Aspirin

By Gail Marsella

Scene One: The year is 1614; the place is now eastern Massachusetts. Four members of the Wampanoag tribe have developed high fevers. The shaman ventures out into the forest, where he carefully collects some leaves, roots, and bark from a willow tree. He returns home, grinds up the plant material, and brews it in water. The patients drink the hot herbal tea, and bathe in a cooled solution of the ground bark. Within hours, the fevers are lower, and the sick people are resting comfortably.

Scene Two: The year is 1846; the place is London, England. On the day of the Prince's annual ball, the Grand Duchess is suffering from severe arthritic joint pain. She sends for her doctor, and is given oil of wintergreen to swallow. In a short time the inflammation in her joints lessens, and she can move without pain. The duchess attends the ball, and fulfills her social obligations.

Scene Three: The year is 1999. A high school student, diligently studying for an exam, develops a headache after several hours of intense concentration. She goes to the medicine cabinet, takes out a bottle marked "aspirin", and swallows two pills with a glass of water. In less than an hour, her headache is gone.

Taking medicine to relieve pain, fever, and inflammation is a ritual that has been repeated through most of recorded history. Willow tree bark extract, oil of wintergreen, and aspirin are similar in molecular structure and metabolic effect. All three belong to a group of chemicals called salicylates, and are some of the oldest and most frequently used drugs. Willow trees contain salicin, oil of wintergreen is methyl salicylate, and aspirin is acetylsalicylic acid (see Figure).

Painful Discoveries

Many cultures have a history of herbal medicine. Studying the chemistry of medicinal plants, however, began in the 1800s. Imagine the difficulties the early chemists faced! Identifying the active ingredient in a mound of willow tree bark was a formidable task. From the hundreds of chemicals contained in the bark, it was nearly impossible to purify the single chemical capable of relieving pain and fever.

In 1859 German chemist Hermann Kolbe synthesized salicylic acid in his laboratory by heating phenol with carbon dioxide. Unfortunately, salicylic acid is irritating to the stomach so much so that many patients preferred their aches and fever to the severe heartburn caused by the remedy. So the search was on for a chemical that was similar to salicylic acid but without the side effects.

In 1899, another German named Felix Hoffman suggested acetylsalicylic acid as a good alternative to salicylic acid. He had been searching for a drug that would give his elderly father relief from arthritis, and he stumbled upon acetylsalicylic acid after trying phenyl salicylate and sodium salicylate without success. The new drug was named aspirin. Hoffman was an employee of the Bayer Company, which marketed the new remedy with great success. Today, Americans swallow nearly 50 million tablets a day.

Aspirin can be made by reacting acetic acid with salicylic acid to produce acetylsalicylic acid, the same procedure used by Dr. Hoffman nearly a century ago. When acetylsalicylic acid ages, it may decompose and return to salicylic acid and acetic acid. If you have an old bottle of aspirin around the house, open it and take a sniff. It may smell like vinegar, because vinegar is dilute acetic acid.

Something for Everyone

Researchers have been puzzled by the many and varied actions of aspirin. This one drug not only relieves fever, pain, and inflammation, but also inhibits blood clotting. It helps prevent some types of heart attacks if taken regularly. None of these effects seems to be very closely related. Despite its many years of use, aspirin's mode of action is only partly understood.

Unlike many painkillers that act directly on the nervous system, aspirin seems to relieve pain primarily by stopping the production of hormone-like chemical messengers called prostaglandins. They are produced in small quantities by the same tissue as the one they act upon, and degrade within a few minutes. During their short lifetime they exert a powerful influence on the body. Prostaglandins regulate digestion, kidney output, reproduction, blood circulation, and some nervous system functions.

Aspirin interferes with the action of one particular enzyme, cyclooxygenase, which acts at the beginning of a chain of prostaglandin synthesis. As a result, all the prostaglandins produced by this chain of reactions are suppressed. Aspirin's numerous effects reducing fever, enlarging blood vessels, reducing clotting of the blood come from altering the balance of prostaglandins, even though aspirin itself disturbs only a single reaction.

Stomach Upset

"Over-the-counter" drugs do not require a doctor's prescription but that doesn't mean they're not potent medicines. Aspirin is an effective painkiller and fever reducer, but it causes side effects in some people. The most common complaint is an upset stomach. One strategy for reducing stomach irritation is to combine the aspirin with a buffer a combination of chemicals that reduces acidity. The resulting product, "buffered aspirin", is a genuine improvement for the small percentage of people who are susceptible to this kind of stomach irritation, but it has no value to the rest of us.

For patients who are under a doctor's orders to take aspirin around the clock every day, stomach irritation can become a serious issue. Drug companies introduced specially coated aspirin tablets that pass through the stomach without dissolving. This coating resists gastric acid, but dissolves quickly in the basic environment of the small intestine. Called "enteric" aspirin, these tablets effectively eliminate stomach irritation. However, they cannot work until the stomach contents are passed to the intestine several hours after the tablet is ingested.

The discovery that aspirin works by inhibiting prostaglandin opened new avenues of medical research. A specific prostaglandin that promotes coagulation of the blood and another that inhibits coagulation have been identified. Following the clue that aspirin reduces most forms of inflammation but not the inflammation of asthma unearthed a new group of prostaglandins. Researchers have learned a lot from the once-mysterious ingredient of the bark of the willow tree.

Reference

Roueche, B. The Medical Detectives; Plume: New York, 1991.