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.
