Aspirin

Background

Aspirin is one of the safest and least expensive pain relievers on the marketplace. While other pain relievers were discovered and manufactured before aspirin, they only gained acceptance as over-the-counter drugs in Europe and the United States after aspirin's success at the turn of the twentieth century.

Today, Americans alone consume 16,000 tons of aspirin tablets a year, equaling 80 million pills, and we spend about $2 billion a year for non-prescription pain relievers, many of which contain aspirin or similar drugs.

Currently, the drug is available in several dosage forms in various concentrations from .0021 to .00227 ounces (60 to 650 milligrams), but the drug is most widely used in tablet form. Other dosage forms include capsules, caplets, suppositories and liquid elixir.

Aspirin can be used to fight a host of health problems: cerebral thromboses (with less than one tablet a day); general pain or fever (two to six tablets a day; and diseases such as rheumatic fever, gout, and rheumatoid arthritis. The drug is also beneficial in helping to ward off heart attacks. In addition, biologists use aspirin to interfere with white blood cell action, and molecular biologists use the drug to activate genes.

The wide range of effects that aspirin can produce made it difficult to pinpoint how it actually works, and it wasn't until the 1970s that biologists hypothesized that aspirin and related drugs (such as ibuprofen) work by inhibiting the synthesis of certain hormones that cause pain and inflammation. Since then, scientists have made further progress in understanding how aspirin works. They now know, for instance, that aspirin and its relatives actually prevent the growth of cells that cause inflammation.

History

The compound from which the active ingredient in aspirin was first derived, salicylic acid, was found in the bark of a willow tree in 1763 by Reverend Edmund Stone of Chipping-Norton, England. (The bark from the willow tree—Salix Alba—contains high levels of salicin, the glycoside of salicylic acid.) Earlier accounts indicate that Hippocrates of ancient Greece used willow leaves for the same purpose—to reduce fever and relieve the aches of a variety of illnesses.

During the 1800s, various scientists extracted salicylic acid from willow bark and produced the compound synthetically. Then, in 1853, French chemist Charles F. Gerhardt synthesized a primitive form of aspirin, a derivative of salicylic acid. In 1897 Felix Hoffmann, a German chemist working at the Bayer division of I.G. Farber, discovered a better method for synthesizing the drug. Though sometimes Hoffmann is improperly given credit for the discovery of aspirin, he did understand that aspirin was an effective pain reliever that did not have the side effects of salicylic acid (it burned throats and upset stomachs).

Bayer marketed aspirin beginning in 1899 and dominated the production of pain relievers until after World War I, when Sterling Drug bought German-owned Bayer's New York operations. Today, "Aspirin" is a registered trademark of Bayer in many countries around the world, but in the United States and the United Kingdom aspirin is simply the common name for acetylsalicylic acid.

The manufacture of aspirin has paralleled advancements in pharmaceutical manufacturing as a whole, with significant mechanization occurring during the early twentieth century. Now, the manufacture of aspirin is highly automated and, in certain pharmaceutical companies, completely computerized.

While the aspirin production process varies between pharmaceutical companies, dosage forms and amounts, the process is not as complex as the process for many other drugs. In particular, the production of hard aspirin tablets requires only four ingredients: the active ingredient (acetylsalicylic acid), corn starch, water, and a lubricant.

Raw Materials

To produce hard aspirin tablets, corn starch and water are added to the active ingredient (acetylsalicylic acid) to serve as both a binding agent and filler, along with a lubricant. Binding agents assist in holding the tablets together; fillers (diluents) give the tablets increased bulk to produce tablets of adequate size. A portion of the lubricant is added during mixing and the rest is added after the tablets are compressed. Lubricant keeps the mixture from sticking to the machinery. Possible lubricants include: hydrogenated vegetable oil, stearic acid, talc, or aluminum stearate. Scientists have performed considerable investigation and research to isolate the most effective lubricant for hard aspirin tablets.

Chewable aspirin tablets contain different diluents, such as mannitol, lactose, sorbitol, sucrose, and inositol, which allow the tablet to dissolve at a faster rate and give the drug a pleasant taste. In addition, flavor agents, such as saccharin, and coloring agents are added to chewable tablets. The colorants currently approved in the United States include: FD&C Yellow No. 5, FD&C Yellow No. 6, FD&C Red No.3, FD&C Red No. 40, FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, a limited number of D&C colorants, and iron oxides.

The Manufacturing
Process

Aspirin tablets are manufactured in different shapes. Their weight, size, thickness, and hardness may vary depending on the amount of the dosage. The upper and lower surfaces of the tablets may be flat, round, concave, or convex to various degrees. The tablets may also have a line scored down the middle of the outer surface, so the tablets can be broken in half, if desired. The tablets may be engraved with a symbol or letters to identify the manufacturer.

Aspirin tablets of the same dosage amount are manufactured in batches. After careful weighing, the necessary ingredients are mixed and compressed into units of granular mixture called slugs. The slugs are then filtered to remove air and lumps, and are compressed again (or punched) into numerous individual tablets. (The number of tablets will depend on the size of the batch, the dosage amount, and the type of tablet machine used.) Documentation on each batch is kept throughout the manufacturing process, and finished tablets undergo several tests before they are bottled and packaged for distribution.

The procedure for manufacturing hard aspirin tablets, known as dry-granulation or slugging, is as follows:

Weighing

• 1 The corn starch, the active ingredient, and the lubricant are weighed separately in sterile canisters to determine if the ingredients meet pre-determined specifications for the batch size and dosage amount.

Mixing

• 2 The corn starch is dispensed into cold purified water, then heated and stirred until a translucent paste forms. The corn starch, the active ingredient, and part of the lubricant are next poured into one sterile canister, and the canister is wheeled to a mixing machine called a Glen Mixer. Mixing blends the ingredients as well as expels air from the mixture.
• 3 The mixture is then mechanically separated into units, which are generally from 7/8 to 1 inches (2.22 to 2.54 centimeters) in size. These units are called slugs.

Dry screening

• 4 Next, small batches of slugs are forced through a mesh screen by a hand-held stainless steel spatula. Large batches in sizable manufacturing outlets are filtered through a machine called a Fitzpatrick mill. The remaining lubricant is added to the mixture, which is blended gently in a rotary granulator and sifter. The lubricant keeps the mixture from sticking to the tablet machine during the compression process.

Compression

• 5 The mixture is compressed into tablets either by a single-punch machine (for small batches) or a rotary tablet machine (for large scale production). The majority of single-punch machines are power-driven, but hand-operated models are still available. On single-punch machines, the mixture is fed into one tablet mold (called a dye cavity) by a feed shoe, as follows:
  • The feed shoe passes over the dye cavity and releases the mixture. The feed shoe then retracts and scrapes all excess mixture away from the dye cavity.
  • A punch—a short steel rod—the size of the dye cavity descends into the dye, compressing the mixture into a tablet. The punch then retracts, while a punch below the dye cavity rises into the cavity and ejects the tablet.
  • As the feed shoe returns to fill the dye cavity again, it pushes the compressed tablet from the dye platform.
• On rotary tablet machines, the mixture runs through a feed line into a number of dye cavities which are situated on a large steel plate. The plate revolves as the mixture is dispensed through the feed line, rapidly filling each dye cavity. Punches, both above and below the dye cavities, rotate in sequence with the rotation of the dye cavities. Rollers on top of the upper punches press the punches down onto the dye cavities, compressing the mixture into tablets, while roller-activated punches beneath the dye cavities lift up and eject the tablets from the dye platform.

Testing

• 6 The compressed tablets are subjected to a tablet hardness and friability test, as well as a tablet disintegration test (see Quality Control section below).

Bottling and packaging

• 7 The tablets are transferred to an automated bottling assembly line where they are dispensed into clear or color-coated polyethylene or polypropylene plastic bottles or glass bottles. The bottles are topped with cotton packing, sealed with a sheer aluminum top, and then sealed with a plastic and rubber child-proof lid. A sheer, round plastic band is then affixed to the circular edge of the lid. It serves as an additional seal to discourage and detect product tampering.
• 8 The bottles are then labeled with product information and an expiration date is affixed. Depending on the manufacturer, the bottles are then packaged in individual cardboard boxes. The packages or bottles are then boxed in larger cardboard boxes in preparation for distribution to distributors.

Quality Control

Maintaining a high degree of quality control is extremely important in the pharmaceutical manufacturing industry, as well as required by the Food and Drug Administration (FDA). All machinery is sterilized before beginning the production process to ensure that the product is not contaminated or diluted in any way. In addition, operators assist in maintaining an accurate and even dosage amount throughout the production process by performing periodic checks, keeping meticulous batch records, and administering necessary tests. Tablet thickness and weight are also controlled.

Once the tablets have been produced, they undergo several quality tests, such as tablet hardness and friability tests. To ensure that the tablets won't chip or break under normal conditions, they are tested for hardness in a machine such as the Schleuniger (or Heberlein) Tablet Hardness Tester. They are also tested for friability, which is the ability of the tablet to withstand the rigors of packaging and shipping. A machine called a Roche Friabilator is used to perform this test. During the test, tablets are tumbled and exposed to repeated shocks.

Another test is the tablet disintegration test. To ensure that the tablets will dissolve at the desirable rate, a sample from the batch is placed in a tablet disintegration tester such as the Vanderkamp Tester. This apparatus consists of six plastic tubes open at the top and bottom. The bottoms of the tubes are covered with a mesh screen. The tubes are filled with tablets and immersed in water at 37 degrees Fahrenheit (2.77 degrees Celsius) and retracted for a specified length of time and speed to determine if the tablets dissolve as designed.

Where To Learn More

Books

HIJSA'S Pharmaceutical Dispensing, 6th edition, Mack Publishing Company, 1966.

History of Pharmacy, 4th edition, The American Institute of History of Pharmacy, 1986.

An Introduction to Pharmaceutical Formulation, Pergamon Press, 1965.

Mann, Charles C. The Aspirin Wars: Money, Medicine & One Hundred Years of Rampant Competition. Alfred A. Knopf, Inc. 1991.

Remington's Pharmaceutical Sciences, 17th edition, Mack Publishing, 1985.

Periodicals

Draper, Roger. "A Pharmaceutical Cinderella (History of Aspirin)," The New Leader. January 13, 1992, p. 16.

Weissmann, Gerald. "Aspirin," Scientific American. January, 1991, pp. 84-90.

Wickens, Barbara. "Aspirin: What's in a Name?," Maclean's. July 16, 1990, p. 40.

—Greg Ling

Aspirin

Definition

Aspirin is a medication given to relieve pain and reduce fever. The name "aspirin" was originally a trademark, first used when the drug was introduced in Europe in 1899. Aspirin was developed by a German chemist named Felix Hoffman as a treatment for his father's arthritis.

Purpose

Aspirin is still used to relieve many kinds of minor aches and pains—headaches, toothaches, muscle pain, menstrual cramps, joint pains associated with arthritis, and the general achiness that many people experience with colds and flu. Some people take aspirin daily to reduce the risk of stroke, heart attack, or other heart problems.

Description

Aspirin, also known as acetylsalicylic acid, is not a prescription drug. It is sold over the counter in many forms, from the familiar white tablets to chewing gum and rectal suppositories. Coated, chewable, buffered, and extended-release forms are available. Many other over-thecounter medications contain aspirin. Alka-Seltzer Original Effervescent Antacid Pain Reliever (R), for example, contains aspirin for pain relief as well as sodium bicarbonate to relieve acid indigestion, heartburn, and sour stomach.

Aspirin belongs to a group of drugs called salicylates. Other members of this group include sodium salicylate, choline salicylate, and magnesium salicylate. These drugs are more expensive and no more effective than aspirin; however, they are a little easier on the patient's stomach. Aspirin is quickly absorbed into the bloodstream and provides rapid and relatively long-lasting pain relief. Aspirin in high doses also reduces inflammation. Researchers believe these effects are due to aspirin's ability to block the production of pain-producing chemicals called prostaglandins.

In addition to relieving pain and reducing inflammation, aspirin also lowers fever by acting on the hypothalamus, which is the part of the brain that regulates temperature. The brain then signals the blood vessels to dilate (widen), which allows heat to leave the body more quickly.

Recommended dosage

Adults

pain relief or fever reduction. The usual dosage is one to two tablets every three to four hours, up to six times per day.

risk reduction for stroke. One tablet four times a day or two tablets twice a day.

risk reduction for heart attack. Aspirin may be used as a first-line treatment for a heart attack. The patient should chew a single uncoated aspirin tablet, since chewing makes it easier for the body to absorb the medication rapidly. Aspirin will not stop a heart attack, and proper emergency care is essential; however, an aspirin tablet may reduce the amount of damage done by the heart attack.

Patients should check with a physician for the proper dose and number of times per week they should take aspirin to reduce the risk of a heart attack. The most common dose for this purpose is a single baby aspirin tablet taken daily. Enteric-coated aspirin is often used, since it reduces the risk of stomach irritation.

Children

Parents should consult the child's physician about the proper dosage for their child's condition.

Precautions

Aspirin—even children's aspirin—should never be given to children or teenagers with flu-like symptoms or chickenpox. Aspirin can cause Reye's syndrome, a life-threatening condition that affects the nervous system and liver. As many as 30% of children and teenagers who develop Reye's syndrome die. Those who survive may have permanent brain damage.

Parents should consult a physician before giving aspirin to a child under 12 years of age for arthritis, rheumatism, or any condition that requires long-term use of the drug.

No one should take aspirin for more than 10 days in a row unless instructed to do so by a physician. Anyone with fever should not take aspirin for more than three days without a physician's advice. In addition, no one should take more than the recommended daily dosage.

People in the following categories should not use aspirin without first checking with their physician:

• Pregnant women. Aspirin can cause bleeding problems in both the mother and the developing fetus. Aspirin can also cause the infant's weight to be too low at birth.
• Women who are breastfeeding. Aspirin can pass into breast milk and affect the baby.
• People with a history of bleeding problems.
• People who are taking such blood-thinning drugs as warfarin (Coumadin).
• People who have had recent surgery. Aspirin increases the risk of bleeding from an incompletely healed incision.
• People with a history of stomach ulcers.
• People with a history of asthma, nasal polyps, or both. Patients with these disorders are more likely to be allergic to aspirin.
• People who are allergic to fenoprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate sodium, naproxen, sulindac, tolmetin, or an orange food coloring known as tartrazine. They may also be allergic to aspirin.
• People with AIDS or AIDS-related complex who are taking AZT (zidovudine). Aspirin can increase the risk of bleeding in these patients.
• People taking any of the drugs listed below under Interactions.
• People with liver damage or severe kidney failure.

Aspirin should not be taken before a surgical procedure, as it can increase the risk of excessive bleeding during surgery. People scheduled for an operation should check with their surgeon to find out when they should discontinue taking aspirin.

Aspirin can cause stomach irritation. Taking aspirin with food or milk, or drinking an eight-ounce glass of water with it may help to prevent damage to the stomach lining. Some patients find that using coated or buffered aspirin reduces the risk of stomach upset. Patients should be aware, however, that drinking alcoholic beverages can make the stomach irritation worse.

Patients with any of the following symptoms should stop taking aspirin immediately and call their physician:

• a sensation of ringing or buzzing in the ears
• hearing loss
• dizziness
• stomach pain that does not go away

Patients should discard any aspirin that has developed a vinegary smell. That is a sign that the medication is too old and ineffective.

Side effects

The most common side effects of aspirin include upset stomach, heartburn, loss of appetite, and small amounts of blood in the stool. Less common side effects are rashes, hives, fever, vision problems, liver damage, thirst, stomach ulcers, and bleeding. People with asthma, rhinitis, polyps in the nose, or allergies to aspirin may have trouble breathing after taking the drug.

Interactions

Aspirin may increase, decrease, or change the effects of many drugs. Aspirin can increase the toxicity of such drugs as methotrexate (Rheumatrex) and valproic acid (Depakote, Depakene). Taken with such blood-thinning drugs as warfarin (Coumadin) and dicumarol, aspirin can increase the risk of excessive bleeding. Aspirin counteracts the effects of certain other drugs, including angiotensin-converting enzyme (ACE) inhibitors and beta blockers, which lower blood pressure, and medicines used to treat gout (probenecid and sulfinpyrazone). Blood pressure may drop unexpectedly and cause fainting or dizziness if aspirin is taken along with nitroglycerin tablets. Aspirin may also interact with diuretics , diabetes medications, other nonsteroidal anti-inflammatory drugs (NSAIDs), seizure medications, and steroids. Anyone who is taking these drugs should ask his or her physician whether they can safely take aspirin.

Resources

books

"factors affecting drug response: drug interactions." section 22, chapter 301 in the merck manual of diagnosis and therapy, edited by mark h. beers, md, and robert berkow, md. whitehouse station, nj: merck research laboratories, 1999.

wilson, billie ann, rn, phd, carolyn l. stang, pharmd, and margaret t. shannon, rn, phd. nurses drug guide 2000. stamford, ct: appleton and lange, 1999.

periodicals

cryer, b. "gastrointestinal safety of low-dose aspirin." american journal of managed care 8 (december 2002) (22 suppl): s701-s708.

grattan. c. e. "aspirin sensitivity and urticaria." clinical and experimental dermatology 28 (march 2003): 123-127.

macdonald, t. m., and l. wei. "effect of ibuprofen on cardioprotective effect of aspirin." lancet 361 (february 15, 2003): 573-574.

nordenberg, tamar. "'an aspirin a day'—just another cliché?" fda consumer (march-april 1999): 2-4.

organizations

american society of health-system pharmacists (ashp). 7272 wisconsin avenue, bethesda, md 20814. (301) 657-3000. <www.ashp.org>.

aspirin foundation of america. (800) 432-3247; fax (202) 737-8406. <www.aspirin.org>.

united states food and drug administration (fda). 5600 fishers lane, rockville, md 20857-0001. (888) info-fda. <www.fda.gov>.

Nancy Ross-Flanigan

Sam Uretsky, PharmD

Aspirin

Definition

Aspirin is a medicine that relieves pain and reduces fever.

Purpose

Aspirin is used to relieve many kinds of minor aches and pains—headaches, toothaches, muscle pain, menstrual cramps, the joint pain from arthritis, and aches associated with colds and flu. Some people take aspirin daily to reduce the risk of stroke, heart attack, or other heart problems.

Description

Aspirin-also known as acetylsalicylic acid-is sold over the counter and comes in many forms, from the familiar white tablets to chewing gum and rectal suppositories. Coated, chewable, buffered, and extended release forms are available. Many other over-the-counter medicine contain aspirin. Alka-Seltzer Original Effervescent Antacid Pain Reliever, for example, contains aspirin for pain relief and sodium bicarbonate to relieve acid indigestion, heartburn, and sour stomach.

Aspirin belongs to a group of drugs called salicylates. Other members of this group include sodium salicylate, choline salicylate, and magnesium salicylate. These drugs are more expensive and no more effective than aspirin. However, they are a little easier on the stomach. Aspirin is quickly absorbed into the bloodstream and provides quick and relatively long-lasting pain relief. Aspirin also reduces inflammation. Researchers believe these effects come about because aspirin blocks the production of pain-producing chemicals called prostaglandins.

In addition to relieving pain and reducing inflammation, aspirin also lowers fever by acting on the part of the brain that regulates temperature. The brain then signals the blood vessels to widen, which allows heat to leave the body more quickly.

Recommended dosage

Adults

TO RELIEVE PAIN OR REDUCE FEVER. One to two tablets every three to four hours, up to six times per day.

TO REDUCE THE RISK OF STROKE. One tablet four times a day or two tablets twice a day.

TO REDUCE THE RISK OF HEART ATTACK. Check with a physician for the proper dose and number of times per week aspirin should, if at all, be taken.

Children

Check with a physician.

Precautions

Aspirin-even children's aspirin-should never be given to children or teenagers with flu-like symptoms or chickenpox. Aspirin can cause Reye's syndrome, a life-threatening condition that affects the nervous system and liver. As many as 30% of children and teenagers who develop Reye's syndrome die. Those who survive may have permanent brain damage.

Check with a physician before giving aspirin to a child under 12 years for arthritis, rheumatism, or any condition that requires long-term use of the drug.

No one should take aspirin for more than 10 days in a row unless told to do so by a physician. Anyone with fever should not take aspirin for more than 3 days without a physician's consent. Do not to take more than the recommended daily dosage.

KEY TERMS

Diuretic— Medicine that increases the amount of urine produced and relieves excess fluid buildup in body tissues. Diuretics may be used in treating high blood pressure, lung disease, premenstrual syndrome, and other conditions.

Inflammation— Pain, redness, swelling, and heat that usually develop in response to injury or illness.

NSAIDs— Nonsteroidal anti-inflammatory drugs. Drugs such as ketoprofen and ibuprofen which relieve pain and reduce inflammation.

Polyp— A lump of tissue protruding from the lining of an organ, such as the nose, bladder, or intestine. Polyps can sometimes block the passages in which they are found.

Prostaglandin— A hormonelike chemical produced in the body. Prostaglandins have a wide variety of effects, and may be responsible for the production of some types of pain and inflammation.

Reye's syndrome— A life-threatening disease that affects the liver and the brain and sometimes occurs after a viral infection, such as flu or chickenpox. Children or teenagers who are given aspirin for flu or chickenpox are at increased risk of developing Reye's syndrome.

Rhinitis— Inflammation of the membranes inside the nose.

Salicylates— A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain, reduce inflammation, and lower fever.

People in the following categories should not use aspirin without first checking with their physician:

• Pregnant women. Aspirin can cause bleeding problems in both the mother and the developing fetus. Aspirin can also cause the infant's weight to be too low at birth.
• Women who are breastfeeding. Aspirin can pass into breast milk and may affect the baby.

• People with a history of bleeding problems.
• People who are taking blood-thinning drugs, such as warfarin (Coumadin).
• People with a history of ulcers.
• People with a history of asthma, nasal polyps, or both. These people are more likely to be allergic to aspirin.
• People who are allergic to fenoprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate sodium, naproxen, sulindac, tolmetin, or the orange foodcoloring tartrazine. They may also be allergic to aspirin.
• People with AIDS or AIDS-related complex who are taking AZT (zidovudine). Aspirin can increase the risk of bleeding in these patients.
• People taking certain other drugs (discussed in Interactions).
• People with liver damage or severe kidney failure.

Aspirin should not be taken before surgery, as it can increase the risk of excessive bleeding. Anyone who is scheduled for surgery should check with his or her surgeon to find out how long before surgery to avoid taking aspirin.

Aspirin can cause stomach irritation. To reduce the likelihood of that problem, take aspirin with food or milk or drink a full 8-oz glass of water with it. Taking coated or buffered aspirin can also help. Be aware that drinking alcohol can make the stomach irritation worse.

Stop taking aspirin immediately and call a physician if any of these symptoms develop:

• ringing or buzzing in the ears
• hearing loss
• dizziness
• stomach pain that does not go away

Do not take aspirin that has a vinegary smell. That is a sign that the aspirin is too old and ineffective. Flush such aspirin down the toilet.

Because aspirin can increase the risk of excessive bleeding, do not take aspirin daily over long periods-to reduce the risk of stroke or heart attack, for example-unless advised to do so by a physician.

Side effects

The most common side effects include stomachache, heartburn, loss of appetite, and small amounts of blood in stools. Less common side effects are rashes, hives, fever, vision problems, liver damage, thirst, stomach ulcers, and bleeding. People who are allergic to aspirin or those who have asthma, rhinitis, or polyps in the nose may have trouble breathing after taking aspirin.

Interactions

Aspirin may increase, decrease, or change the effects of many drugs. Aspirin can make drugs such as methotrexate (Rheumatrex) and valproic acid (Depakote, Depakene) more toxic. If taken with blood-thinning drugs, such as warfarin (Coumadin) and dicumarol, aspirin can increase the risk of excessive bleeding. Aspirin counteracts the effects of other drugs, such as angiotensin-converting enzyme (ACE) inhibitors and beta blockers, which lower blood pressure, and medicines used to treat gout (probenecid and sulfinpyrazone). Blood pressure may drop unexpectedly and cause fainting or dizziness if aspirin is taken along with nitroglycerin tablets. Aspirin may also interact with diuretics, diabetes medicines, other nonsteroidal anti-inflammatory drugs (NSAIDs), seizure medications, and steroids. Anyone who is taking these drugs should ask his or her physician whether they can safely take aspirin.

Resources

PERIODICALS

"What's the Best Pain Reliever? Depends on Your Pain." Consumer Reports May 1996: 62.

aspirin or more accurately acetylsalicylic acid, is the best known and most commonly used drug after alcohol. Aspirin was originally a trade name, coined by the German company Bayer when the drug was introduced in 1899. The name comes from a combination of A for acetyl and spirin (from Spiraea, the plant family containing salicylates). In 1918 the US Supreme Court ruled that the name ‘aspirin’ had been so widely advertised that it had become the common name for the drug and the US Patent office cancelled Bayer's rights to the name.

Originally salicylates (salts of salicylic acid) were obtained from the bark and leaves of willow and poplar trees; indeed ‘salicylate’ derives from the title of the willow genus, Salix. From early times it was known that salicylates could reduce pain, temperature during fever, and inflammatory swelling (analgesic, antipyretic, and anti-inflammatory actions, respectively).

Instructions for the use of such extracts can be found in Eber's Papyrus (c.1550 bc) and in the writings of Celsus, Pliny the Elder, and Dioscorides in the first century, and of Galen in the second. The four cardinal signs of inflammation, namely rubor, calor, dolor, and tumor (redness, heat, pain, and swelling), were described in De Re Medica in 30 ad. Celsus described the use of ‘boiled vinegar extracts of willow leaves for the relief of pain from prolapse of the uterus and other conditions’. It is possible that this procedure with weak acetic acid (vinegar) may have converted naturally occurring salicylate to the acetyl form, that is aspirin itself. The acetyl derivative was thought by Bayer to reduce the nausea and gastrointestinal symptoms associated with salicylic acid itself. In 1980, 97 million kilograms of aspirin were produced in the US alone.

It was to take more than three thousand years after the first descriptions of the therapeutic value of salicylates before their actions were understood. Many of the effects of aspirin are now known to be due to the inhibition of an enzyme in the body, cyclooxygenase. This enzyme converts a lipid, arachidonic acid, into substances called endoperoxides, which are in turn converted to prostaglandins I₂, E₁, E₂, D₂, and F_2α, and to thromboxanes A₂ and B₂. Inhibition of formation of prostaglandins and thromboxanes is what prevents many of the symptoms that are relieved by aspirin. The complex biochemical reactions involved in the conversion of arachidonic acid were worked out in Sweden by Bergstrom and Samuelsson, while the effects of prostaglandins and thromboxanes on biological systems were investigated by John Vane and his colleagues in England. All three shared the Nobel Prize for their work in 1982.

Prostaglandins E₁ and E₂ disturb the temperature-regulating centre in the brain, resetting body temperature to a higher level, resulting in fever. By inhibiting the production of prostaglandins, aspirin reduces the temperature in fever; but it has no effect on normal body temperature since no prostaglandins are usually being generated in the temperature-regulating centre. Tissue damage also leads to the production of prostaglandins, which sensitize the endings of the nerve fibres that convey the sensation of pain. Thus aspirin relieves the pain associated with injury or trauma by preventing the formation of prostaglandins. Prostaglandin E₂ and prostaglandin I₂ (prostacyclin) are powerful dilators of blood vessels, making injured areas appear reddened. Other agents released in inflammation (e.g. histamine and bradykinin) increase the permeability of blood vessels. The combination of increased permeability and vasodilation (enlargement of the vessels) allows fluid to escape from the circulation and collect in the damaged tissues, giving rise to swelling — another symptom that is reversed by aspirin.

Considerable interest centres on the recent discovery that low doses of aspirin, taken regularly, reduce the chances of heart attack and stroke caused by blood clots. Aggregation of blood platelets is one of the early processes of clot formation and anything that reduces platelet ‘stickiness’ will help to prevent clots. Platelets synthesize thromboxane A₂, which promotes their aggregation, while the cells lining the blood vessel synthesize prostacyclin, a powerful anti-aggregatory agent as well as a vasodilator. Aspirin irreversibly inhibits the cyclooxygenase enzyme in platelets, so the platelets cannot generate thromboxane A₂ until they are replaced (in 7–10 days). What is needed to prevent clot formation is the prevention of thromboxane formation together with the preservation of prostacyclin. This can be achieved with low concentrations of aspirin. Higher concentrations of aspirin inhibit the formation of both agents.

One of the common side effects of aspirin is a feeling of nausea, which may be accompanied by bleeding in the stomach. The stomach lining (mucosa) produces prostaglandins, which protect the mucosa itself from attack by gastric acid. Local suppression of prostaglandin formation by aspirin, especially when a tablet lies against the mucosa, can lead to acid attack of the mucosa, even ulceration. The chances of this are greatly reduced by using ‘soluble’ forms of aspirin which disperse the drug more effectively.

Alan W. Cuthbert

Aspirin

Aspirin grew out of a group of drugs called "patent medicines." These medications—some of questionable quality—were very popular from the 1600s to later years of the 1800s. The name "patent" comes from the fact that when a medication was patented (or registered), its formula was owned by the patent holder and no one else could duplicate or sell it. Some early patent medicines had exotic names like "Daffy's Elixer" and "Dr. Hooper's Female Pills." Whatever the name, however, most patent drugs were not terribly effective. Concerns began to grow, especially in the United States, about what was in the patent formulas. Many had very high alcohol levels or were laced with addictive drugs like opium and heroin. The passage of the Pure Food and Drug Act of 1906 forced all patent medicine makers to list the ingredients of every bottle they sold. An 1938 addition to the law made testing of all medications mandatory; effectiveness tests were added 1968.

Not all patent medicines were phony. Nineteenth-century chemists knew that salicylic acid had pain-relieving qualities, but the acid burned throats and upset stomachs. In 1853 French chemist Charles F. Gerhardt synthesized (formed by bringing together separate parts in a laboratory) a primitive form of acetylsalicylic acid, or aspirin. In 1897 Felix Hoffmann of the Bayer Company found a better method to synthesize the drug and discovered that his version overcame the unpleasant side effects while maintaining the therapeutic effects of the acid. In 1899 Bayer began marketing the new product as Aspirin, a trade name. Bayer lost the use of the trade name in 1919 as part of Germany's concessions to the Allies at the end of World War I (1914-1918), and the name aspirin passed into generic use.

One aspirin-based product, Anacin, was invented by a Wisconsin dentist in 1918. Today, people use aspirin to help with a variety of ills, from headaches to body aches. Aspirin has also been recently tested (and promoted) as a way to control the onset of heart attacks.

aspirin acetyl derivative of salicylic acid (see salicylate ) that is used to lower fever, relieve pain, reduce inflammation, and thin the blood. Common conditions treated with aspirin include headache, muscle and joint pain, and the inflammation caused by rheumatic fever and arthritis. Aspirin is believed to act against fever, pain, and inflammation by interfering with the synthesis of specific prostaglandins in the body. Because of its ability to inhibit the formation of blood clots, aspirin is also used in low doses to prevent heart attack and stroke and to control unstable angina. The drug's usefulness in preventing certain cancers, the dangerous high blood pressure that sometimes occurs during pregnancy (toxemia), and migraine headaches is also under investigation.

Normal dosage may cause nausea, vomiting, diarrhea, or gastrointestinal bleeding. Large doses cause acid-base imbalance and respiratory disturbances and can be fatal, especially in children. Aspirin also has been linked to the development of Reye's syndrome (a combination of acute encephalopathy and fatty infiltration of internal organs) in children who have taken it for viral infections. Acetaminophen (Tylenol), which does not cause gastric irritation but does lower fever and relieve pain, is often substituted for aspirin.

Aspirin, although usually made synthetically now, was originally derived from salicin, the active ingredient in willow bark. Willow bark had been used for centuries in folk medicine in certain parts of the world. Acetylsalicylic acid was first prepared by the German chemist Felix Hoffmann, an employee of Friedrich Bayer & Co., in 1897. It is now the active ingredient in more than 50 over-the-counter preparations; estimates put American consumption at 80 billion tablets annually.

See analgesic .

aspirin (acetylsalicylic acid) (ass-prin) n. a widely used drug that relieves pain and also reduces inflammation and fever. It is taken by mouth for the relief of headache, toothache, neuralgias, etc. It is also taken to reduce fever in influenza and the common cold, and daily low doses are used in the prevention of coronary thrombosis and strokes in those at risk. Aspirin works by inhibiting the production of prostaglandins; it may irritate the lining of the stomach, causing nausea, vomiting, pain, and bleeding. It has been implicated as a cause of Reye's syndrome and should therefore not be given to children below the age of 16 years unless specifically indicated.

aspirin (acetylsalicylic acid) A drug that reduces inflammation, combats fever, and alleviates pain. Aspirin works by inhibiting the formation of prostaglandins, which are major factors in the inflammation process. It also reduces the aggregation of blood platelets, hence its use in maintaining blood flow following heart and circulatory disorders.

aspirin (acetylsalicylic acid) Drug widely used to reduce fever, and as an analgesic to relieve minor pain. Recent evidence indicates aspirin can inhibit the formation of blood clots and in low doses can reduce the danger of heart attack and stroke. Aspirin can irritate the stomach and in overdose is toxic and can cause death.

as·pi·rin / ˈasp(ə)rin/ • n. a synthetic compound, C₆H₄(OCOCH₃)COOH, used medicinally to relieve mild or chronic pain and to reduce fever and inflammation. Also called acetylsalicylic acid. ∎  (pl. same or aspirins ) a tablet containing this.

aspirin acetylsalicylic acid, an analgesic and febrifuge. XIX. — G., shortened from Acetylirte Spirsäure ‘acetylated spiraeic acid’ + -IN.

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