Acid-Related Diseases of the Upper Gastrointestinal Tract

in Understanding Pharmacology for Pharmacy Technicians
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KEY TERMS AND DEFINITIONS

Dyspepsia

(literally “bad digestion”) persistent or recurrent discomfort (indigestion) in the upper abdomen characterized by a range of symptoms, including bloating, belching, nausea, stomach fullness (inability to finish a normal meal), and heartburn. Dyspepsia may be related to certain foods, beverages, or medications and is a common symptom of acid-related diseases such as peptic ulcer disease.

Erosions

single or multiple superficial lesions (areas of tissue damage), which may occur in the esophagus, stomach, or duodenum and affect primarily the mucosal lining of the gastrointestinal (GI) tract.

Esophagitis

injury to the lining of the esophagus (esophageal mucosa) related to abnormal gastric acid exposure. Esophagitis ranges from mild to severe and symptoms do not correlate directly with the degree of severity.

Gastritis

inflammation of the lining of the stomach (gastric mucosa) without ulceration. Gastritis may be acute (eg, related to medications such as nonsteroidal anti-inflammatory drugs, alcohol) or chronic (eg, related to Helicobacter pylori infection).

Gastroesophageal reflux disease (GERD)

an acid-related disorder caused primarily by malfunctioning of the lower esophageal sphincter (valve) and altered esophageal motility leading to a backward flow (reflux) of stomach contents into the esophagus. Although gastroesophageal reflux is a normal process, it is a disease when symptoms such as heartburn or esophageal injury occur.

Heartburn

heartburn is the most common typical symptom of gastroesophageal reflux disease and is characterized by a burning discomfort arising from behind the breast bone and moving up toward the neck and throat. Heartburn may also be associated with certain foods, medications, and other acid-related diseases such as peptic ulcer disease.

Hiatal hernia

passage of the upper portion of the stomach from below the diaphragm into the chest secondary to weakening of the diaphragm muscles and abdominal pressure. Some patients are asymptomatic while others have symptoms related to gastroesophageal reflux disease.

Peptic ulcer disease (PUD)

peptic ulcers occur in the stomach (gastric ulcer) and duodenum (duodenal ulcer) and are considered a chronic disease. Ulcers are typically singular, confined, and in contrast to erosions, extend deeper into the submucosa and the muscle layer.

Stress-related mucosal bleeding (SRMB)

bleeding that is associated with stress-related damage to the lining of the GI tract (“stress ulcer”).

Stress-related mucosal damage (SRMD) or stress ulcer

the terms stress-related mucosal damage or stress ulcer are used to describe acute, superficial, scattered damage to the lining of the stomach of critically ill patients. Unlike chronic peptic ulcers, stress ulcers are painless, but both can lead to life-threatening bleeding.

Upper endoscopy

upper endoscopy, sometimes referred to as esophagogastroduodenoscopy (EGD), is a procedure performed by a physician and involves placing a tube with a light (called an endoscope) through the mouth into the esophagus, stomach, and duodenum. It has a small camera that allows the operator to view the upper gastrointestinal tract, which is magnified on an outside viewing monitor. The endoscope can be fitted with surgical instruments to allow the operator to perform procedures or obtain tissue samples for biopsy.

Upper gastrointestinal (UGI) bleeding

bleeding that occurs within the upper gastrointestinal tract, which may be related to medications, diseases, or other causes.

Upper gastrointestinal (UGI) radiography

a noninvasive radiologic procedure, which consists of the patient drinking a solution of barium sulfate. The barium coats the upper gastrointestinal tract and when exposed to x-rays, abnormalities (eg, ulcers, erosions, strictures) of the esophagus, stomach, or small intestine become visible.

Upper gastrointestinal (UGI) tract

the gastrointestinal tract is responsible for digestion, absorption, and elimination of food. It is divided into “upper” and “lower” sections beginning with the mouth and ending with the anus. The main structures of the upper gastrointestinal tract include the mouth, pharynx, esophagus, stomach (gastrum), and duodenum (first part of the small intestine). The lower GI tract (subject of Chapter 22) includes the remainder of the small intestine, along with the large intestine, rectum, and anus.

pH

a scale used to express a solution’s acidity or alkalinity. The scale ranges from 0 to 14, with lower values being more acidic and higher values being more basic. Seven is neutral.

Prodrug

a medication that is inactive until it is ingested and metabolized by the body into a pharmacologically active medication.

LEARNING OBJECTIVES

After completing this chapter, you should be able to

  1. Define the following:

    • Upper gastrointestinal tract.

    • Acidic pH.

    • Basic pH.

    • Dyspepsia.

    • Gastritis.

    • Gastric erosions.

    • Peptic ulcer disease.

    • Gastroesophageal reflux disease.

    • Heartburn.

    • Esophagitis.

    • Hiatal hernia.

    • Stress-related mucosal damage or stress ulcer.

  2. Describe the anatomy and normal physiology of the upper gastrointestinal tract and discuss the role of gastric acid in acid-related diseases.

  3. Identify the causes and risk factors for dyspepsia, peptic ulcer disease, gastroesophageal reflux disease, and upper gastrointestinal bleeding.

  4. List the most common signs, symptoms, and complications of dyspepsia, peptic ulcer disease, gastroesophageal reflux disease, and upper gastrointestinal bleeding.

  5. Describe the nonpharmacologic treatment of dyspepsia, peptic ulcer disease, and gastroesophageal reflux disease.

  6. Explain the pharmacotherapeutic effects of antacids, H2-receptor antagonists, proton pump inhibitors, sucralfate, bismuth salts, and misoprostol, and list their most common side effects and drug interactions.

  7. State the brand and generic names of the most widely used antacids, H2-receptor antagonists, proton pump inhibitors, sucralfate, bismuth salts, and misoprostol, along with their routes of administration, available dosage forms, and common dosages.

  8. Recognize common drug regimens for the treatment of dyspepsia, peptic ulcer disease, gastroesophageal reflux disease, and upper gastrointestinal bleeding.

Diseases of the upper gastrointestinal (UGI) tract include a wide range of disorders, the majority of which involve stomach (gastric) acid. Acid plays an important role in the development of symptoms and the damage that is caused to the lining (mucosa) of the UGI tract. The most common acid-related diseases include dyspepsia (indigestion), peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and stress-related mucosal damage (SRMD) or stress ulcers.1 A serious complication of PUD, GERD, and SRMD is upper gastrointestinal (UGI) bleeding, which may be life threatening. Stress-related mucosal bleeding (SRMB) is usually asymptomatic and is associated with a high mortality.

Acid-related diseases of the UGI tract in the United States are associated with decreased quality of life, time away from work, mortality, and a large financial burden on the healthcare system.1 Billions of dollars are spent annually on the diagnosis of acid-related diseases, hospitalizations, and medications used to treat these diseases. In some cases, patients can self-treat with oral over-the-counter (OTC) medications, while others require more complicated drug regimens and/or parenteral drug therapy.

Anatomy and Physiology of the Upper Gastrointestinal Tract

The UGI tract begins with the mouth and ends in the small intestine at the junction of the duodenum (first part of the small intestine) and jejunum (second part of the small intestine). The esophagus is a muscular tube, which lies behind the heart and connects the oropharynx to the stomach (Figure 20-1). It is lined with a thick layer of mucosa, which protects it from abrasive and irritating foods, beverages, and medications. The lower esophageal sphincter (LES) is a valve that guards against stomach contents refluxing back into the esophagus. When the sphincter relaxes, it permits food to empty into the stomach. Spontaneous motility (peristalsis) of the esophagus moves swallowed substances toward the stomach. Alterations in the esophageal mucosa, weakening of the LES, and decreased esophageal motility can contribute to GERD.

FIGURE 20-1.
FIGURE 20-1.

Diagram of the upper gastrointestinal tract.

The esophagus delivers substances such as food, beverages, and medications to the stomach. The stomach is a very acidic environment, which aids in the digestion or breakdown of ingested substances and delivers these substances to the small intestine. Figure 20-1 shows the relationship of the stomach to the esophagus and the duodenum. This figure also demonstrates the four regions of the stomach (cardia, fundus, body, and antrum). The stomach contains many specialized cells important to digestion, as well as to protection of the stomach lining. Parietal cells in the stomach secrete hydrochloric acid, which aids in digestion; G cells secrete gastrin, which regulates acid secretion; chief cells secrete pepsinogen, which is converted to pepsin and helps digest protein; and mast cells secrete histamine, which is one of the three major stimulants of gastric acid (along with gastrin and acetylcholine). Epithelial cells in the stomach lining secrete mucus and bicarbonate, which work together with prostaglandins to maintain blood flow to this protective mucosal layer. The protective stomach lining has a neutral pH of 7.0, which helps repel stomach acid and is the primary reason why the stomach lining is not damaged by hydrochloric acid (which in the fasting state has an acidic pH of approximately 2.0). Medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and bacteria such as Helicobacter pylori (H. pylori) can damage the protective mucosal barrier, allowing stomach acid to enter and resulting in ulcers and erosions.2

The small intestine consists of three sections: the duodenum, jejunum, and ileum. The duodenum extends from the pylorus to the jejunum where the UGI tract ends, and the lower GI tract begins. The pylorus (Figure 20-1) regulates the passage of partially digested foods and other substances into the duodenum and acts like a sphincter, which guards the opening between the stomach antrum and the duodenum. Peptic ulcers occur most frequently in the duodenal bulb (first part of the duodenum) as acidic gastric contents enter the duodenum from the stomach.

Pharmacologic Agents Used to Treat Acid-Related Diseases of the Upper Gastrointestinal Tract

Medications used to treat acid-related UGI tract diseases are divided into two groups: drugs that decrease stomach acidity and drugs that do not alter stomach acid.13 (Medication Table 20-1; Medication Tables are located at the end of the chapter). Antacids, the histamine2-receptor antagonists (H2RAs), and the proton pump inhibitors (PPIs) all decrease stomach acidity and thus increase stomach pH. Sucralfate, bismuth salts, misoprostol, and alginic acid all provide benefits without altering stomach acid. This section focuses on how these medications work, their effectiveness, use in special populations, the most important side effects, and major drug interactions. The therapeutic uses of each drug group are discussed in the sections on the treatment of the specific UGI diseases.

TABLE 20-1.

Proton Pump Inhibitor Alternative Dosage Formulations and Administration1,2a

Proton Pump Inhibitor

Administration Options

Omeprazole (oh ME pray zol)

Capsule opened and granules mixed in juice or sprinkled on soft food (applesauce) and given orally or by NG tube; oral suspension containing sodium bicarbonate in package for NG tube; extemporaneously compounded suspension in sodium bicarbonate can be compounded and administered by NG tube

Lansoprazole (lan SOE pra zole)

Capsule opened and granules sprinkled on soft food (applesauce); capsule granules mixed in juice and given orally or by NG tube; extemporaneously compounded suspension in sodium bicarbonate can be prepared and administered by NG tube; oral suspension in package for oral use (not NG); orally disintegrating tablet for oral or NG tube use

Pantoprazole (pan TOE pra zole)

Extemporaneously compounded suspension in sodium bicarbonate can be prepared and administered by NG tube; IV administration

Esomeprazole (es oh ME pray zol)

Capsule opened and granules sprinkled on soft food (applesauce); capsule granules mixed in water and given by NG tube; capsule granules mixed in juice and given orally or by NG tube; IV administration

Dexlansoprazole (dex lan SOE pra zole)

Capsule opened and granules sprinkled on soft food (applesauce)

IV = intravenous; NG = nasogastric.

a

Pronunciations have been adapted with permission from USP Dictionary of USAN and International Drug Names (USP Dictionary) © 2022.

Antacids

Antacids are oral dosage formulations of inorganic salts used to relieve infrequent mild to moderate UGI symptoms, such as indigestion, sour stomach, and heartburn.13 They are available OTC as tablets and liquid suspensions of a single salt (calcium, magnesium, aluminum, and sodium) or as a combination of several salts (eg, magnesium and aluminum). Antacid salts undergo a chemical reaction with acid in the stomach, which results in neutral salts and other neutralization products. By neutralizing some of the acid in the stomach, antacids can lead to a reduction in symptoms associated with acid-related UGI disorders. This requires neutralizing enough acid to raise the pH of the gastric environment to 4.0–5.0. All antacid neutralization reactions utilize similar chemical reactions, but depending on the initial salt, different neutralization products may result. Calcium carbonate is the most potent antacid, followed by sodium bicarbonate, and then the magnesium and aluminum salts, but differences in antacid potency can be adjusted for by increasing or decreasing the antacid dose. Antacids relieve symptoms quickly (within minutes), but the effect is short-lived and lasts only about 30 minutes when taken on an empty stomach.13

PRACTICE POINT

The duration of antacid effect may be prolonged by administering the antacid within 1 hour of a meal, thus increasing the duration of action for up to 3 hours. Symptom relief often depends on the antacid dose, with a larger dose resulting in greater neutralization of acid, higher pH, and greater relief of UGI symptoms. Some patients may require relatively large and frequent dosages to achieve symptomatic relief.

Specific antacid salts are associated with different adverse effects, which often guide the selection of an antacid. For instance, aluminum-containing antacids are associated with constipation, especially when taken in higher daily dosages. In contrast to aluminum salts, magnesium-containing antacids are associated with a dose-related diarrhea. At low doses, diarrhea may not occur, but as the daily dose is increased, diarrhea may become troublesome. Some antacids combine magnesium and aluminum salts to counter their different adverse effects, but diarrhea usually remains the predominant effect.

Prolonged use of calcium can result in high levels of calcium in the blood (hypercalcemia).1 Although calcium salts are often associated with constipation, most individuals who take calcium-containing antacids do not experience constipation or diarrhea. If calcium salts are taken in combination with sodium bicarbonate, milk-alkali syndrome may result. Milk-alkali syndrome is a disorder in which high calcium blood concentrations increase the pH of the blood above its normal level, causing alkalosis. This pH change can reduce kidney function.

Sodium can cause the body to retain fluid. For this reason, antacids containing sodium should not be selected for patients with fluid-affected disorders such as hypertension, heart failure, ascites, and chronic kidney disease. They also may disrupt the natural electrolyte balance if used for prolonged periods. On a practical level, the carbon dioxide that is produced in the neutralization reaction between sodium bicarbonate and stomach acid can cause belching, bloating, flatulence (excess gas in the stomach or intestine), and distension (stretching or enlarging of the abdomen).

All antacids have the potential to interfere with the body’s uptake of medications that depend on an acidic environment in the stomach for either dissolution or absorption.1 Drugs for which this is a particular concern include the antifungal medications ketoconazole and itraconazole (Sporanox®), iron, the antituberculosis medication isoniazid, and the anticonvulsant medication phenytoin (Dilantin®). By increasing stomach pH (decreasing acidity), antacids can also hasten the dissolution of enteric-coated medications such as aspirin. Finally, aluminum, calcium, and magnesium ions produced during acid neutralization can bind to certain medications, such as tetracycline (eg, doxycycline) and fluoroquinolone antibiotics (eg, ciprofloxacin), to decrease their absorption and ultimately their effectiveness.

PRACTICE POINT

It is possible to avoid most of the major drug interactions associated with antacids by dosing other medications 2 hours before or 4 hours after taking the antacid.

Alginic Acid and Simethicone

Alginic acid or simethicone are sometimes combined with antacids, but neither has any effect on stomach acid. Alginic acid forms a foam layer that floats on top of the stomach contents and is thought to provide added protection to the esophagus when the acidic stomach contents reflux into the esophagus. Simethicone is a defoaming agent that is often added to antacid preparations as an antiflatulent to help break up gas bubbles in the GI tract and aid in the elimination of intestinal gas.

H2-receptor Antagonists

The H2RAs block histamine at the H2-receptor on the parietal cells in the stomach, thus inhibiting acid secretion. There are currently three H2RAs available in the United States, cimetidine (Tagamet®), famotidine (Pepcid®), and nizatidine, available by prescription, as well as cimetidine and famotidine OTC products (Medication Table 20-1). The oral H2RAs are slower to act (30–45 minutes) than antacids but provide symptom relief over a longer period (about 6–8 hours). Famotidine is also available as a combination product with antacids, thus providing a quick onset of action as well as a longer duration of effect. Cimetidine and nizatidine are available as oral solutions that are stable almost indefinitely at room temperature and may be used until the expiration date assigned by the manufacturer. Famotidine is available as an oral suspension that is only stable for 30 days at room temperature (77°F) once reconstituted. Only cimetidine and famotidine are available for injection.

PRACTICE POINT

The famotidine and nizatidine liquid formulations contain sugar, whereas cimetidine formulations are flavored with sugar alcohols or artificial sweeteners. Formulations without added sugar may be more appropriate for patients with diabetes or other conditions requiring control of carbohydrate intake.

Famotidine is the most potent of these medications and cimetidine is the least potent. However, when the H2RAs are taken in recommended dosages to treat a specific indication, they provide similar relief of symptoms and rates of ulcer or esophageal healing. Because H2RA action is not tied to meals, they can be used to treat nocturnal (nighttime) or fasting symptoms.

PRACTICE POINT

The H2RAs may be used at the onset of symptoms or taken 30–45 minutes to 1 hour before an event to prevent anticipated symptoms associated with a meal or exercise.

Cimetidine and famotidine are eliminated from the body through metabolism in the liver and excretion by the kidney. Nizatidine is primarily eliminated by the kidneys. Dosage reductions for all three H2RAs are recommended in patients with reduced kidney function. In general, no adjustment is needed in patients with liver dysfunction.

The oral H2RAs are safe and well tolerated. Some of the more common adverse effects include diarrhea, constipation, mild dizziness, headache, drowsiness, lethargy, confusion, and rashes. A reversible fall in blood platelet numbers (thrombocytopenia) may occur with all H2RAs, but the incidence is low. The injectable formulations are generally safe as well. Cimetidine has been associated with antiandrogen effects, including enlargement of breast tissue (gynecomastia) and erectile dysfunction (impotence). Both effects are reversible with discontinuation of cimetidine. The risk of adverse effects is increased in the elderly, patients with reduced kidney function, and those taking high H2RA doses.

PRACTICE POINT

For many years, ranitidine was among the most widely used H2Ras. It was found, however, that ranitidine had detectable levels of N-nitrosodimethylamine (NDMA), a probable human carcinogen. NDMA may increase over time when the product is stored at higher than room temperatures, with the possibility that patients taking these products would consume unacceptable levels of NDMA. In April 2020 all prescription and over-the-counter ranitidine (Zantac®, other brands, and generics) were removed from the market by the U.S. Food and Drug Administration (FDA).

The H2RAs share the potential to alter the dissolution and absorption of drugs that are dependent on an acidic gastric environment. The list of affected medications is like that of the antacids (eg, the antifungals ketoconazole and itraconazole). Cimetidine inhibits the liver metabolism of many medications and can lead to clinically important drug interactions. This is the case for medications that have a narrow therapeutic window, such as warfarin and phenytoin. The concurrent use of agents that interact with cimetidine generally leads to the recommendation of another H2RA. Famotidine and nizatidine do not interact in a way that disrupts the metabolism of other drugs, so they are free from these drug interactions.13

PRACTICE POINT

Cimetidine has numerous interactions with other medications metabolized by the liver, so may not be a good choice for many patients. Practitioners usually reserve its use for patients with simple medication regimens that contain no interacting drugs. If potentially interacting medications are present in the patient’s medication profile, famotidine or nizatidine may be better choices.

One of the effects seen with the H2RAs is tachyphylaxis.4 Tachyphylaxis is a decreased response (or developing tolerance) to a drug after repeated doses in a relatively short period of time. Increasing the dose of the drug will not increase or restore response. This is a particular problem with intravenous (IV) dosage forms of H2RAs, and it has been observed with oral H2RAs as well. It may occur in a few days to several weeks or months.

PRACTICE POINT

Tachyphylaxis can be avoided by using H2RAs only when needed rather than giving them on a regularly scheduled basis (eg, every night, twice daily).4

Proton Pump Inhibitors

The PPIs are used for more frequent symptoms and more severe forms of acid-related diseases, as they are potent inhibitors of gastric acid secretion.1 They act by binding to H+/K+ ATPase, or the so-called proton pump, of the parietal cells in the stomach. This is involved in the last step in the secretion of gastric acid. PPIs achieve a sustained increase in stomach pH (reduced acidity) even after meals when acid secretion would otherwise tend to increase greatly. The PPIs are prodrugs that require an acidic environment in the parietal cells of the stomach where they are converted to their active form. Thus, the PPI must be either enteric-coated in the form of enteric-coated granules or tablets or mixed with sodium bicarbonate (Medication Table 20-1). This provides protection for the drug from stomach acid until it is absorbed into the vascular system and gets to the parietal cell, where it is activated. The PPIs work best when taken before a meal so that the proton pumps are actively secreting acid.

PRACTICE POINT

To achieve the best effect, it is recommended that patients take a PPI 30–60 minutes prior to eating. One common dosing recommendation is to take the medication in the morning 30 minutes before the first meal of the day. If a second dose is needed, it is best taken 30 minutes before the evening meal.

The PPIs currently available in the United States include omeprazole (Prilosec®), omeprazole/sodium bicarbonate (Zegerid®), lansoprazole (Prevacid®), rabeprazole (Aciphex®), pantoprazole (Protonix®), esomeprazole (Nexium®), and dexlansoprazole (Dexilant®)13 All are available by prescription in a variety of dosage forms (Table 20-1). Omeprazole (Prilosec OTC®), generic omeprazole, omeprazole/sodium bicarbonate (Zegerid OTC®), and lansoprazole (Prevacid 24 HR®) are available OTC. Only pantoprazole and esomeprazole are currently available for injection.

The acid-inhibiting effects of the PPIs usually last for about 20–24 hours, which exceeds their time in the body. All PPIs are similar when taken in recommended doses to relieve symptoms and heal peptic ulcers and esophagitis. Standard PPI dosages are superior to the H2RAs in relieving acid-related symptoms as well as ulcer and esophageal healing. Dosage reductions are recommended in patients with severe liver impairment but not required in patients with kidney failure.

The PPIs are well tolerated, and adverse effects associated with their short-term use are similar to those observed with the H2RAs. However, there are various safety warnings from the U.S. Food and Drug Administration (FDA) concerning the association of potential side effects with long-term use of PPIs. These side effects are increased risk of fractures, low magnesium (hypomagnesemia), pneumonia, Clostridium difficile-associated diarrhea, vitamin B12 deficiency, dementia, kidney failure, and systemic lupus erythematosus.511 It is important to note that the majority of published studies in this area are “observational,” meaning that they do not prove a cause and effect relationship between PPIs and these outcomes; instead they show an association with these issues to the extent that the FDA has provided safety warnings.

PRACTICE POINT

When patients use long-term PPI therapy, vitamin B12 levels may drop, likely due to a decreased release of the vitamin from foods processed through the less acidic environment of the stomach. This may be particularly important for the elderly, vegetarians, and people who drink significant amounts of alcohol, all of whom are at higher risk of vitamin B12 deficiency.

The PPIs, like the H2RAs, have been associated with a decreased dissolution and absorption of medications that depend on an acidic environment. All the PPIs are metabolized by the liver, but omeprazole and esomeprazole have the greatest potential to interact with medications metabolized by the liver, such as warfarin and phenytoin. However, drug interactions with omeprazole and esomeprazole are much less common than those observed with cimetidine. The concurrent use of omeprazole or esomeprazole with clopidogrel may decrease the antiplatelet effects of clopidogrel via a CYP-450 2C19 drug interaction. This is a category D drug interaction,12 which means practitioners should likely consider modifying therapy to avoid the drug interaction. Data suggests that pantoprazole, rabeprazole, or lansoprazole may not interact with clopidogrel to the same extent (category C).13 Clinical studies and platelet function data have inconsistently demonstrated clinically significant outcomes (eg, negative cardiac-related outcomes and mortality).1417 Therefore, the current recommendation is to avoid the drug interaction with clopidogrel and omeprazole or esomeprazole and to use an alternative PPI (eg, pantoprazole).

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Aciphex has been confused with Aricept and Accupril. Prilosec has been confused with Prozac. Protonix has been confused with protamine and Lotronex.

Sucralfate

Sucralfate (Carafate®) is an aluminum salt of a complex sugar known as a disaccharide (Medication Table 20-1). It is available only by prescription. Sucralfate heals peptic ulcers by forming a protective barrier that coats the lining of the stomach, thus permitting the ulcer to heal by protecting it from damage due to acid, pepsin, and bile salts. It may also stimulate prostaglandins in the stomach lining, which could lead to further protective effects. In contrast to the antacids, H2RAs, and PPIs, sucralfate does not neutralize or decrease gastric acid secretion.

PRACTICE POINT

Sucralfate tablets are large and can be difficult for patients to swallow. In these cases, the liquid suspension formulation is available. Many sucralfate tablets (brand and generics) are scored to enable patients to break them in half before taking them.

Constipation is the most common adverse effect seen with sucralfate and is related to the aluminum content of the drug. Aluminum also binds dietary phosphate and could lead to low serum phosphate levels. Sucralfate may be associated with the development of a bezoar (a mass of undigested material in the stomach). Because of the aluminum content, sucralfate should be avoided in patients with kidney failure. Sucralfate potentially interacts with many medications by binding to them in the esophagus and stomach, thereby decreasing their availability. Medications that can be affected include warfarin, fluoroquinolone antibiotics (eg, ciprofloxacin, levofloxacin), phenytoin, levothyroxine, and ketoconazole.

PRACTICE POINT

Taking sucralfate 2 or more hours after any potentially interacting medications will minimize the risk of a drug interaction.

Bismuth Salts

Bismuth salts are used for a wide range of GI complaints, although they do not neutralize or inhibit gastric acid secretion. The mechanisms by which they exert beneficial effects are not completely understood, but bismuth may have a topical (local) effect on the stomach lining, promoting protective responses. It is likely that bismuth also has some antimicrobial activity, particularly with regard to H. Pylori. The two bismuth salts with GI indications in the United States are bismuth subsalicylate (Pepto Bismol)—see Medication Table 20-1—and bismuth subcitrate (as a combination product for treatment of H. pylori).

ALERT!

Bismuth subsalicylate should be avoided in children recovering from or suffering with influenza. The risk of Reye’s syndrome, a potentially fatal condition, increases with exposure to salicylates.

ALERT!

The risk of bleeding and toxicity increases when the patient is taking bismuth subsalicylate concurrently with other salicylate medications. Bismuth subsalicylate should be avoided in patients with kidney failure as salicylates can accumulate and result in salicylate toxicity. Patients who are allergic to salicylates, such as aspirin, are likely to be allergic to bismuth subsalicylate.

PRACTICE POINT

Tablet and liquid formulations containing bismuth cause a blackening of the stool, but the tongue may also blacken with liquid formulations. Normal coloration returns after stopping the bismuth product. Black-colored stools (melena) may also be a sign of UGI bleeding.

Misoprostol

Misoprostol (Cytotec) acts to reduce the risk of ulcers or ulcer-related bleeding in patients taking aspirin or other NSAIDs. It is a man-made analog of a naturally occurring prostaglandin. In the body, misoprostol contributes to numerous effects that are protective to the stomach. It increases the production of mucus and bicarbonate, increases blood flow to the stomach lining, and decreases the rate of turnover of mucosal cells. Misoprostol also inhibits the secretion of stomach acid, but the effect is less than that seen with the H2RAs.

ALERT!

Misoprostol carries a warning that indicates that it can cause abortion, premature birth, or birth defects and therefore is contraindicated in pregnant women.

Misoprostol also has abortive properties and should not be used in women of childbearing age without adequate birth control. Women must have a negative serum pregnancy test and must be capable of effectively using contraception before receiving a prescription for misoprostol.

PRACTICE POINT

For women of childbearing potential, initiation of the misoprostol should only occur on the second or third day of the menstrual period.

Misoprostol’s major adverse effect is dose-dependent diarrhea (diarrhea increases as the dose increases) that occurs in about one-third of patients. Abdominal cramping is also troublesome. Less common adverse effects include nausea, flatulence, and headache.

Treatment of Acid-Related Diseases of the Upper Gastrointestinal Tract

This section briefly discusses the etiology, pathophysiology, risk factors, clinical presentation, and complications of dyspepsia, PUD, GERD, and UGI bleeding. Emphasis is placed on nonpharmacologic (nondrug) and pharmacologic treatment.

Dyspepsia

Dyspepsia is a very common complaint among patients, although patients with dyspepsia do not often seek medical attention. In many cases, occasional dyspepsia is brought on by ingesting spicy foods, acidic foods, or beverages (eg, tomato or orange juice), or eating too much or too fast. Avoidance of troublesome foods and beverages and improved eating habits usually lead to improvement or elimination of symptoms. Medications such as the NSAIDs (eg, aspirin, naproxen, ibuprofen, piroxicam) are the most important cause of drug-induced dyspepsia, but symptoms do not necessarily correlate with damage to the stomach lining (eg, erosions or ulcers). Other medications that may produce dyspepsia include theophylline, potassium supplements, and digoxin. In most cases, taking the medication with food, decreasing the dose, or stopping the drug reduces or eliminates symptoms.

In contrast, some patients complain of relapsing and long-lasting dyspeptic symptoms, which may or may not be associated with a known underlying cause. Occasionally, chronic dyspeptic symptoms occur in otherwise healthy individuals for whom diagnostic tests do not reveal a cause (eg, peptic ulcer) for their symptoms.18 Thus, nonulcer dyspepsia is used to describe this condition. However, in a subset of patients with chronic dyspepsia, diagnostic tests confirm the presence of PUD, GERD, or gastric malignancy.19

Because it is not always possible to determine the cause of dyspepsia, treatment is aimed at relieving the dyspeptic symptoms with an antacid, H2RA, or PPI. Food-induced symptoms can be avoided by eliminating troublesome foods and beverages or can be treated with an antacid or an OTC H2RA. Reducing the dose or discontinuing treatment usually relieves drug-induced dyspepsia, but antacids, H2RAs, or a PPI may be necessary if the drug dose cannot be reduced, or the drug cannot be discontinued. Dyspepsia, which is neither food- nor drug induced, is initially managed by physicians with a 1-month trial of either an H2RA or PPI. Treatment of PUD- or GERD-related dyspepsia is aimed at treating the underlying disease. A small number of patients, for whom the etiology cannot be determined, do not respond well to drug treatment.

Peptic Ulcer Disease

PUD is a chronic acid-related disease characterized by a distinct, confined, lesion (ulcer) found most often in the lining of the stomach (gastric ulcer) or the first part of the small intestine (duodenal ulcer) of ambulatory patients. Although peptic ulcers usually occur as a single lesion, multiple ulcers may be present. Stress ulcers (stress-related mucosa damage) in contrast, are multiple acute ulcers that occur primarily in critically ill hospitalized patients. About 10% of the U.S. population develops chronic PUD in their lifetime, with a similar prevalence in men and women. The natural course of PUD is characterized by ulcer recurrence and is influenced by H. pylori infection and NSAID use.

CASE STUDY

Eugene Gonzalez is a 48-year-old man who is seen by his doctor for complaints of burning stomach pain. Several weeks ago, he noticed the gradual onset of a localized burning pain in the upper stomach (epigastric region) that occurred daily, especially between meals and sometimes at night. Mr. Gonzalez indicates that taking antacids relieves the pain but that it often returns within 30 minutes. He denies any NSAID use and has a negative history for PUD.

CASE STUDY

Julia Rosenberg is a 66-year-old woman with a long history of PUD related to various NSAIDs she has taken to relieve symptoms of arthritis. She currently takes ibuprofen 400 mg twice daily, aspirin 81 mg daily, and atenolol 50 mg daily. Two months ago, she was hospitalized for a bleeding gastric ulcer. The ibuprofen was stopped temporarily, and a PPI was prescribed to heal the ulcer. Last week an EGD was performed, and ulcer healing was confirmed. Her physician tells her to reinstitute the ibuprofen 400 mg twice daily.

Etiology, Pathophysiology, Risk Factors

Most peptic ulcers in the stomach and duodenum are caused by H. pylori bacteria or NSAIDs and occur in the presence of normal gastric acid secretion. Zollinger-Ellison syndrome (ZES), a rare form of PUD, is caused by increased gastric acid secretion resulting in multiple, severe ulcers. Certain viral infections, chemotherapy, or radiation exposure may cause peptic ulcers, but these ulcers are uncommon.

Helicobacter pylori-Related Ulcers

H. pylori is a spiral-shaped, gram-negative bacterium that, when acquired, resides in the lining of the stomach or the duodenum. It attaches to the gastroduodenal lining and secretes toxic substances that cause chronic gastritis and peptic ulcers. Although 30% to 40% of the U.S. population is infected with the organism, only 20% of infected individuals develop ulcer symptoms.20 A small number (1%) of individuals with long-standing H. pylori-related gastritis will develop gastric cancer.20 The prevalence of H. pylori varies worldwide, but it is linked to poor socioeconomic conditions. Most individuals acquire H. pylori during childhood and likely co-infect other individuals living in the same household.

Nonsteroidal Anti-inflammatory Drug-Induced Ulcers

NSAIDs, including aspirin (acetylsalicylic acid; ASA), are available by prescription and OTC and rank among the most widely used class of medications in the United States, especially in individuals older than 65 years.19 There is overwhelming evidence linking NSAIDs with stomach erosions, stomach ulcers, and ulcer-related complications, as hospitalizations and mortality are increased in chronic NSAID users.19 NSAIDs act directly on the stomach lining to cause erosions, but ulcers (which are deeper than erosions) are related to the ability of the NSAID to systemically inhibit naturally occurring protective prostaglandins in the stomach lining (see the section on Anatomy and Physiology).

Prostaglandins in the body are produced by two pathways: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The COX-1 pathway promotes gastroduodenal protection while the COX-2 pathway mediates inflammation and pain. Thus, depletion of COX-1 by NSAIDs and ASA promotes the formation of ulcers and bleeding. Currently available NSAIDs inhibit both COX-1 and COX-2 to varying degrees and have both a beneficial anti-inflammatory action and a potentially toxic effect on the stomach lining. Rofecoxib (Vioxx) and valdecoxib (Bextra), previously available selective COX-2 inhibitors, were withdrawn from the U.S. market because of risk for cardiovascular events (eg, myocardial infarction and thrombotic stroke). Celecoxib (Celebrex) remains available but has a similar risk profile to nonselective COX inhibitors.

CASE?

Which of the peptic ulcer patients in the cases included here is more likely to be infected with H. pylori?

The risk of developing an NSAID-induced ulcer increases in individuals with a previous ulcer or ulcer complication, those older than 60 years of age, taking multiple or high dosages of NSAIDs, taking an NSAID plus ASA (even low cardioprotective ASA dosages such as 81 mg/day), and those taking concomitant corticosteroids, anticoagulants, or antiplatelet drugs.19

Clinical Presentation, Complications, and Diagnosis

Patients with PUD present with mild to severe epigastric pain (pain located in the upper abdomen) or an acute life-threatening UGI complication. The pain is often described as burning but may be a feeling of abdominal discomfort or fullness. Some individuals complain of dyspeptic symptoms, including bloating or belching, while others may have nocturnal pain that awakens them from sleep. In some patients, ulcer pain is precipitated by food while in others pain is relieved by food. The absence of epigastric pain does not necessarily imply that an ulcer is not present. Changes in the character of the pain or signs and symptoms such as nausea, vomiting, and weight loss may suggest ulcer-related complications such as UGI bleeding, perforation, or pyloric obstruction, which is related to the formation of scar tissue. Ulcer pain typically resolves with treatment, but recurrence of pain may suggest that the ulcer is not healed or that it recurred.

The diagnosis of PUD is usually based on the history and physical examination, visualization of the ulcer either by upper endoscopy or upper gastrointestinal (UGI) radiography, and tests to confirm H. pylori infection. Gastric acid secretory studies and fasting serum gastrin tests are reserved for patients with severe or complicated disease. Routine laboratory tests may not be very helpful, except in patients suspected of having ulcer-related complications. Patients with PUD have a high probability of H. pylori infection and should be tested so that appropriate treatment can be instituted.

H. pylori infection may be diagnosed by either endoscopic or nonendoscopic methods. Endoscopy not only permits direct visualization of the ulcer, but also enables tissue samples (biopsies) to be obtained and tested for the presence of H. pylori. The nonendoscopic tests, however, are less invasive and are inexpensive. The most widely available and most often used nonendoscopic tests include a blood test (serology) that detects antibodies to H. pylori and a breath test that uses radiolabeled urea (urea breath test, UBT) to detect active infection. Serology (blood testing) is most convenient as it can be performed in the physician’s office, but its diagnostic accuracy is less than that of the UBT. A stool antigen test is also available, but it is not widely used in the United States. Please note, both the H. pylori breath test and the stool antigen test can have false negatives in patients taking a PPI, bismuth, or antibiotics.

Goals of Therapy

The goals for treating PUD are to accelerate ulcer healing, prevent ulcer recurrence, and reduce ulcer-related complications with cost-effective and safe medications. Failure to cure the H. pylori infection may cause recurrent ulcers and the continuing risk of ulcer complications. Patients at risk of NSAID-induced ulcers should receive prophylactic cotherapy to reduce the risk of ulcer recurrence.

Nonpharmacologic (Nondrug) Therapy

There is no specific “ulcer diet” for patients with PUD. However, patients who are unable to tolerate certain spicy foods, citrus, caffeine, or alcohol-containing beverages should avoid these items. Patients should be encouraged to reduce stressful situations and stop cigarette smoking. Endoscopic or radiologic procedures may be required for diagnosis, and surgery may be necessary for ulcer-related complications such as UGI bleeding.

Pharmacotherapy

Helicobacter pylori-Related Ulcers

Successful eradication of H. pylori and ulcer healing require combining an antisecretory drug (eg, PPI) with multiple antibiotics with or without a bismuth salt. The effectiveness of clarithromycin triple therapy is limited in areas where H. pylori resistance exceeds 15%.2 Typically, three- and four-drug regimens are recommended, but only those regimens that have been adequately studied should be used for eradication and ulcer healing.20

CASE?

In-office serologic (blood) testing for H. pylori was positive and UGI radiology confirmed a small duodenal ulcer. Mr. Gonzalez’s physician prescribed a three-drug regimen to eradicate the infection and heal the ulcer. Why does he have to take three drugs to treat his peptic ulcer?

PRACTICE POINT

A PPI-based, three-drug regimen is usually the first-line treatment for H. pylori-positive patients with an active ulcer, a documented history of a prior ulcer, or a history of ulcer-related complications.

The recommended treatment for H. pylori infection (Table 20-2) in the United States consists of either bismuth quadruple therapy or concomitant (non-bismuth quadruple) therapy. It is recommended not to substitute for the primary antibiotics with either of these regimens. Bismuth-containing quadruple therapy (10 or 14 days) is a first-choice treatment as it results in satisfactory eradication rates, but nonadherence to the complicated drug regimen can make this challenging for patients if not previously used. This regimen consists of metronidazole, tetracycline, a PPI or H2RA, and bismuth subsalicylate. All medications except the PPI should be taken four times a day with meals and at bedtime.

TABLE 20-2.
Drug Regimens Used to Treat Helicobacter pylori-Related Peptic Ulcers 2,20,21a

Regimen/Medications

Frequency

Duration

Clarithromycin-Based Three-Drug Regimen

Clarithromycin 500 mg (kla RITH roe mye sin)

Twice daily

14 days

Amoxicillin 1 g (a mox i SIL in) or

Metronidazole 500 mg (me troe NI da zole)

Twice daily

2 or 3 times daily

14 days

PPI

Twice daily

14 days

Levofloxacin-Based Three-Drug Regimen

Levofloxacin 500 mg (lee voe FLOKS a sin)

Once daily

14 days

Amoxicillin 1 g (a mox i SIL in)

Twice daily

14 days

PPI

Twice daily

14 days

Levofloxacin-Based Sequential Therapy

Amoxicillin 1 g (a mox i SIL in)

Twice daily

Days 1–10

Levofloxacin 500 mg (lee voe FLOKS a sin)

Once daily

Days 6–10

Metronidazole 500 mg (me troe NI da zole)

Twice daily

Days 6–10

Load

Levofloxacin 250 mg (lee voe FLOKS a sin)

Once daily

7–10 days

PPI (eg, omeprazole [oh MEP ra zole])

Once daily

7–10 days

Nitazoxanide (nye ta ZOX a nide) 500 mg

Twice daily

7–10 days

Doxycycline 100 mg (doks i SYE kleen)

Once daily

7–10 days

Rifabutin-Based Three-Drug Regimen

Rifabutin 50 mg (rif a BYOO tin)

3 times daily

14 days

Amoxicillin 1 gram (a mox i SIL in)

3 times daily

14 days

PPI (omeprazole 40 mg)

3 times daily

14 days

High-Dose Dual Therapy

Amoxicillin 1 g 3 times daily or 750 mg 4 times daily (a mox i SIL in)

3-4 times daily

14 days

PPI

3-4 times daily

14 days

Clarithromycin-Based Sequential Therapy

Amoxicillin 1 g (a mox i SIL in)

Twice daily

Days 1–5

Clarithromycin 500 mg (kla RITH roe mye sin)

Twice daily

Days 6–10

Metronidazole 500 mg (me troe NI da zole)

Twice daily

Days 6–10

PPI

Twice daily

Days 1–10

Clarithromycin-Based Hybrid Therapy

Amoxicillin 1 g (a mox i SIL in)

Twice daily

Days 1–14

Clarithromycin 250-500 mg plus

Twice daily

Days 7–14

Metronidazole 250-500 mg (me troe NI da zole)

Twice daily

Days 7–14

PPI

Once or twice daily

14 days

Bismuth-Based Four-Drug Regimenb

Tetracycline 500 mg (tet ra SYE kleen)

Four times daily

10–14 days

Metronidazole 250-500 mg (me troe NI da zole)

Four times daily

10–14 days

Bismuth subsalicylate 525 mg (BIZ muth) (sub sa LIS i late)

Four times daily

10–14 days

PPI or H2RA

Once or twice daily

10–14 days

Non-Bismuth-Based Four-Drug Regimen

Clarithromycin 250-mg (kla RITH roe mye sin)

Twice daily

1–10 days

Amoxicillin 1 g (a mox i SIL in)

Twice daily

1–10 days

Metronidazole 250-500 mg (me troe NI da zole)

Twice daily

1–10 days

PPI

Once or twice daily

1–10 days

H2RA = histamine2-receptor antagonist; PPI = proton pump inhibitor.

a

Pronunciations have been adapted with permission from USP Dictionary of USAN and International Drug Names (USP Dictionary) © 2022.

b

Commercially available, prepackaged products include Helidac®, which contains bismuth subsalicylate, metronidazole, and tetracycline, and Pylera®, which contains bismuth subcitrate, metronidazole, and tetracycline.

The concomitant (non-bismuth quadruple) therapy (10 or 14 days) is another first-line treatment with good efficacy. This regimen consists of clarithromycin, amoxicillin, metronidazole, and a PPI. All medications should be taken twice daily. The PPI should be taken 30–60 minutes before a meal along with the three antibiotics, but it should not be continued beyond 2 weeks after stopping the antibiotics unless it is used to treat another disease (eg, GERD). A single daily PPI dose may be less effective than twice daily when used as part of a four-drug H. pylori treatment regimen.

A three-drug regimen containing a PPI, clarithromycin, and either amoxicillin or metronidazole for 7, 10, or 14 days has a higher incidence of resistance in the United Sates. This combination should only be used in areas where clarithromycin resistance is < 15%. Sequential treatment consisting of 5 days of a PPI plus amoxicillin, followed by 5 additional days of a PPI plus clarithromycin plus metronidazole has been shown to be more effective than the combination of a PPI plus both amoxicillin and clarithromycin for 7 days.20

Third-choice treatment options are used when other regimens are unsuccessful and typically include antibiotics from other classes, such as a fluoroquinolone (eg, levofloxacin), LOAD (levofloxacin, omeprazole or other PPI, nitazoxanide, [brand name Alinia®], and doxycycline) therapy, or hybrid therapy (Table 20-2).

PRACTICE POINT

Substitution of one PPI for another in the regimens described is acceptable and does not improve or worsen H. pylori eradication. An H2RA should not be substituted for a PPI in a three-drug regimen, as the H2RA may not be as effective as the PPI. However, an H2RA may be used as part of the bismuth-based, four-drug regimen. Comparable eradication rates occur when bismuth subcitrate is used in place of bismuth subsalicylate.

The antibiotics that have been most studied as part of an initial H. pylori regimen are clarithromycin, amoxicillin, metronidazole, tinidazole, nitazoxanide, rifabutin, doxycycline, and tetracycline.2,20 Substitution of clarithromycin for tetracycline is acceptable, but adverse effects are increased. Other antibiotic substitutions may be less effective. Specifically, ampicillin should not be substituted for amoxicillin, doxycycline should not be substituted for tetracycline, and azithromycin or erythromycin should not be substituted for clarithromycin.

ALERT!

Amoxicillin should not be prescribed for penicillin-allergic patients, and metronidazole should be avoided if ethanol (as part of alcoholic beverages or even as a component of some liquid medications) is consumed because metronidazole reacts with ethanol to cause numerous adverse effects (this is called a disulfiram-like reaction).

Adverse effects vary with different drug regimens. Metronidazole increases the frequency of adverse effects when the dose is greater than 1 g/day. Taste disturbances (metallic taste) may occur with metronidazole and clarithromycin. Antibiotic-associated diarrhea may also occur.

Nonsteroidal Anti-inflammatory Drug-Induced Ulcers

Drugs used to treat acid-related diseases are also used to heal an active ulcer caused by NSAIDs and to reduce the risk of (prevent) an NSAID-induced ulcer and ulcer-related UGI complications (eg, bleeding). When the patient has an active ulcer, the NSAID should be discontinued. Consider switching to acetaminophen, tramadol, or a short-acting narcotic. Most ulcers heal with a standard dosage regimen of an H2RA, PPI, or sucralfate (Medication Table 20-1) if the NSAID is stopped. Treatment with a PPI is preferred because it provides a more rapid rate of symptom relief and ulcer healing (4 weeks) than an H2RA or sucralfate (6–8 weeks).1,2 The PPIs are interchangeable for this indication as long as they are used in their recommended oral dosages (Medication Table 20-1).

If NSAID therapy must be continued despite ulceration, consideration should be given to using a potentially less ulcerogenic NSAID or reducing the NSAID daily dose. Ulcer healing can occur if the NSAID is continued, but it will take longer (12 weeks) and requires the use of a potent acid suppressant.1,2 Thus, the PPIs are also the drugs of choice when the NSAID cannot be discontinued.1,19 If H. pylori is present, the patient should be treated with an eradication regimen that contains a PPI.1,2

PRACTICE POINT

The PPIs are the drugs of choice for healing NSAID-induced ulcers and for reducing the risk of NSAID-induced ulcers.

Various management strategies have been used to reduce the risk of NSAID-induced ulcers and UGI bleeding in high-risk patients. The use of enteric-coated preparations such as aspirin reduces the irritating effects on the stomach but does not stop ulcers from forming. Taking an NSAID with food or milk may reduce NSAID-related dyspepsia but does not prevent ulcers. Antacids and sucralfate should not be used for preventive purposes, as there is insufficient evidence to support their use for this indication. Taking an H2RA along with the NSAID (cotherapy) works to reduce NSAID dyspepsia, but it is not effective in reducing the risk of stomach ulcers when given in standard prescription dosages (eg, famotidine 40 mg/day).2 It is possible that higher H2RA dosages (eg, famotidine 40 mg twice daily) may reduce the risk of NSAID-induced stomach ulcers, but it most likely does not reduce the risk of UGI bleeding. Misoprostol (Medication Table 20-1) cotherapy reduces the risk of NSAID-induced stomach ulcers and ulcer-related complications such as UGI bleeding. However, multiple daily dosing, abdominal cramping, dose-related diarrhea, and abortive effects limit adherence as well as its effectiveness.

CASE?

Is Ms. Rosenberg a candidate for prophylactic cotherapy once the NSAID has been reinstituted after the ulcer was healed? If so, what is the preferred agent?

The PPIs are as effective as misoprostol for reducing the risk of NSAID ulcers and have the added advantage of fewer troublesome adverse effects. The PPIs are superior to the H2RAs when used for this indication. All PPIs, when used in recommended oral dosages, reduce the risk of NSAID-induced stomach ulcers and ulcer-related UGI complications. All the PPIs have a similar efficacy and safety profile and are interchangeable.

Selective COX-2 inhibitors such as rofecoxib and valdecoxib are associated with a lower risk of GI toxicity, but they are no longer available in the United States because of their association with serious cardiovascular thrombotic effects. Celecoxib is a currently available COX-2 inhibitor; however, it bears the same FDA labeling in regard to GI and cardiovascular risks as all other available NSAIDs. Data shows that celecoxib has a lower relative risk of GI and cardiovascular events compared to nonselective NSAIDS and therefore may be used more in practice. Gastroprotective benefits are reduced in patients using aspirin with celecoxib. Thus, it is recommended to use PPI cotherapy with celecoxib if low-dose aspirin is being used. Finally, increased cardiovascular risk and the acute side effects possible with NSAIDs (eg, fluid retention, hypertension, renal toxicity) require that the lowest effective dose of celecoxib be used as it is at least as beneficial as a nonselective NSAID plus a PPI.

Gastroesophageal Reflux Disease

CASE STUDY

Tara Dryden is a 44-year-old woman who saw her doctor 2 months ago complaining of heartburn and a frequent acid taste in the back of her throat, which is occurring almost daily. The doctor diagnosed her with GERD and started her on famotidine.

GERD is a common acid-related disease caused by the reflux (backward movement) of acid and other stomach contents into the esophagus, which results in symptoms such as heartburn and may cause damage to the esophageal lining. The prevalence of GERD (including symptoms of heartburn and esophageal damage) in the Western world is about 10%–20%.1 Patients with GERD may have a decreased quality of life and are at risk for serious complications, which includes esophageal cancer.1

Etiology, Pathophysiology, Risk Factors

The most common cause of gastroesophageal reflux is temporary relaxation of the LES (Figure 20-1). The LES remains contracted (at high pressure) unless food or liquid is being swallowed. When relaxation of the LES occurs, gastric contents, including acid, bile, and other stomach enzymes, enter the esophagus. This is a very common occurrence (even in healthy individuals), and although these acidic contents encounter the esophageal lining, most individuals do not develop symptoms or esophageal damage. This is because waves of esophageal contractions and relaxations force contents back into the stomach, while swallowing saliva (containing bicarbonate) acts to reduce the acidity of the stomach contents.1 In patients who develop GERD, transient relaxations of the LES become more common and the contact time of the acid and esophageal lining is increased, which leads to mucosal damage and symptoms. Other risk factors include diet and lifestyle, medications, and medical conditions, which either reduce LES pressure or the ability of the LES to function properly. Obesity, bending over, and wearing tight-fitting clothing increases intra-abdominal pressure and places more strain on the LES. Some foods (eg, high-fat meals, chocolate, and mint) can reduce the LES pressure, while acidic foods and beverages (eg, tomatoes, citrus) can irritate the esophageal lining. Medications, including the calcium channel blockers, benzodiazepines, narcotic analgesics, beta-adrenergic agonists, and nitrates, decrease LES pressure. The most common medical conditions associated with GERD are hiatal hernia and gastroparesis, a partial paralysis of the stomach, which can occur in patients with diabetes.

Clinical Presentation, Complications, and Diagnosis

The most common typical symptoms of GERD are heartburn and acid regurgitation, a sour taste in the back of the throat caused by refluxed stomach acid. Other symptoms include belching, hiccups, nausea, vomiting, and feeling full earlier during a meal (early satiety). More worrisome (alarm) symptoms include difficult or painful swallowing, unexpected weight loss, vomiting, and blood in vomit or stool.3

CASE?

What are the most serious consequences that could result from Mrs. Dryden’s GERD?

Complications associated with GERD include erosive esophagitis, stricture formation (narrowing of the esophagus, which can cause difficulty in swallowing), Barrett’s esophagus, and adenocarcinoma (a type of cancer) of the esophagus. Erosive esophagitis results from damage of the lining (mucosa) of the esophagus caused by exposure to stomach acid or other irritating substances and varies in severity, from mild inflammation and redness to ulceration and bleeding. Barrett’s esophagus, a precancerous condition, occurs in about 10% of patients who undergo endoscopy for GERD and results from continuous acid exposure and esophageal injury in patients with long-standing GERD. Barrett’s esophagus is associated with an increased risk of adenocarcinoma of the esophagus.22

Some patients have symptoms of GERD that do not appear to involve the esophagus. These manifestations include noncardiac chest pain, nonallergic or nonseasonal asthma, chronic hoarseness or laryngitis, and even dental erosions. These may be the only symptoms the patient describes to the doctor. Specialized testing and evaluation are necessary to determine if GERD is the cause of these symptoms.

There are numerous methods available to establish a diagnosis of GERD and determine if complicated disease is present. Upper endoscopy allows the physician to visualize and determine the extent of the damage to the esophageal lining, identify hiatal hernia or strictures, and screen for Barrett’s esophagus or cancer. Upper GI radiography or barium esophagram (also sometimes called a barium swallow test) permits identification of erosions, ulcerations, strictures, and hiatal hernia. Continuous 24-hour intraesophageal pH monitoring enables the physician to determine when and at what times the pH in the esophagus is low; this demonstrates the reflux of acid into the esophagus. The most common test to evaluate GERD is an empiric trial (test) of a PPI.23 Patients who respond to a short trial of PPI once or twice daily receive a tentative diagnosis of GERD and are managed without costly workups. However, a positive response does not differentiate between GERD and other acid-related diseases such as PUD.

PRACTICE POINT

Patients should keep a diary to record their GERD symptoms and attempt to relate them to lifestyle or diet. This diary should be brought to their healthcare provider for discussion and review to determine the best course of action in eliminating the patient’s symptoms.

Goals of Therapy

The goals for treating GERD are to relieve symptoms, promote esophageal healing, prevent symptomatic relapse and complications, and provide cost-effective and safe drug therapy. Remember that GERD is a chronic disease with the potential for serious complications like those of diabetes or hypertension and may require long-term maintenance therapy.

Nonpharmacologic (Nondrug) Therapy

The first step in managing GERD is to discuss lifestyle and dietary changes, which may benefit the patient’s symptoms.3 Lifestyle recommendations include the elevation of the head of the bed by 6–8 inches using wooden blocks under the headboard, not eating within 3 hours of bedtime, weight loss, smoking cessation, and avoidance of alcohol. Specific dietary recommendations include avoiding those foods known to worsen GERD symptoms (eg, foods with high fat content, spicy foods, caffeinated beverages, and citrus- or tomato-containing foods). While these modifications may have some benefit in reducing GERD symptoms, they are not likely to completely cure most patients. Nonetheless, patients should be made aware of these recommendations. Some OTC and prescription medications can cause or worsen GERD symptoms and should be avoided or changed to medications without such effects when possible.

CASE?

Why do you think Mrs. Dryden’s doctor changed her medication for GERD from famotidine to omeprazole?

Pharmacotherapy

Mild Disease

Most patients with mild or infrequent heartburn can be managed with OTC medications, sometimes with advice from a pharmacist. Patients must first be evaluated to determine if they are a candidate for self-treatment. Exclusions for self-treatment include evidence of alarm symptoms, and nonesophageal or severe symptoms as described in the Clinical Presentation, Complications, and Diagnosis section under the Gastroesophageal Reflux Disease heading.3 Those who present with these symptoms should be referred to their physician for further evaluation. Antacids and H2RAs remain the OTC drugs of choice for managing mild and infrequent symptoms. Antacids (Medication Table 20-1) provide the fastest relief of symptoms and can be dosed every 1–2 hours as long as the maximum dosage is not exceeded and adverse effects are not problematic. For patients who do not respond adequately to antacids or who require substantial doses to control symptoms, an OTC H2RA or PPI may be considered.

The OTC H2RAs are indicated for patients with infrequent mild to moderate heartburn. They have a longer duration of action than antacids but can take up to an hour for the onset of symptom relief. They can be taken before meals or at bedtime before most heartburn occurs. The OTC H2RAs may be taken at either one half or full prescription dose (Medication Table 20-1). They are all similar in potency when used in recommended dosages. Patients should not use more than two doses a day or continue treatment for more than 2 weeks at a time.

Another option is the OTC PPIs omeprazole and lansoprazole, but they should be reserved for patients with frequent heartburn (2 or more days per week). Although the onset of symptom relief (2–3 hours) is slower than with the H2RAs, they provide superior relief of symptoms throughout the day and night when compared to the H2RAs. Patients should be instructed to take OTC PPIs 30 minutes prior to breakfast on an empty stomach to maximize its acid-inhibiting action.

PRACTICE POINT

OTC omeprazole and OTC lansoprazole should be reserved for patients with frequent heartburn and should be taken daily for 2 weeks. A second course of therapy should be separated by at least 4 months unless directed by a physician as the need for more frequent use might indicate more severe disease.3

ALERT!

Patients who continue to require OTC medications beyond 2 weeks, do not achieve adequate relief of symptoms, or develop symptoms suggesting more complicated disease should be referred to a primary care provider for further evaluation.

Moderate to Severe Disease

Patients with moderate to severe GERD symptoms will most likely require a PPI, and 75%–85% of patients will obtain acceptable relief with this option.1 Studies have also suggested that patients may not gain any greater heartburn relief by increasing to maximum doses. Healing of esophageal erosions is possible after 8–12 weeks of continuous H2RA therapy, but it requires the highest doses and only approximately 50% of patients will achieve complete healing.1 One of the factors that may be responsible for these findings is that tolerance (the body becomes less responsive to the drug’s effects) develops with continued therapy.

CASE?

Over the next few months after starting famotidine, Mrs. Dryden described partial relief of her symptoms but was still having some heartburn after meals. What might be the next type of therapy her doctor would prescribe? Would it be a replacement for the famotidine or an addition to it?

The PPIs are the drugs of choice for most patients because of their ability to reduce stomach acid for a prolonged period. Numerous studies have demonstrated that the PPIs are superior to the H2RAs in relief of symptoms and healing of erosive esophagitis.22 The majority of patients will have an acceptable response to once daily dosing; however, those with severe or nocturnal symptoms and those presenting with severe esophagitis may require twice daily dosing. There is little data to suggest that one PPI is better than another when used in equivalent doses, but newer options may be more beneficial in healing patients with very severe disease when dosed once a day.1

Some patients may have nocturnal (nighttime) symptoms despite once or twice daily PPI therapy and may require the addition of an H2RA at bedtime. There is no conclusive evidence for this practice as tolerance to the H2RA may develop with continued use.4,23 One way to avoid potential tolerance is for the patient to take the H2RA only at bedtime if nighttime symptoms are anticipated (eg, after eating foods known to cause late-night symptoms or eating within 3 hours of bedtime).

CASE?

How long should Mrs. Dryden plan on continuing medication treatment for her GERD?

Long-term Maintenance Therapy

GERD is a chronic disease and in many cases patients will require long-term or even lifelong therapy. Depending on the severity of the disease, up to 80% of patients will have a recurrence of symptoms or esophagitis within 6 months of discontinuing therapy.1 This may place patients at an increased risk of developing complications. For this reason, long-term maintenance therapy is often recommended. Patients with moderate to severe symptoms or esophagitis who have received 8–12 weeks of a PPI and are symptom-free, should be continued on PPI maintenance therapy to reduce the risk of symptomatic recurrence. Patients with mild disease who are well controlled on a PPI may be “stepped down” to an H2RA to determine if they can be maintained on a less potent agent. However, most studies indicate that only about 50% of these patients remain asymptomatic on an H2RA, while the others must be restarted on a PPI.1 Thus, patients should remain on the least potent medication that prevents symptom recurrence.

Upper Gastrointestinal Bleeding: A Very Serious Complication

CASE STUDY

Jose Vasquez is a 69-year-old man who comes to the emergency department complaining of black tarry stools during his last bowel movement. He is quite pale and during his initial examination is found to have a low blood pressure and elevated heart rate. After further questioning, he states that he has taken large amounts of ibuprofen over the last few months for his back pain.

UGI bleeding occurs in approximately 300,000 patients per year in the United States. These patients are at high risk of dying from this serious condition (approximately 10%) and despite advances in medical and drug therapy, this death rate has not changed for more than 40 years. Patients at highest risk for mortality (death) include older patients (> 60 years of age) and patients who already have additional serious chronic diseases, such as cardiac, liver, or kidney disease. Although most patients with UGI bleeding will survive, patients who rebleed after therapy to stop the bleeding or who develop initial bleeding while they are in the hospital have a high mortality rate (approximately 40%–50%).1

Etiology, Pathophysiology, Risk Factors

PUD and SRMD (stress-related mucosal damage, or stress ulcer) are the most common reasons for UGI bleeding. Other causes include variceal bleeding (bleeding within the esophagus associated with liver disease), erosive esophagitis, Mallory Weiss tears (tearing of the tissue between the stomach and esophagus, which is usually associated with coughing or vomiting), and cancer. The most common causes of PUD bleeding are NSAID-induced ulcers and H. pylori-related ulcers.1

Patients admitted into the intensive care units (ICUs) of hospitals are at an especially high risk of bleeding from SRMD, which is associated with critical illness. Bleeding from these lesions can begin very quickly (within 24 hours of admission). Although stomach acid is central to the development of SRMD, numerous other factors are involved. Normally, prostaglandins within the stomach lining provide a protective barrier against stomach acid (see the section on Anatomy and Physiology). Stress associated with critical illness depletes the protective prostaglandins, resulting in an imbalance between the protective factors in the stomach lining and stomach acid, which causes the SRMD. Risk factors associated with SRMD and bleeding include pulmonary failure, which requires mechanical ventilation, and disruption in blood clotting (referred to as coagulopathy). Severe sepsis syndrome (the body’s overactive response to infection) is sometimes considered a risk factor as well. Other risk factors include organ failure, transplants, burns, head injuries, and use of blood thinners or corticosteroids.1

Peptic Ulcer Bleeding

Clinical Presentation, Complications, and Clinical Course

Patients with bleeding peptic ulcers usually present with coffee ground emesis (coagulated blood in vomit), hematochezia (red or maroon blood in stools—typically from a massive GI bleed), or melena (dark tarry stools). 21` Patients with these signs or symptoms represent a medical emergency that must be dealt with immediately as these patients can quickly go into hypovolemic shock (cardiovascular instability caused by a substantial loss in blood volume). The patient needs to be rapidly stabilized with volume resuscitation by giving large amounts of intravenous (IV) fluids (e.g. normal saline) and may potentially require blood products. 24

The patient will usually have a nasogastric tube inserted and be placed on suction to determine if the GI tract is the source of the bleed, to remove gastric contents (lavage), and to determine if the patient is continuing to bleed. Most patients will have an endoscopy performed within 24 hours of admission to the hospital to determine the site and significance of the bleeding.24 This will allow the physician to test for H. pylori infection and perform interventions to attempt to stop the bleeding. Most identified peptic ulcers have a low risk of rebleeding with appropriate therapy. However, some ulcers are so deep that a blood vessel is visible, or the ulcer continues to bleed. These ulcers are associated with a high risk of rebleeding and mortality. Patients with UGI bleeding require close monitoring and medications aimed at reducing stomach acid to allow for more rapid ulcer healing.

Goals of Therapy

The primary goals of therapy when managing PUD bleeding is to quickly stabilize the patient with IV fluids and possibly blood products and to restore hemostasis (stop bleeding and restore blood volume) through endoscopic and pharmacologic intervention. For patients with serious GI bleeding, this usually means giving an agent that increases stomach pH to > 6 for a prolonged period.1 Finally, attempts will be made to prevent further complications, such as rebleeding or the development of new ulcers. This is accomplished through long-term pharmacotherapy directed at reducing stomach acid to allow for complete ulcer healing (see the discussion earlier of NSAID-induced ulcers). For patients with H. pylori infection, treatment is aimed at eradicating the infection (see the section on H. pylori-related ulcers).

CASE?

What are the goals of therapy if Mr. Vasquez’s UGI bleed was related to a peptic ulcer?

Pharmacotherapy

Drug therapy directed toward reducing stomach acid is the preferred way to improve hemostasis and prevent rebleeding in patients with peptic ulcer bleeding. Although once a mainstay in managing patients with UGI bleeding, the H2RAs have fallen out of favor because of their inability to maintain a stomach pH of > 6 (near neutral) over a 24-hour period and because tolerance to their effects may develop. The PPIs are the drugs of choice for prevention of PUD rebleeding after successful endoscopy as they reduce rates of rebleeding, the need for surgery, and additional endoscopic procedures.

CASE?

The ICU physician has ordered IV pantoprazole for Mr. Vasquez, even though he is taking other medications by mouth. When can the hospital pharmacy expect the IV to be discontinued and changed to an oral PPI?

The most appropriate PPI dose and method of administration remains uncertain. Patients at low risk of bleeding are usually managed with an oral PPI and discharged from the hospital after endoscopic intervention. Patients at high risk of rebleeding are usually started on IV PPI therapy consisting of a rapid IV loading dose (80 mg of pantoprazole or esomeprazole) and a continuous IV infusion (8 mg/hr of esomeprazole or pantoprazole). The IV infusion should be continued for up to 72 hours (as the patient is at highest risk of rebleeding during this time), after which the patient should be converted to oral PPI therapy, which is continued for at least 8–12 weeks.21

Stress-Related Mucosal Bleeding

Clinical Presentation, Complications, and Clinical Course

Patients with SRMB may present with small amounts of blood in the stomach contents when a nasogastric tube is being used for feedings or medication administration, or small amounts of blood may be identified in stool samples that are tested for its presence. Others may present with large amounts of blood or coffee ground–like material in the patient’s vomit, in nasogastric aspirates, or with bloody diarrhea.1 This type of bleeding, along with a drop in blood pressure, increase in heart rate, or drop in laboratory blood volume measurements, is considered life-threatening bleeding and must be evaluated immediately.

The stomach ulcerations associated with SRMD differ from chronic peptic ulcers in that they are numerous, do not extend as deeply into the stomach lining, develop very early in the critically ill hospitalized patient, and progress to a very serious condition, which can lead to increased hospital lengths of stay or even death. One major drawback in managing SRMB is that, due to their extensive distribution throughout the stomach, they usually cannot be managed with endoscopic therapy and must be treated with medications.1 Thus, the most important consideration in SRMB is prevention of the bleeding.

Goals of Therapy

The primary goal of therapy associated with SRMD is prevention of bleeding. Patients must be assessed for risk and started on optimal prophylactic therapy when warranted. Patients with one of the three primary indications (intubation, blood clotting disruption, or sepsis) or who have two or more of the other risk factors discussed should have SRMB prophylaxis started immediately, unless contraindicated.

Pharmacotherapy

Numerous options exist for the prevention of SRMB, with the majority directed at reducing stomach acid. The use of liquid antacids is superior to placebo, but their administration is cumbersome because of the need for frequent administration (eg, every 1–2 hours) and the need to provide continuous stomach acid pH monitoring. Liquid antacids are also associated with a number of adverse events (eg, electrolyte abnormalities, constipation, and diarrhea).2

Sucralfate is another option with proven benefit, but up to four doses per day are needed, and the fact that it does not increase stomach pH may limit its usefulness. Sucralfate only acts as a barrier between the acidic environment and the stomach lining. It also inhibits the absorption of other medications, may clog nasogastric tubes, cause constipation, and may cause aluminum toxicity in renal failure.2

The H2RAs have been widely used for SRMB prophylaxis. Benefits include the fact they can be given IV as a continuous or intermittent infusion and have demonstrated superiority in reducing SRMB when compared to antacids and placebo. All the H2RAs require a dosage reduction in renal dysfunction (a common finding in critically ill patients).1 The H2RAs also have the potential to cause pneumonia in hospitalized patients since acid is protective against microbes within the stomach. When stomach pH is increased, these pathogens might survive, and if stomach contents are aspirated into the lungs this could lead to the development of pneumonia.1 The PPIs are the preferred option for prevention of SRMB because of their profound effect on stomach acid. Although there is very little evidence to indicate that PPIs are superior to H2RAs, more potent acid suppression appears to provide improved efficacy, but the potential for pneumonia remains.1

PRACTICE POINT

Some IV preparations may be given by slow IV push while others require that they be diluted in an appropriate volume of fluid for IV administration. Always refer to the package insert for appropriate administration options and corresponding labeling.

As noted earlier, there are a number of PPI administration options available (Table 20-1), which allow for use in different circumstances encountered in the critical care setting (eg, patients who cannot take anything by mouth, have nasogastric tubes, or have difficulty swallowing). Adverse events associated with PPI prophylaxis are rare, but there may be an increased risk of hospital-acquired pneumonia and increased GI infections due to bacterial overgrowth.1,2

Regardless of which SRMB prophylaxis regimen is selected, the patient must be continually monitored for signs and symptoms of bleeding (presence of blood in nasogastric aspirate, vomit, or stool). Finally, it is important to ensure that medications used to prevent SRMB are discontinued when the patient is no longer at risk or has been transferred from the critical care setting, as many are continued and eventually the patient is discharged on these medications without an appropriate indication.

SUMMARY

Acid-related diseases of the upper gastrointestinal (UGI) tract involve stomach acid and include dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and stress-related mucosal damage (SRMD). The proper selection and use of antacids, H2RAs, proton pump inhibitors (PPIs), sucralfate, bismuth salts, and misoprostol, will relieve symptoms, heal or prevent ulcers and esophagitis, as well as treat or prevent PUD and SRMB, thus improving quality of life, decreasing mortality, and decreasing the medical and financial burden to our society.

ACKNOWLEDGMENT

The author wishes to acknowledge Randolph V. Fugit, PharmD, BCPS, Stuart D. Rockafellow, PharmD, and Rosemary R. Berardi, PharmD, FCCP, FASHP, FAPhA, authors of this chapter in the first edition of this text.

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REVIEW QUESTIONS

  1. Why does Mr. Gonzalez have to take three drugs to treat his peptic ulcer?

  2. Would Ms. Rosenberg be a candidate for prophylactic cotherapy once the ulcer is healed? If so, what is the preferred agent?

  3. What are the most serious consequences of long-standing GERD?

  4. Why might Mrs. Dryden’s doctor have changed her medication for GERD from ranitidine to omeprazole?

  5. What are the goals of therapy if Mr. Vasquez’s UGI bleed is related to a peptic ulcer?

MEDICATION TABLE

MEDICATION TABLE 20-1.

Selected Oral Medications Used to Treat Acid-Related Upper Gastrointestinal Disorders in Adults13a

Class/Agents

Brand Name

Generic

Rx

Usual Adult Dosage Range (Rx)

OTC

Usual Adult Dosage Range (OTC)

Notes

Antacids (selected)

Calcium-containing (KAL see um)

Tums Regular Strength

X

X

2–4 tablets as needed; up to 15 tablets/day

Each tablet contains 500 mg calcium carbonate; chew tablets

Tums EX 750

X

X

2–4 tablets as needed; up to 10 tablets/day

Each tablet contains 750 mg calcium carbonate; chew tablets

Maalox Quick Dissolve Regular Strength

X

X

2–3 tablets as needed; up to 12 tablets/day

Each tablet contains 600 mg calcium carbonate; chew tablets

Mylanta Ultimate Strength

X

X

2–4 tablets between meals and at bedtime as needed; up to 10 tablets/day

Each tablet contains 700 mg calcium carbonate and 300 mg magnesium hydroxide; chew tablets

Magnesium-containing (mag NEE zhum)

Philips Milk of Magnesia Original

X

X

1–3 tsp q 4 hr as needed; up to 4 times/day

Each 5 mL contains magnesium hydroxide 400 mg

Magnesium- and aluminum-containing (mag NEE zhum) (a LOO mi num)

Mylanta Maximum Strength Liquid

X

X

2–4 tsp before meals and at bedtime as needed; up to 12 tsp/day

Each 5 mL contains aluminum hydroxide 400 mg, magnesium hydroxide 400 mg, and simethicone 40 mg

Maalox Regular Strength Liquid

X

X

2–4 tsp 4 times a day as needed; up to 16 tsp/day

Each 5 mL contains aluminum hydroxide 200 mg, magnesium hydroxide 200 mg, and simethicone 20 mg

Gaviscon Extra Strength Liquid

X

X

2–4 tsp 4 times a day as needed; up to 16 tsp/day

Each 5 mL contains aluminum hydroxide 254 mg, magnesium carbonate 237 mg, and alginic acid as an inactive ingredient

Magnesium- and calcium-containing (mag NEE zhum) (KAL see um)

Mylanta Supreme Liquid

X

X

2–4 tsp 4 times a day as needed; up to 18 tsp/day

Each 5 mL contains magnesium hydroxide 135 mg, and calcium carbonate 400 mg

Aluminum-containing (a LOO mi num)

Alternagel

X

X

1-2 tsp 4 times a day as needed; up to 18 tsp/day

Each 5 mL contains aluminum hydroxide 600 mg

Sodium-containing (SOE dee um)

Alka Seltzer Heartburn Relief

X

X

2 tablets in 4 ounces of water q 4 hr as needed; up to 8 tablets/day

Each tablet contains 1,940 mg sodium bicarbonate and 1,000 of citric acid

Alka Seltzer Original

X

X

2 tablets in 4 ounces of water q 4 hr as needed; up to 8 tablets/day

Each tablet contains 1,916 mg sodium bicarbonate, 1,000 mg citric acid, and 325 mg aspirin

Histamine-2 Receptor Antagonists

Cimetidine

(sye MET i deen)

Tagamet

X

X

400 mg 4 times daily or 800 mg twice daily

Tagamet HB

X

X

200–400 mg daily

Famotidine

(fa MOE ti deen)

Pepcid

X

X

20–80 mg daily

X

10–20 mg daily (maximum 40 mg/day)

Pepcid AC

X

X

10–20 mg daily

Pepcid AC Maximum Strength

X

20–40 mg daily

Pepcid Complete

X

X

10–20 mg daily

Contains famotidine 10 mg, calcium carbonate 800 mg, and magnesium hydroxide 165 mg

Nizatidine

(ni ZA ti deen)

X

X

150–300 mg daily

Proton Pump Inhibitors

Omeprazole

(oh ME pray zol)

Prilosec

X

X

20-80 mg daily

Take 30 min before morning meal; if twice daily, take second dose 30 min before dinner

Prilosec OTC

X

X

20 mg daily

Take 30 min before morning meal; take daily for 14 days

Omeprazole/sodium bicarbonate (oh ME pray zol) (SOE dee um bye KAR bon ate)

Zegerid

X

X

20–80 mg daily

Take 30 min before morning meal; if twice daily, take second dose 30 min before dinner; each capsule contains 20 or 40 mg omeprazole with 1,100 mg sodium bicarbonate (equivalent to 304 mg of sodium); because 20- and 40-mg dosages contain the same amount of bicarbonate, two 20-mg capsules should not be substituted for the 40-mg capsule

Pantoprazole

(pan TOE pra zole)

Protonix

X

X

40–80 mg daily

Take 30 min before morning meal; if twice daily, take second dose 30 min before dinner

Lansoprazole

(dex lan SOE pra zole)

Prevacid

X

X

15–60 mg daily

Take 30 min before morning meal; if twice daily, take second dose 30 min before dinner

Prevacid 24 HR

X

X

15 mg daily

Take 30 min before morning meal; take daily for 14 days

Rabeprazole

(ra BE pray zole)

Aciphex

X

X

20–40 mg daily

Take 30 min before morning meal; if twice daily, take second dose 30 min before dinner

Esomeprazole

(es oh ME pray zol)

Nexium

X

X

20–80 mg daily

X

20 mg daily

Take 30 min before morning meal; if twice daily, take second dose 30 min before dinner

Dexlansoprazole

(dex lan SOE pra zole)

Dexilant

X

30–60 mg daily

Take 30 min before morning meal; if twice daily, take second dose 30 min before dinner

Other

Sucralfate (soo KRAL fate)

Carafate

X

X

1–4 g daily

Take potentially interacting oral medications 1 hr before the next dose of sucralfate

Misoprostol

(mye soe PROST ole)

Cytotec

X

X

400–800 mcg daily

Contraindicated in pregnant women; serum pregnancy test required in women of childbearing age; diarrhea is dose dependent

Bismuth subsalicylate (biz muth) (sub sa LIS i late)

Pepto Bismol Original Liquid

X

X

2 tbsp q 30 min to 1 hr as needed; up to 16 tbsp/day

Each 15 mL contains bismuth subsalicylate 262 mg; caution in patients with salicylate allergy; bismuth salts darken stool; liquid products may darken tongue

OTC = over the counter; Rx = prescription.

a

Pronunciations have been adapted with permission from USP Dictionary of USAN and International Drug Names (USP Dictionary) © 2022.