00:01
Now, when we take all of these together, we
have to look at multiple innervation systems
so that we can understand
the overall effect.
00:09
So in the vascular system, it is acted
upon by alpha 1, alpha 2 and beta 2.
00:15
So, let's take a look at each of
these in this special circumstance.
00:22
The alpha 1 agonists. The prototypical alpha 1
agonist is phenylephrine. It contracts smooth muscle
in the splanchnic blood vessels, so
that means the one that goes to the gut.
00:35
And it increases blood pressure by
incresing the total peripheral resistance.
00:41
Now, one of the side effects of
phenylephrine is reflex bradycardia.
00:47
Now, I'm going to spend a little
bit of time to explain this.
00:52
We would think that an agonist of a sympathomimetic drug
or a sympathomimetic system would cause a fast heart rate.
00:59
But what we're talking about here is a very
specific drug that is only acting on blood vessels,
it's not acting on the heart. So the heart
is free to respond however it wishes.
01:11
When the heart senses that the blood pressure
is higher, it will slow itself down,
thinking that there's too
much adrenaline around.
01:20
Right. So that's why you get reflex
bradycardia from phenylephrine.
01:26
The other issue too is that the baroreceptors also have
connections to the vagus nerve which innervates the heart,
so the vagus nerve will actually slow down the heart as well.
That's why phenylephrine causes the reflex bradycardia
eventhough it's considered the sympathomimetic. And
the reason why is cause it's an alpha 1 agonist.
01:47
Okay. Does that sound like it make sense?
Alright, let's move on.
01:52
What about the alpha 2 agonist?
The classical alpha 2 agonist is clonidine.
02:01
Now, I just finished telling you that alpha
1 agonist will increase the blood pressure,
and now I'm going to tell you that alpha 2
agonist are decreasing the blood pressure.
02:11
Why is that happening? Well, let's
take a look at the blood vessel itself.
02:16
Yes, alpha 2 agonist
cause vasoconstriction.
02:20
So, clonidine for example,
or other alpha 2 agonist
causes some mild constriction
of the blood vessels.
02:26
However, clonidine also crosses
the blood brain barrier.
02:30
And it accumulates in the brain.
02:32
And now what it's
doing is it's acting
to reduce sympathetic
outflow and blood pressure.
02:38
Why?
Well, if you have an excessive amount of
adrenaline crossing through your system,
and it's sensed by the brain,
you know that the brain is saying,
"Uhh ohh, we're really in trouble.
We need to reduce our sympathetic outflow."
So, it's taking advantage
of a feedback loop.
02:53
That's why clonidine
reduces blood pressure.
02:56
Now, I should mention very
quickly that clonidine
is not our favourite form
of blood pressure agent,
I'm going to talk about it more
in our hypertension lectures.
03:05
The problem with clonidine
is because it acts centrally,
you can also get orthostatic
drops when you stand up.
03:14
Okay, let's go on to
the beta 2 agonist.
03:17
So, remember that the beta 2
receptor is in the lungs, right?
There's two lungs, one heart,
so beta 1 is heart, beta 2 is lungs.
03:25
Albuterol, salbutamol.
Salbutamol is better known as ventalin.
03:29
There is going to be some vasodilation
in the skeletal muscle with these drugs.
03:35
But you have to usually take a very
high dose in order to achieve that.
03:40
There are maybe some reduction in blood
pressure with the usage of ventalin.
03:45
In general, I've never seen
that in clinical practice.
03:48
There is some vasodilations
in the lungs as well.
03:51
Cocaine is also an agonist.
03:55
And remember that cocaine, when taken
in the nose causes vasoconstriction.
04:01
Cocaine, as crack cocaine,
causes vasodilation,
and that's why crack cocaine
is absorbed so quickly,
because where it's landing
it's dilating the blood vessels
and getting into the
blood much more quickly.
04:13
We are going to talk more about cocaine
and crack in our toxicology lectures.
04:20
So, let's talk about toxicity.
04:22
With catecholamines, they rarely cause
clinical problems as medications.
04:28
It's quite rare because
they're quite short lived.
04:30
However, I do want you to go back
and read up on "pheochromocytoma".
04:34
It's a relatively rare kind of
tumour of the adrenal gland.
04:38
And it's best done if you read
it on your own in a textbook.
04:43
Dopamine. If you give
excess amount of dopamine,
you can sometimes cause digital
ischemia and mesenteric ischemia.
04:50
We kind of mentioned that in the
case that I was talking about earlier
where you risk losing
fingers and you risk causing
infarcts of the bowel with
excess of levels of dopamine.
05:01
And finally,amphetamines
and cocaine
which I've very briefly touched
on and will cover later.