Celebrex® (celecoxib): Another treatment for inflammation!

Alberto PonceOrganic Chemistry 12BSpring 2006http://posa0886.tripod.com

http://www.rcsb.org/pdb/static.do?p=explorer/viewers/webmol.jsp

Abstract• Until recently, a single cyclooxygenase (COX)

enzyme was thought to be responsible for all of the catalysis of Arachidonic Acid into a prostaglandin. It has now been shown that two forms of this protein, COX-1 and COX-2, exist. COX-1 is expressed in most cells and is thought to be responsible for producing the prostaglandins that provide gastrointestinal tolerability. COX-2 is an inducible form that is present only in inflammatory states. Recently, a second generation of NSAIDs has been developed for the treatment of rheumatoid arthritis and osteoarthritis. These drugs selectively inhibit the COX-2 protein, thus reducing inflammation. One such drug, celecoxib, marketed by Pfizer under the brand name Celebrex®.

What is Celebrex®?• Celebrex® is a Non-Steroidal Anti-

Inflammatory Drug that specifically targets a protein called Cyclooxygenase (COX-2) that causes inflammation in tissues.

• Created and distributedby Pfizer Labs

http://www.rcsb.org/pdb/static.do?p=explorer/singleimage.jsp&structureId=1pxx&type=asym&size=500

The essential mechanism of inflammation

http://pubs.acs.org.libaccess.sjlibrary.org/isubscribe/journals/chreay/103/i03/figures/cr020464af00001.html

The representation of how celecoxib binds with COX-2

http://pubs.acs.org.libaccess.sjlibrary.org/isubscribe/journals/jacsat/122/i39/figures/ja001018cf00001.html

Celebrex® in action

http://pubs.acs.org.libaccess.sjlibrary.org/isubscribe/journals/jacsat/122/i39/figures/ja001018cf00007.html

Anti-inflamatory drugs

http://pubs.acs.org.libaccess.sjlibrary.org/isubscribe/journals/chreay/103/i03/figures/cr020464af1.html

Types of anti-inflammatory medicine

Celebrex®

• FDA issued warning • was voted to stay on

market • FDA recommending

limited use

Vioxx• FDA approved in May

1999• Recalled on 9/30/04• Twice as likely to

suffer heart attacks and strokes with extended use

Tablet of Celebrex®

• Each tablet can contain 100 mg, 200 mg, or 400 mg of celecoxib

• Active • Celecoxib

• Inactive• Croscarmellose

sodium• Edible inks• Magnesium stearate• Gelatin• Lactose monohydrate• Povidone• Sodium lauryl sulfate• Titanium dioxide

Uses of Celebrex®

• Prescribed by a MD to patients that have symptoms of the arthritis, acute pain and swelling, or even menstrual cramps in women.

• In fact, celecoxib has recently been approved by the FDA as the first drug for treatment of adenomatous polyposis, a hereditary disease that leads to colorectal cancer.

Side Effects and Risk Factors

• headache• abdominal pain• diarrhea• nausea• insomnia• drowsiness

• stomach ulcers• liver damage• kidney problems• fluid retention• Myocardial infarction*

*Only when taken in a regular basis for >18months

Summary and Conclusion

• Further research and testing are in progress though it has been found that Celecoxib does skin irritation as an allergic reaction to NASAIDs plus some gastrointestinal ulceration, bleeding, and suppression of renal functions.

• In addition, recently studies suggest that COX-2-selective anti-inflammatory drugs may become a new option in the treatment of Alzheimer's disease.

• FDA recommends limited use of this drug

References• Analysis of Binding Affinities for Celecoxib Analogues with COX-1 and

COX-2 from Combined Docking and Monte Carlo Simulations and Insight into the COX-2/COX-1 SelectivityPlount Price, M.L. and Jorgensen, W.L.J. Am. Chem. Soc., 122, 39, 9455 - 9466, 2000, 10.1021/ja001018c

• Cyclooxygenase (COX) Inhibitors: A Comparative QSAR StudyGarg, R., Kurup, A., Mekapati, S.B., and Hansch, C.Chem. Rev., 103, 3, 703 - 732, 2003, 10.1021/cr020464a

• http://www.rcsb.org • http://www.adrugrecall.com• http://www.fda.gov• http://www.medicalnewstoday.com/index.php?newsid=7621• http://www.medsafe.govt.nz• "NSAID linked to fatal allergic reaction." (celecoxib)(Brief Article)

Practice Nurse, April 26, 2002 p59(1). Science Resource Center. Thomson Gale.<http://0-galenet.galegroup.com.library.sjeccd.org:80/servlet/SciRC?ste=1&docNum=A131224903>

• Seedher, Neelam. Soulubility Enhancement of COX-2 Inhibitors Using Various Solvent Systems. AAPS PharmSciTech. 2003; 4(3) article 33