Have a fever?
Maybe a headache?
Many people choose to take acetylsalicylic acid, or aspirin, for relief of their symptoms.
In fact, aspirin has been used by humans for more than 2,500 years ever since some person
realized that chewing willow leaves seemed to treat their discomfort.
This is because willow leaves contain salicin, which is turned into salicylic acid in the
body.
Chemists such as Charles Frederic Gerhardt and Felix Hoffman later experimented with
salicylic acid to find ways of making it last longer and become less toxic in the body,
which led to the creation of aspirin.
Most people have experienced and appreciated firsthand the soothing effects of aspirin,
but how does it actually work?
In this episode of Medicurio, we will discuss the mechanism of aspirin, its side effects,
and other uses of this drug aside from fever and pain relief.
The body has many ways to fight an infection.
It could raise the temperature and cause a fever, making the environment inhospitable
for any pathogen invading the body.
In addition, immune cells in the body are stimulated to release a wide variety of toxic
chemicals that can kill any invaders as well as chemicals that stimulate more immune cells
as backup, a process known as inflammation.
Of course, the higher temperature and released chemicals also damage your own cells, which
is why you may feel pain during a fever.
Despite this, fevers are not necessarily a bad thing – it is a natural and usually
effective way for your body to fight infection, and aspirin and other fever-reducing drugs
should only be used if the fever has lasted many days or the body temperature is very
high, both of which increase the risk of permanent damage to the body.
So what tells the body to turn up the heat, or the immune cells to release their chemicals?
Nobody really knew for many years even after aspirin began to be sold.
In 1971, more than 70 years after aspirin first entered the market, British pharmacologist
John Vane discovered that a family of fat-derived molecules known as prostaglandins seemed to
be responsible for causing fever, inflammation, and pain, and that aspirin treated these symptoms
by preventing production of prostaglandins.
For his breakthrough discovery, he was awarded the 1982 Nobel Prize in Medicine, which he
shared with two Swedish biochemists, Bengt Samuelsson and Sune Bergstrom, who also did
extensive research on these prostaglandins.
How does aspirin prevent prostaglandin production?
Understanding this requires figuring out the synthesis pathway of prostaglandins, which
was accomplished a few years after Vane’s discovery.
Prostaglandins are derived from fatty acids in the cell membrane.
These fatty acids are cut off of membrane lipids by an enzyme known as phospholipase
A2.
Afterwards, an enzyme called cyclooxygenase, as its name implies, creates a ring in the
fatty acid and adds some oxygens to form an intermediate prostaglandin, which is further
modified into a variety of different prostaglandins with an incredible diversity of functions.
These functions include acting on the hypothalamus to increase body temperature, stimulating
immune cells in inflammation, and sensitizing nerves to pain, as well as initiating clotting
in blood, constricting and dilating blood vessels, producing mucous in the stomach to
protect the stomach lining from stomach acid, and so many other functions.
What aspirin does is that it stops cyclooxygenase from working, which blocks prostaglandin synthesis
and results in temporary reduction of prostaglandin-induced pain, fever, and inflammation until cyclooxygenase
activity returns to normal.
This inflammation doesn’t have to just come from infections – inflammation from some
autoimmune diseases such as rheumatic arthritis can also be relieved using aspirin.
However, since prostaglandins aren’t just involved in discomfort as mentioned earlier,
using aspirin also stops other body functions as well.
Sometimes this is a surprising benefit – for example, one of the prostaglandins that aspirin
prevents from synthesizing is thromboxane A2, which is involved in activating platelets
to initiate blood clotting.
This means by taking a low dose of aspirin every day, it becomes harder for blood to
clot.
This is extremely useful in preventing diseases caused by blood clots such as heart attacks
and stroke and low-dose aspirin is actually recommended for older aged people who have
a higher risk of suffering from those diseases.
On the other hand, aspirin also decreases production of protective mucous in the stomach,
which means that stomach acid can burn through the stomach, leading to gastric ulcers and
dangerous internal bleeding.
Since there is also less clotting occurring, this side effect becomes even more dangerous.
Therefore, taking aspirin to reduce the risk of heart attack or stroke is not recommended
for people who are at low risk of developing those diseases anyways, as well as people
who have a tendency of developing gastric ulcers or have genetic problems with clotting
such as hemophilia.
Some other possible side effects of aspirin include worsening of asthma in some asthmatics.
Another family of fat-based molecules, called leukotrienes, can also be formed from the
fatty acids cleaved by phospholipase A2.
These leukotrienes cause narrowing of airways and more mucous production, making breathing
difficult.
When cyclooxygenase is inhibited, there are more fatty acids available to be converted
into leukotrienes, which sometimes exacerbates the symptoms of asthma.
Finally, you may have seen “baby aspirin” on the shelves at your local pharmacy.
This is not for babies or young children!
Aspirin is not recommended for children because it may cause Reye’s syndrome, which involves
life-threatening damage to both the liver and brain.
The mechanism of this disease is not quite understood, but almost 90% of cases involve
children taking aspirin during a viral infection.
“Baby aspirin” is called that because historically it was used for babies and therefore
is at a lower dose.
Nowadays, it is actually used to prevent blood clotting as mentioned earlier.
Look for alternative fever relief drugs such as ibuprofen or acetaminophen if a child has
had a fever for a long time.
Speaking of other fever relief drugs, it turns out that aspirin is not the only drug that
works by inhibiting cyclooxygenase.
Other common drugs such as ibuprofen, acetaminophen, and naproxen also inhibit cyclooxygenase and
therefore have similar effects as aspirin.
You may recall from previous videos that steroids are also used to prevent inflammation such
as in autoimmune diseases.
Steroids work differently by inhibiting phospholipase A2, but also have multiple other functions
that can lead to more side effects, such as Cushing’s syndrome.
Since aspirin and other cyclooxygenase inhibitors are not steroids and can still decrease inflammation,
they are called non-steroidal anti-inflammatory drugs.
Aspirin is truly an amazing drug that has such a wide range of symptoms it can treat,
whether it is fever, headache, inflammation, or pain, and can even be used to prevent heart
attacks and strokes.
It has been taken by humans ever since the time of the ancient Greeks and Egyptians and
a Nobel Prize was even awarded for aspirin research.
Very cool for a very common drug that many people don’t even bother looking twice at.
Check out the description below for a more in-depth explanation of aspirin’s mechanism
as well as some cool trivia about this drug.
Thanks for watching, and see you next time on Medicurio.