Non Steroidal Antiinflammatory Drugs(NSAIDS) One of the most common classes of drugs out there.

 First off, as usual, cell physiology. Arachidonic acid, is a precursor to prostaglands which includes prostaglandins, prostacyclins and thromboxane.

Arachidonic acid is found on the cell membrane and it’s hydrated or released from the cell membrane by the phospholipase A2.

Then it is converted into the inflammatory mediators by cyclooxygenase 1 and cyclooxygenase 2 also known as COX-1 and COX-2.

Different inflammatory mediators are produced from arachidonic acid base on which COX enzyme that works on it. It can be converted into thromboxane A2 by COX-1, which is a vaso-constrictor.

Prostaglandins may also be produced by COX-1 activity or Arachidonic acid.

These prostaglandins gives gastric epithelium cell protection by stimulating the production of mucous that protects against the stomach acid.

Prostacyclins maybe produced by COX-2 activity which causes vasodilation and inhibit platelet aggregation, meaning it helps to maintain a Non thrombogenic service, within the vessel.

COX-1 and COX-2 can produce prostaglandins, that lead to vasodilation in afferent arteriole of the glomerulus. Therefore, preserving blood flow to the kidney. These top 4 functions are part of non physiological maintenance.

But aside injury or inflammation, COX-2 converts arachidonic acid into prostaglandins, that leads to increase in vascular permeability, pain sensitivity and fever.

Most NSAID’s lead to reversible inhibition of COX-1 and COX-2. Therefore considered as non selective.

1. Reversible COX-1 and COX-2 inhibitors.

– Ibuprofen; is one example. It has analgesic effect, anti-pyretic effect and antiinflammatory effect.

Other examples include

– Diclofenac

– ketrolac which is mostly used for analgesic properties.

– Indomethacin which accelerates the closure of ductus arteriosus, which maybe used in patent ductus arteriosus (PDA).

– Meloxicam

– Piroxicam is another example, as well as ,

– Naproxen.

 Some have more COX-2 inhibition than COX-1 inhibition and therefore are associated with less side effects. Meloxicam and Piroxicam are examples.

The one we all know; Aspirin is next.

2. Irreversible COX-1 and COX-2 Inhibitor

– Aspirin actually irreverse the inhibit of COX-1 and COX-2 due to Acetylation.

Low dose aspirin, typically 81mg is used as an anti-platelet.

High dose aspirin, isn’t used much for inflammation nowadays.

But higher doses inhibits COX-1 and COX-2 and so it does have an antiinflammatory effect.

We’re going to discuss about the side effects of NSAID’s, but aspirin specifically, has

Reye’s 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.

Antidotes

Charcoal and Bicarbonates maybe given as antidotes. given as antidotes.

Lastly,before the general side effects of NSAIDs, we have COX-2 selective NSAIDs.

3. COX-2 selective Inhibitors

– Celecoxib ; this only inhibits COX-2. Therefore, limited side effects. But the down side is a result of increase in cardiovascular risk. Due to the fact that it will loosen the non thrombogenic protection vessels.

Also, Celecoxib is a sulfa drug.

Which means people allergic to sulfonamide cannot take it.

So side effects of NSAIDs include:

Side effects

1. Gastric ulcer and Gastric erosion;

this is because, the NSAIDs are often acids. But also, due to the inhibition of gastric secretion, that protects, the gastric epithelium.

Often times, people taking NSAID’s are given proton pump inhibitors or misoprostol which is a prostaglandin E1 analogue alongside the NSAID to protect against acidosis.

2. Bleeding

They can also lead to gastric bleeding especially from the potential gastric intestinal ulcer.

•Bleeding may also be worsened due to the inhibition of Thromboxane A2, that usually activates platelets and is therefore, in favor of clot formation.

 Finally , we gave the potential renal side effects.

3. Renal side effects;

Hypertension:

First off, you can have an increase in blood pressure as a result of lower sodium excretion and lack of blood flow to the kidney that may occur due to the lack of the afferent arteriole dilation.

Acute kidney injury;

Is another potential side effects often once again due to the reduced blood flow to the kidney, due to afferent arteriole vaso-constriction.

Another potential side effect is the acute interstitial nephritis. Next is

Reduced drug clearance

Clearance of other drugs may also be affected. We have to think about other medication that the patient may be taking. E.g lithium. So taking just lithium, that may end up causing toxicity.

Another side effect is aplastic anemia; that happens mostly with indomethacin.

 Finally we have hyperkalemia.

Hyperkalemia;

As a result of decreased sodium delivery to the collecting duct. Remember that sodium and potassium are exchanged that so if there’s not enough of sodium, getting into the collecting duct, that it can’t exchange for potassium.

So less potassium is excreted and ends building up inside the body. Less sodium delivery to the collecting duct, once again is due to the decreased afferent arteriole vasodilation, meaning that lower glomerular filtration rate.

The second reason for hyperkalemia is the -less prostaglandin -> innovation of the renal prostaglandins by the NSAIDs, can lead to less renin being released, so less aldosterone being produced, which means less potassium being excreted.

Therefore , prostaglandin E2 actually increases potassium secretion.

Lastly in this article, we have the contraindications

Contraindications to NSAIDs

1. Chronic kidney disease

2. Dehydration

3. Cirrhosis

4. Heart failure which are all linked to kidney function or kidney perfusion.

5. 3rd trimester pregnancy; during this stage in pregnancy, due to the ability to close the ductus arteriosus