NSAIDs or non-steroidal anti-inflammatory drugs are one of the most common classes of drugs out there and I know I say that a lot first off as usual some physiology arachidonic acid is a precursor to prostitutes which includes prostaglandins prostacyclin and from boxing arachidonic acid is found on the cell membrane and is hydrolyzed or released from the cell membrane by phospholipase a2 then it is converted into the inflammatory mediators by cyclooxygenase one and cyclooxygenase two also known as cox-1 and cox-2 different inflammatory mediators are produced from arachidonic acid based on which Cox enzyme works on it it can be converted into thromboxane a2 by a cox one which is a potent platelet activator as well as a vasoconstrictor prostaglandins may also be produced by cox one activity on arachidonic acid and these prostaglandins give gastric epithelial cell protection by stimulating production of mucus now protects against stomach acid prostacyclin x' may be produced by cox-2 activity which causes vasodilation and inhibits platelet aggregation meaning it helps to maintain a non thrombogenic surface within the vessel cox-1 and cox-2 can produce prostaglandins that leads a phase of dilation of the afferent arteriole of the glomerulus therefore preserving blood flow to the kidney these top four functions are part of normal physiological maintenance but are sites of injury or inflammation cox-2 converts arachidonic acid into prostaglandins that lead to increased vascular permeability pain sensitivity and fever most NSAIDs lead to reversible inhibition of cox-1 and cox-2 and therefore are considered as non selective ibuprofen is one example it has analgesic effects and super active effects and anti-inflammatory effects other examples include declare Fennec ketorolac which is mostly used for cell music properties indomethacin which accelerates the closure of the ductus arteriosus and so it may be used in a patent des arteriosus meloxicam and peroxy comma other examples as well as naproxen some have more cox-2 inhibition than cox-1 inhibition and therefore are associated with less side effects meloxicam and peroxy kam are examples the one we all know aspirin is next aspirin actually irreversibly inhibits cox-1 and cox-2 due to acetylation low-dose aspirin typically 81 milligrams is used to block mainly cox-1 activity and is used as an anti platelet high dose aspirin isn't used as much for information nowadays but higher doses inhibit cox-1 and cox-2 and so it does have an anti-inflammatory effect we're going to cover side-effects of NSAIDs in a minute but aspirin specifically has braised syndrome which is a form of encephalopathy and hepatic failure that is seen when it is given to children you can also have aspirin toxicity which can lead to respiratory alkalosis followed by metabolic acidosis charcoal and bicarbonate may be given as antidotes lastly before the side effects we have cox-2 selective NSAIDs the example being celecoxib this only inhibits cox-2 therefore limiting side effects but the downside is a resulting increase in cardiovascular risk due to the fact that we're losing the non thrombogenic protection in the vessels also celecoxib is a sulphur drug meaning people allergic to cellphone amides cannot take it so side-effects of NSAIDs include first of all gastric erosion and gastric ulcers this is because they themselves are often acids but also due to the inhibition of mucus secretion that protects the gastric epithelium oftentimes people taking NSAIDs are given proton pump inhibitors or misoprostol which is a prostaglandin e1 analog along side the end set to protect against the else's secondly they can also lead to a risk of bleeding especially from potential GI horses bleeding may also be worsened due to the inhibition of from boxing a to that usually activates platelets and is therefore in favor of clot formation finally we have the potential renal side-effects this is why I put a picture of the kidney in this video because there are so many potential renal side effects first off we can have an increase in blood pressure as a result of a lower sodium excretion and a lack of blood flow to the kidney that may occur due to the lack of the afferent arteriole a dilation acute kidney injury is another potential side effect often once again due to the reduced blood flow to the kidney due to the afferent arteriole razor constriction another potential side effect is acute interstitial nephritis clearance of other drugs may also be affected we have to think about other medications that the patient may be taking such as lithium that may end up causing toxicity another side effect is aplastic anemia that happens mostly with indomethacin although neutropenia can happen with more finally we have hyperkalemia as a result of decreased sodium delivery to the collecting duct remember that sodium and potassium are exchanged there so if there's not enough sodium getting to the collecting duct then it can't be exchanged for potassium so less potassium is excreted and ends up building up inside the body less sodium delivery to the collecting duct once again is due to the decreased afferent arteriole of vasodilation meaning a lower glomerular filtration rate the second reason for hyperkalemia is that the inhibition of the renal prostaglandins by the end sets can lead to less renin being released and so less aldosterone being produced meaning less potassium being excreted one disclaimer Seidner is a prostaglandin e2 actually increases potassium secretion to finish the video we have the contraindications to answers these include chronic kidney disease dehydration cirrhosis heart failure which are all linked to kidney function or kidney perfusion and finally during the third trimester in pregnancy due to their ability to close the ductus arteriosus [Music]