This is a very short introduction lecture to the Adrenergic Agonists. Basically, I want
this lecture to be just a jumping pad or a starting point or a definition of terms or
ideas so that you know where you need to study next after this lecture. The Adrenergic Agonists
are also known as Sympathomimetics and I do use those terms interchangeably through the
lecture so don't be confused by that. I will real quick explain what these three things
are: The Direct, Indirect and Mixed-Action Adrenergic Agonists and then from there, you
can pick what you need to see next. So, what does it mean to be a direct sympthathomimetic
or a direct adrenergic agonist? It basically comes down to the mechanism of how the signal
is propagated or the effect is carried on. The picture on the right is a pre synaptic
nerve and a post-synaptic nerve with a synapse in the middle. If you zoom in on the synapse,
this is where the action is. These are the receptors. The normal physiology here at the
presynaptic nerve is that the action potential or the nerve impulse is propagated down to
the end of the presynaptic nerve here. There is a series of cellular changes which causes
vessicles filled with neurotransmitters to fuse to the membrane and then spill their
contents. The neurotransmitters then go on to stimulate their receptors. Alright, so
this is the normal physiology. The receptors are stimulated by the neurotransmitter. Alright,
the green star here represents a direct sympathomimetic drug. It works the same way. It directly acts
on the adrenergic receptor, that's why it's called a direct adrenergic receptor agonist.
On the left side, you'll see this short list of drugs. These are examples of direct acting
sympathomimetics, or adrenergic agonists. So, we've explained what the direct-acting
adrenergic agonists do, let's now talk about what the indirect and mixed-action adrenergic
agonists do. We know that neurotransmitter is released from the vessicles and goes off
and binds the receptors. We also know that direct-acting adrenergic agonists also directly
bind the receptors, so how do indirect-acting adrenergic agonists work? Well, one way that
this could work is to increase the release of neurotransmitter. So take this purple star,
for example. This purple star represents a drug that does just that. Through a series
of mechanisms (and they are different for different drugs) it binds to the membrane
and causes more neurotransmitter to spill out, so the receptor you can see is stimulated,
but the drug didn't directly stimulate it. What's another way? Well, notice that neurotransmitter
kind of hanging out in the synaptic gap there, a couple of things happen usually. We know
that not all of the neurotransmitter that is release from the presynaptic side is used
to stimulate the receptors. Some of it is taken back up into the presynaptic nerve,
it is recycled. So, our next drug is represented by this orange star. This drug acts to block
that re-uptake, again, the receptors are stimulated more, but the drug didn't directly stimulate
it. So, it's indirectly increasing the amount stimulation that these receptors get. So,
lastly, there's still neurotransmitter hanging out in the synaptic gap. Some of that neurotransmitter
is metabolized, and I'm going to use an example of it being metabolized right here in the
gap. Various enzymes degrade and remove the neurotransmitter from that gap. Well, what
if we had another drug, take for example this red star. What if it is a drug that blocks
the action of those degrading enzymes? The receptors are stimulated, but not directly
by the drug. The Mixed-Action Adrenergic Agonists: They do pretty much what they sound like they
do. They increase the release of Neurotransmitter, kind of similar to the mechanism of the purple
star drug, and they also directly act on the receptors. Okay, let's go on. Okay, now on
to the Knowledge Challenge for this lecture. Now, you may or may not know these drugs,
if you do, this will be a good review, if you don't, just try and pick up concepts or
categories, if you can. I'm going to quiz you on the mechanism of action of each one
of these drugs, starting with Epinephrine. Which receptors does Epinephrine work on?
Alpha 1, Alpha 2, Beta 1, Beta 2. Norepinephrine: It's almost the same as epinephrine, except
without the Beta 2. Dopamine: Alpha 1, Beta 1, Dopamine 1 and 2. How about Dobutamine?
Just Beta 1. Isoproterenol: Beta 1 and 2, it's a non-selective Beta. Albuterol: Beta 2
Oxymetazoline: Alpha 1 and Alpha 2, however, it favors Alpha 1 over Alpha 2. Clonidine:
Alpha 2. Phenylephrine: Alpha 1. Now, on to the indirect-acting adrenergic agonists, starting
with Amphetamine. Well, Amphetamine causes an increase in the release of neurotransmitter,
or norepinephrine, from the presynaptic nerve. It also inhibits monoamine oxidase which is
an enzyme that degrades catecholamines. Cocaine works by blocking the re-uptake of neurotransmitter
into the presynaptic nerve or terminal. Lastly, the mixed-action Adrenergic Agonists, starting
with Ephedrine and Pseudoephedrine: both of these are similar in their mechanism of action,
they both stimulate Alpha and Beta receptors, but also cause an increase in release of neurotransmitter
from the presynaptic nerve.