Which group of drugs causes gastric irritation?

From the Guidelines

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common cause of gastric irritation, and their use can lead to serious gastrointestinal complications, including bleeding, perforation, and obstruction, as evident from studies such as 1. The most common NSAIDs that cause gastric irritation include ibuprofen, naproxen, aspirin, diclofenac, and indomethacin. These medications cause gastric irritation by inhibiting prostaglandin synthesis, which reduces the protective mucus layer in the stomach and decreases bicarbonate secretion, as discussed in 1. Other medications that can cause gastric irritation include:

• Corticosteroids, such as prednisone and dexamethasone, which impair mucosal defense mechanisms
• Potassium supplements, particularly in pill form
• Certain antibiotics like tetracyclines and macrolides
• Iron supplements
• Bisphosphonates used for osteoporosis treatment, such as alendronate and risedronate
• Some chemotherapy drugs and alcohol can also significantly irritate the gastric mucosa. To minimize gastric irritation, these medications should be taken with food or milk, or as directed by a healthcare provider, and in some cases, a proton pump inhibitor or H2 blocker may be prescribed alongside these medications to protect the stomach lining, as recommended in 1. It is essential to note that the risk of gastric irritation and complications can be minimized by assessing the patient's baseline risk and using strategies such as the selective use of NSAIDs, co-therapy with gastroprotectives, and testing for Helicobacter pylori infection, as suggested in 1. The use of lower-dose NSAIDs, the decreasing prevalence of H. pylori, and the increasing use of proton-pump inhibitors have contributed to a decrease in NSAID-associated GI complications and deaths in recent years, as reported in 1. However, it is crucial to be aware of the risk factors that increase the likelihood of GI complications, including a history of previous peptic ulcer, advanced age, concomitant use of corticosteroids, anticoagulants, and high-dose NSAIDs, as highlighted in 1. By understanding the causes and risk factors of gastric irritation and taking preventive measures, healthcare providers can help minimize the risk of serious gastrointestinal complications associated with NSAID use.

From the FDA Drug Label

NSAIDs can cause serious side effects, including: ... stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting Gastroscopic studies at varying doses show an increased tendency toward gastric irritation at higher doses. Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines: anytime during use without warning symptoms that may cause death

NSAIDs cause gastric irritation.

• Key factors that increase the risk of gastric irritation include:
  • Higher doses of NSAIDs
  • Longer use of NSAIDs
  • Past history of stomach ulcers or bleeding
  • Use of other medications such as corticosteroids, anticoagulants, SSRIs, or SNRIs
  • Smoking
  • Drinking alcohol
  • Older age
  • Poor health
  • Advanced liver disease
  • Bleeding problems 2 2

From the Research

Gastric Irritation Caused by Drugs

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric irritation, as they can disrupt the epithelial barrier and inhibit cyclo-oxygenase (COX), leading to damage in the gastrointestinal (GI) tract 3, 4, 5, 6, 7
• The mechanisms of gastric injury include topical irritant actions and the inhibition of COX-1 isoform in the mucosa, which can be attenuated by antisecretory agents or mucosal protective agents 6, 7
• Examples of NSAIDs that can cause gastric irritation include aspirin, which can impair mucosal defenses and cause "back-diffusion" of acid, leading to further injury 6
• Other mechanisms by which NSAIDs may induce or contribute to mucosal injury include inhibition of mucosal prostaglandin synthesis, reduction and alteration of mucus secretion, and interference with cell turnover 6

Protective Agents and Therapeutic Approaches

• Protective agents such as sucralfate, prostaglandins, omeprazole, and histamine (H2)-receptor antagonists have been shown to provide partial protection against NSAID-induced gastric mucosal damage 6
• The use of COX-2 selective agents, such as coxibs, has been shown to be a successful therapeutic approach to reducing NSAID-induced GI damage, as they inhibit prostanoid biosynthesis at inflammatory sites but not in the gut 7
• Newer therapeutic approaches, such as the development of NO-containing NSAIDs, have also shown promise in reducing mucosal injury 7