Nonsteroidal Anti-inflammatory Drugs

NSAIDs have analgesic, anti-inflammatory and antipyretic activity. They variably inhibit the activities of cyclooxygenase isoenzymes (COX-1 and COX-2); consequently, the synthesis of PGE2.31 COX-1 is expressed in all healthy tissues, including platelets, and has primary homeostatic or “housekeeping” responsibilities. COX-2 is expressed primarily in the brain, kidneys, female reproductive system, and bone; and it is induced by inflammatory cytokines in other tissues. COX-2 is not found in platelets.

By reducing the synthesis of PGE2, the prototypical sensitizing agent, NSAIDs increase the response threshold of primary afferent sensory neurons by chemical activators such as protons, ATP, and bradykinin.14,17,18 By reducing PGE2 synthesis, NSAIDs also increase vascular tone; and decrease vascular permeability, the recruitment of leukocytes, and the synthesis of leukocyte-derived mediators of inflammation. Consequently, NSAIDs are disease-modifying analgesics.

Acetylsalicylic acid (ASA) is effective in the treatment of most types of mild-to-moderate pain. However, ASA irreversibly inhibits platelet function, precipitates asthma-like symptoms in susceptible patients, and increases the risk of Reye’s syndrome in children and adolescents during viral syndromes. High doses and chronic use can also cause GI ulceration. Since more effective and less toxic analgesics are available, ASA is used primarily for cardio-protection and stroke prevention.

Ibuprofen is the gold standard against which new analgesics are evaluated. Other oral NSAIDs such as naproxen and naproxen sodium offer no apparent advantage over ibuprofen.31 Ketorolac is available in both oral and parenteral formulations. The use of the oral formulation is restricted to those patients who have received the drug parenterally during the perioperative period.32 Celecoxib, a selective COX-2 inhibitor, offers no advantage over other NSAIDs in treating odontogenic pain.31

NSAIDs are rapidly absorbed from the stomach and the upper small intestine. The onset of analgesia is 30 to 60 minutes. NSAIDs are distributed throughout the body and cross the placenta. Depending on the agent and dosing, their duration of action is between 4 to 12 hours. NSAIDs are metabolized in the liver by first-order kinetics; however, after larger doses, the enzymes become saturated, which leads to zero-order kinetics and increased half-lives. Metabolites are excreted primarily by the kidneys.