Long Summary
Aspirin, a member of the salicylic acid class of non-steroidal anti-inflammatory drugs (NSAIDs), has been widely used for its antipyretic, analgesic, and anti-inflammatory properties. Its origins trace back to ancient times when compounds from willow leaves and meadowsweet were used to treat fever, owing to the presence of salicin, a precursor to salicylic acid. However, early forms of salicylic acid caused significant gastric irritation and unpleasant taste, limiting its clinical adoption.
The modern form of aspirin was synthesized in 1899 by Felix Hoffman at Bayer Pharmaceuticals by acetylating salicylic acid, resulting in acetyl salicylic acid. This modification is critical as it allows aspirin to irreversibly inhibit cyclooxygenase (COX) enzymes by transferring its acetyl group to specific serine residues (serine 529 in COX-1 and serine 516 in COX-2). Unlike other NSAIDs, which competitively inhibit COX enzymes temporarily, aspirin permanently disables the enzyme until new enzymes are synthesized by the body.
Aspirin's irreversible COX inhibition makes it particularly effective in preventing blood clotting at low doses. Platelets, which lack nuclei, cannot regenerate COX enzymes once inhibited by aspirin, reducing their ability to produce pro-clotting prostaglandins such as TXA2. Meanwhile, endothelial cells lining blood vessels can renew COX enzymes and produce anti-clotting prostaglandins like PGI2. This imbalance favors anti-clotting activity and underlies aspirin's blood-thinning effects, making it valuable for cardiovascular disease prevention.
Furthermore, aspirin acetylation of COX-2 uniquely leads to the production of aspirin-triggered lipoxins (ATLs), such as 15-epilipoxin A4, which possess powerful anti-inflammatory properties. This contributes to aspirin's enhanced anti-inflammatory action beyond COX inhibition. Despite many clinical benefits, aspirin is contraindicated in certain patients due to hypersensitivity; notably, 10-25% of asthmatics experience worsened symptoms, and its use in children with viral infections is avoided due to the risk of Reye's syndrome, a rare but serious condition causing liver and brain swelling.
For fever management in children and young adults, acetaminophen (Tylenol) is preferred over aspirin because it does not provoke Reye's syndrome and has fewer gastric side effects. Overall, aspirin remains a clinically important NSAID with wide-ranging uses in pain relief, fever reduction, inflammation, and cardiovascular protection, balanced by its potential side effects and contraindications.
