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 )
NSAIDs may reduce the benefit of drugs used for treating hypertension because NSAIDs may increase blood pressure . NSAIDs decrease the elimination of lithium ( Eskalith ) and methotrexate ( Rheumatrex ) potentially leading to their toxicity , and reduce the action of diuretics (" water pills") by reducing blood flow to the kidneys. NSAIDs increase bleeding by decreasing the activity of blood platelets and therefore formation of blood clots. When used with other drugs that also increase bleeding, for example, warfarin ( Coumadin ), the likelihood of bleeding complications is increased. Prolonged use of NSAIDs with drugs that increase bleeding should be avoided.