Non-steroidal anti-inflammatory agents (NSAIDs) help alleviate the symptoms of fever, edema, and pain linked to inflammation by inhibiting the synthesis of prostaglandins. Central to this mechanism is arachidonic acid (AA), a precursor molecule transformed by cyclooxygenase (COX) enzymes into a series of inflammatory and thrombogenic compounds. COX-1 is consistently active and influences physiological functions in tissues like the kidney, GI tract, and platelets, and is responsible for synthesizing thromboxane A2 (TXA2). COX-2 is induced by inflammation and is expressed in vascular endothelial and smooth muscle cells. Both variants convert AA into prostanoids, encompassing inflammatory molecules such as prostaglandins, thromboxane, and prostacyclin. NSAIDs exert their therapeutic effects by inhibiting these pathways.
However, the inhibitory action of NSAIDs isn't devoid of repercussions. Diminished production of protective prostaglandins, for instance, can precipitate gastritis and ulcers, as COX-1 is pivotal for the synthesis of gastric cytoprotective prostaglandins. Additionally, COX-2 plays a role in fostering a non-thrombogenic surface on vascular endothelium and over-inhibition of COX-2 by certain NSAIDs can heighten the risk of thrombotic events. NSAIDs such as ibuprofen, indomethacin, and celecoxib possess unique characteristics and potential side effects, including gastrointestinal damage, bleeding, and renal complications stemming from a reduction in glomerular filtration rate (GFR). Acetaminophen acts as an antipyretic and analgesic (not anti-inflammatory), via inhibition of COX-2. Acetaminophen is known for depleting glutathione and can cause severe hepatotoxicity, which can be treated with n-acetylcysteine.
NSAIDs, short for non-steroidal anti-inflammatory drugs, act by inhibiting cyclooxygenase (COX) enzymes. COX-1 and COX-2 convert arachidonic acid into prostaglandins--important mediators of inflammation that contribute to pain and swelling. By disrupting this conversion, NSAIDs exert their anti-inflammatory and analgesic effects.
COX-1 and COX-2, while both cyclooxygenase variants, have distinct roles. COX-1, found in various tissues, synthesizes gastric cytoprotective prostaglandins, and dilates the afferent arteriole and supports kidney functions. COX-2 primarily emerges during inflammation, producing prostaglandins that elicit pain and swelling, increase vascular permeability, and also support renal blood flow. NSAIDs, by inhibiting both COX-1 and COX-2, help reduce the inflammatory and pain-inducing effects of these enzymes. Selective COX-2 inhibitors, such as celecoxib, aim to provide anti-inflammatory action with fewer gastrointestinal complications.
Prostaglandins are products generated from arachidonic acid through the activity of COX enzymes, and are essential in the inflammation process. They heighten blood vessel permeability, amplify pain signals, and instigate fever. Additionally, COX derivatives like prostacyclin and thromboxane have roles in inflammation and the clotting cascade, respectively.
NSAIDs such as aspirin, indomethacin, ibuprofen, and celecoxib are commonly prescribed for gout. The inhibition of COX enzymes, like COX-1 and COX-2, results in decreased prostaglandin production, which helps alleviate the pain and inflammation associated with gout flare-ups.
Binhibiting prostaglandin synthesis, NSAIDs can affect renal function, especially in those already with renal vulnerabilities. Prostaglandins play a role in maintaining renal blood flow, and their inhibition by NSAIDs may result in dimished renal perfusion, especially in those with pre-existing renal disease This can manifest as salt and water retention, elevated blood pressure, edema, and in prolonged scenarios, chronic kidney disease (CKD).