Gastric mucosal damage by nonsteroidal anti-inflammatory drugs

This brief review on gastric mucosal damage by nonsteroidal antiinflammatory drugs (NSAIDS) considers some aspects that generally receive little attention. Inhibition of prostaglandin (PG) synthesis is generally thought to be an important, but not the only, cause of the damage. Consideration should be made of the length of time and extent to which PG synthesis must be inhibited for damage to occur, of a possible differential effect on the various prostanoids, and of whether leukotrienes are involved. NSAID inhibition of PG synthesis may differ in the gastric mucosa as compared to other sites. Some evidence indicates that gastric mucosal damage correlates better with the drug potency for inhibition of PG synthesis than with potency x dose, particularly with drugs having a short or moderate half-life. The dose, which determines how much drug reaches the gastric mucosa via the blood-stream, might assume a progressively greater importance as the half-life increases. Inhibiting the synthesis of damaging thromboxane A2 by NSAIDs might help counteract the deleterious block of PG synthesis. If these hypotheses are correct, the gastric mucosal damage from NSAIDs absorbed locally may be less with low-potency/high-dose drugs having low gastric absorption and retention, and which dissolve in gastric juice without leaving particles in contact with the mucosa. With NSAIDs reaching the gastric mucosa locally or via the blood circulation, the damage at therapeutic doses might be less with drugs having a weaker effect on gastric as compared to other types of cyclo-oxygenases, a short or moderate half-life, and strong anti-thromboxane/antileukotriene activity.