Gastroprotection and nonsteroidal anti-inflammatory drugs (NSAIDS). Rationale and clinical implications.
There is no doubt that nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal injury. The most serious consequences are gastric and duodenal ulcers which can cause bleeding and perforation, and which may lead to the premature death of 3000 to 4000 patients in the UK annually. The immediate actions of NSAIDs operate at a subcellular level; in particular altering of mitochondrial function which causes depletion of ATP and renders the cell vulnerable to oxidant stress. Secondary consequences follow, such as the inhibition of prostaglandin synthesis which delays cellular repair. While adaptation can be shown in volunteers despite continued NSAID ingestion, studies in patients suggest mucosal damage develops continuously and cumulatively even with low doses of aspirin. Histamine H2-receptor antagonists and proton pump inhibitors heal NSAID-related ulcers, though healing rates with H2-antagonists are slower in patients who continue NSAID treatment. They have little role in preventing damage. In addition to acid suppression, prostaglandin analogues cause bicarbonate secretion and enhance mucosal blood flow. They have a specific role in both prevention and treatment of NSAID-related damage. The use of misoprostol offers a rational approach to reduce the high prevalence of unwanted gastroduodenal damage from NSAIDs. On a purely financial basis more information is needed before routine coprescribing can be recommended. However, for any patient on NSAIDs with a previous ulcer or for patients aged over 60 years (where the risks and seriousness of complications are markedly increased), the use of misoprostol should be considered. Further developments in prostaglandin analogues may reduce their adverse effects and perhaps thereby improve their efficacy at symptom control.
Hayllar
J
J
Division of Gastroenterology, Northwick Park Hospital, Harrow, Middlesex, England.
Macpherson
A
A
Bjarnason
I
I
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D010437:Peptic Ulcer / Q000517:prevention & control; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D011465:Prostaglandins, Synthetic