric pH is >4 over a 24-hour period with once-daily dosing. Adapted from DY Graham and A Tansel. Clin Gastroenterol Hepatol 2018; 16:800.

2. Compared to twice-daily use of other PPIs, once-daily dexlansoprazole is less "potent".