History, Mechanism of action, Adverse affects
Acetylsalicylic acid, commonly known as aspirin, is the most popular therapeutic drug in the world. It is an analgesic (pain-killing), antipyretic (fever-reducing), and anti-inflammatory sold without a prescription as tablets, capsules, powders, or suppositories. The drug reduces pain and fever, is believed to decrease the risk of heart attacks and strokes, and may deter colon cancer and help prevent premature birth. Often called the wonder drug, aspirin can have serious side effects, and its use results in more accidental poisoning deaths in children under five years of age than any other drug.
In the mid- to late-1700s, English clergyman Edward Stone chewed on a piece of willow bark and discovered its analgesic property after hearing a story that declared a brew from the bark was "good for pain and whatever else ails you." The bark's active ingredient was isolated in 1827 and named salicin for the Greek word salix, meaning willow. Salicylic acid, first produced from salicin in 1838 and synthetically from phenol in 1860, was effective in treating rheumatic fever and gout but caused severe nausea and intestinal discomfort. In 1898, a chemist named Hoffmann, working at Bayer Laboratories in Germany and whose father suffered from severe rheumatoid arthritis, synthesized acetylsalicylic acid in a successful attempt to eliminate the side effects of salicylic acid, which, until then, was the only drug that eased his father's pain. Soon the process for making large quantities of acetylsalicylic acid was patented, and aspirin—named for its ingredients acetyl and spiralic (salicylic) acid—became available by prescription. Its popularity was immediate and worldwide. Huge demand in the United States brought manufacture of aspirin to that country in 1915 when it also became available without a prescription.
Aspirin's recommended therapeutic adult dosage ranges from 600-1,000 mg and works best against "tolerable" pain; extreme pain is virtually unaffected, as is pain in internal organs. Aspirin inhibits (blocks) production of hormones (chemical substances formed by the body) called prostaglandins that may be released by an injured cell, triggering release of two other hormones that sensitize nerves to pain. The blocking action prevents this response and is believed to work in a similar way to prevent tissue inflammation. Remarkably, aspirin only acts on cells producing prostaglandins—for instance, injured cells. Its effect lasts approximately four hours.
This action is believed to occur at the anterior (frontal) hypothalamus, a portion of the brain that regulates such functions as heart rate and body temperature. The body naturally reduces its heat through perspiration and the dilation (expansion) of blood vessels. Prostaglandins released in the hypothalamus inhibit the body's natural heat-reducing mechanism. As aspirin blocks these prostaglandins, the hypothalamus is free to regulate body temperature. Aspirin lowers abnormally high body temperatures while normal body temperature remains unaffected.
One prostaglandin, thromboxane A2, aids platelet aggregation (accumulation of blood cells). Because aspirin inhibits thromboxane production, thus "thinning the blood," it is frequently prescribed in low doses over long periods for at-risk patients to help prevent heart attacks and strokes.
Aspirin's availability and presence in many prescription and non-prescription medications makes the risk of accidental overdose relatively high. Children and the elderly are particularly susceptible, as their toxicity thresholds are much lower than adults. About 10% of all accidental or suicidal episodes reported by hospitals are related to aspirin.
As aspirin slows down platelet accumulation, its use increases risk of bleeding, a particular concern during surgery and childbirth. Aspirin's irritant effect on the stomach lining may cause internal bleeding, sometimes resulting in anemia.
Reye syndrome is an extremely rare disease, primarily striking children between the ages of three and 15 years after they have been treated with aspirin for a viral infection. Reye syndrome manifests as severe vomiting, seizures, disorientation, and sometimes coma, which can result in permanent brain damage or death. The cause of Reye is unknown, but the onset strongly correlates to the treatment of viral infections with aspirin, and incidents of Reye in children on aspirin therapy for chronic arthritis is significant. In 1985, these observations were widely publicized and warning labels placed on all aspirin medications, resulting in a decline in the number of children with viruses being treated with aspirin and a corresponding decline in cases of Reye's syndrome.
Other adverse affects
Aspirin can adversely affect breathing in people with sinusitis or asthma, and long-term use may cause kidney cancer or liver disease. There is some evidence that it delays the onset of labor in full-term pregnancies and, as it crosses the placenta, may be harmful to the fetus.
See also Analgesia; Anti-inflammatory agents; Anticoagulants
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"Aspirin's Next Conquest: Does it Prevent Colon Cancer?" Journal of the National Cancer Institute (February 2, 1994): 166-68.
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Marie L. Thompson
Science EncyclopediaScience & Philosophy: 1,2-dibromoethane to Adrenergic