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).
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Salicylates
have been used as
painkillers since ancient
times. Salicin can be
extracted from the bark of
willow trees, and methyl
salicylate is found in
wintergreen plants or
teaberry. Aspirin was first
prepared by the acetylation
of salicylic acid. |
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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. |