Table of ContentsView AllTable of ContentsTypesTraditional NSAIDsCOX-2 InhibitorsWarnings
Table of ContentsView All
View All
Table of Contents
Types
Traditional NSAIDs
COX-2 Inhibitors
Warnings
Cyclooxygenase(COX) is an enzyme that formsprostaglandins,prostacyclins, andthromboxanes—substances called “prostanoids” that are responsible for the inflammatory response.If you have ever experiencedinflammation-related pain—for example, due toarthritis—you’ve felt cyclooxygenase at work.
COX is known as a rate-limiting enzyme because it serves as the major pathway or key for the formation of these prostanoids. But COX isn’t all bad—it’s even necessary for normal cellular processes.
Peter Dazeley / Photographer’s Choice / Getty Images
Nonsteroidal anti-inflammatory drugs (NSAIDs) affect COX to reduce inflammation.While they often do this successfully, some may negate some of the positive effects of COX in their efforts.
Where Is Cyclooxygenase Found in the Body?
There are actually two forms of the cyclooxygenase enzyme: COX-1 and COX-2. Both are involved in inflammation, but only COX-1 has a beneficial effect on the body as well.
Both COX-1 and COX-2 produce the prostaglandins that contribute to pain, fever, and inflammation. But since COX-1’s primary role is to protect the stomach and intestines and contribute to blood clotting, using drugs that inhibit cyclooxygenase can lead to unwanted side effects.
Traditional NSAIDs' Effect on Cyclooxygenase
Because of this and similar effects, they’re not recommended if you have or have had stomach ulcers, asthma, high blood pressure, heart disease, kidney disease, or liver disease.
COX-2-Selective NSAIDs
In the late 1990s, drug companies developed several NSAID medications that also inhibit prostaglandins, but target only COX-2. The goal of these NSAIDs is to reduce pain and inflammation without losing the protection of COX-1 in the gastrointestinal tract.
These medications, known as COX-2 inhibitors, were Celebrex (celecoxib), Vioxx (rofecoxib), and Bextra (valdecoxib).Of these, Celebrex is the only COX-2 inhibitor that remains on the market in the United States today. Vioxx and Bextra were both withdrawn from the U.S. market due to the potential for increased risk of heart attack and stroke.
COX-2 inhibitors target pain and inflammation with fewer gastrointestinal side effects. They also don’t seem to affect platelets the way non-selective NSAIDs do, which means that COX-2 inhibitors may not increase bleeding risk as much as COX-1 inhibitors when used with blood thinners, likewarfarin.
Your healthcare provider may prescribe a COX-2 inhibitor instead of a traditional NSAID if you need both inflammation and pain relief, are on blood thinners, and/or have had ulcers or gastrointestinal bleeding or you’re at risk for these issues. If you simply need pain relief, Tylenol (acetaminophen) may be considered instead.
NSAID Warnings
Summary
Cyclooxygenase is not something you’ll likely ever have to think much about. But knowing what it is and what it does can help you better understand why a healthcare provider may or may not recommend certain medications for you.
While NSAIDs and COX-2 inhibitors are both consideredtreatment options for osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, the benefits and risks must be considered for each individual.Your healthcare provider will consider your personal cardiac risk, medical history, age, and current medications to determine the best option for you.
12 Sources
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Ghlichloo I, Gerriets V.Nonsteroidal Anti-inflammatory Drugs (NSAIDs). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547742/
Hawkey CJ.COX-1 and COX-2 inhibitors.Best Pract Res Clin Gastroenterol. 2001;15(5):801–820. doi:10.1053/bega.2001.0236
Vane JR, Bakhle YS, Botting RM.Cyclooxygenases 1 and 2.Annu Rev Pharmacol Toxicol. 1998;38:97–120. doi:10.1146/annurev.pharmtox.38.1.97
Seibert K, Zhang Y, Leahy K, et al.Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain.Proc Natl Acad Sci U S A. 1994;91(25):12013–12017. doi:10.1073/pnas.91.25.12013
Saad J, Pellegrini MV.Nonsteroidal Anti-Inflammatory Drugs (NSAID) Toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526006/
Brune K, Patrignani P.New insights into the use of currently available non-steroidal anti-inflammatory drugs.J Pain Res. 2015;8:105–118. doi:10.2147/JPR.S75160
Zarghi A, Arfaei S.Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships.Iran J Pharm Res. 2011;10(4):655-683.
Sibbald B. Rofecoxib(Vioxx) voluntarily withdrawn from market.CMAJ. 2004;171(9):1027–1028. doi:10.1503/cmaj.1041606
Burton B.COX 2 inhibitor rejected in North America but retained in Europe.BMJ. 2007;335(7624):791. doi:10.1136/bmj.39370.401597.13
U.S. Food & Drug Administration.FDA Drug Safety Communication: FDA Strengthens Warning That Non-aspirin Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Can Cause Heart Attacks or Strokes.
Walker C.Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac[published correction appears in Int J Rheumatol. 2019 Jun 2;2019:8635073].Int J Rheumatol. 2018;1302835. doi:10.1155/2018/1302835
Arthritis Foundation.NSAIDs.Solomon DH.Overview of Selective COX-2 Inhibitors. UpToDate.U.S. Food and Drug Administration (FDA).FDA Drug Safety Communication: FDA Strengthens Warning That Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Can Cause Heart Attacks or Strokes.
Arthritis Foundation.NSAIDs.
Solomon DH.Overview of Selective COX-2 Inhibitors. UpToDate.
U.S. Food and Drug Administration (FDA).FDA Drug Safety Communication: FDA Strengthens Warning That Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Can Cause Heart Attacks or Strokes.
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