CV Effects of Autonomic Agonists Flashcards
What changes happen in heart in response to parasymp stimulation (via muscarinic receptors)?
SA node: less automaticity (slower spontaneous depolarization)
Atrial myocardium: lower inotropy
AV node: increased refractoriness (slower AV conduction)
The His-Purkinje and ventricular myocardium aren’t affected much.
Review: What neurotransmitter do both the sympathetic and parasympathetic nervous system use at ganglionic synapses?
Acetylcholine.
And yet… Ach is really talked about as stimulating the PSNS, not SNS.
What effect does muscarinic have on the systemic vasculature?
Causes arterioles to vasodilate.
Not much effect on veins.
Putting the effects on the heart together with the effects on the vasculature, what happens when you have a “parasympathetic discharge” (i.e. lots of PSNS signaling)?
Vaso-vagal reaction: bradycardia + vasodilation = significant drop in bp -> syncope.
(why some people faint when frightened)
Why can’t you just give people acetylcholine?
It gets cleared too rapidly by acetylcholinesterase.
So you give an acetylcholinesterase inhibitor to create this effect.
Usefulness of edrophonium, an acetylcholinesterase inhibitor?
Duration of effect?
Edrophonium is a short-acting (i.e. 30s per bolus).
It induces AV block, and can be used to aid diagnosis of supraventricular tachycardia.
It isn’t used more because it causes GI parasympathetic stimulation (cramps and diarrhea).
(Most places use adenosine, because it doesn’t have GI side effects.)
Longer acting acetylcholinesterase drugs?
-stigmine drugs (they came up in B&B for Alzheimer’s)
Insecticides and sarin….
Agonism of both alpha-1 and alpha-2 causes what?
What does each cause the other doesn’t?
Vasoconstriction
Alpha-1 causes GU smooth muscle constriction.
Alpha-2 causes platelet aggregation.
Effects of beta-1 agonism?
Increased inotropy and chronotropy.
Activation of renin secretion by juxtoglomerular cells.
Effects of beta-2 agonism?
Vasodilation
Bronchodilation
Effect of beta-3 agonism? (don’t worry about it)
Increased lipolysis.
Which adrenergic receptor mediates direct effects on the heart? (increased inotropy, decreased AV refractoriness, increased SA rate)
beta-1
Which adrenergic receptor mediates constriction of veins, and vasoconstriction of arterioles leading to skin, kidneys, and gut?
alpha-1
Which adrenergic receptor mainly mediates vasodilation of skeletal muscle and bronchodilation?
beta-2
How does receptor specificity vary between endogenous and synthetic adrenergic agonists?
Endogenous agonists have affinity for multiple receptors.
Synthetic agonists have been designed to have more specificity.
Epinephrine receptor affinity?
mixed alphia, beta-1, beta-2 agonist
Norepinephrine (NE) receptor affinity profile?
mixed alpha, beta-1 agonist
little beta-2 activity
Dopamine receptor affinity profile?
mixed alphia, beta-1 affinity (little beta-2 affinity)
Isolated delta activity at low levels.
I.e. it acts pretty much like NE at high levels.
What’s the effect of epinephrine on HR, CO, and SVR?
HR and CO increased.
SVR doesn’t change much.
Effect of epineprhine on mean arterial pressure (MAP)?
It increases it (due to increases in CO and not changing SVR - MAP = CO * SVR, roughly)
What’s probably the reason why epinephrine doesn’t change SVR much?
Vasoconstriction from alpha agonism balances the vasodilation from beta-2.
Why doesn’t NE cause vasodilation?
It doesn’t have beta-2 activity.
What’s the effect of NE on SVR, HR, and CO?
SVR is increased.
HR is decreased (due to baroreceptor reflex)
CO is unchanged. (increases in SVR, vagal signaling balance beta-1 effects)
What are the effects of dopamine on vasculature at low, intermediate, and high doses?
Low: delta-1 agonism vasodilates renal arterioles.
Intermediate: beta-1 + delta-1 activity increases CO without increasing SVR much.
High: acts like NE, with increased SVR, decreased HR, and unchanged CO.
So… what is dopamine really good for at low to intermediate doses?
It acts as a pressor without decreasing renal blood flow.
You would think that this would make it a great for various kinds of shock e.g. septic, but there’s a lot of data out there that shows NE has a lower mortality rate vs. dopamine when used for shock….
Primary receptor activity of phenylephrine?
Alpha agonist
Primary receptor activity of dobutamine?
Beta-1 agonist
Primary receptor activity of isoproterenol?
Mixed beta-1, beta-2 agonist
Effect of phenylephrine on SVR, HR, and CO?
Increased SVR
Decreased HR
Decreased CO
Increased MAP, but shunts blood away from skin, gut, kidneys.
(not sure what advantage this has over dopamine as a vasopressor)
Effect of isoproterenol on SVR, HR, and CO? Utility?
SVR decreased
HR increased
CO increased
doesn’t change MAP much, maybe small increase.
Useful for transplanted hearts… and not much else.
Dobutamine effects?
Relatively pure inotrope.
Increases CO, and slightly increases HR, but has little effect on systemic circulation.
Say you have a patient in septic shock. What receptor(s) do you want to agonize, and which adrenergic agonists would accomplish this?
You want to increase SVR by agonizing alpha receptors -and you don’t want beta-2 activity.
This makes norepinephrine and phenylephrine viable choices here (and dopamine, one would think).
Preferred adrenergic agonist for cardiogenic shock?
Dobutamine - beta-1 activity increases inotropy and chronotropy.
(but I suppose you want to be careful of “whipping the heart” and increasing metabolic demand if it’s ischemic)
You don’t want isoproterenol here, as it would cause BP to drop.
