Historical introduction

Salicylic acid, the active substance in plants used for thousands of years as medicaments, was synthesised by Kolbe in Germany in 1874. MacLagan1 and Stricker2showed that it was effective in rheumatic fever. A few years later sodium salicylate was also in use as a treatment for chronic rheumatoid arthritis and gout as well as an antiseptic compound.

Felix Hoffman was a young chemist working at Bayer. Legend has it that his father, who was taking salicylic acid to treat his arthritis, complained to his son about its bitter taste. Felix responded by adding an acetyl group to salicylic acid to make acetylsalicylic acid. Heinrich Dreser, the Company's head of pharmacology, showed it to be analgesic, antipyretic, and anti-inflammatory.3 Bayer introduced the new drug as “aspirin” in 1899 and sales have increased ever since.

In the latter part of the 20th century several other non-steroidal anti-inflammatory drugs (NSAIDs) were discovered, including antipyrine, phenacetin, phenylbutazone and, more recently, the fenamates, indomethacin and naproxen. Despite the diversity of their chemical structures, these drugs all share the same therapeutic properties. They alleviate the swelling, redness and pain of inflammation, reduce a general fever, and cure a headache. They also share, but not equally, a number of side effects including damage to the gastric mucosa, delay in the birth process, and damage to the kidney. A particularly interesting “side effect”, now used prophylactically, is the anti-thrombotic effect. Many clinical trials have shown that aspirin given once a day in doses as low as 75 mg will help to prevent heart attacks or strokes.

When a chemically diverse group of drugs shares not only the same therapeutic qualities (which in themselves have not much connection with each other), but also the same side effects, it is a fairly safe bet that their actions …