Have you ever had
a headache? Chances are you have; almost all of us do
once in a while. And chances are you took some kind of
medicine to ease your headache. That medicine was most likely
a relative of aspirin.
You may also have taken aspirin or its relatives for other
problems, like inflammation (swelling of joints or other parts
of the body) or fever. But did you know that about 80
billion aspirin tablets are taken per year for these
problems, as well as many others? For example, millions of
people take aspirin to help prevent heart
attacks! There are good reasons a doctor might say,
"Take two aspirin and call me in the morning"!
In this edition of HowStuffWorks,
Dr. Luke Hoffman leads an exploration of aspirin. You will
learn about the many benefits of aspirin, as well as some good
reasons NOT to take this medication! You will also come to
understand why Bayer has called aspirin "the wonder drug that
A Short History
Aspirin is a member of a
family of chemicals called salicylates (see below for
chemistry and structure). These chemicals have been
known to people interested in medicine for centuries.
One of the first and most influential physicians,
Hippocrates, wrote about a bitter powder extracted from willow
bark that could ease aches and pains and reduce fevers as long
ago as the fifth century B.C. In the 1700s, the
scientist Reverend Edmund Stone wrote about the success of the
bark and the willow in the cure of the "agues," or fevers with
aches. With a bit of chemical detective work, scientists
found out that the part of willow bark that was (1) bitter and
(2) good for fever and pain is a chemical known as
This chemical can be converted (changed) by the body after
it is eaten to another chemical, salicylic acid.
It was a pharmacist known as Leroux who showed in 1829 that
salicin is this active willow ingredient, and for many years
it, salicylic acid (made from salicin for the first time by
Italian chemist Piria), and close relatives were used at high
doses to treat pain and swelling in diseases like arthritis
and to treat fever in illnesses like influenza (flu).
The problem with these chemicals was that they upset the
user's stomach fairly badly. In fact, some people had
bleeding in their digestive tracts from the high doses of
these chemicals needed to control pain and swelling. One
of these people was a German man named Hoffmann. His arthritis
was pretty bad, but he just couldn't "stomach" his salicylic
acid. Enter this man's son, German chemist Felix
Hoffmann, who worked for a chemical company known as
Friedrich Bayer & Co. Felix wanted to find a
chemical that wouldn't be so hard on his dad's stomach lining;
reasoning that salicylic acid may be irritating because it is
an acid, he put the compound through a couple of chemical
reactions that covered up one of the acidic parts with an
acetyl group, converting it to acetylsalicylic acid
(ASA). He found that ASA not only could reduce fever and
relieve pain and swelling, but he believed it was better for
the stomach and worked even better than salicylic acid.
Unfortunately, Hoffmann had to wait for fame. He
finished his initial studies in 1897, and his employers didn't
pay much attention to it because it was new and they were
cautious -- they didn't think it had been tested enough. By
1899, though, one of Bayer's top chemists, a scientist named
Dreser, had finished demonstrating the usefulness of the
potent new medicine and even gave it a new name:
aspirin. It is believed that the name comes from
a plant relative of a rose that makes salicylic acid (several
plants make this compound, not just the willow). The
Bayer company could then support the tested medicine; they
spread the word and marketed the new pill widely.
Over the next hundred years, this medicine would fall in
and out of favor, at least two new families of medicines would
be derived from it, and innumerable research articles would be
published about aspirin. Thousands have been published in the
past five years alone! One of the most important pieces of
research about aspirin came in the early 1970s, when a British
scientist named John Vane and his colleagues showed how
aspirin works (see the following sections). His work was so
important that he and his colleagues were awarded the Nobel
Prize in Medicine in 1982. Dr. Vane was even made a British
knight for his work!
What is a Headache?
No one completely
understands how pain works. Actually, a lot is known
about pain, but the more we find out the more questions
arise. So let's take a simplified view.
Pain is really something you feel in your brain.
For example, let's say you hit your finger with a hammer
(please don't try this at home). The part of your finger
that is damaged has nerve endings in it -- these are
little detectors in your joints and your skin that feel things
like heat, vibration, light touch from things like the mouse you're
holding, and, of course, big crushing shocks like being hit
with a hammer. There are different receptors for each of
these types of sensations. The damaged tissue in your
finger also releases some chemicals that make those nerve
endings register the crushing shock even stronger -- like
turning up the volume on your stereo so you can hear it
better. Some of these chemicals are
prostaglandins, and working cells in the
damaged tissues make these chemicals using an enzyme called
cyclooxygenase 2 (COX-2).
Because of the prostaglandins, the nerve endings
that are involved now send a strong signal through nerves in
your hand, then through your arm, up your neck and into your
brain, where your mind decides this signal means, "HEY!
PAIN!" The prostaglandins seem to contribute just a
portion of the total signal that means pain, but this portion
is an important one. In addition, prostaglandins not
only help you to feel the pain of the damaged finger, but they
also cause the finger to swell up (this is called
inflammation) to bathe the tissues in fluid from your
that will protect it and help it to heal. Remember this
is a simplified version of the pain story; lots of chemicals
seem to be involved in this process, not just prostaglandins.
This pathway works very well as far as telling you your
finger is hurt. The pain serves a purpose here: It
reminds you that your finger is damaged and that you need to
be careful with it and not use it until it's healed. The
problem is that, sometimes, things hurt without the hammer or
for any other good reason. For example, sometimes you
get a headache,
probably because your scalp and neck muscles are
contracted from stress or because a blood vessel in your brain
has a spasm. Many people have arthritis, which is
swelling and pain in the joints such as the knuckles or knees,
and this problem can not only make people uncomfortable, it
can damage the joints permanently. And many women have
pain in their abdomens during their periods,
usually known as cramps, for no known useful reason.
These processes appear to involve prostaglandins as well.
What Does Aspirin Do?
Aspirin helps these
problems by stopping cells from making prostaglandins.
Remember the enzyme, COX-2? It is a protein made by your
body's cells whose job is to take chemicals floating around in
your tissues and turn them into prostaglandins.
COX-2 can be found in lots of normal tissues, but
much more of it is made in tissue that has been damaged in
some way. Aspirin, it turns out, sticks to COX-2 and won't let
it do its job; it's like a lock you put on your bicycle.
The bicycle won't move with the lock on, and COX-2 can't work
with aspirin stuck in it. So by taking aspirin, you
don't stop the problem that's causing the pain, like the tight
muscles in your scalp, or the cramping in your abdomen, or the
hammer-damaged finger. But it does "lower the volume" on
the pain signals getting through your nerves to your brain.
One common question about aspirin and other medicines is,
"How does it know how to get to where the pain
is?" The answer is that it doesn't! When you take
aspirin, it dissolves in your stomach or the next part of the
digestive tract, the small intestine, and your body absorbs it
there. Then it goes into the bloodstream
and it goes through your entire body. Although it is
everywhere, it only works where there are prostaglandins being
made, which includes the area where it hurts.
You may ask, "How come I have to keep taking aspirin if
it works so well?" As with almost all chemicals,
your body has ways of getting rid of aspirin. In this
case, your liver, stomach, and other organs change aspirin
to... surprise! Salicylic acid! This chemical then
slowly gets changed a bit more by the liver, which sticks
other chemicals onto the salicylic acid so that your kidneys can
filter it out of your blood and send it out in your urine.
This whole process takes about four to six hours, so you need
to take another pill at that time to keep the effect going.
The problem with the fact that aspirin goes through your
entire bloodstream is that your body needs prostaglandins for
some reasons. One place they are useful is in the
stomach; it turns out another enzyme called COX-1 makes
a prostaglandin that seems to keep your stomach lining nice
and thick. Aspirin keeps COX-1 from working (it keeps
most prostaglandins from being made equally well -- it's
"nonselective"), and your stomach lining gets thin, allowing
the digestive juice inside to irritate it. This is
probably the biggest reason why aspirin and its relatives
upset stomachs (not only because it's an acid, as Hoffmann had
COX-2 also works in some normal tissues like the brain and
kidney; at normal amounts, one dose of aspirin probably
doesn't affect these areas much. And there are other places in
the body where prostaglandins have a job in normal tissues,
such as the blood...
What Else is it Good For?
In the last few
decades, it has been found that aspirin's action of stopping
prostaglandin production has effects on things besides pain,
inflammation, and the stomach.
For example, some types of prostaglandins cause tiny
particles in your blood (known as platelets)
to stick together to form a blood clot. By
inhibiting prostaglandin production, aspirin slows down clot
production. Although this can be bad, such as with a
bloody nose -- in which case you want a clot to form -- blood
clots can be damaging as well, such as in causing heart
attacks by clogging the blood vessels that bring
oxygen and energy to the beating heart.
For this reason, many adults now take aspirin to prevent heart
attacks, and it also helps people who have already had a heart
attack stay alive. Surely Hoffmann (and the Bayer
company) could never have predicted this effect. And as
noticed at least as far back as Hippocrates in ancient Greece,
aspirin and its relatives also lower fevers; this seems
to be an effect on a part of the brain known as the hypothalamus,
which controls temperature (as well as other body functions).
A lot of research is being done now to find out if aspirin
can be used for other problems; it has already shown some
promise in helping with problems as diverse as cataracts in
gum disease, and high
blood pressure during pregnancy!
Does it Have Side Effects?
Just like all
medicines, aspirin isn't all good. It has effects on the
body that you and your doctor don't want (side
effects). Some of them have already been mentioned;
for example, if you hit your finger with a hammer and it's
bleeding, an aspirin may help the pain and swelling, but the
wound may take longer to clot and stop bleeding. Also,
it can be very upsetting to the stomach, especially at the
high doses often used in arthritis.
Aspirin also isn't used as much for fevers in children
since research has suggested that aspirin given to kids with
flu, chickenpox, or other viral
sicknesses may cause a potentially deadly problem called
Aspirin also changes the way your kidneys
make urine, can cause some people to have trouble breathing
(rarely), and can be dangerous at very high doses.
For these reasons, chemists have found other chemicals
closely related to aspirin that have some of its good effects
and lack some of its bad effects. For example,
ibuprofen and naproxen (or Motrin and Naprosyn,
respectively) also treat pain, swelling and fever, but they
seem to have less of an effect on platelets than aspirin does.
These medicines are called the non-steroidal
antiinflammatory drugs (NSAIDs) because they
decrease swelling but they aren't steroids, which are the most
potent antiinflammatory chemicals we have. Another
family of medicines related to aspirin includes
acetaminophen (or Tylenol), which decreases fevers and
pain, but it doesn't affect either swelling or your stomach as
much as the true NSAIDs do.
Felix Hoffmann was sure that aspirin would make a good drug
for arthritis. But as he struggled to prove it to his cautious
employer, how could he have known it would save lives, and in
so many ways? So the next time you get out the hammer, think
of Felix and set aside an aspirin or two. He deserves the
tribute, and it's best to be prepared for hitting the wrong
For more information, check out the links on the next page.
Lots More Information!
More Great Links
About the Author
Lucas Hoffman ("please call me Luke") is a resident in
Pediatrics at the University of Washington in Seattle. He was
raised in New Mexico, and he went to college at the University
of California at Berkeley. He then attended medical school and
graduate school at the University of California in San
Francisco, where he worked on designing inhibitors of viruses
like influenza and HIV. He now lives with his wife Ellen, a
science journalist (whose work can be seen at the site
http://faculty.washington.edu/chudler/neurok.html), and his
dog Talisker, an occasional headache, in Seattle.