- [Voiceover] Hey, guys.
This is Dr. Joel with MedImmersion.
You are watching a flash flood review series video
where I review the highest yield stuff for your board exams
in as little time as possible.
In this video, I'm going to be talking about the
potassium channel blockers, which are a class
of the antiarrhythmic agents.
I'll cover some general principles about the class
as a whole, and then a few specific drugs in that category,
or in this class.
It's gonna be awesome, so stick around.
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Okay.
Let's jump into it.
This lecture is going to cover a subset of
the antiarrhythmics, the potassium channel blockers.
I'll give you an introduction as to what they are.
Then, talk about some general principles that will
include the mechanism of action, clinical uses, adverse
or side effects, and then I will cover a couple of the
highest yield examples in this class.
Alright.
First of all, if you need to review the entire topic
of the antiarrhythmics, with a little bit of cardiac
physiology, you should really go over and watch
The Antiarrhythmic Agents Lecture first.
This lecture, right now, is a little bit more focused,
and I assume that you know a couple of things
about antiarrhythmics.
So, the potassium channel blockers, in the Vaughn Williams
Antiarrhythmic Agent Classification,
are the Class III antiarrhythmics.
You should know that.
And we use the potassium channel blockers and the Class I,
or sodium channel blockers, for rhythm control.
The Class IIs and Class IVs are more rate control.
Four drugs that we're gonna talk about amiodarone,
ibutilide, dofetilide, and sotalol, which you can remember
by the mnemonic AIDS.
As for the mechanism of action, these block myocardial
potassium channels, and that has its primary effect
on the specific potassium channels that are responsible
for the delayed rectifier current, which have a very
important contribution on the length of the
action potential, and thus, the effective refractory period
of cardiac myocytes.
And to explain that a little bit further.
Have you ever wondered why exactly the action potential
of a neuron through the spinal cord or a
peripheral neuron looks different than the action potential
in myocardium.
Well, it's built that way on purpose.
The plateau phase, or the prolongation of the
action potential, or the refractory period,
gives cardiac tissue special properties that prevent it
or contribute to prevention of arrhythmias.
So, the picture on the left is what maybe a bland neuron
action potential might look like in the peripheral
nervous system.
On the right, we have a cardiac action potential.
And both of these are pretty bland images.
They're not exactly right.
But the point here is that there's a plateau where the cell
stays in its non-polarized state for
a little bit longer, for a period of time.
Potassium plays a big part in that.
The initial depolarization is caused by a rapid influx
of sodium.
And then, it's maintained in that depolarized state
by both calcium and potassium trading places across
the cell membrane in relatively small amounts.
In phase three, which is the repolarization phase,
finally there's a delayed switch, or a delayed rectifier
current of potassium, which finally turns on and allows
an efflux of positive ions, allowing the
membrane potential to come back down to a very
negative number.
So, hopefully you can see why if we mess around with
the potassium channels that contribute to phase three,
we prolong or at least change the shape of the cardiac
action potential, which, of course, would have an effect
on some kinds of arrhythmias.
So, it was pretty easy to see, I think, from that previous
picture that delaying the potassium efflux during the
repolarization phases increases or stretches out the
action potential duration and also the effective
refractory period.
Also, these do not have any effect on the sodium channels,
meaning that the conduction velocity, or phase zero,
wouldn't be affected or decreased.
And visually, it looks like this, the action potential
stretched out and the effective refractory period
is increased.
Also, that means that the QT interval is prolonged.
Okay.
Does that make sense?
We use the Class III antiarrhythmic agents for
rhythm control.
Because they change the effective refractory period,
they can help cancel out pre-excitation accessory pathways
and other mechanisms by which you might have
a tachyarrhythmia.
So, like a A-Fib, A-Flutter, V-Fib, and V-Tach.
Also, Wolff-Parkinson-White syndrome, which is
a pre-excitation syndrome that uses
a accessory pathway.
So, as for the adverse effects, or the side effects,
in this slide, I'm really going to talk about these drugs
as a class, or as a whole.
And I will talk about the individual side effects that
each drug is famous for in the next or upcoming slides.
So, as a class, these drugs are famous because of the
reverse use dependence principle, which means that
their effect, or their prolongation of the action potential
duration, increases at lower heart rates.
Well, that's not where we actually want the drugs to work.
We want the drugs to work at high or fast heart rates,
tachycardias.
So, this just increases the susceptibility of the myocardium
to early depolarizations at low heart rates, which is why
these drugs aren't wildly popular.
We use them, but there are other drugs that we use
before them, oftentimes.
So, a huge side effect of these drugs, which you have
to know, is that they increase the risk for Torsades.
Now to talk about a few individual drugs,
starting with amiodarone.
Amiodarone is five out of five.
You have to know this.
This is a very important drug.
You're gonna see it, and you're gonna be asked about it
in your clinical rotations.
It's important because we use it in ACLS and also for other
arrhythmias in the CCU.
And the numbers on the left hand side of every bullet
are the yield, or the importance, of each point of data.
So, starting first in the mechanism of action,
slightly different from than what we previously said,
amiodarone actually has properties of all four
of the classes of the antiarrhythmics.
That's pretty cool, and that's important.
The next two bullet points there in the mechanism of action,
we've already talked about, and we should understand.
For clinical use, five out of five ventricular arrhythmias,
V-Tach, V-Fib, you got to know it.
Slightly less important than that is A-Fib.
And much less than that, like we don't use it at all
really for A-Flutter.
But it would work.
It would have some effect.
Side effects.
The first, second, and third, thyroid toxicity,
pulmonary fibrosis, and hepatotoxicity.
You need to know those.
That's why they say remember to check your PFTs, LFTs,
and TFTs when starting amiodarone.
It's true.
Those are very common side effects, and you're gonna be
tested on them.
Less frequent than those top three are some of these
other lower ones, which you can commit to memory
if you want to.
But as long as you have the high-yield stuff,
you're probably gonna be good for your tests.
Next is ibutilide, which is slightly less high-yield
than amiodarone.
I'm gonna give it a four out of five.
There's not a lot new here about the mechanism of action.
However, the clinical use shifts just a little bit.
This has a little bit more use in atrial arrhythmias.
So, like A-Fib and A-Flutter.
Side effects. Torsades.
I talked about that.
Torsade de pointes is an important side effect for
these drugs.
And possibly, this medication could cause hypertension.
As for the last two Class III antiarrhythmics in this
discussion, these two are even less high-yield than
the previous two I've talked about.
Dofetilide, I'm gonna say it's a two out of five,
and sotalol maybe a three out of five just because
sotalol has an interesting point about it.
Dofetilide, pretty dangerous drug.
There's a lot of first world countries who don't use it,
or it's not available in, because it's so dangerous.
In the United States, you need special training to even
deliver it.
So, not real common.
Sotalol is interesting because it has, in addition to
its Class III antiarrhythmic properties, it has a little bit
of Class II activity as well.
It non-selectively binds the Beta-1 and Beta-2
adrenergic receptors, which makes it unique and, therefore,
makes it interesting and, therefore, makes it fun on tests.
So, you should know that about sotalol.
However, if you're crammed for time, I would focus
on the first two drugs that we talked about and save these
if you have time later.
Alright, guys.
Knowledge Challenge #1.
What is the mechanism by which cardiac cells maintain
their electrochemical gradient?
And actually, this would apply to neurons as well.
Well, the answer is A), the sodium potassium ATPase,
or the sodium potassium pump, which pumps three sodium ions
out for every two ions of potassium that it pumps in
at the cost of ATP, which is why B) and D)
are wrong.
Technically, if I would have flipped those so that it said
sodium efflux and potassium influx, you could have argued
that hey that's what the sodium potassium pump does.
But that's not what I said.
So, you're wrong, wrong, wrong, wrong,
wrong, wrong, wrong wrong.
And C) is also not correct because that's an enzyme
that converts ATP into cyclic AMP, which isn't important
in this particular mechanism.
Knowledge Challenge #2.
Which phase of the cardiac action potential is the
plateau phase?
Well, the answer is phase two.
Phase zero, which isn't one of the choices, phase zero is
the rapid depolarization phase.
Phase one is a initial repolarization phase, followed by
phase two, which is the plateau phase, followed by
phase three, which is the complete repolarization,
and phase four, which is a resting phase.
Knowledge Challenge #3.
You're almost there.
Good job if you stuck with it this long.
Which Vaughn Williams antiarrhythmic class do the
beta-blockers belong to?
Well, Dr. Joel, you didn't talk about the beta-blockers
in this lecture.
You are cheating, sir.
Yes I am. Yes I am.
Class II, the beta-blockers are Class II.
Class I are the sodium channel blockers.
Class III are the potassium channel blockers.
If you don't know that after this lecture, then I am
a terrible teacher.
And Class IV are the calcium channel blockers.
Okay.
Thanks for watching, guys.
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