Prevention and treatment of non-steroidal anti-inflammatory drug-induced gastro-duodenal damage: rationale for the use of antisecretory compounds

Gastro-duodenal mucosa possesses an array of defensive mechanisms and non-s teroidal anti-inflammatory drugs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid lend. The presence of acid appears to be a conditio sine qua non for non-steroida l anti-inflammatory drug-injury, which is in fact pH-dependent. The acute d amage induced by acid non-steroidal anti-inflammatory drugs, bike aspirin, can be markedly reduced or even prevented by raising intragastric pH with a ntacids or antisecretory compounds. Animal studies have clearly shown that not only the degree, but also the duration, of acid inhibition is an import ant factor for prevention of non-steroidal anti-inflammatory drug-induced m ucosal damage. As a consequence, proton pump inhibitors (PPIs) appear to be more effective that H-2-receptor antagonists both in preventing and treati ng gastro-duodenal lesions. While acid suppression seems to be the only eff ective mechanism for ulcer healing prevention of non-steroidal anti-inflamm atory drug-injury might also rely on the mucosal protective activity of the se compounds. Clinical pharmacological studies, performed in healthy volunt eers, have shown that - as in laboratory animals - elevation of intragastri c pH by means of antacids or antisecretory compounds protects against acute NSAID-induced damage. Unlike H-2-blockers, PPIs protect from nonsteroidal anti-inflammatory drug-injury not only the duodenum, but also the stomach, where the majority of mucosal lesions are usually located Although elevatio n of intragastric pH affects non-steroidal anti-inflammatory drug pharmacok inetics and pharmacodynamics in laboratory animals, a lack of drug-to-drug interaction between PPIs and some of these compounds has been reported in h umans. To summarize, clinical and experimental pharmacology support the use of PPIs for the prevention and treatment of non-steroidal anti-inflammator y drug-induced gastro-duoctenal damage. Acid suppression could however; rep resent only one of the many mechanisms by which these compounds protect gas tro-duodenal mucosa. Further studies are, therefore, needed to better eluci date the respective role of the various pharmacological actions in their mu cosal protective activity as well as to assess the clinical relevance of ea ch of them.