Il primo inibitore specifico della ciclossigenasi-2 potra cambiare il nostro modo di utilizzare la terapia antinfiammatoria?

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.