non-steroidal anti-inflammatory drugs (NSAIDs) irritate gastroduodenal mucosa, suppress prostaglandin production, impair the ability of the mucosa to repair (reduction in gastric mucosa blood flood), inhibiting platelets function
HOW? Will block COX-2 to reduce inflammation [GOOD] but also block COX-1 [BAD]
Arachidonic Acid —> [COX] –> Prostaglandin
- COX 1: constitutively expressed in most cells and plays an important role in the GI mucosal protection, renal blood flow regulation and normal platelet function
- COX 2: largely inducible by inflammation and is thought to generate prostaglandins that are responsible for pain and inflammation
PGE2, remains a critical factor in gastric homeostasis. Prostaglandin E2 inhibits acid secretion through the EP3 receptor and the fluctuation of its levels as a result of NSAID therapy remains a major concern in preserving the integrity of the gastric mucosa
1. Wallace JL. How do NSAIDs cause ulcer disease? Baillieres Best Pract Res Clin Gastroenterol. 2000 Feb;14(1):147-59.