Mechanism of Action

Striking COX1:COX2 Inhibition Balance in OA and RA 

Facts

  • Nonsteroidal anti-inflammatory (NSAIDs) are related to a spectrum of toxic effects, especially gastrointestinal (GI) effects, due to inhibition of cyclooxygenase-1 (COX-1).1
  • The selective cyclooxygenase-2 (COX-2) inhibitor- Celecoxib, is associated with lower rates of adverse GI, renal, and CV effects in rheumatoid arthritis (RA) and osteoarthritis (OA) patients.2

Non-steroidal anti-inflammatory drugs (NSAIDs) competitively inhibit cyclooxygenase (COX) and their anti-inflammatory action is induced by the COX-2 inhibition.3,4 Here, we discuss the mechanism of action (MOA) of NSAIDs and the advantages of COX-2 selective inhibition of celecoxib over other NSAIDs in the treatment of RA and OA.

The Mechanism of Action of NSAIDs5

Celebrex Mechanism of Action

All About Celecoxib6

  • Celecoxib is 375 times more selective to COX-2 than to COX-1.
  • Celecoxib, a diaryl-substituted pyrazole, is the first highly selective COX-2 inhibitor indicated to alleviate the signs and symptoms of OA and RA in adults
  • Celecoxib is absorbed rapidly, distributed widely, and metabolized extensively in the GI tract, tissues, and in the liver, respectively

Key Takeaways

Celebrex_Mechanism Of Action

Abbreviations: COX: cyclooxygenase; ns-NSAID: non-selective non-steroidal anti-inflammatory drug; GI: gastrointestinal.

References:

1.Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA. 2000 Sep;284(10):1247-55.
2.Nissen SE, Yeomans ND, Solomon DH, Lüscher TF, Libby P, Husni ME, Graham DY, Borer JS, Wisniewski LM, Wolski KE, Wang Q. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. 
N Engl J Med. 2016 Dec; 375:2519-29.
3.Zarghi A, Arfaei S. Selective COX-2 inhibitors: a review of their structure-activity relationships.IJPR. 2011 Dec;10(4):655.
4.Goldenberg MM. Celecoxib, a selective cyclooxygenase-2 inhibitor for the treatment of rheumatoid arthritis and osteoarthritis. Clin Ther. 1999 Sep;21(9):1497-513.
5.Warner TD and Mitchell JA. COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs. Lancet. 2008; 371:270-3.
6.Fung HB, Kirschenbaum HL. Selective cyclooxygenase-2 inhibitors for the treatment of arthritis. Clin Ther. 1999 Jul;21(7):1131-57.
7.Vane JR, Botting RM. Mechanism of action of nonsteroidal anti-inflammatory drugs. Am J Med. 1998;104(3A):2S-8S.

Please click on Prescribing Information link to view safety and adverse events information of Celebrex®.

For the use only of registered medical practitioners or a hospital or a laboratory.

PP-CEL-IND-0080 02/06/2021