Aspirin

Aspirin, or acetylsalicylic acid , (acetosal) is a salicylate drug often used as an analgesic (to relieve minor aches and pains), antipyretic (to reduce fever), and as an anti-inflammatory. It also has an antiplatelet ("blood-thinning") effect and is used in long-term, low doses to prevent heart attacks and blood clot formation in people at high risk for developing blood clots.

High doses of aspirin may also be given immediately after an acute heart attack; these doses may inhibit the synthesis of prothrombin and therefore produce a second and different anticoagulant effect, although this is not well understood.

The main undesirable side effects of aspirin are gastrointestinal distress—including ulcers and stomach bleeding—and tinnitus, especially in higher doses. Another adverse effect is increased bleeding in menstruating women, due to aspirin's anticoagulant properties. In children under 12 years of age, aspirin is no longer used to control flu-like symptoms or the symptoms of chickenpox, due to the risk of Reye's syndrome.

Aspirin was the first-discovered member of the class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs), not all of which are salicylates, although they all have similar effects and most have some mechanism of action which involves non-selective inhibition of the enzyme cyclooxygenase.

Trademark issues

The brand name Aspirin was coined by the Bayer company of Germany. The name "aspirin" is composed of a- (from acetylirte, meaning acetylated) -spir- (from the plant genus Spiraea) and -in (a common, easily pronounceable ending for drug names at the time). On March 6, 1899, Bayer registered the name Aspirin as a trademark.

Bayer began marketing aspirin in July 1899. It was originally sold as a powder and was an instant success; in 1914, Bayer introduced aspirin tablets.

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Although Bayer had registered Aspirin as a trademark in 1899, the German Patent Office refused to grant Bayer a patent for the drug based on the grounds that neither the product nor the process of preparation were novel.In 1905, Bayer sued Chemische Fabrik von Heyden in Britain for infringing the British patent on aspirin granted to it in 1900. Hayden claimed that existing prior art, in particular Kraut's work, invalidated Bayer's patent. Bayer advanced the argument that they were first to prepare a pure form of aspirin. The judge agreed with Hayden and invalidated the Bayer patent. A similar struggle took place in the U.S. Circuit court in Chicago; however, in the U.S., Bayer's patent was upheld in 1909. This created a situation where aspirin in the U.S. was three times more expensive than in Canada, and ten times more expensive than in Europe, resulting in rampant smuggling of aspirin, which Bayer unsuccessfully tried to contain.

After World War I, Bayer lost the right to use the trademark in many countries because the Allies seized and resold its foreign assets. The right to use the aspirin trademark in the United States (along with all other Bayer trademarks) was purchased from the U.S. government by Sterling Drug in 1918. Even before the patent for the drug expired in 1917, Bayer had been unable to stop competitors from copying the formula and using the name elsewhere, so, with a flooded market, the public was unable to recognize aspirin as coming from only one manufacturer, and in 1921, a landmark ruling by Billings Learned Hand established "aspirin" as a genericized trademark. Sterling was ultimately acquired by Bayer in 1994, but this did not restore the U.S. trademark. Other countries (such as Canada and many countries in Europe) still consider aspirin a protected trademark.

In some countries the name Aspirin is used as a generic name for the drug instead of the manufacturer's trademark. In countries in which Aspirin remains a trademark, the initialism ASA (for acetylsalicylic acid), or another initialism that matches the local-language term, is used as a generic term.

Mechanism of action

Structure of COX-2 inactivated by Aspirin. In the active site of each of the two monomers, Serine 530 has been acetylated. Also visible is the salicylic acid which has transferred the acyl group, and the heme cofactor.

In 1971, the British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed that aspirin suppresses the production of prostaglandins and thromboxanes. For this discovery, he was awarded both a Nobel Prize in Physiology or Medicine in 1982 and a knighthood.

Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its competitive and irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.

Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A₂ in platelets, producing an inhibitory effect on platelet aggregation. This anticoagulant property makes aspirin useful for reducing the incidence of heart attacks. 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A₂ release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.

Prostaglandins are local hormones (paracrine) produced in the body and have diverse effects in the body, including but not limited to transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are primarily caused by blood clots, and their reduction with the introduction of small amounts of aspirin has been seen to be an effective medical intervention. The side-effect of this is that the ability of the blood in general to clot is reduced, and excessive bleeding may result from the use of aspirin