Nonsteroidal antinflammatory drugs (NSAIDs) are one of the most commonly used drugs throughout the world; they effectively reduce pain and inflammation in several acute and chronic musculo-skeletal conditions. NSAIDs inhibit cycloxygenase (COX) activity, the enzyme that catalyzes the synthesis of cyclic endoperoxides from arachidonic acid to form proinflammatory and other forms of prostaglandins (PGE2). Proinflammatory PGE2 produced by COX- 2 at the site of inflammation are pivotal in increasing local inflammation and inducing pain sensation. However, physiological prostanoids, produced by constitutive COX-1 at the gastric mucosa level, sustain complex events that protect the mucosa cells. Inhabitation of gastric COX-1 activity is responsible for the main side effect encountered during NSAIDs therapy: ulceration of gastrointestinal tract. Such a side effect is complicated by the ability of NSAIDs to affect also COX-1 activity in platelets with consequent reduction in proaggregant thromboxane synthesis. Identification of patients at higher risk for gastrointestinal tract ulceration (or bleeding) is mandatory to avoid serious and sometimes life-threatening complications and to select patients who can benefit of preventive therapy with proton pump inhibitor or misoprostol. In addition, PGE2 inhibition of the constitutive COX-1 in the kidney mediates fluid and electrolyte disturbances. It has been described that new NSAID compound (celecoxib) displays specific selectivity for COX-2 only, leaving unaffected the constitutive COX-1. Such a compound can offer a new alternative to treat patients who require analgesic and antinfiammatory therapy.
|Translated title of the contribution||The first specific COX-2 specific inhibitor and its possible use for antiinflammatory treatment|
|Journal||Annali Italiani di Medicina Interna, Supplement|
|Publication status||Published - 1999|
ASJC Scopus subject areas
- Clinical Neurology