Acetylsalicylic Acid

Acetylsalicylic Acid

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Aspirin (acetylsalicylic acid, see Figure 1) was introduced as an analgesic (pain-relieving agent) in the late nineteenth century by chemists at Bayer, a German pharmaceutical company. Acetylsalicylic acid is a prodrug and is transformed in the body to salicylate, the active form of the drug. Salicylates are also anti-inflammatory (i.e., prevent swelling and phenomena related to swelling associated with trauma or allergic response). Salicylates were initially isolated from white willow (Salix alba ) bark, from which the name of the drug is derived. Indeed, ancient Greek physicians, notably Hippocrates and Dioscorides, suggested chewing on willow bark to relieve pain.

Although aspirin is chiefly extolled for its analgesic properties, it has other equally important therapeutic benefits. Aspirin is an antipyretic (feverreducing) agent and is used to reduce elevated body temperature. Since the 1980s aspirin has been prescribed for the prevention of heart attack and stroke. Recent studies suggest that aspirin may guard against colon cancer.

Acetylsalicylic acid is a weak acid (pK_a = 3.5) that can be absorbed across the mucosal lining of the stomach. However, most of the drug is absorbed from the upper regions of the small intestine. Once the drug has entered the bloodstream it is hydrolyzed to acetic acid and salicylic acid (see Figure 2).

The most widely recognized mode of action of the salicylates is the inhibition of the formation of prostaglandins. Prostaglandins are 20-carbon molecules having side chains of varying degrees of saturation and oxidation , synthesized from polyunsaturated fatty acids in the body in response to tissue damage. The localized release of prostaglandins in response to injury or invasion by foreign agents (antigens) results in an increased blood flow to the affected area, and stimulation of the sensory nerve endings that mediate pain. Salicylates inhibit prostaglandin synthesis by binding to prostaglandin cyclooxygenases (the enzymes responsible for transforming fatty acids into prostaglandins), thereby inactivating the enzymes.

Aspirin is one of the most widely used drugs in modern society. It is most frequently used to treat mild to moderate pain or to reduce fever. Because of its anti-inflammatory action, aspirin is prescribed to individuals who suffer from joint inflammation conditions such as rheumatoid arthritis and osteoarthritis. In addition to its antipyretic, anti-inflammatory, and analgesic properties, aspirin is also prescribed to patients at high risk for heart attack

or stroke. Salicylates retard the clotting of blood by inhibiting platelet aggregation. When platelets aggregate, clotting is promoted and blood flow through vessels and valves is impeded. A stroke results when blood flow to regions of the brain is blocked. Aspirin inhibits enzymes in platelet membranes responsible for the formation of platelet aggregation factors, and thus reduces the risk of blood clots. Enzyme inhibition may also be responsible for aspirin's purported anticancer action. Recent findings suggest that regular doses of aspirin reduce the risks of some cancers (particularly colon cancer). Although scientists do not know how aspirin reduces the risk of cancer, they suspect it could be related to its anti-inflammatory effects and its ability to inhibit enzymes produced by some cancer cells.

Not all of aspirin's health effects are beneficial. Salicylate therapy is associated with many adverse side effects, generally pertaining to the gastrointestinal system. Gastric ulcers and gastric bleeding can occur in individuals on high doses of aspirin. More worrisome is the occurrence of Reye's syndrome in children with viral illnesses such as influenza or chicken pox who have been given aspirin. Reye's syndrome is a serious condition characterized by sudden vomiting, violent headaches, and, in 20 to 30 percent of cases, death. Because of the potential risk of Reye's syndrome in young people administered aspirin, many physicians and the Food and Drug Administration (FDA) warn against the use of salicylates in children under sixteen years of age.

FRIEDRICH BAYER (1825–1880)

In 1863 Friedrich Bayer cofounded a dye manufacturing company in Germany. Eight years after his death, in 1888 the company opened a pharmaceutical division. A decade later, employee Felix Hoffman, concerned over his father's aches and pains, discovered a useful chemical in the waste of the dye process. Known as aspirin, it remains a popular painkiller over 100 years later.

—Valerie Borek

see also Acetaminophen; Acid-Base Chemistry; Hydrolysis; Ibuprofen.

Nanette M. Wachter

Bibliography

Chevallier, Andrew (1996). The Encyclopedia of Medicinal Plants. New York: D.K. Publishing.

Kolata, Gina (2003). "Aspirin, and Cousins, Take a New Role in the War on Cancer." New York Times, March 11, 2003. Section F:1.

Williams, David A.; and Lemke, Thomas L. (2002). Foye's Principles of Medicinal Chemistry, 5th edition. Baltimore: Lippincott Williams & Wilkins.