If you’re coming fresh off the Covid-19
video about remdesivir and are hungry for
more information, then this is the video for
you!
This is ELI5Pharma and today we’re going
to be talking about glucocorticosteroids,
with a notable mention of dexamethasone.
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Keeping up with the trend of Covid19, if you’re
a keen bean reading machine devouring all
the news and scientific journals, or you follow
my Facebook page (link in description), you’ve
probably heard all about dexamethasone, a
glucocorticosteroid.
The wonder drug that is not only cheap but
can also save up to a third of hospitalised
patients with severe complications.
What does it do?
It stifles the immune system.
(cricket noises).
Wait wait wait hang on a second, you
and my teacher from fifth grade
and my university professor
and my mum
and my uncle
and my aunt
and my pet rock
all said that the immune system
is meant to protect you from nasties
like Covid-19.
So, if you stop it from doing its job, won’t
Covid19 run wild?
Biology is complex and is often unpredictable.
Pharmacology is even worse, because
you need to identify the problem and then
provide the solution that you think might
work.
(internally screaming)
This might be why the news that dexamethasone
helps people recover faster from Covid-19
a little bit confusing.
It may however, make more sense than we actually
think.
I’ll keep this brief and define the madness
behind the rationale of why dexamethasone
The normal way of thinking would be that the
reason why people may have serious complications
or issues from Covid-19 is because of the
virus itself.
The 5head way of thinking would be that the
complications are caused by the immune system.
Why?
Because the immune system is extremely destructive.
Like weapons.
Weapons are necessary for defending yourself,
but can also cause collateral damage.
So whilst your immune system is ravaging the
virus, it’s also ravaging parts of your
body which can, but not always, lead to some
serious complications.
This is the reasoning behind why dexamethasone
may decrease recovery time, but is also the
reasoning in the first place as to why dexamethasone
was used!
Now lets get into the how it works.
Dexamethasone is an example of a glucocorticosteroid,
which I’m going to abbreviate now as GCS.
GCS’s are a part of a subfamily of drugs
called corticosteroids, which is a part of
a family of drugs called “steroids”.
You may have heard of steroids in the press
as drugs that athletes abuse, but these types
of drugs are known as anabolic steroids.
All steroids have this characteristic structure
of three (not six) hexagons and one pentagon ring attached,
so by just looking at the chemical structure
of a drug you can easily identify which is
a steroid and which isn’t.
Lets rewind back to GCSs, which have been
used generally for immune system related diseases
such as asthma, Crohn’s disease, and sometimes
even food allergies.
They basically tell the immune system to chill
out.
Lets put this into a metaphor.
You’re chilling on your couch playing some
video games or binging Netflix, when your
dad or mum, or the immune system, comes in
and starts screaming at you to get off your
lazy rear to go and study.
The GCSs would be your report card, cause
when they read it, they’ll get off your
back.
This assumes that you were either a high scoring
student, or parents with very low expectations
of you.
You can fight me in the comments section about
how lame and inaccurate the metaphor is to
you.
You might be thinking that at this point in
the video I’m stalling for time to talk
about exactly how GCSs works, and yes unfortunately
you are right – there is no clear understanding
of how exactly GCS works.
But here are the core facts.
Our cell is in itself like a person: it’s
got a skin called the “cell membrane”,
the blood called “cytosol”, and organs
which are called, well, “organelles”.
One of the organelles is called the nucleus,
which is like the brain of the cell.
It houses all of the genetic information of
the cell, which is DNA.
DNA encodes the instructions for the cell
on what to do such as what to produce.
DNA in cells that are a part of the immune system
produce cytokines, which can be pro-inflammatory,
or make the immune system stronger and more
destructive.
There are also anti-inflammatory cytokines
which restrain the immune system, but during
a situation like an infection, the cytokines
that are produced are generally pro-inflammatory.
Pro-inflammatory cytokines are like nitrous
if the immune cell is like that sweet car
you decided to deck out – they make that
car go faster, and in the process produce
a ridiculous amount of noise (or damage).
Hanging about in the cytosol are glucocorticoid
receptors, which you can probably guess in
the name, is bound to and activated by GCS.
Our body actually produces GCS,
so drugs like dexamethasone essentially mimic
the body’s own GCS.
Once the receptor is bound by GCS, it then
moves straight into the nucleus of the cell.
Once there, it can actually interact with
the DNA directly.
And what does this translate to?
Multiple things.
For instance, it’s known that the production of interleukin-6, a pro-inflammatory cytokine, is
decreased.
The production of Interleukin-8, which is involved
in recruiting immune cells to join the fight,
is also decreased.
GCS’s have also shown to affect the production
of many other cytokines, and hence is the
reason why we aren’t certain on exactly
how they work.
What we are sure of is that the overall effect is that
the immune system is no longer as powerful
and therefore not causing as much destruction.
Your parents are now off your back, and you
can continue playing whatever video game or
watching whatever Netflix series you’re
binging.
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are always welcome!
