HOW NSAIDS WORK

Tavishi

NSAID stands for non steroidal anti inflammatory drug- essentially, anti-inflammatory drugs usually used for pain management which aren't corticosteroids. NSAID is a fancy classification for the household drugs like aspirin and ibuprofen, and for more obscure prescription medications like mefenamic acid and diclofenac.

NSAIDs function by reducing the amount of prostaglandins produced. Prostaglandins play a large role in pain, creating not only contractions of the uterus during menstruation, but also causing vasodilation, resulting in inflammation. In order to block inflammation, which is what causes a lot of the pain we perceive, we first reduce the amount of prostaglandins produced by inhibiting the source: cyclooxygenase enzymes. Cyclooxygenase enzymes, or COX, create prostaglandins from the precursor fatty acid arachidonic acid. NSAIDs target the enzymes COX-1 or COX-2. Most NSAIDs, like ibuprofen are non selective, and can inhibit both COX-1 and COX-2. Some NSAIDs, like celebrex, are selective, and can only inhibit COX-2.

Above is arachidonic acid, which gives rise to a multitude of other molecules which aren't prostaglandins. Although COX-1 and COX-2 are variants of the same sort of enzyme, they differ quite a bit in function. COX-1 consistently produces small amounts of prostaglandins to manage cytoprotection within the mucosal lining of the stomach. COX-2 on the other hand primarily produces prostaglandins to cause inflammation. And therein lies the issue: the inhibition of COX-1 by NSAIDs can lead to a variety of negative effects. Because of this, NSAID usage when excessive can result in the thinning of the mucosal layer in the stomach and other organs, making you prone to gastric ulcers (although bear in mind most gastric ulcers are caused by H. pylori, not stomach acid) Because most NSAIDs are non-selective, most NSAIDs affect COX-1. As the daughter of a nephrologist, I've been warned about the danger of excessive NSAID usage since before I could sit in the front seat of a car.

As mentioned earlier, prostaglandins cause vasodilation. Thus, when prostaglandins are inhibited, vasoconstriction can occur, raising blood pressure. When NSAIDs are prescribed, chronic high blood pressure can occur, and can cause severe effects if NSAIDs are used over the counter in excess over long periods of time. These effects can be both renal and cardiovascular: in kidneys, NSAID usage over long periods of time can lead to chronic kidney disease, and in the heart, the high blood pressure can lead to strokes and heart failure in the long term. If looking to read more about the terrifying statistics of NSAID usage and cardiovascular events, I'd highly suggest this article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778977/ In nephrology patients, NSAID usage is generally limited. Prostaglandins in the kidneys play a role in lower blood pressure maintaining glomerular filtration. With high NSAID usage, glomerular filtration decreases. When coupled with medications nephrology patients typically take, like ACE inhibitors like benazepril which lowers blood pressure, can cause kidney failure and other complications. Essentially, NSAID usage can be dangerous in patients with preexisting conditions. And when taken routinely, even when over the counter, NSAID usage can increase risk for cardiovascular disease and other complications tremendously. However, NSAIDs remain a useful tool to manage pain on occasion and in reasonable amounts.