00:01
Adrenal gland pathology, we will dive into
the medulla and the important clinical significance
and many of those associations that we will
see with it, do not underestimate what we
have to say about the adrenal medulla.
00:17
First and foremost, understand this is often
referred to as being the sympathoadrenal system.
00:22
Why?
Because when we have a fight or flight response,
sympathetic response from the adrenal medulla
wherein the biochemical pathway of forming
epi, epinephrine; at the very end on your
right is epinephrine.
00:37
You have an enzyme here that you want to be
familiar with known as phenylethanolamine-N-methyltransferase,
PNMT, the abbreviation that you’ll be oh
so comfortable with and familiar when you’re
actually forming epi, epi, epi.
00:51
For example, when there is pheochromocytoma,
obviously it’s going to be one of the discussions
there will be increased activity of this very
enzyme.
00:59
It would be nice if you would be able to identify
it.
01:02
In the meantime, you have some other enzymes
here that you should be familiar with from
CNS pharmacology.
01:09
All of these coming from tyrosine, tyrosine
hydroxylase, DOPA decarboxylase, Dopamine-beta-hydroxylase…
all those enzymes are incredibly important
as you know in different parts of your pharmacologic
discussions.
01:23
With your epinephrine, it works on every single
adrenergic receptor known to man and the pneumonic
that’s quite cute that you may want to use
is called BLOW.
01:33
What does that even mean?
At low doses of epinephrine, it works on beta
receptors; at higher doses ,we then work on
our alpha receptors therefore then works like
your norepinephrine.
01:47
Alpha 2 receptors obviously was going to inhibit
centrally the release of your norepinephrine,
if you remember [Inaudible 00:01:54] and such,
beta-1 receptors and beta-2 receptors at low
doses of epinephrine will in fact work on
these.
02:03
In the meantime, what you want to pay attention
to in the very last column here would be your
signal transduction ligand binding is that
when you are dealing with alpha-1 receptors,
you should be thinking about your blood vessels
and undergoing vasoconstriction and here,
the second messenger will be GQ.
02:21
Thus, you’re thinking about ip3 phospholipase
c and increased calcium, therefore bringing
about vasoconstriction.
02:29
All of the others that we’re seeing here
will be some form of cyclic AMP.
02:34
If it’s alpha-2, please know this, it’s
decreased cyclic AMP because it works through
GI.
02:40
Clear?
Biochemistry here with some physio and pathology.
02:44
Beta-1 and beta-2 will be increased cyclic
AMP... once again, welcome to beta receptors
GS.
02:52
Remember that beta-2 will cause smooth muscle
relaxation via cyclic AMP because it will
then do what?
Good, remember that myosin light chain kinase?
It will phospholate the myosin light chain
kinase rendering it inactive, thus you’re
not going to have smooth muscle contraction
bringing about smooth muscle vasodilation…
from pharmacology here as well.
03:19
You want to be very clear about the influence
of beta-2 with smooth muscle vasodilation
and relaxation and also with nitric oxide.
03:28
Epinephrine, it is a stress hormone, behaves
like your cortisol, glucagon.
03:38
Increased rate and force of contraction, if
it’s on the heart beta-1 receptors; increased
metabolic rate, dilation of your bronchioles,
why?
Beta-2, bronchodilation.
03:49
Stimulation of lipolysis in fat cells like
it would expect with your glucagon.
03:54
It stimulates an enzyme within adipocyte called?
Good, hormone sensitive lipase.
04:02
There will be dilation of the pupil as you
can expect with sympathetic activity in the
pupil, mydriasis and inhibition of GI secretion…
epinephrine.
04:12
Norepinephrine, constriction of blood vessels
and for the most part, with that vasoconstriction
will bring about increase in systemic vascular
resistance.
04:20
You know this physiologically as also being
called total peripheral resistance and thus
will increase blood pressure.
04:27
Norepinephrine, its primary effect on your
blood vessel via alpha-1 receptor; epinephrine
just about every single receptor.
04:34
At low dose beta, at high dose alpha behaves
like norepi.