Aspirin (S24E1)

All right, welcome to the deep dive. We sift
through a ton of information, find those hidden
gems, and, well, bring them straight to you.
It's basically like a crash course on actually
knowing stuff. Yeah, exactly. Today we're going
deep. really deep into the world of aspirin.
You know, for this deep dive, we've looked at
so much material, like we've gone all the way
back to how aspirin was even discovered. Wow.
We've dug into the regulations, the science,
even how aspirin is seen by, you know, society
at large. So like the whole nine yards. Pretty
much, yeah. That's amazing. The goal here is
to uncover the complete story of aspirin. And
that's from its ancient roots to its impact,
you know. in our lives today. And trust me, there
are going to be some surprises along the way.
Oh, I'm sure. I mean, aspirin is something we
kind of all just have around, right, like in
our medicine cabinets. Yeah, it's ubiquitous.
But where did this all even begin? Like, seriously,
back to the basics. Well, the story goes back
way further than most people realize. OK, so
the active ingredients in aspirin, they're these
things called salicylic acid derivatives. OK.
And you know what? People have been using these
for pain relief for thousands of years. It's
really fascinating. No way, really? Oh, yeah.
You have ancient Sumerian and Egyptian texts,
stuff like the Ebers Papyrus mentioning willow
tree extracts. Willow, like the tree. Yep, exactly.
They were using those to fight pain and fever,
just like we do today. So they were already using
willow bark back then. Wow. And it goes on even
in ancient Greece, like Hippocrates, the big
name in medicine. Even he recommended willow
bark tea. For fever. Yeah, fever. 5th century
BCE we're talking, so you can see what we know
as aspirin today. It has these incredibly deep
roots. So like centuries of just using natural
raw aspirin. That's pretty cool. Yeah, definitely.
When did we actually, like, make aspirin in a
lab, you know? The first deliberate creation
of acetylsalicylic acid, ASA, was in 1853. ASA.
Yeah, another name for aspirin. Gotcha. A French
chemist named Charles Frederick Gerhart did it.
OK. He reacted sodium salicylate with acetyl
chloride, boom, ASA. So he, like... made it,
but then nothing happened. Yeah. He didn't really
try to market it or anything. It was just kind
of, you know, a lab experiment. OK. So we had
the discovery, but not the medicine. That's where
Bayer steps in, right? Kix. The aspirin company.
Yeah. Bayer, in 1897, they wanted to make salicylate
-based drugs, but with less irritation. And one
of their chemists, Felix Hoffman, working under
Arthur Eichengren, they managed to synthesize
this pure, stable form of ASA. And this one actually
worked well. It did. This was the form that was
really good at relieving pain and fever, yeah.
There was some debate about who really discovered
it, wasn't there? Yeah, there's a bit of a historical
mystery there. Yeah. Decades later, Eichengren
said he was the one calling the shots, that Hoffman's
role was, well, less important. Historians are
still debating that, but either way, Bayer ran
with it, right? Developed it further. Yep. And
that's where the name aspirin comes from, I guess.
You got it. Yeah. Bayer trademarked aspirin in
1899. 1899. A from acetyl. Spur is from spirea.
Spirea, what is that? It's meadowsweet, a clam
with salicin in it. And the in ending, well that
was super common for medicines back then. And
you know, the same year, 1899, Bayer starts selling
aspirin, gives info to doctors, and boom, it
becomes a global best seller. Pretty amazing.
It's kind of crazy how a brand name just becomes
like... part of our language. Absolutely. Aspirin.
Well, aspirin. Everyone knows it. From a powder
to a little pill. That was a big deal. Oh, no,
absolutely. At first, it was sold as a powder,
which was kind of messy. But then in 1900, they
made it into those tablets. Much easier. So much
easier. I sense why it got even more popular.
Yeah. And a lot of places, you didn't even need
a prescription. Plus, it got added to the official
drug list, the pharmacopias. So a huge success.
right out of the gate. But I'm guessing that
didn't last forever. Didn't they have those aspirin
wars? Yeah, you're right. The 1920s and 30s,
things got really competitive. After World War
I, the aspirin trademark got lost in a bunch
of countries. Really? It became a generic name.
So anyone could make it? Pretty much, yeah. And
companies like Sterling Drug jumped in big time.
They even bought Bayer's US operations for a
while. Wow. Yeah, it was a real battle for market
share. aggressive marketing, lawsuits, you name
it, all because this drug was making a ton of
money. Makes sense. And then what happened in
the mid -20th century? Weren't there new pain
relievers then? Right. You had acetaminophen
hitting the scene in 1956. Tylenol. Yep. And
then ibuprofen in 62. Advil Motrin. Exactly.
And you know, people felt those are easier on
their stomachs, so some switched over from aspirin
for everyday pain. So aspirin took a bit of a
hit, but... Wait, didn't it have a comeback?
It did, and a big one. How did that happen? It's
a story of, you know, scientific discovery. In
1971, a British pharmacologist, Sir John Vane,
he figured out that aspirin actually works by
inhibiting something on cyclooxygenase, COX for
short. COX, okay. That's an enzyme that's crucial
for making prostaglandins, which cause inflammation,
pain, and fever. So aspirin shuts that down.
Basically, yeah, that discovery finally explained
what people had been observing for centuries.
And didn't he win a Nobel Prize for that? Absolutely,
in 1982. Wow, that's huge. Yeah, and his research
didn't stop there. It also reviewed that aspirin
can thin the blood, preventing blood clots. And
that's because it blocks the production of thromboxane,
which makes platelets sticky and likely to clump
together. So that's the key to his heart benefits.
Exactly. Throughout the 60s, 70s, and 80s, there
were these massive clinical trials proving aspirin's
power to prevent blood clots. Wow. This led to
it becoming widely used for reducing heart attacks
and stroke risk. It's worth noting, though, that
a lot of those early trials mostly men. It's
a problem, right. It took a while, but that sparked
some really important changes in how medical
research is done to make it more inclusive. That's
important. But so by the late 20th century, aspirin
was basically reborn, right, from pain relief
to preventing heart problems. Yeah, it became
a cornerstone of cardiovascular disease prevention.
It really was a renaissance for aspirin. It went
from Willow Bark to, you know, going to the moon
with the Apollo astronauts. Wait, really? The
moon? Yeah, and it even got into the Guinness
Book of World Records. Not bad. for a little
pill. That's amazing. Yeah. So let's talk about
how doctors actually use aspirin today. Okay,
so aspirin is a versatile medication with a few
main uses. It's great for mild to moderate pain,
things like tension headaches, dental pain, muscle
aches. Okay. It's also an antipyretic, meaning
it lowers fever in adults. So it tackles pain.
and fever. Yeah. And here's an interesting thing.
Aspirin combined with caffeine, that combo boosts
pain relief, which is why you see it in some
migraine meds. Makes sense. For those tension
headaches, aspirin by itself or with other painkillers
is often the first choice for treatment. It can
also help with migraine attacks, especially when
you team it up with acetaminophen and caffeine.
But isn't there like a big warning about using
it with kids? Yeah, that's a really important
point. Aspirin generally isn't recommended for
children. or teens who have a fever or, you know,
those viral illnesses like the flu or chicken
pox. OK. There is a risk of this rare but serious
condition called Ray's syndrome. Oh, right, I've
heard of that. Back in 1986, the FDA made it
mandatory to put warning labels on all aspirin
products about this risk. Since then, aspirin
use in kids has dropped significantly, which
is good, and thankfully, so have the cases of
Ray syndrome. So when you hear baby aspirin now,
it usually means the low -dose aspirin adults
take for heart health, not for kids' pain or
fever. So definitely important to remember that
distinction. Now what about aspirin as an anti
-inflammatory? I know it's used for that too.
Yeah, you're right. Higher doses of aspirin have
those anti -inflammatory properties. In the past,
it was a main treatment for chronic conditions
like rheumatoid arthritis and rheumatic fever.
It helps with joint pain, swelling, and inflammation.
But the problem is those high doses needed for
this can cause more side effects, especially
in the stomach. So nowadays, doctors tend to
go for other NSAIDs, those are non -steroidal
anti -inflammatory drugs, for long -term use
because they're generally safer. But aspirin
still has its place. It's used for things like
acute rheumatic fever and pericarditis, where
both its anti -inflammatory and anti -clotting
actions are helpful. So it's still in the game.
Definitely. And there's another unique situation,
Kawasaki disease. Kawasaki disease. It's a rare
inflammatory illness that affects children. OK.
And aspirin is used alongside intravenous immunoglobulin
therapy. So even though it's usually not for
kids, there are exceptions. Yeah. In this specific
case, the benefits outweigh the risks. It helps
reduce fever and prevents complications with
the coronary arteries. Interesting, and of course
we can't forget its role in preventing those
cardiovascular events. Right, that's where aspirin
has really shined. Low -dose aspirin, usually
75 to 100 milligrams a day, it works by stopping
those platelets from sticking together. Tiny
cells in your blood that form clots. Oh, right,
right. So by thinning the blood, it helps prevent
those dangerous clots that can cause heart attacks
and ischemic strokes. It's a standard treatment
for people who have already had a heart attack,
unstable angina, and ischemic stroke, or if they've
been diagnosed with cardiovascular disease. Secondary
prevention, right? Yeah. For those higher risk
folks, low dose aspirin every day significantly
reduces the risk of another event. And the benefits,
they usually outweigh the slightly increased
risk of bleeding. Pretty clear benefits there.
What about preventing a first heart attack or
stroke though? Ah, so that's primary prevention
and it's a bit more complex. It used to be that
doctors would recommend a daily low dose baby
aspirin to pretty much everyone as a preventative
measure. But then around 2018, a bunch of big
studies, Arise, Ascend, Aspire, they showed that
for people without a history of heart problems,
the benefits of aspirin weren't as big as initially
thought, and they could be outweighed by the
bleeding risk. Oh interesting, so the advice
changed. Yeah, guidelines became more selective.
For example, the U .S. Preventive Services Task
Force, they now recommend that for adults between
40 and 59 with a higher risk of cardiovascular
disease, the decision to start aspirin should
be made on a case -by -case basis with their
doctor. And they also now advise against starting
aspirin for primary prevention for people 60
or older. So not a one -size -fits -all solution.
Nope, not at all. The focus now is on a personalized
approach. You gotta weigh the risk of a heart
attack or stroke against the risk of bleeding.
So are there other potential uses for aspirin
that are being researched? Oh, there are a few
things. Like what? Well, some studies suggest
that taking low -dose aspirin over a long time
might reduce the risk of colorectal cancer in
certain people. Really? Cancer? Yeah, it's still
being researched, but it could be that aspirin's
anti -inflammatory effects have something to
do with it. Hmm. That's fascinating. It's actually
led to some recommendations for low -dose aspirin
in middle -aged folks who are at higher risk
for both heart disease and colorectal cancer.
Double whammy prevention. Exactly. And there's
more. Aspirin might also help prevent preeclampsia
during pregnancy. Preeclampsia. It's a serious
condition that can develop during pregnancy.
Oh, OK. Low dose aspirin is now recommended for
high risk women. There's even research on aspirin's
possible benefits for neurodegenerative diseases
and psychiatric disorders, where inflammation
seems to play a role. Interesting. Though the
evidence for things like Alzheimer's and dementia
is still pretty inconclusive. Still more to learn.
Oh, absolutely. Plus, you know, aspirin's in
all sorts of combination meds for migraines and
colds too. And don't forget, it's on the World
Health Organization's list of essential medicines,
which means it's considered fundamental for basic
health care around the world. So, really a powerhouse
of a drug. But how do they even make aspirin?
Like, on a large scale? The process is surprisingly
straightforward. It all starts with a chemical
reaction called esterification of salicylic acid.
Break that down for me. So on an industrial scale,
they usually begin with salicylic acid. Often
that's made from phenol through something called
the Colby Schmidt reaction. Right. But the key
step is reacting that salicylic acid with acetic
anhydride. Acetic anhydride. Yeah, it's the thing
that adds an acetyl group to the salicylic acid
molecule. This reaction usually needs an acid
catalyst, something like sulfuric or phosphoric
acid, to speed it up. And that reaction creates,
well, aspirin. Aspirin, got it. The chemical
name is acetylsalicylic acid. And it also creates
acetic acid as a byproduct. OK. The basic equation
looks like this. Salicylic acid plus acetic anhydride
with an acid catalyst gives you acetylsalicylic
acid plus acetic acid. So it's like a chemistry
101 reaction. Exactly. In fact, it's a common
experiment in college chem labs. Wow, cool. But
once the reaction is done, you need to separate
and purify the aspirin, which is done through
crystallization. You cool the mixture, and the
aspirin forms these crystals that can be filtered
out and washed. To get it really pure, they often
do a second round of crystallization using different
solvents. So like a double filter? Yeah, you
could say that. Makes sense. Quality control
has got to be super important with medicine.
Well, for sure. Aspirin makers have strict quality
control measures in place. So like, how do they
do that? They test things like how quickly the
tablets dissolve because that affects how the
body absorbs the medicine. They also measure
exactly how much of the active ingredient is
present using techniques like titration or HPLC.
High performance liquid chromatography. It's
basically a very precise way of separating and
identifying every component in a mixture. It's
a way to make absolutely sure that it's pure
aspirin. So like no extra stuff. Exactly. And
they also test for impurities, especially free
salicylic acid because that can be irritating.
There are these official standards like the United
States Pharmacopeia that outline all the tests
and limits aspirin has to meet. Sounds pretty
rigorous. Yeah, it is. Luckily, because the process
is so simple and has been around for so long,
aspirin production is very reliable and cheap,
which makes it accessible globally. You know,
it's funny, even with a drug this well studied,
there are still discoveries. Like, in 2005, they
found a second crystalline form of aspirin, although
that didn't really change how we use it. Wow,
that's wild. But yeah, aspirin manufacturing
is a great example of efficient production that
makes this medicine affordable and accessible
for people all over. From a simple reaction to
serious quality control, that's quite a journey.
Now, what about the regulations? Like, how is
aspirin regulated, given how old it is? Well,
that's an interesting story. I bet. Because when
Bayer introduced it, you know, back in 1899,
modern drug regulations didn't exist. Early laws,
like the 1906 Food and Drugs Act in the US, they
were mainly about honest labeling, not proving
how well something worked. Oh, wow. Aspirin just
kind of took off based on its obvious benefits
and got listed in those official drug lists,
the pharmacopias around the world. So it's kind
of grandfathered in. Yeah, by the time tougher
regulations came around in the U .S., like the
1938 Federal Food, Drug, and Cosmetic Act and
the 1962 Kefauver -Harris Amendments, aspirin
was already considered an old drug, already seen
as safe and effective for what it was used for.
So it kind of skipped the usual approval process?
Yeah, pretty much. In the U .S., the FDA mainly
oversees aspirin as an over -the -counter or
OTC drug. OTC, right. And it's regulated under
the FDA's OTC monograph. system for analgesic,
antipyretic, and anti -grammatic drugs. That's
a mouthful. I know, right? But basically, that
system sets the rules for selling aspirin over
the counter, like what doses are OK, what you
can use it for, and what warnings need to be
on the label. Each company doesn't have to get
separate approval for their product as long as
they follow those rules. Makes sense. But they
still need to meet the quality standards and
the labeling needs those FDA mandated warnings,
like the one about Ray's syndrome in kids, possible
allergies, and the stomach bleeding risk. Right,
the usual warnings. Yeah, a lot of countries
have similar OTC regulations. What about when
they discovered new uses for aspirin, like for
preventing heart attacks? How did the regulations
handle that? As the research built up showing
aspirin's value for heart health, regulators
had to figure out how to get this info out there.
to doctors and patients. Yeah, exactly. The FDA
in the US, they allowed labels that mentioned
aspirin's role in secondary prevention, you know,
preventing another heart attack or stroke in
people who'd already had one. OK. So that new
info from the studies became part of the official
guidelines. Low dose aspirin became a standard
recommendation, even though it was still an OTC
drug. So like. Doctors could prescribe it, but
you didn't need a prescription to buy it. Yeah,
that's right. You started seeing heart -healthy
aspirin being advertised, usually with a note
to talk to your doctor first. Right, right. But
when it came to primary prevention, you know,
preventing a first heart attack, regulators were
more careful. Okay. In 2014, the FDA rejected
Bayer's request to market aspirin specifically
for primary prevention because they weren't convinced
the benefits outweighed the bleeding risks for
everyone. So being cautious. Yeah, they wanted
really strong evidence to justify a broader use
for something that was so easily available. Makes
sense. Are there like different rules for aspirin
in different countries? Oh, yeah. Definitely.
How so? In some European countries, low dose
aspirin for heart health, it's actually prescription
only. Really? Yeah, it's to make sure a doctor
is involved in that decision, assessing risks
and all that. But higher doses for pain, those
might be OTC. So it's like aspirin for your heart
is taken more seriously than aspirin for a headache.
Yeah, you could say that. Interesting. In the
UK, for instance, you might find the low dose
aspirin behind the counter, but the higher dose
for pain is just out on the shelves. It's all
about balancing access with medical oversight.
Makes sense. And then you've got those medical
guidelines from groups like the European Society
of Cardiology and the U .S. Preventive Services
Task Force. These aren't laws, but doctors rely
on them to know when to recommend aspirin. So
like, expert advice. Exactly. And globally, you
know, aspirin is still on that WHO list of essential
medicines, which means it's seen as fundamental
for basic health care worldwide. So it's pretty
widely accepted as an important drug. Absolutely.
And the way it's regulated keeps evolving, constantly
being monitored and reassessed based on new evidence
and safety concerns. So you could say that aspirin's
approval has been more of a gradual process over
decades, building up this understanding of its
benefits. benefits and risks. It's not just a
one -time thing. It's constantly evolving. Yeah,
exactly. Makes sense. Well, let's move on to
some of the controversies and legal issues around
aspirin. It can't all be smooth sailing with
a drug that's been around this long, right? You're
right. Aspirin has had its fair share of controversies
and legal battles. We quit. One of the first
big ones was about the name aspirin itself. Really?
The name? Yep. Remember how Bayer lost the trademark
in a bunch of countries after World War I? Well,
in the US, aspirin became a generic term in the
early 1920s. So... Tons of companies started
selling acetylsalicylic acid, all calling it
aspirin. Those were the aspirin wars. A lot of
competition. Wow. Bayer had to sell its aspirin
under different names in the US for years. It
wasn't until 1994 that they spent a lot of money
to get back the US trademark rights for aspirin.
It's actually pretty unusual for a medicine to
have this double life being a trademark in some
places and a generic name in others. That's weird.
What about safety concerns? I know there were
some issues with kids. Yeah, the link between
aspirin and Ray's syndrome, that was a huge issue.
Ray's syndrome, right. In the 70s and early 80s,
research showed that kids who took aspirin after
having a viral infection, like the flu or chicken
pox, had a higher risk of getting Ray's syndrome.
It's pretty serious, right? Yeah, it's rare,
but it can be fatal. Oh, wow. It affects the
brain and liver. So health officials warned everyone.
And in 1986, the FDA made it a rule that all
aspirin products had to have a warning label
saying not to give it to kids or teens with viral
fevers. And similar warnings went out worldwide.
Some parents even sued the companies making aspirin
because their kids got Ray's syndrome after taking
it. So it was a really big deal. It was. Thankfully,
after those warnings, aspirin use in kids dropped,
and so did cases of Ray syndrome. They stopped
marketing baby aspirin for infants, and now that
term basically means low -dose aspirin for adults'
heart health. That's good that they took action
and things improved. Definitely. What other controversies
have there been with aspirin? Well, the risk
of bleeding, especially in the stomach and sometimes
hemorrhagic strokes, those have been ongoing
concerns, particularly with long -term low -dose
use. While it didn't always lead to lawsuits,
it's definitely been a source of debate and some
public confusion. There was a time when doctors
recommended a daily low -dose aspirin to almost
everyone to prevent heart problems. But then
New research, especially those trials around
2018, showed that it was more complicated than
that. The benefits weren't as clear for people
without a history of heart problems and the bleeding
risk was a bigger concern. So guidelines changed
and some got more restrictive. less aspirin for
prevention overall. Yeah, that's the general
trend. And you know what? The FDA actually warned
Bayer in 2014 about marketing aspirin for primary
prevention because of this. Interesting. It goes
to show that the whole idea of balancing aspirin's
benefits with its risks, it's an ongoing process.
It needs clear communication from experts to
doctors and the public. Definitely. Were there
big product recalls or anything like that with
aspirin? Surprisingly, aspirin has had a pretty
clean record compared to some other drugs. No.
I guess because its chemistry is simple and it's
been around for so long, people really understand
its properties well. But there have been a few
isolated incidents, like... during that Tylenol
scare back in the 80s where people were tampering
with the pills. Oh yeah, I remember hearing about
that. Yeah, there were a few copycat cases with
aspirin and other OTC meds too. Wow, scary. It
wasn't a problem with aspirin itself, but it
did lead to improvements in tamper -resistant
packaging for all OTC drugs. That makes sense.
And the FDA has sent warning letters to companies
for selling aspirin combos that weren't properly
approved or made claims they couldn't back up.
Oh. Like in 2009, Bayer got in trouble for selling
a mix of low dose aspirin and calcium supplements,
claiming it was good for heart health and preventing
cancer. But they didn't have the research to
prove it. So even with an old drug like aspirin,
you got to follow the rules. Yeah, of course.
Any ethical controversies surrounding aspirin?
Well, one of the biggest ones involved research.
A lot of those early big trials that showed how
well aspirin worked for preventing heart problems,
they mostly used men as participants. Right,
we talked about that. Yeah. And those findings
were then applied to everyone, including women.
But later research showed that women might respond
differently to aspirin. Like one study in 2005
found that aspirin didn't really protect women
under 65 from a first heart attack, but it did
lower their stroke risk. Oh, so there are differences.
Yeah, and that lack of representation in those
early studies was criticized, rightfully so.
I imagine so. It actually helped to push for
big changes in how research is done. Now, places
like the National Institutes of Health, they
require researchers to include women and other
underrepresented groups in their studies, unless
there's a really good reason not to. So aspirin
kind of help make research more inclusive. In
a way, yeah. It highlighted how leaving out certain
groups can skew the results and lead to misleading
conclusions. Makes sense. Now, what about aspirin's
impact on the economy and the market? Oh, that's
a whole other story. Aspirin has gone from being
this highly profitable patented drug in the early
1900s to, well, a pretty basic low cost commodity.
Like making aspirin these days is dirt cheap,
just pennies a pill. But the painkiller market
globally, it's massive. billions of dollars.
Huge. Even though aspirin share has gone down
a bit since acetaminophen and ibuprofen came
along, it's still a big player, especially as
an OTC drug. So even if it's cheap to make, they
sell a ton of it. Exactly. And it's not just
sold as aspirin. It's in loads of cold and flu
meds too, which means it's everywhere. That's
true. I never thought about that. Even in the
US, where most people buy it over the counter,
millions of prescriptions for aspirin are written
every year. And that doesn't even count the OTC
sales. So it's still a major player. Definitely.
For Bayer, aspirin was a gold mine back in the
day. But then they lost those patent and trademark
rights, and generic competition exploded. Prices
went way down. The aspirin wars in the 20s and
30s, that was all about companies trying to stand
out in a crowded market, spending tons on advertising
and tweaking their formulas a bit. So it's a
classic example of a brand -name drug becoming
a generic. Exactly. But Bayer still makes money
from the aspirin trademark, especially in countries
where they still own it. OK. When they got back
the US trademark in 1994, it was a big deal for
them. Right. And now you see both brand name
aspirin and generic acetyl salicylic acid, or
ASA, on the shelves. It's interesting. Even when
the generic is chemically the same, some people
still prefer the brand name and are willing to
pay more. I guess the name just has that power.
It does. And we see this with those heart healthy
aspirin products, too. It's just regular aspirin,
but marketed differently. Clever marketing. Totally.
Overall, aspirin's impact on the economy over
the past 120 years has been massive. It was a
key part of the growth of the pharmaceutical
industry and is still a vital affordable medicine
worldwide, especially in places where resources
are limited. Makes sense. Even small changes
in recommendations, like the shift in thinking
about primary prevention, can have a ripple effect
on the entire market for this drug. It's amazing
how much one drug can affect so many things.
I know, right? Now, for the last part, let's
talk about aspirin's impact on culture and society.