page_title: Nonsteroidal anti-inflammatory drug
section_title: History
hierarchical_section_title: Nonsteroidal anti-inflammatory drug / History
caption_attribution_description: One of the first advertisements for Bayer Aspirin aimed at American consumers, just before the U.S. patent for aspirin was to expire.
context_page_description: Nonsteroidal anti-inflammatory drugs are members of a drug class that reduces pain, decreases fever, prevents blood clots, and in higher doses, decreases inflammation. Side effects depend on the specific drug but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.
  The term nonsteroidal distinguishes these drugs from steroids, which while having a similar eicosanoid-depressing, anti-inflammatory action, have a broad range of other effects. First used in 1960, the term served to distance these medications from steroids, which were particularly stigmatised at the time due to the connotations with anabolic steroid abuse.
  NSAIDs work by inhibiting the activity of cyclooxygenase enzymes. In cells, these enzymes are involved in the synthesis of key biological mediators, namely prostaglandins, which are involved in inflammation, and thromboxanes, which are involved in blood clotting.
  There are two types of NSAIDs available: non-selective and COX-2 selective. Most NSAIDs are non-selective and inhibit the activity of both COX-1 and COX-2.
context_section_description: From the era of Greek medicine to the mid-19th century, the discovery of medicinal agents was classed as an empirical art; folklore and mythological guidance were combined in deploying the vegetable and mineral products that made up the expansive pharmacopeia of the time. Myrtle leaves were in use by 1500 BCE. Hippocrates (460–377 BCE) first reported using willow bark and in 30 BCE Celsus described the signs of inflammation and also used willow bark to mitigate them. On 25 April 1763, Edward Stone wrote to the Royal Society describing his observations on the use of willow bark-based medicines in febrile patients. The active ingredient of willow bark, a glycoside called salicin, was first isolated by Johann Andreas Buchner in 1827. By 1829, French chemist Henri Leroux had improved the extraction process to obtain about 30g of purified salicin from 1.5 kg of bark.
  By hydrolysis, salicin releases glucose and salicyl alcohol which can be converted into salicylic acid, both in vivo and through chemical methods. The acid is more effective than salicin and, in addition to its fever-reducing properties, is anti-inflammatory and analgesic. In 1869, Hermann Kolbe synthesised salicylate, although it was too acidic for the gastric mucosa. The reaction used to synthesise aromatic acid from a phenol in the presence of CO2 is known as the Kolbe-Schmitt reaction.
  By 1897 the German chemist Felix Hoffmann and the Bayer company prompted a new age of pharmacology by converting salicylic acid into acetylsalicylic acid—named aspirin by Heinrich Dreser. Other NSAIDs like ibuprofen were developed from the 1950s forward.
  In 2001, NSAIDs accounted for 70,000,000 prescriptions and 30 billion over-the-counter doses sold annually in the United States.
caption: One of the first advertisements for Bayer Aspirin, published in The New York Times in 1917
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