In this video I discuss the alpha and beta adrenergic receptors as well as the key physiologic differences between the drugs, epinephrine, norepinephrine, and isoproterenol.
Everybody welcome to topic 189 in our countdown of the 200 highest yield topics on us emily start our discussion talking about adrenergic receptors we think about the sympathetic nervous system we’re thinking about a division between the alpha and beta receptors as the major edge energic receptors now beta one activation leads to increased contractility and heart
Rate now typically heart failure drugs like dobutamine are gonna be great for this especially in the later stages of heart failure because they can increase their contractility like we said bring up the heart rate this is typically done through a gs mechanism and i think of that in the sense that the beta 1 receptor is stimulating the heart and so it’s going to
Require a stimulatory gpcr cascade also a stimulation of any beta receptor in general whether it be beta 1 beta 2 or beta 3 all calls lipolysis and all beta receptors are activated through the gs cascade so now let’s compare the beta 2 receptor with the alpha 1 receptor and i know i feel it seems like i’m jumping around but these two receptors you want to clearly
Distinguish in your mind based on their mechanism of action so the beta 2 receptor it leads to vascular and nonvascular smooth muscle relaxation so vasodilation and blood vessels or relearn a relaxation of sphincters or uterine smooth muscle for example or the airways where you can get bronchodilation for example in premature labor we would use a beta-2 agonist
To relax the uterine smooth muscle so in general we can say that the beta 2 receptor relaxes smooth muscle okay the other thing that it does that that’s not on here that you want to take note of is it also stimulates the release of insulin and glucagon now in general the sympathetic nervous system will stimulate the release of glucagon but what’s interesting
About the beta 2 receptor is it also stimulates insulin release so not only are you going to be putting glucose in the bloodstream to gluconeogenesis from the glucagon release of the sympathetic nervous system but you’re also going to be releasing a counteracting insulin which can cause a hyperinsulinemia with hyperglycemia if there was too much stimulation of
The beta 2 receptor now the one receptor will have the opposite effect of the beta two receptor in terms of its effects on vascular smooth muscle so if you remember that beta 2 causes dilation or relaxation of smooth muscle remember that the alpha 1 receptor does the opposite it causes contraction of smooth muscle whether that be a sphincter like the internal
Urethral sphincter or whether it be a blood vessel where it’s causing basal constriction also alpha 1 will cause pupillary dilation and in general it assists with the detrusor muscle contraction so just think contraction with alpha 1 receptor now we said beta receptors are all gs and they can also cause lipolysis right those are the two big things that all beta
Receptor to do the alpha receptors however actually don’t use the gs cascade speed alpha 1 receptor uses the gq cascade the way i kind of remember that is gqi remember the ip3 and the diacylglycerol leading to a release of calcium intracellularly i’m thinking calcium contraction gq cascade alpha 1 now if you stimulated the same amount of alpha one receptors in
Beta 2 receptors alpha 1 receptors would win assuming they were stimulated equally so alpha 1 receptors get kind of the check mark in terms of equal stimulation between beta 2 and alpha 1 now we have the alpha 2 receptors the alpha 2 receptor is very different from the others this receptor actually is typically found on presynaptic nerve terminals this is a site
Where norepinephrine for example after being released via exocytosis into the synaptic cleft it can actually bind presynaptic leon the neuron that released it and cause inhibitory effects and this is where these alpha 2 receptors will typically be located alpha 2 also has other effects with contractility but this is the major major effect that you want to remember
So remember that alpha 2 receptors are inhibitory to the sympathetic nervous system and so you can get kind of a cholinergic like response from alpha 2 stimulation because they’re inhibiting the sympathetic nervous system because they’re inhibitory it’s easy to remember that their gp cr is actually going to be the inhibitory g inhibitory cascade because they’re
Inhibiting the sympathetic nervous system finally we’ll talk about beta 3 receptors here and beta 3 receptors don’t have quite as long as a list of things going on but the big thing about them that i want you to remember is they’re involved with detrusor relaxation and thermogenesis so here we have picture of that bladder with our internal urethral sphincter and
Then our external sphincter now the bladder itself we can see we talked a little bit about muscarinic antagonists already in this series locking this m3 receptor in cases of urge incontinence and oxybutynin was one of the big drugs that we talked about for that but we can also see that if if you inhibited the m3 receptor you would cause an issue so relaxation or
If you stimulated the beta 3 receptor you can also cause detrusor relaxation okay so they have similar effects you’re either inhibiting the cholinergic response with oxybutynin or you can use the beta 3 agonist to stimulate to choose the beta 3 receptor to relax the detrusor muscle and then here we can see that this urethral sphincter down here is stimulated via
The alpha 1 receptor and remember alpha 1 stimulation causes contraction right alpha 1 is contraction gq cascade and so that can contract this internal urethral sphincter and prevent urine outflow and that’s why if you use the alpha 1 antagonist or someone with like b ph for example right if they have a very enlarged prostate if you use an alpha one and tagging
This you can relax this muscle and help get your an outflow to prevent urinary obstruction and finally the pudendal nerve which is completely somatic so it’s under voluntary control is in charge of this externally liquor here okay now let’s compare epinephrine norepinephrine and isoproterenol before we start number one think of total peripheral resistance as the
Diastolic blood pressure i want you to think of those kind of synonymously or proportionally okay so if diastolic pressure goes up it’s a reflection of the total peripheral resistance when you’re looking at these drugs so let’s see what epinephrine does so first of all it’s come it’s non selective so it actually can bind to a variety of alpha and beta 1 receptor
Because it’s binding to beta 1 receptors it’s going to cause an increase in the heart rate right we said beta 1 receptors is reflection of heart rate and contractility so it’s going to increase the heart rate and it’s also going to increase the contractility and so that’s why you see this kind of increase in pressure here from the beta 1 receptor particularly
Systolic blood pressure because that’s a reflection of the contractility now the diastolic blood pressure on the other hand is actually going to come down and the reason for that because remember we’re also stimulating beta 2 and beta 2 receptors causes vasodilation says here that the alpha receptors are stimulated less in general and so because of that we get more
Vasodilation than vasoconstriction if we stimulated the beta 2 and alpha receptors equally the alpha receptor would win but because we’re stimulating more beta-2 receptor the beta 2 receptors win so here’s the big things to remember from epinephrine because it’s not selective it’s gonna stimulate beta 1 so it’s gonna increase the cellular pressure and heart rate it’s
Also gonna stimulate beta 2 and so that’s gonna cause a decrease in total peripheral resistance particularly because there’s more beta to stimulation than alpha it also is gonna cause an increase in cardiac output whenever you decrease total peripheral resistance or decrease diastolic blood pressure the heart rate usually will compensate with reflex tachycardia if
You increase the total peripheral resistance the heart rate will usually have a reflex bradycardia so not only are you going to be increasing the heart rate because of the direct effects of beta 1 you’ll also be increasing the heart rate with epinephrine because of the vasodilation from beta 2 receptors having a reflex tachycardia effect on the heart rate as well
Gap between the systolic blood pressure and the diastolic blood pressure is going to be the pulse pressure okay so systolic blood pressure – diastolic blood pressure is the pulse pressure and you can see when use epinephrine you increase the pulse pressure as well so now let’s talk about norepinephrine so norepinephrine it’s kind of the opposite of epinephrine
So it’s gonna have more effect at alpha receptors particularly alpha one receptors some affected alpha 2 and then a little effect at beta 1 receptors okay so how does this all play out so remember just think of the major effects that the drug is exerting so norepinephrine major effects is that alpha once we know alpha 1 is definitely going to increase our total
Peripheral resistance and our diastolic blood pressure by causing constriction through that gq cascade so because of that it’s also going to decrease the heart rate right we said reflex bradycardia there’s a very little beta 1 stimulation it’s not enough stimulation to overcome a reflex bradycardia so you’re gonna get a decrease in heart rate from norepinephrine
So how about the systolic blood pressure so this is a blood pressure is also going to go up from the direct effects of the beta 1 receptors on contractility as well as from the increased resistance or the increased afterload from the alpha 1 induced vasoconstriction so that’s gonna spike the the blood pressure to go quite a bit higher so the mean arterial pressure
Is certainly gonna be higher with norepinephrine than with epinephrine because you’re having the systolic blood pressure increase as well as the diastolic blood pressure even though the systolic blood pressure is going up and the diastolic blood pressure is going up they’re not going up at equal rates and because of that there is going to still be an increase in
The pulse pressure with norepinephrine similar to epinephrine the big difference though here is the decrease in heart rate the increased diastolic blood pressure and because of this remember mean arterial pressure is equal to cardiac output times total peripheral resistance because of the decrease in heart rate from the reflex bradycardia and the increases in the
Stroke volume the cardiac output actually remains flat here with norepinephrine so there’s no major change in the cardiac output just that the pressures are increasing that the heart rate is decreased finally we have isoproterenol stimulates beta 1 and beta 2 receptors equally and it’s just targeting the beta receptor what happens in this case so although beta 1
Receptors are stimulated to increase contraction the large drop in vascular resistance is gonna come from beta 2 stimulation and this is gonna have a greater effect on the overall pressure because the large array of vascular arteries will significantly decrease the diastolic blood pressure so when you have just vasodilation we don’t have any alpha stimulation here
At all so we have just vasodilation increase in heart rate and contractility that stimulation of all of that vasodilation is going to significantly drop the dice out pressure and total peripheral resistance and the beta 1 stimulation will help increase contractility increasing the systolic blood pressure so you’re gonna have a huge change in the pulse pressure this
Particular drug of the three the thing that’s how you’ll to remember about it is it causes the largest increase in the pulse pressure for this reason the mean arterial pressure is going to drop overall from the dramatic drop in the diastolic blood pressure now remember beta 1 is gonna stimulate the heart rate and then the huge drop in the diastolic blood pressure
Or total peripheral resistance will cause a reflex tachycardia on top of the increased stimulation from beta 1 so that’s gonna bring the heart rate up a ton and this is all ultimately going to increase the cardiac output big use is to remember for epinephrine is anaphylaxis right you can give them an epipen and then cardiac arrest epinephrine is used for that as
Well and then for norepinephrine refractory shock where you’ve given fluids to try to get the pressures up and you know nothing seems to be working and you just start hitting them with norepinephrine now the adverse effect of that obviously we talked about all that alpha stimulation can increase the pressures and cause a reflex bradycardia and again because alpha
Receptors are at the internal urinary sphincter as particularly alpha one receptors that can cause urinary retention because you’re contracting that internal sphincter preventing urine release and the one that i’ve seen many times working with patients that have had been given processors like nephron to resuscitate them is these this digit necrosis that you can
See here gangrenous tissue that you see on the distal appendages so when you use the pressors and you’re trying to resuscitate somebody the distal appendages are the last site to get oxygen from the vessels and if they’re contracted there’s not enough oxygen to be distributed to this distal tissue and because of that this tissue can eventually become necrotic if
Pressors are given for long enough or if if the tissue doesn’t receive oxygen and you know some time frame so i know it says in a lot of places that i super turner oil is used for like heart block and that kind of thing really you want to avoid isoproterenol at all costs at anyone with heart issues heart failure coronary artery disease i know it says in a lot of
The books that you can use it for heart block which which may be true i mean so maybe some cardiologists do that but in general you know it’s it’s really a drug that doesn’t have a lot of clinical use right now okay so again to recap the big three first thing beta 2 receptors remember vascular and nonvascular smooth muscle dilation whether that be in the airways
Whether that be in the blood vessels alpha 1 receptors are doing the opposite they’re causing contraction remember all beta receptors use gs alpha 1 is gq alpha 2 z me inhibitory so it’s gi in terms of their gpc our epinephrine norepinephrine and isoproterenol all increase the pulse pressure i super terminal has the largest increased and just remember epinephrine
Is pretty non selective but it favors beta receptor stimulation norepinephrine favors alpha stimulation particularly alpha 1 and that isoproterenol is just a beta stimulator that has equal stimulation of beta 2 and beta 1 and if there’s any important images to kind of wrap your mind around it’s probably this one and there’s also a really good depiction of this in
First-date it’s depicted a little bit differently but it’s the same general concepts as what we discussed here so now let’s do a question that is cumulative from the video series so it’s not necessarily from this video but it’s from one of the videos of this series so far pause the video and i’ll give you guys five seconds after the pause video thing comes on the
Screen and then we’ll go through the answer okay so the answer to this is increase in red blood cell volume what we’re basically being asked here is what are the physiologic changes of pregnancy so let’s go through each of the wrong answers and then we’ll kind of recap it with the right answer so a decrease in cardiac output so remember in pregnancy cardiac output
Is increase by substantial increases in the plasma volume mainly during the second trimester which is a huge increase in plasma volume from the second trimester the decrease in or throw point in stimulation so remember ipoh secretion is increased because although the plasma volume goes way up the red blood cell mass also goes up but it doesn’t go up to the same
Degree so plasma volume goes way up red blood cell mass only goes up a little bit and because of that you end up getting a decrease in the hematocrit or hemoglobin because it gets too diluted from all the plasma volume and so ipoh is stimulated to be released that is because of the decrease in haematocrit or hemoglobin which should normalize by delivery so there
Is actually an increase in orthopedist emulation that’s go to deep increase in respiratory functional residual capacity so remember the frc particularly in the later stages of pregnancy begins to decline and that’s because as the uterus and the fetus grow they push up on the diaphragm and upwardly displace it and lead to a decrease in your residual volume extra
Tori reserve volume and a decrease in the frc increases in serum prolactin concentration well it is true that you have increases in serum prolactin after pregnancy but bring pregnancy not so much and that’s because prolactin levels are increased due to a decrease in dopamine release because dopamine is an inhibitor of prolactin and that dopamine release is stimulated
From suckling also there’s decreased progesterone post pregnancy and that also causes an increase in serum prolactin finally like we said there is an increase in red blood cell volume it’s just not as large of an increase as there is in plasma volume thank you guys for watching we’ll see you in the next video
Transcribed from video
Epinephrine, Norepinephrine, and Isoproterenol: 200 Highest Yield Topic Countdown- USMLE Step 1 By Cognitionis
