Overview of Peptic Ulcer Disease

Goldie L. Peters, PharmD; Jennifer L. Rosselli, PharmD, BCPS; Jessica L. Kerr, PharmD, CDE


US Pharmacist 

In This Article

Etiology and Pathophysiology

Peptic ulcer disease encompasses gastric, duodenal, and esophageal ulcers, with common etiologies of Helicobacterpylori infection, NSAID use, and stress-related mucosal damage (TABLE 1). Due to the more invasive involvement of the gastric muscularis mucosa, PUD differs from the more superficial acid-related disorders such as erosions and gastritis.[3] Peptic ulcers are typically named for their anatomical location, such as gastric or duodenal ulcers, and increased gastric acid is the primary cause. For the purpose of this article, only etiologies of H pylori and NSAID-induced PUD will be discussed. In addition to these etiologies, other controversial environmental risk factors including cigarette smoking, psychological stress, caffeine intake, and alcohol ingestion may increase the risk for the development of PUD.[3–5]

The disease process of PUD is multifactorial based on etiology and risk factors. Ulcers may occur with hypersecretion of hydrochloric acid and pepsin, causing an imbalance between gastric luminal factors and degradation in the defensive function of the gastric mucosal barrier. Mucosal defenses include mucus, secretion of bicarbonate, mucosal blood flow, and epithelial cell defense. When acid and pepsin invade a weakened area of the mucosal barrier, histamine is released. Histamine will stimulate parietal cells to secrete more acid. With the continuation of this vicious cycle, erosion occurs to form the ulcer.[3–5]

Although over 50% of the population has chronic H pylori infection, only 5% to 10% develop ulcers.[4]Hpylori is a pH-sensitive bacterium that can infiltrate the gastric mucosal layer to reside in a neutral-pH environment. Acutely, the infection or colonization may ironically produce a hypochlorhydric environment. It is thought that this protective mechanism for the organism occurs due to the increase of urease, which hydrolyzes urea and converts it to ammonia and carbon dioxide. H pylori contributes to mucosal injury by multiple mechanisms (TABLE 2).[4,6]

Ulcers induced by nonselective NSAIDs can occur due to a topical irritation of the gastric epithelial cells and reduced protective prostaglandin synthesis.[4] Due to their pharmacologic properties, many acidic NSAIDs cause alterations in the hydrophobic mucosal gel layer. The topical irritation may be the first insult to injury; however, inhibition of cyclooxygenase (COX) is the greatest concern. NSAIDs inhibit the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins. COX-2 exists throughout the body, producing prostaglandins associated with inflammation and pain, whereas COX-1 is located in the stomach, kidney, intestines, and platelets. Isoforms COX-1 and COX-2 are inhibited by nonselective NSAIDs. As a result of COX-1 inhibition, adverse effects such as ulcers or GI bleeds may occur.[3–5]


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