Epinephrine is a high-yield topic. We give it a 5 out of 5. It's also known as adrenaline.
Don't let this confuse you, it just depends on which part of the world you live in. Here
in America, we prefer Epinephrine. In other parts of the world, they prefer Adrenaline,
but if you break the two words down, you can see they are almost the same. "Epi" on top
of "Nephrine," the kidney. "Ad" which is on top of "Renaline," which is also the kidney.
One is Latin, One is Greek. It's just saying the same thing in a different way. Epinephrine
is a natural hormone and neurotransmitter. It's a catecholamine, which basically just
means that it has a benzine with two hydroxyl side groups and it is derived from the amino
acid, tyrosine. We are not covering the synthesis of these hormones in this lecture, but we
have another lecture dedicated to it. See that lecture if you need more information.
Most of the synthesis of adrenaline in our bodies happens in the medulla in the adrenal
glands. Lastly, Epinephrine is a nonselective Alpha and Beta agonist. It just isn't very
picky. On to the mechanism of action. And I guess I should explain to you that the numbers
on the left-hand side of these bullets, represent the "yield" or the importance of each bullet
as far as your test-taking or your general knowledge. The higher the number here, 5 out
of 5 being the highest, the higher the number, the more important that you know that piece
of data. As I've already told you, it's a nonselective agonist of Alpha & Beta adrenoreceptors.
That's the first bullet, but if you skip down to the very bottom bullet (you see this generally
in textbooks), basically what they are trying to say is that Epinephrine as a molecule has
equal affinities for each of these receptors. But that doesn't necessarily translate well
into physiology. The truth of the physiology is a little more complex, and that's what
the other bullets are talking about. So, at a high dose of epinephrine, Alpha effects
are going to dominate. At lower doses, or lower concentrations in the body or the blood,
beta effects are going to dominate. And, I remember that by thinking "B" low. So Betas
dominate at lower doses. "B low" So think about what, for example, if I gave someone
a local injection of lidocaine with some epinephrine in it, which is very common, that's going
to be a high dose in that local area. Alpha effects are going to dominate, which means
mainly you're going to see Alpha 1 effects. Which is basically very strong vasoconstriction,
which is very useful if you are excising, say a lesion or a mole because it constricts
down on the blood vessels, the wound doesn't bleed very much, and also, secondarily, the
lidocaine sticks around in the area for a little longer. Alpha 2, on the other hand,
is decreasing the sympathetic tone to the area. Because the sympathetic presynaptic
nerve is not releasing as much neurotransmitter, however, that doesn't really matter because
the receptors are being stimulated by the Epinephrine, not by the naturally released
neurotransmitter. For another example, how about the Beta effects? We have a patient
who is very allergic to peanuts, accidentally eats some and begins to have an anaphylactic
reaction to that, and are beginning to have a difficult time breathing. They inject themselves
with an EpiPen, so in the local area where they shoot themselves in the leg, it's going
to be a very high-dose and they are going to have some localized vasoconstriction, but
as that spreads out throughout the body, they are going to have a lot of Beta effects, such
as the bronchodilation of the lungs they are also going to get some tachycardia and increased
blood pressure. Those are the Beta effects. So just because it stimulates the receptors
equally, that doesn't mean it translates directly over to kind of a straight across the board,
physiologic response on all the receptors. One of the favorite questions that you will
see or talk about in school, is this chart on the right here. The effects of Epinephrine
are Heart Rate, Blood Pressure and Peripheral Vascular Resistance. So, to explain this chart,
the x-axis is time and the y-axis varies: it could either be the heart rate, the blood
pressure or the peripheral vascular resistance, so it's different for each one of these three.
The dashed line here is the moment in time when the epinephrine is introduced to the
system. So what do you think the heart rate will do when the epinephrine gets to the heart?
The heart rate is going to increase and then slowly go back down after the drug is metabolized.
What about the blood pressure? What do you think the blood pressure is going to do with
epinephrine? Well, you need to remember that blood pressure is broken down into two parts,
the systolic and the diastolic. The systolic is going to go, which way? Up. The Beta 1
receptors are being stimulated, so the heart is going to contract harder and faster. This
is going to increase the systolic blood pressure. What about the diastolic blood pressure? Well,
it's actually going to go down a little bit, so you're going to have a widening of the
pulse pressure. That is because, partly at least, of this last point: the peripheral
vascular resistance will actually go down. Why will that happen? "I thought Alpha 1 was
a peripheral vasoconstrictor?" Well, that's true, but the dose isn't high enough to constrict
down all those peripheries. You are actually going to be in the Beta range. And, remember,
Beta 2 is a dilator. So, this isn't the last time that you'll see this chart. This is a
popular chart to discuss and even test questions will come off of this. Clinical uses of Epinephrine
include cardiac arrest resuscitation, and this should make sense because of the effect
that epinephrine has on the heart, it stimulates it, it gets it going again. Next, you can
use it for extreme cases of bronchospasm, such as acute asthma and anephylaxis and we
talked about that, that makes sense, right? The Beta 2 effects are going to open up the
bronchii, so for this next bullet, I hinted at it before, but I didn't explain it very
well. Epinephrine is very commonly mixed with lidocaine for dermatological procedures, such
as removing a mole. The reason is that the lidocaine by itself would quickly be washed
away from the area by the action of the capillary blood. So, within only a few minutes, you
would lose your anesthetic and the patient would be in pain. If you inject a lidocaine-epi
mix, well, the Epinephrine causes strong vasoconstriction in that area, thus it increases the length
of time that the anesthetic is in the area. Also, you'll notice if you use this, that
the skin right around where you inject, blanches, and that's for the same reason. Because the
blood vessels are constricting down. That's also useful, because then when you excise
the mole, or do your work, there's much less bleeding. It gives you a chance to achieve
hemostasis a little easier. Lastly, open-angle glaucoma, not closed-angle glaucoma, open-angle
glaucoma, basically it decreases the intraocular pressure by decreasing the production of aqueous
humor and by clamping down on vessels. You don't want to give it in closed-angle glaucoma
because it's going to cause mydriasis and clamp down even further on the outflow through
the trabecular meshwork, that's basically the muscles on the side of the pupil, and
thus squeezing off or pinching off all those little canals that allow the natural draining
of aqueous humor, thus making your closed-angle glaucoma even worse. Last slide for Epinephrine:
The Side Effects. We have talked in detail, I think, about these top two bullet points.
Basically, we know that epinephrine is going to cause the blood pressure, the systolic
blood pressure, to go up. Sometimes, way up. Also, we know that it's going to cause the
heart to beat faster and that's what the third point is about. Sometimes, a lot faster, sometimes
within the range of being dangerous. What if you have someone with a preexisting heart
condition or a known issue of being prone to superventricular tachycardia or other tachyarrhythmias?
Well, you need to be careful with epinephrine. You don't want to cause that. The last thing
you want is a heart attack in someone that you were just trying to treat for a mild allergic
reaction. So, just keep an eye on that. Just be careful. Lastly, anxiety. Epinephrine is
going to make you very anxious, tremulous, fidgety and shaky. It just isn't a very comfortable
drug to take. Now, how about two quick knowledge challenge questions. The first one: What is
the mechanism of the decrease in the diastolic blood pressure with epinephrine? The correct
answer is the last answer: D Stimulation of Beta 2 receptors. Do you remember the graph
that we talked about before? What happens to the peripheral vascular resistance with
epinephrine? It actually goes down because of Beta 2 stimulation. Remember, Beta 2 is
a vasodilator. Now, I know what you are thinking: We talked about Epinephrine being a vasoconstrictor
and we talked about how we use that with Lidocaine and other things. Well, you need to keep in
mind, the dose. Very high doses: Alpha effects predominate. So, in a local injection, in
that local area, there's a very high concentration of Epinephrine. But, if we're giving Epinephrine
to somebody for systemic use, or if the body is releasing Epinephrine, as a natural hormone,
the concentration is much less, systemically. And then, do you remember how I said "B - Low"
for Beta Effects at low doses? That's right, that's what we're talking about here. Beta
2 dilation is going to over-power Alpha 1 constriction at normal, physiologic concentrations,
so there is going to be a decrease in the peripheral vascular resistance and the diastolic
blood pressure is going to go down, despite the systolic blood pressure going up. And
that happens because of Beta 1 stimulation which results in an increase in cardiac output
and cardiac output is a function of the stroke volume and the heart rate, both of which are
affected by Beta 1. So, if you picked Beta 2, awesome. Now, on to the second question.
And this one is a little bit tricky. I'm not sure if it's fair, but I'm going to go with
it anyway. True or False: Epinephrine (also known as Adrenaline) is the primary neurotransmitter
of the sympathetic nervous system. So, it's true that epinephrine is pivotal to our fight
or flight response, our sympathetic response, but is it the primary neurotransmitter for
the sympathetic nerves? No. It's actually Norepinephrine. Do you remember that? Do you
remember what neurotransmitter is released from the presynaptic side or sympathetic nerves?
Norepinephrine. It's by far, norepinephrine. So, while again, epinephrine is very pivotal
to the sympathetic response, or the adrenaline surge or what we feel when we are being chased
by a lion, it's not what's primarily released from the presynaptic nerve.