PUD is classified as a chronic inflammatory disorder resulting in the erosion of the mucosa of the stomach or duodenum. Usually, the erosion is a result of gastric acid and pepsin, which are normally available to hydrolyze protein and food so that they can be absorbed by the intestine. However, sometimes the production of gastric acid and pepsin results in ulcer formation. Ulcers also occur in the esophagus and other areas of the GI tract, but not as frequently as in the stomach and duodenum. Risk for developing ulcers increases with age, smoking, alcohol, a history of peptic ulcer disease or GI bleeding, and increased doses of nonsteroidal anti-inflammatory drugs (NSAIDs).19,35
Duodenal ulcers usually occur in the beginning portion of the duodenum and gastric ulcers usually occur in the lower one-third of the stomach, also called the antrum. PUD is often asymptomatic, but signs and symptoms can include a slight dull ache, discomfort 2 to 3 hours after meals and during the middle of the night, poor appetite, bloating, burping, nausea, and vomiting. Such discomfort can often be relieved by food and antacid medications.
The cause of PUD is multifactoral, ranging from increased acid secretion to factors that decrease the protective mucosal barrier. Neurologic impulses (sight, smell, or taste) can also trigger the secretion of acid. Damage to the mucosal barriers can occur as a consequence of alcohol abuse, cigarette smoking, or continual use of aspirin and NSAIDs. Helicobacter pylori (H. pylori) bacterial infection may also directly inflame and damage the mucosal barrier or alter the regulation of gastric acids. Because there are many factors that can cause ulcers, investigators have divided the etiology into three categories: (1) ulcers associated with H. pylori; (2) ulcers caused by NSAID use; and (3) ulcers caused by acid hypersecretion.14
H. pylori is a bacterium of the helicobacter genus. Its mode of transmission is unknown, but it is thought to be from person to person.9 H. pylori can be found almost anywhere in the stomach but is usually concentrated in the antrum. Inflammation of the antrum is the most common cause of gastritis,2,28,40 and elimination of H. pylori from this site usually resolves this condition. The exact cause of gastritis caused by H. pylori is unknown, but it is thought to result from either production of a cytotoxin, a breakdown of mucosal defenses, or adhesion to epithelial cells.6 As a result, the lining of the stomach and duodenum weakens and allows the acid to penetrate, causing an ulcer.
Nonsteroidal Anti-inflammatory Drugs
Use of NSAIDs is the most common cause of PUD in patients who are not infected with H. pylori.19 NSAID use can damage the stomach lining through inhibition of prostaglandin synthesis. Prostaglandins stimulate mucus and bicarbonate secretion, maintain mucosal blood flow, and participate in epithelial regeneration and cell growth. Without this process, the stomach lining would be vulnerable to acid.
Gastric Acid Hypersecretion
Acid secretion in individuals who suffer from PUD has been found to be close to normal. Only when hypersecretion occurs do most individuals suffer from ulcers. The hypersecretion can cause ulcers either by injuring the cells of the mucosa or by activating pepsin. When hypersecretion is the cause of ulcers, it may be the result of Zollinger-Ellison syndrome. Zollinger-Ellison syndrome is a rare condition in which a tumor activates the secretion of gastrin, which then stimulates gastric acid release. Only approximately 0.1 percent of all duodenal ulcers occur from Zollinger-Ellison syndrome.
Peptic Ulcer Disease Drug Treatment and Adverse Effects
Treatment of PUD is directed toward relieving ulcer pain, accelerating ulcer healing, and minimizing ulcer recurrence. The following classes of drugs are used for treatment of PUD: H2-receptor antagonists, proton pump inhibitors, antacids, sucralfate, bismuth compounds, and antibiotics (Table 8–1). Some of these drug classes are available as over-the-counter (OTC) drugs used to treat PUD. As with all OTC items, it is imperative to follow the doses and indications recommended on the drug label. Not following these recommendations may cause unwanted and perhaps severe adverse effects. Therefore anyone who has any questions about which medication to administer or the proper dose should consult his or her physician or local pharmacist.
Table 8–1Drugs Used to Treat H. pylori, GERD, and PUD ||Download (.pdf) Table 8–1 Drugs Used to Treat H. pylori, GERD, and PUD
|Drug—Generic (Brand) ||Classification ||Indication ||Action |
|Bismuth (Pepto-Bismol) ||Bismuth ||H. pylori ||Destroys H. pylori bacteria |
|Metronidazole (Flagyl) ||Antimicrobial ||H. pylori ||Destroys H. pylori |
|Clarithromycin (Biaxin) |
|Amoxicillin (Amoxil) |
|Cimetidine (Tagamet) ||H2 antagonist ||PUD, GERD, H. pylori ||Blocks H2 receptors to suppress acid secretion |
|Famotidine (Pepcid) |
|Ranitidine (Zantac) |
|Nizatidine (Axid) |
|Omeprazole (Prilosec) ||Proton-pump inhibitor ||PUD, GERD, H. pylori ||Inhibits proton-pump acid secretion |
|Lansoprazole (Prevacid) |
|Rabeprazole (Aciphex) |
|Pantoprazole (Protonix) |
|Esomeprazole (Nexium) |
|Sucralfate (Carafate) ||Mucosal protectant ||PUD ||Binds to ulcer and forms a protective barrier |
|Metoclopramide (Reglan) ||Prokinetic ||GERD ||Stimulates gastric motility |
H2 receptor antagonists decrease gastric acidity by inhibiting histamine from being released by parietal cells. Histamine activates H2 receptors along the GI tract to increase acid secretion. Common H2 receptor antagonists include cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid). Multiple dosing has been shown to be more effective than single dosing with respect to suppressing gastric acids.20,33 These drugs can also treat gastroesophageal reflux and hypersecretory gastric states by increasing the pH of gastric contents.3,4,17,27
H2 receptor antagonists rarely cause serious adverse effects. However, mild adverse effects can include diarrhea, constipation, headache, stomach cramps, dizziness, and rash. These drugs should be used with caution in patients who have renal failure or liver damage because they are not effectively cleared by the kidney and liver.
Proton-pump inhibitors inhibit gastric acid secretion by blocking the H+/K+ adenosine triphosphatase system found at the surface of gastric parietal cells.3,4,27,37 Omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), esomeprazole (Nexium), and pantoprazole (Protonix) are drugs used to effectively treat PUD by blocking the final step of acid production.3,4,17,27,37
The main adverse effects of proton-pump inhibitors are stomach pain and diarrhea. Additional possible adverse effects include abdominal distress, headaches, muscle aches, chest pain, sedation, gas, nausea, vomiting, and rash.3,4,27,37
Antacids neutralize the acid found in the stomach by buffering it and increasing the stomach's pH. Importantly, antacids have no effect on acid production, unlike the H2 receptor antagonists and proton-pump inhibitors. Although antacids heal ulcers, they are primarily used for the relief of ulcer pain or dyspepsia when used in combination with other anti-ulcer drugs. Antacids are discussed more thoroughly in this chapter in the context of gastroesophageal reflux disease.
Sucralfate (Carafate) is an prescription-only agent that, when exposed to acid, forms a viscous paste that adheres to the ulcer crater, forming a protective barrier. The drug binds only to the damaged mucosa and maintains the barrier for up to 6 hours. Sucralfate is effective in the short-term treatment of duodenal ulcers and is comparable to H2 antagonists. Sucralfate is generally well tolerated; its most frequent adverse effect is constipation.
Bismuth compounds have been used to treat gastrointestinal disorders for many years. The most common agent used today is bismuth subsalicylate (Pepto-Bismol). The mechanism by which bismuth heals ulcers remains uncertain, but theories include providing a local gastroprotective effect, stimulating endogenous prostaglandins, and suppressing H. pylori infection.
Bismuth subsalicylate preparations may contain varying amounts of salicylate and therefore may cause problems for patients taking aspirin or other salicylate-containing drugs. It may cause salicylate toxicity in individuals who are on aspirin therapy. Patients should also be aware that bismuth reacts with hydrogen in the colon to from a compound that blackens the stool.
Antibiotics are used in the treatment of H. pylori. Antibiotic drug therapy is associated with various treatment success rates (on average 80 to 95%). The most common antibiotics used for treatment of H. pylori include clarithromycin (Biaxin), metronidazole (Flagyl), and amoxicillin (Amoxil). Adverse effects of these antibiotics are mostly GI symptoms such as diarrhea and nausea. Both clarithromycin and metronidazole are known to cause an abnormal taste in the mouth and headache.