Pharmacology of cyclooxygenase-2 inhibitors and preemptive analgesia in acute pain management.
OBJECTIVE
NSAIDs have served as analgesic, antiinflammatory, and antipyretic medicines for over a century. A novel class of NSAIDs, cyclooxygenase-2 inhibitors, was introduced in 1999. All NSAIDs and aspirin inhibit active sites of cyclooxygenase-1 and cyclooxygenase-2. Recent studies have demonstrated an important role of cyclooxygenase-2 inhibitors in the management of acute pain processes.


RESULTS
There have been many reports related to an 'imbalance theory' suggesting that cyclooxygenase-2 inhibitors create an 'imbalance' between thromboxane and prostacyclin (reduction of prostacyclin), resulting in a prothrombic state; however, these drugs were designed to have improved gastrointestinal safety profiles by being more selective of the cyclooxygenase-2 pathway. Although balance and regulation of hemostasis is influenced in part by the balance of prostacyclin and thromboxane A2, many other substances are involved in thrombosis and include the coagulation cascade, fibrinogen and plasminogen pathways, numerous endogenous substances such as adenosine, nitric oxide, and serotonin.


CONCLUSIONS
On the basis of many human studies, one may conclude that perioperative cyclooxygenase-2 inhibitors, in standard doses, decrease opioid consumption. Future investigations that include different multimodal techniques, for example combining cyclooxygenase-2 inhibitors with regional blocks, may help elucidate and clarify the true benefits of perioperative cyclooxygenase-2 inhibitors in acute pain management strategies.
Kaye
Alan D
AD
Department of Anesthesiology, LSU School of Medicine, New Orleans, Louisiana 70112, USA. akaye@lsuhsc.edu
Baluch
Amir
A
Kaye
Aaron J
AJ
Gebhard
Ralf
R
Ralf
Gebhard
G
Lubarsky
David
D
D000208:Acute Disease; D000698:Analgesia / Q000379:methods*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010146:Pain / Q000188:drug therapy*; D011292:Premedication / Q000009:adverse effects / Q000379:methods*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors