NSAIDs are prescribed very frequently by all kinds of specialists, some are even available as over the counter medications. Here are some interesting facts on NSAIDs…
- The history of Aspirin provides an interesting example of the translation of a compound from the realm of herbal folklore to contemporary therapeutics. The use of willow bark and leaves to relieve fever has been attributed to Hippocrates but was most clearly documented by Edmund Stone in a 1763 letter to the president of The Royal Society.
- Similar properties were attributed to potions from meadowsweet (Spiraea ulmaria), from which the name Aspirin is derived1.
- Salicin was crystallized in 1829 by Leroux, and Pina isolated Salicylic Acid in 1836.
- In 1859, Kolbe synthesized Salicylic Acid, and by 1874, it was being produced industrially. It soon was being used for Rheumatic fever, Gout, and as a general Antipyretic. However, its unpleasant taste and adverse GI effects made it difficult to tolerate for more than short periods1.
- In 1899, Hoffmann, a chemist at Bayer Laboratories, sought to improve the adverse-effect profile of Salicylic Acid (which his father was taking with difficulty for arthritis). Hoffmann came across the earlier work of the French chemist, Gerhardt, who had Acetylated Salicylic Acid in 1853, apparently ameliorating its adverse-effect profile, but without improving its efficacy, and therefore abandoned the project.
- Hoffmann resumed the quest, and Bayer began testing AcetylSalicylic Acid (ASA) in animals by 1899—the first time that a drug was tested on animals in an industrial setting—and proceeded soon thereafter to human studies and the marketing of Aspirin1.
- Acetaminophen was first used in medicine by von Mering in 1893.
- However, it gained popularity only after 1949, when it was recognized as the major active metabolite of both Acetanilide and Phenacetin. Acetanilide is the parent member of this group of drugs. It was introduced into medicine in 1886 under the name Antifebrin by Cahn and Hepp, who had discovered its Antipyretic action accidentally. However, Acetanilide proved to be excessively toxic.
- A number of chemical derivatives were developed and tested. One of the more satisfactory of these was Phenacetin. It was introduced into therapy in 1887 and was extensively employed in analgesic mixtures until it was implicated in Analgesic-abuse Nephropathy, Hemolytic anemia, and bladder cancer; it was withdrawn in the 1980s1.
- Male sex is associated with higher the risk of an upper GI complication, which twice as high in men than women2.
- UK general practices found a 55% increased risk of MI for those taking Diclofenac, compared to those taking no tNSAIDs or COX-2 inhibitors in the previous 3 years (p < 0.05)3.
- NSAIDs particularly Aspirin or Ketoprofen provide relief in Systemic Mastocytosis. In this condition PG D2 released from mast cells in large amounts causes severe episodes of flushing, vasodilation, & hypotension. However, Aspirin & NSAIDs can cause mast cell degranulation, so blockade with H1 & H2 receptor antagonists should be established before NSAIDs are initiated1.
- Bartter syndrome includes a series of rare disorders (frequency 1/100,000 persons) characterized by Hypokalemic, Hypochloremic Metabolic alkalosis with normal blood pressure and hyperplasia of the Juxtaglomerular apparatus. Fatigue, muscle weakness, diarrhea, and dehydration are the main symptoms. Renal COX-2 is induced, and biosynthesis of PGE2 is increased. Treatment with Indomethacin, combined with potassium repletion and Spironolactone, is associated with improvement in the biochemical derangements and symptoms. Selective COX-2 inhibitors also have been used.
- Chemoprevention of cancer is an area in which the potential use of aspirin and/or NSAIDs is under active investigation. Epidemiological studies suggested that frequent use of Aspirin is associated with as much as a 50% decrease in the risk of colon cancer (Kune et al., 2007)1.
- The findings that the protective effect of Aspirin against cancer, particularly Colorectal Cancer, does not appear to be dose dependent and the maximal effect is detected at low doses—which are the same recommended for the prevention of CV disease—strongly support the hypothesis that the inhibition of platelet function is an important determinant4.
- Observational studies have suggested that NSAID use, in particular Ibuprofen, is associated with lower risk of developing Alzheimer's disease. However, more recent prospective studies, including a randomized, controlled clinical trial comparing Celecoxib, Naproxen, and placebo (ADAPT Research Group, 2008), did not find a significant reduction in Alzheimer's dementia with the use of NSAIDs1.
- NSAIDs and Paracetamol are not promising therapeutics for altering the progression of cognitive decline in MCI and Alzheimer disease individuals. However, Diclofenac use was associated with slower cognitive decline, and as this was the only NSAID to do so, this suggests that COX inhibition is not the likely mechanism of action5.
References
1. 1. Goodman
& Gilman's The Pharmacological Basis of Therapeutics, 12th
Edition
2. 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338361/#B22
3. 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC558288/
4. 4. NSAIDs and Aspirin Recent Advances and Implications for Clinical Management
