A peptic ulcer is a defect in the upper gastrointestinal mucosa that extends through the muscularis mucosa into deeper layers of the gut wall. There are two major risk factors for peptic ulcer disease – Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs including low-dose aspirin are some of the most commonly used drugs. They have good efficacy and a long history of clinical use, but can cause peptic ulcers which may have fatal complications. Given widespread use of NSAIDs and aspirin, the associated gastrointestinal toxicities have substantial implications for the healthcare system.The therapeutic effects of NSAIDs are mediated by their inhibition of prostanoid biosynthesis. Prostanoid derivatives arise from the conversion of arachidonic acid by cyclo-oxygenase (COX) isoenzymes following cell injury.
There are two distinct isoforms of COX. COX-1 is present in the majority of cells including endothelial cells, gastrointestinal epithelium and platelets, and functions continuously. In contrast COX-2 is present in only a few tissues and is induced by inflammation.NSAIDs exert their therapeutic anti-inflammatory and analgesic effects by inhibiting COX-2. The gastric and renal toxicities of the drugs are related to inhibition of the COX-1 isoform. There is a spectrum of COX-1 and COX-2 inhibition across the class of NSAIDs.Peptic ulcer disease is a well-recognised complication of NSAID use. Inhibition of COX-1 in the gastrointestinal tract leads to a reduction of prostaglandin secretion and its cytoprotective effects in gastric mucosa. This therefore increases the susceptibility to mucosal injury. Inhibition of COX-2 may also play a role in mucosal injury.

References

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