Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure , liver dysfunction , those taking diuretics and ACE inhibitors , and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
SOURCES: Byron Cryer, MD, spokesman, American Gastroenterological Association; associate professor of medicine, University of Texas Southwestern Medical Center, Dallas. Nieca Goldberg, MD, spokeswoman for the American Heart Association; chief of women's cardiac care, Lennox Hill Hospital, New York; author, Women Are Not Small Men: Lifesaving Strategies For Preventing And Healing Heart Disease In Women . John Klippel, MD, president and CEO, Arthritis Foundation, Atlanta. Scott Zashin, clinical assistant professor, University of Texas Southwestern Medical Center; author of Arthritis Without Pain . American College of Rheumatology web site. Arthritis Foundation web site. American Heart Association web site. American College of Gastroenterology web site. American Gastroenterological Association web site. American Academy of Family Physicians web site. American Academy of Allergy, Asthma, and Immunology web site.
In the 1990s, researchers discovered that two different COX enzymes exist: COX-1 and COX-2. COX-1 is present in most tissues, including the stomach lining. It’s also involved in kidney function. COX-2 is the enzyme primarily present at sites of inflammation . Both COX-1 and COX-2 convert arachidonic acid to prostaglandin, resulting in pain and inflammation. The anti-inflammatory action of NSAIDs is mainly due to inhibition of COX-2, and their unwanted side effects (like bleeding ulcers) are largely due to inhibition of COX-1. ( 12 )