00:01
Welcome to Pharmacology by Lecturio.
00:04
Today, we’re gonna talk about a very complex topic called
the biologic medications.
00:10
This deals with the pharmacology of inflammation.
00:13
Now from a real world perspective we would never categorize
these drugs under one section
but I’m just going to explain them to you so it makes a
little bit more sense in the grand scheme of things.
00:23
You can then read about them later when you’re doing a
system, say, respiratory.
00:28
Now, in general, when we talk about drugs that suppress the
immune system,
we divide them into intracellular mechanisms of action and
extracellular mechanisms of action.
00:39
When we talk about intracellular, we talk about those that
initiate the inflammation pathway
so you can talk about antimetabolite drugs, you can talk
about macrolides or you can talk about IMDs.
00:52
Now, an example of a antimetabolite is something like a
azathioprine.
00:57
So we’ve actually talked about these drugs already in some
of our viral lectures
and some of our other inflammation lectures.
01:03
What this does is it inhibits or interrupts purine
synthesis.
01:08
You can also interrupt pyrimidine synthesis so leflunomide
is a great example of this particular mechanism of action.
01:16
Finally, you can have antifolate medications.
01:19
Methotrexate is a classic example of an antimetabolite that
works intracellularly.
01:26
We also have macrolides, now the macrolides we commonly
think of as antibiotics
but these are also macrolides.
01:35
These drugs are like tacrolimus or other drugs in this drug
class
and what they do is they block a certain type of protein
called calcineurin.
01:48
There are others as well in this drug class.
01:50
Finally, there are what we call the IMDs - these are
angiogenesis inhibitors.
01:56
Great example is the thalidomide.
01:58
Thalidomide was made famous by patients who ended up being
born with no arms and no legs
because they were given to pregnant women.
02:07
Now the drug itself wasn’t the problem the problem
was that during the manufacture of thalidomide, there was
enantiomers.
02:14
Enantiomers are examples of my left and right hand, they're
enantiomers of each other.
02:19
The wrong enantiomers were being mixed in the product and it
was the enantiomer that was fetotoxic,
the original drug was not.
02:28
The other type of intracellular agents are receptor
antagonists.
02:32
So for example, you can have interleukin receptor antagonist
or mTOR antagonists.
02:39
Now when you look at the mTOR antagonists you can see drugs
that are very familiar to us
and these are often used in transplant medicine to suppress
the immune system
so that you don’t have a reaction to your newly transported
organ.
02:53
Extracellular immunosuppressive drugs are quite wide
and varied and these are containing some of the most
exciting drugs in history.
03:03
The antibody based extracellular drugs include polyclonal
and monoclonal drugs.
03:09
So the polyclonal drugs are old, they’re the anti-thymocyte
globulin and the anti-lymphocyte globulin -
these are polyclonal in the sense that they are acting on
multiple sites,
they have multiple strains so it’s not a specified targeted
kind of a drug like the monoclonal antibodies are.
03:27
The monoclonal antibodies are probably the most exciting
thing to happen to medicine in the last 200 years.
03:34
Monoclonal antibodies are so specific and they are so
relatively speaking free of a side effects
that they are revolutionizing every single branch of
medicine.
03:47
Now the monoclonal anti-bodies can target the serum, can
target the cellular or can target any other area.
03:54
It’s a huge area and obviously, the schematic is not done to
size
because of monoclonal antibodies there are thousands of them
where perhaps there are maybe 10 or 12 in the other
categories.
04:06
For example, in terms of your serum targets you can have
those drugs that target complement C5
or you can have those drugs that target IgE so omalizumab
is a classic example of an IgE monoclonal antibody.
04:23
There’s interferon based treatments, there’s other types of
interleukin 12 or interleukin 17A -
there’s hundreds and hundreds of different targets that you
can have in the serum.
04:35
Cellular targets are huge as well. You can have everything
from CD 3 to CD 154.
04:42
Literally, there’re hundreds of the CD base cellular
targets. Some of the more commonly once
that we know about is the CD 20 targeter of rituximab which
we’ll talk about in a minute.
04:56
Now we have other unsorted ones, so I’m not gonna go into
all of them,
I think that it’s just important to know that some of the
monoclonal antibodies
will have various targets, one of the one’s that I’m
thinking of in particular is [inaudible 05:25]
which is actually used in cholesterol control of all things,
so monoclonal antibodies are wide and varied.
05:19
We're talking here about immunosuppressive drugs but they
can be many different targets,
they can also have immunosuppressive activity.
05:25
In terms of extracellular activity, we also have some fusion
inhibitors
which we commonly think of as viral treatments but we can
also have immunosuppressive drugs
that work in the same areas.
05:39
We also have agents that work against tumor necrosis factor
so for example etanercept is an agent that works against
TNFi.
05:51
So there you have it.
05:52
There’s an overall schemata of the inflammatory
immunosuppressive agents.
05:58
There are a lot of them, there are hundreds of them
but when you start talking about the individual agents in
trying to figure out
where they fit in into the schema, if you have schema like
this to put it all together,
it starts to make a little bit more sense.
06:11
Also have a look at my other lecture that went over the
entire immune system sort of in three minutes and it’ll
help.