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0:07
what's up ninja nerds in this video today we are going to be talking about the adrenergic antagonists so this is going to be really a discussion on alpha blockers and beta blockers if you really want to think about that but what we have to do before we actually start talking about alpha blockers and beta blockers is we really need to go through our basics talk about the adrenergic neurons how norepinephrine is actually made how it's released how it's recycled talk about whenever it hits the
0:30
different types of receptors what are the target organs that those receptors are found on what's the physiological function etc then what we'll do is we'll start talking about some of those actual antagonists the alpha blockers and beta blockers what i want you guys to do though before we actually get started here is if you really do like this video if it makes sense please support us and the best way that you guys can do that is by hitting that like button commenting on
0:52
the comment section and please subscribe also down in the description box we'll have a link to our website where you can check out some awesome notes and illustrations that our engineer team has helped to make so please do that it helps us to continue to keep making free videos for you guys enjoyment all right let's start talking about this stuff without further ado so here we have an adrenergic neuron so this is a neuron that's going to be releasing neuroepinephrine
1:12
now when norepinephrine is released you have to know particularly how it's made so we start off with a very specific type of amino acid you know this amino acid is called tyrosine and tyrosine is actually taken up into these nerve terminals that make norepinephrine so this is going to be norepinephrine that's getting released out into this synaptic cleft here right so all these like neurotransmitters here primarily norepinephrine now when tyrosine gets taken up in order
1:36
for it also to be brought in it has to be brought in via co-transporter so tyrosine sodium co-transporter the tyrosine will get taken into this neuron and then once it's brought into the neuron it actually gets converted into something called l-dopa then it gets converted into something called dopamine and then dopamine will actually get taken up into this little vesicle here and it's actually really cool because once it's taken into this vesicle there is specific enzymes that can actually
2:00
metabolize dopamine and convert it into noroepinephrine so that's kind of the process by how we make the norepinephrine within these nerve terminals that release norepinephrine now how does the norepinephrine in this vesicle fuse with the actual cell membrane to release the norepinephrine out into the synaptic cleft great question we have an action potential that runs down this neuron when the action potential runs down this neuron it actually stimulates these particular channels
2:26
here called voltage-gated calcium channels when these voltage-gated calcium channels are stimulated due to an action potential running down this nerve calcium rushes in like it's going out of style when calcium rushes in it's a very strong stimulator of synaptic vesicle fusion so then that synaptic vesicle containing all this cute little norepinephrine here is going to now fuse with the cell membrane and via the process of exocytosis pop that norepinephrine out there into the synaptic cleft
2:54
now once the norepinephrine is on the synaptic cleft it has a couple different options or a couple different pathways that it can go one is it can go and bind on to all these different types of receptors here that do a lot of different things so it can bind on to these receptors here look at these puppies here look at all these cute little receptors here so you have one receptor here this is an alpha-1 receptor you can have another one here called an alpha 2 receptor so these are
3:18
your alpha adrenergic receptors you can have another one and guess what these are oh you guessed it a beta 1 receptor a beta 2 receptor oh we're not done there's a beta 3 receptor as well now once the norepinephrine binds on to these particular receptors it exerts a particular physiological response all i really want you to know is is that when alpha-1 receptors are stimulated they activate a g-protein and this is specifically called a gq protein and this works to increase two particular
3:48
molecules one is called ip3 and the other one is called dag the overarching theme though between these is that they increase your calcium levels and what happens is when you increase calcium level within particular cells especially muscle cells smooth muscle cells it causes contraction we'll talk about what that smooth muscle contraction looks like when we talk about the organs that this happens in that's a pretty cool concept we're going to increase or stimulate this
4:16
contraction of smooth muscle on the alpha 2 receptors though it works via something called a g-inhibitory protein and that works to actually drop your levels of cyclic amp and that's important because what this will do is when you have cyclic amp levels reduced on top of that it also increased potassium efflux this can really inhibit particular types of processes that actually cause hyperpolarization of particular neurons or cells and really what ends up happening is that these
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cells no longer secrete or release particular substances and so it can inhibit a very special type of secretion and we'll talk about what those secretion molecules are a little bit later the other thing is we can have beta receptors now beta receptors is really interesting because all of these beta receptors hit the same g protein a g stimulatory protein and g stimulatory proteins depending upon what kind of cell they're in can have a very interesting type of response so
5:11
what happens here is for beta two and beta three it's the same thing and so is it for beta one just slightly a little bit different here for g stimulatory what it does is it increases cyclic amp right and when you increase the cyclic amp what you do is you actually do cause a very interesting type of process which it does help to stimulate contraction of very specific types of muscle cells it helps to be able to stimulate conduction of very special types of cells and it also helps to be able to
5:42
stimulate secretion by particular types of cells so it may stimulate contraction conduction and secretion for the beta 2 receptors here where it's a little bit wonky you may increase the cyclic amp level so you're like oh well if you increase cyclic amp it's going to cause contraction that's not necessarily true because it depends upon the smooth muscle or the type of tissue that we're present in and so in this situation what happens with both of these the cyclic amp levels they work to be able
6:13
to inhibit or decrease the contraction and so in other words they actually induce relaxation and this is a different interesting kind of thing because in beta receptors it was stimulating contraction of very specific type of muscle tissue and this is cardiac muscle tissue for this one we're actually inhibiting contraction so beta 1 i want you to think about it as a stimulatory beta 2 beta 3 they're kind of a little bit a weird way more of an inhibitory kind of
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function is which is odd right when you think about it because it's increasing cyclic amp but the way that it actually works is it phosphorylates specific types of enzymes and then inactivates those enzymes inhibiting them from being able to perform out particular functions such as contraction secretion etc so because i really want you to think about this kind of process here is really inhibiting contraction and then instead causing relaxation effect that's
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really the way i want you to think about this process here okay now with that being said we have an idea now how norepinephrine exerts its effects on these different types of receptors the other thing that's really important here is that norepinephrine is actually done doing its work another thing they can do is it can actually be metabolized so you know there's an enzyme out here called catechol methyl transferase and what it does is it takes norepinephrine and
7:28
actually breaks it down right so it takes the norepinephrine and then breaks it down into a metabolite and this is a metabolite that is no longer active so it inhibits the effect of norepinephrine now norepinephrine can't do its job anymore it's now been broken down can't do nothing nada that's one option this is so let's put here this is one particular pathway another pathway is that norepinephrine may bypass that enzyme and then via special transporter get taken back up in
7:57
to the actual synaptic vesicle so here's our norepinephrine getting taken back up into the vesicle this is via a noroepinephrine reuptake transporter and by this transporter we get norepinephrine to be recycled so that it can be utilized again okay but that's not always the case sometimes an open effort when it gets recycled or taken back up into the vesicle yes some of it may actually be put back into the vesicle and be re-utilized but sometimes this norepinephrine
8:24
can get metabolized into an inactive metabolite and this is done by a very special enzyme found inside of these mitochondria called a monoamine oxidase enzyme so you have two particular types of enzymes here's a monoamine oxidase and what it can do is it can stimulate the second way of being able to inactivate norepinephrine and turn it into an inactive metabolite and that is via this monoamine oxidases so that's the basic concept that i want you guys to understand about
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norepinephrine is how is it made how is it released what are the receptors that it binds to what's the intracellular mechanism by when it binds to that receptor it produces then when it's done exerting its effect how does it actually get broken down or recycled and re-utilized that's an important concept now the next thing that i want us to talk about here is that you know in our sympathetic nervous system or adrenergic system norepinephrine is not the primary
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neurotransmitter there's another one epinephrine and so we have sympathetic nerve fibers that actually very interesting they go to the adrenal medulla and the adrenal medulla will pump out two particular types of neurotransmitters or hormones if you will one is norepinephrine that accounts for about 80 percent that the adrenal medulla pumps out right the other is epinephrine and that accounts for 20 that the adrenal medulla pumps out but either way these suckers get into the bloodstream
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and when they get into the bloodstream they can actually move and then bind onto these different receptors here on their targets and that's an interesting concept here because when you really look at the actual interesting aspect here of epinephrine and norepinephrine obviously we know norepinephrine prefers the alpha receptors more than it does at the beta receptors we talked about the agonist lecture and epinephrine prefers the beta receptors over the alpha
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receptors why what is it about that when you actually look at their structure it's actually really interesting here because they're called catecholamines right so catecholamines means that they have a special type of ring structure so they both have this ring like structure so this benzene ring structure with these hydroxyl groups popping off of it so they both have this they also have a ch2 group and a ch2 group this one has an amine group this one has an o h and also has an nh
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ch3 group so you see there is a slight difference here and really it comes down to this component here you see how there's an amine group here and then here it has this like methyl group coming off of the amine group which one do you think is which this one here is norepinephrine and then this one here is epinephrine because of this particular side chain this is what increases its affinity for beta receptors and so i really think that that's an interesting concept in comparison to
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this one which doesn't have that big group off of it which actually has less of an affinity for the beta receptors and more for the alpha receptors but when you look at that both of these drugs epinephrine and norepinephrine can bind onto these receptors so when we talk about giving blockers antagonists to epinephrine and orepinephrine we're talking about primary drugs that work to be able to directly work to block epinephrine and norepinephrine at these particular sites so i want to give
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a drug here that blocks the effect of norepinephrine or epinephrine at the alpha receptor it's an alpha blocker i want to give a drug that inhibits the effect of norepinephrine and epinephrine from being able to bind to these receptors producing the opposite response on the beta receptors that's a beta blocker so we have to do now is we have to talk about these alpha blockers and we have to talk about these beta blockers and that's what we're going to do next so let's now talk about some of the
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alpha antagonists or alpha blockers and then what we'll do is we'll talk about some of the beta antagonists or the beta blockers let's get into that all right so what i want to do is i want to go over basically whenever you hit an alpha receptor a beta receptor and with the epinephrine and norepinephrine what's the physiological effect because all an alpha blocker is going to do is block that effect do the exact opposite all a beta blocker is going to do is oppose that effect so think about this
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in alpha 1 receptors we're going to talk about all the effects of the alpha 1 receptors whenever you hit it then we'll talk about alpha 2 beta 1 beta 2 beta 3 respectively for alpha 1 when you hit the alpha 1 receptors what you're going to do is you're going to cause vasoconstriction and because you're going to vasoconstrict you're going to increase the systemic vascular resistance and when you increase the semivascular resistance you're going to increase the
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patient's blood pressure right so that's a that's a definite fact that we know that whenever we do this on the alpha 1 receptor you're going to vasoconstrict the heck out of it so if i give an alpha blocker what do you think an alpha blocker is going to do an alpha blocker i'm just going to kind of go ahead and oppose all of these we're going to an alpha blocker is going to inhibit this particular function so we'll decrease the stemic vascular resistance because
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we'll block the alpha receptor and drop the patient's blood pressure so that's good in hypertension probably right the other thing is that whenever alpha one receptors are hit they're also present on the internal urethrosphere so here's your internal urethra sphincter if we work on this one generally what we do is we increase contraction of that so we squeeze the heck out of it right and that helps to be able to inhibit the urination undesirably which is a great thing when
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you don't want to pee yourself right but if we give something like an alpha blocker what is it going to do it's going to inhibit this particular process it's going to decrease the contraction of the sphincter muscle and it's going to allow for it to relax and it's going to allow for stimulation of urination which is great in situations where patients have urinary retention maybe due to bph or some other particular issue the other thing here is it's going to
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work potentially on the pupil muscle so the pupil muscle it's actually going to do what it's going to stimulate pupils to contract and whenever the pupil contracts what happens is it actually stimulates the dilator people a and so this will actually stimulate pupil dilation and then all you're going to be doing when you give an alpha blocker here is you're going to inhibit the people from contracting and instead you'll subsequently lead to pupil constriction and this can actually be a
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side effect of alpha blockers we'll talk about that later called intraoperative floppy iris syndrome really weird one right all right alpha two receptors now naturally what happens is norepinephrine when it's released from this this is actually a pre-synaptic nerve terminal so pre-synaptic nerve terminal and all this puppy does is it pumps out norepinephrine so we're gonna release norepinephrine have it work on this neuron and then again increase the sympathetic tone so this is all about
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sympathetic tone right so if we're increasing norepinephrine release here we're going to increase sympathetic tone to the heart and the blood vessels so we'll constrict the heck out of the vessels will cause the heart rate to increase we'll cause the contractility to increase all of that stuff but when we give when that what happens is we are we have a normal kind of way of being able to allow for kind of a negative feedback mechanism so this is a natural response
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when norepinephrine is done exerting this effect it actually acts on an alpha 2 receptor and what it does is it actually inhibits further norepinephrine release so it drops the norepinephrine production and then decreases the sympathetic tone that's the natural type of response right that's our natural response to prevent this process if i give a drug like an alpha 2 blocker what i'm doing is is i'm going to inhibit this process here i'm going to inhibit the norepinephrine from being able to
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bind onto the alpha 2 receptor i'm going to inhibit the inhibition of norepinephrine release and i'm going to inhibit the decrease in sympathetic tone so the overarching theme with alpha 2 blockers is that you will increase the sympathetic tone to the heart and that's an important concept and maybe even to the blood vessels as well the next one here is going to be the pancreas we know that on the pancreas we have different types of pancreatic beta cells and pancreatic beta cells we know
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that they actually pump out insulin right and what we know about this is that insulin whenever we produce insulin helps to be able to drop our blood glucose levels when you give normally when our body actually produces insulin during a sympathetic response it would actually inhibit insulin production and then subsequently this would actually cause blood glucose levels to rise that's the normal kind of like response when you stimulate that receptor whenever you actually do this particular
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process here you're inhibiting that so if you inhibit the in the negative process of not releasing insulin you're actually going to increase insulin production and then do what drop the actual blood glucose level so that's another effect here is that you would inhibit the actual not producing insulin so generally what happens is you don't produce insulin because you hit the alpha 2 receptors if you inhibit that you will now produce insulin and then drop the blood glucose
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levels i hope that made sense all right so that's beta two i'm sorry alpha two we go into the beta one so we got alpha one alpha two okay now we got beta one we know that when we hit the beta one receptors we increase the contraction of cardiac muscle we increase the conduction of the non-contractile cardial muscle and then we also potentially stimulate secretion all right whereas with this one we inhibited secretion of norepinephrine inhibited the secretion of insulin but
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we're going to give a drug that's going to block that in increasing the release of norepinephrine increasing the release of insulin in this one we're going to cause contraction smooth muscle right all of these but we're going to inhibit that so we're actually going to do what we're going to inhibit the contraction of the particular smooth muscle by giving the blocker in this situation we're going to do what well when we give um something like epinephrine norepinephrine binds on to
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those beta 1 receptors what they do is they increase the conduction of the heart so they increase the heart rate so they're going to have a stimulatory effect there it's also going to increase the contractility because it's going to bind onto the beta 1 receptors and the cardiac muscle and cause it to squeeze like a son of a gun so because of that you get this kind of inotropic a positive chronotropic effect and a positive inotropic effect so because of that what we want to do is when we give a
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beta blocker is we want to inhibit the increase in heart rate inhibit the increase in contractility so this inhibits cardiac stimulation which may be beneficial in patients who have tachycardia who have some type of process maybe we'll talk about this later where their heart's already squeezing squeezing squeezing so much that there's a high demand and then maybe they have a plaque in their vessel and it's not getting a lot of blood flow so then they you know potentially have
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angina or mi things like that we can use to kind of treat those particular process we'll get into more of that depth a little bit later when we give a beta blocker we're inhibiting this process now the other thing is that in our kidneys we also have beta 1 receptors and these are on the jg cells and the jg cells will actually pump out what's called renin when they're stimulated by the beta 1 receptors and then renin will increase the activity of the renin angiotensin aldosterone system
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which will pump up your blood pressure it'll squeeze your blood vessels it'll increase aldosterone adh which gives you more sodium more water more blood volume and pumps your blood pressure up when i give a drug like a beta blocker i'm going to inhibit the jg cells from releasing renin inhibit the renal angiotensin aldosterone system and help to be able to drop the blood pressure that's a cool concept here so that would be the effect of beta blockers inhibiting the contraction inhibiting
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the conduction inhibiting the secretion the next thing is your beta2 receptors now we do have beta2 receptors that are present on the blood vessels that go to particular types of tissues maybe to the skeletal muscles so skeletal and cardiac muscle and even a little bit into the actual brain so even a little bit there's actually some type of like small beta2 receptors on the blood vessels in the brain near the dura we'll talk about that a little bit later because there's actually a clinical
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point to that but what happens is when you give a beta2 receptor when you hit a beta2 receptor what it's supposed to do is actually supposed to induce vasodilation because you want to increase the blood flow during a sympathetic event you want to increase the blood flow to your skeletal muscle so that you can contract and run your cardiac muscles so it can pump and really kind of get a lot of blood flow to get that muscle to squeeze and do good to help you to run away from
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a bear whatever it is in that sympathetic situation so will vasodilate and increase the blood flow through this area but unfortunately it drops your systemic vascular resistance and can drop your blood pressure a little bit when you give a beta blocker a beta2 blocker it will inhibit this process so it may actually increase the resistance a little bit and increase the blood pressure a little bit in case that's another effect of this as well i'm very minor in the overall scheme of
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things with blood pressure the next thing is the bronchial smooth muscle so you have bronchial smooth muscle lots of beta 2 receptors there right when we have lots of beta 2 receptors here what is it going to do it's going to again what's the overall concept of hitting the beta 2 receptors what do we do we increase cyclic amp to actually cause increased phosphorylation of particular kinases that inhibit smooth muscle contraction so here the smooth muscle is not contracting it's
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dilating but we give a beta blocker to increase it here it's causing again bronchodilation it's kind of relaxing the actual smooth muscle there and so in this situation i want to oppose that but normally what's the normal function here it's to cause broncho dilation so it's to relax that smooth muscle of the bronchioles so what i want to do is if i give a drug like a beta-2 blocker it's going to inhibit bronchodilation and actually cause bronchial constriction all right
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the next thing is that our liver we have lots of beta-2 receptors and this actually is going to stimulate them to increase our blood glucose levels the pancreas we have the pancreatic alpha cells and that actually helps to increase glucagon and then decrease insulin production and then glucagon also helps to increase blood glucose levels when we give a beta blocker what we do is we inhibit the liver from being able to do gluconeogenesis and glycogenolysis which
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helps to increase glucose levels so instead it'll drop the glucose also inhibits glucagon production which also helps to perform gluconeogenesis and glycogenolysis which again is important for being able to increase blood glucose levels so you could potentially cause hypoglycemia and we'll talk a little bit later about one of the actual symptoms that it can actually mask hypoglycemia and awareness we'll talk about that a little bit later but that's the effect
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here so we know that naturally it's to inhibit smooth muscle contraction right so it'll cause it to relax or inhibit secretion of particular types of and i'm sorry to allow for secretion of particular types of molecules such as glucagon if we give a drug that inhibits the smooth muscle relaxation it's going to cause smooth muscle contraction so to squeeze the vessels increase the blood pressure it'll squeeze the bronchial smooth muscle increase the bronchospasm
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and it'll actually do what inhibit the secretion of glucagon and inhibit the glycogenolysis and gluconeogenesis by the liver and help to drop the blood glucose levels the last one is the beta 3 receptors again smooth muscle relaxation is the key feature here and that's the smooth muscle of the bladder and so because of the trusser muscle is one of the big ones that if you actually work on this one you're actually going to inhibit its contraction so if you relax that puppy
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you're going to inhibit urination and that's a great function whenever you're running away from there you don't want to be peeing your pants but in a situation where the patient is actually maybe retaining right what can we do is we can give a beta 3 type of blocker a drug that has beta 3 types of antagonistic activity and that's going to do what stimulate contraction of the bladder stimulate the actual urination process which actually could be potentially beneficial the last thing here
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is that if we also have these types of beta-3 receptors that are present on the adipose tissue this can increase the lipolysis effect and lipolysis is helping to be able to take triglycerides and break them down into like a lot of free fatty acids and generally another molecule called glycerol but i'm going to put free fatty acids generally when you give a beta blocker okay generally there's no specific beta 3 blocker there's just drugs that maybe have no selectivity in other words they don't
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care if they bind to a beta 1 a beta 2 or a beta 3. they could bind onto all of them some of them are very selective they only bind onto beta 1. all right but if i give a drug that has some type of beta 3 blocking effect it inhibits the lipolysis it would inhibit the triglycerides from being broken down into free fatty acids and it could increase the triglycerides potentially within the blood so as you can see some of these things are actually beneficial effects which we
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can utilize and talk about later as indications for some of these types of processes but some of these could be adverse effects and negative effects from the particular drug especially when it comes to the glucose especially when it comes to the triglycerides and we'll talk about some of these other effects a little bit later as well all right my friends now that we've gone over the physiological effects that whenever epinephrine norepinephrine binds to these receptors what do they do
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and now we talked about well oppose everything of those actions with alpha blockers and beta blockers now let's get into the special types of alpha blockers the names of those drugs the indications of them and some of the adverse effects and then we'll do the same thing for the beta blockers let's get it all right so up on the docket alpha blockers alpha antagonist we're going to kind of use that synonymously with the same thing alpha blockers alpha antagonist
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we talk about these let's first say what are the different types of drugs so these are specifically so when i say specifically they're more selective somebody told you that we have an alpha blocker it can bind onto an alpha receptor and prevent epinephrine norepinephrine from being able to exert its effect it produces a kind of negative effect or a i guess you could say a sympatholytic effect right you're trying to block the effect of the sympathetic nervous system so opposing it
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these drugs prefer the alpha 1 receptor they don't really care about the alpha 2 they don't really bind to it so they only prefer the alpha 1. there's a bunch of these drugs so some of them that i actually want you guys to remember is going to be one is called tamsulosin this is a very common one another one is called prasasin another one is called pterazosine another one is called doxazosin so there's a lot of these particular drugs that you're going to see
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particularly on your exam so think about these particular drugs oftentimes you can kind of see that they often end in ocean that's a common theme that you'll see with these now what do these alpha 1 blockers do now remember alpha 1 receptors are present on blood vessels they're present on the sphincter muscles and they're also present on the pupil so let's think about that and oppose all of those effects let's talk about what's beneficial so for an indication of the
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drug and then what's an adverse effect right so first thing is you have alpha interceptors on blood vessels and i love to always say that we have alpha-1 receptors that are present on both the arteries and present on the veins so because of that if i work the alpha 1 receptors on the veins right normally when you squeeze them you help to increase venous return to the heart we're going to block that when i hit the alpha 1 receptors we're going to squeeze the alpha interceptors increase the
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resistance and increase the blood pressure i'm opposing all of these actions so i'm going to for the vein inhibit the alpha 1 receptors i'm going to decrease the venous return and that is going to decrease the actual what the cardiac output one of the problem problems with this effect is that if someone goes from one position to another for an example you stand up from going from a seated position or you're laying flat and you abruptly come up your venous return generally drops a little
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bit now if you block that even more you significantly reduce their venous return so one of the adverse effects that i want you guys to remember because of this is watch out for orthostasis this is a potential adverse effect of really dropping that preload especially in young older individuals who have decreased sympathetic tone and you drop it even more so watch for orthostasis the other effect here is on the arteries right so you're inhibiting the alpha-1 receptors and i'm going to represent
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this in red the alpha-1 receptors on the arteries if you inhibit those you're going to decrease the systemic vascular resistance and drop the blood pressure why is that a beneficial thing well the benefit behind utilizing this is that this can be great and hypertension so we can utilize this as a particular drug to lower the patient's blood pressure in patients who have underlying hypertension but it's not often a first-line drug so i want you to remember that yes we can use this but it's not
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first line and that leads me to the second situation it's often good in patients with an underlying comorbidity such as bph do they have bph because if they also have hypertension this is a great drug then why there's alpha-1 receptors that are present on our cute little sphincter muscle the internal urethra sphincter so if i give a drug that is going to block the alpha-1 receptor here at the internal urethra sphincter what am i going to do well if i inhibit the alpha
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1 receptor at the internal urethra sphincter i will inhibit this muscle it will then no longer be able to contract it'll then relax and if it relaxes then urine that's sitting here in the bladder can drain out and so it'll stimulate urination wouldn't that be great in a situation where a patient has incontinence and the primary reason for their incontinence is a big old bulbous prostate gland it's kind of like surrounding that urethra a little bit and all we need to do is kind
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of open it up a little bit and allow for urine to flow that's a great indication my friends so because of that one of the indications here is it's great in urine incontinence
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secondary to bph so that would be an indication for this particular drug categories okay tamsulosin prazin teraza sandoxazos and all of those things so because of that i want you to remember that you can utilize it in hypertension but you can also utilize it in the urinary incontinence secondary to bph and the combo of these two is beautiful okay let's kind of move this eyeball here a little bit so we have some more room but one of the other big things that i want
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you guys to think about here is the another adverse effect so one of the adverse effects here is definitely orthostasis definitely don't forget that but here's another one when we talk about dropping the blood pressure right so you drop the patient's blood pressure due to a decrease in systemic vascular resistance i want you to think about that reflexive pathway here so you know that whenever you have a patient who you're dropping their blood pressure what does it do to those chemoreceptors
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i'm sorry the barrel receptors that are present in the aorta and the carotid sinuses it inhibits them right or it actually works against them and says hey blood pressure is low my friend and it tells the central nervous system hey blood pressure is low we got to stimulate the heart like a son of a gun and so what it does is it increases the activity of the sympathetic nervous system and then helps to be able to increase the flow to the heart which helps to increase the heart rate
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and so because of this this can be a reflex type of tachycardia so this is actually another adverse effect that i want you guys to watch out for here is reflex tachycardia so one of the adverse effects could be orthostasis due to dropping the venous return on the veins the other thing is that when you drop the patient's systemic vascular resistance and drop their blood pressure it can stimulate the chemoreceptors tell the central nervous system to increase the sympathetic effect and increase the
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heart rate which is a reflex tachycardia so watch for reflex tachycardia is another effect here the last thing here is with the eyeball so now let's actually draw this eyeball here remember i told you that it works again on the pupil muscle okay so that's an extra interesting kind of thing here so you think what does that have to do with anything well when we think about this normally what what do we know we know that we have alpha 1 receptors that are present
31:24
here on this pupil and normally when you stimulate them it's supposed to do what with the sympathetic the dilate you're going to inhibit this when you inhibit this this is going to cause pupil constriction this is a problem if the patient also has some type of cataract surgery that they're undergoing so if they have a cataract surgery and they take this drug around that time of the cataract surgery what can happen is the pupil can constrict and prolapse through
31:53
okay through the actual like defect and it can actually cause what's called intraoperative floppy iris syndrome you're like what the heck so don't forget that this is another potential adverse effect here we're going to write it over here another potential effect here is that this can actually cause the pupil to prolapse through and cause intraoperative floppy iris syndrome okay so the basic things that i want you guys to take away from this particular lecture is that alpha one blockers such
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as these above work to treat hypertension not first line usually second line with a comorbidity such as bph because it also helps to treat bph potential adverse effects of the drug is because it reduces venous return it can cause orthostasis when a patient suddenly gets it from a different position to a standing position it also can cause reflex tachycardia because it drops the systolic blood pressure as i said drops your blood pressure and generally your diastolic blood pressure
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so it goes reflex tachycardia and on top of that because it can cause pupil constriction if you have this patient utilize that during a cataract surgery can actually cause prolapse of the iris which can lead to intraoperative floppy eyer syndrome so watch out for that as well one other indication that you can throw in there if you want to remember is practicing practice that can actually be utilized in ptsd related nightmares because it can actually reduce the alpha one mediated
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stress response during a patient who's sleeping so if you want to remember that one person can also be utilizing ptsd related nightmares but i'm not going to put that in here in this lecture all right now that we covered the selective alpha 1 antagonist let's come down and talk about the interesting drugs that are pretty much alpha one but they have this really interesting alpha two antagonistic activity as well all right my friends so the next drugs the alpha one alpha two antagonists are
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really interesting so this drug category is called phontolamine and phenoxybenzamine so there's two particular drugs here one is called aphentolamine
33:42
and the other one is called phenoxybenzamine can't say i've really used these drugs too often i used it maybe once in my entire career exposure but um phentolamine and phenoxybenzamine are definitely really interesting drugs one little kind of piece of it on their pharmacodynamics though so when you look at how phenoxybenzaminolamine work they would definitely work to block the alpha receptor but the activity when you get to the biochemical level it's a little bit different so let's say
34:13
here i have phentolamine on this cell so this is cell number one so this is phentolamine and then here i have phenoxybenzamine on this cell cell number two so here we're going to have maybe a drug like epinephrine i'm going to just put norepinephrine so here's going to be norepinephrine now norepinephrine wants to bind onto this alpha receptor so let's say that i'm just going to put here this is an alpha receptor here you're going to have a alpha receptor phentolamine is interesting in the sense
34:38
that it actually does bind to the active site where norepinephrine will bind phentolamine will also bind and inhibit norepinephrine from being able to bind there and then it'll exert its inhibitory type of effect here right phenoxy benzamine is a little bit more interesting it actually binds onto this little site here so it binds on to what's called the allosteric site so the allosteric site and what it does is it actually kind of changes the shape of this alpha-1 receptor
35:09
and now this alpha-1 receptor when you change its shape it's no longer able to bind to norepinephrine the same way and have the same kind of effect when norepinephrine will bind to it so it inhibits the actual cell from being able to exert the effects from norepinephrine and it'll still have its inhibitory effect but it's just differences in their pharmacodynamics phenoxybenzamine has a little bit more of a longer lasting type of effect because it has this allosteric like
35:35
regulation so because of that it actually lasts a little bit longer so longer lasting type of effect which is really kind of cool and why it may be more likely to be utilized in certain types of chronic scenarios whereas phentolamine is an active site typical response so it has a shorter duration so because it works on the active site it's a little bit shorter in duration okay shorter duration so that's one of the things i wanted to mention with respect to the
36:06
pharmacodynamics of these two drugs so again you have phontolamine active site inhibitor it kind of has a shorter duration because of that phenoxy benzamine binds onto the allosteric site still inhibits the alpha-1 receptor alpha-2 receptor from being acted on by norepinephrine epinephrine but because it has that allosteric site regulation it definitely can have a longer lasting effect in comparison to fentolomi all right so that's one of the interesting things now
36:28
when we talk about this obviously one of the big big things here is that on blood vessels we have two types of receptors one is we're going to have what's called a beta 2 receptor on our blood vessels and we're going to have a alpha 1 receptor on our blood vessels whenever epinephrine and norepinephrine bind on to these particular spots what happens is that a beta 2 receptor will cause vaso dilation and when you vasodilate you decrease the stomach vascular resistance and you
37:00
decrease the blood pressure with the alpha 1 receptor though you cause vaso constriction and when you vasoconstrict you increase the stemic vascular resistance and you increase blood pressure well what we know is that phentolamine and phenoxybenzamine definitely bind onto the alpha-1 receptors they're they won't bind to the beta two they'll bind to the alpha one receptors and so because these drugs will definitely bind to the the um alpha one receptors this
37:31
is their primary site of action on blood vessels so this would be both of these drugs phenoxy benzominotolamine and they'll inhibit the alpha-1 receptors so they will decrease vasoconstriction they will decrease systemic vascular resistance and they will decrease the patient's blood pressure and that's the overarching theme here and again the way that we know this is that we know that it's going to block things like norepinephrine and epinephrine from being able to bind here
37:59
so it's going to inhibit that type of action so that leads to a really interesting type of effect here where we can think about particular diseases where there is just massive amounts of norepinephrine and epinephrine and one disease is called a pheochromo
38:19
cytoma in field chromocytoma there is an adrenal medulla tumor that this tumor is just pumping out massive amounts of norepinephrine and massive amounts of epinephrine when you have the massive amounts of these particular molecules what are they going to want to go and do they're going to want to go and bind on to alpha 1 receptors and they may also want to bind on to beta beta2 receptors all right think about why this drug is perfect fintolamine and phenoxybenzamine
38:51
if i give this drug when it's pumping out norepinephrine epinephrine it'll block the alpha-1 receptor but allow for it to bind to the beta-2 receptor so it'll allow for it to bind to the beta-2 receptor which helps to improve vasodilation which helps to be able to decrease systemic vascular resistance and decrease the patient's blood pressure which is another beneficial effect while opposing the alpha-1 receptor because the alpha 1 receptor if you inhibit this one you'll cause
39:16
inhibition of vasoconstriction inhibition of systemic vascular resistance that's increasing and then drop their patient's blood pressure because think about if you didn't have this alpha-1 blocker what's norman ephron epinephrine going to do on this receptor oh my gosh it's going to squeeze the heck out of the vessels shoot the patient's blood pressure up because they're going to constrict really really hard and they're going to cause an intense increase in semi
39:36
vascular resistance and increase their blood pressure so because of that this can lead to a hypertensive crisis due to a pheochromocytoma so because of that this would be a good indication for phtolamine and phenoxybenzamine phenoxybenzene definitely more of the longer term phentolamine might be better in kind of the perioperative state whenever you're taking a patient who's going to be going to the or to remove the tumor phentolamine might be a better option
40:05
because it's a little bit like you know shorter acting phenoxy benzamine would be more of the chronic kind of like acting drug but again that's kind of the interesting concept here is that whenever you have this tumor that's pumping out these drugs they can have one of these two receptors to bind onto if you block the one that's going to cause an increase in their blood pressure you'll help to prevent them from having a hypertensive crisis and if you allow for them to bind
40:24
onto the beta2 receptors you'll also help to drop the blood pressure which is again helping to alleviate the hypertensive crisis so pretty cool the other situation here is drugs that actually also cause a hypertensive crisis but these drugs maybe work too specifically this is why i mentioned the process before if you guys remember there is how when we release norepinephrine right here's norepinephrine when norepinephrine gets released what happens is we know that it can actually
40:54
get taken up via this particular transporter right so norepinephrine will actually get taken up via this particular transporter and then from here it can actually be recycled back into these vesicles right via this transporter but we also know that it can be metabolized via this particular enzyme called monoamine oxidase and this helps to inactivate this norepinephrine into its inactive metabolite right and so when we think about this norepinephrine can actually be re-uptaken right it can
41:25
be recycled it can also be metabolized by the monoamine oxidase and then there's another drug called catechol o-methyltransferase that also metabolizes it right now what i want you to understand is that when patients take particular drugs right and i want you to think about two particular indications here one is cocaine cocaine works to be able to inhibit the reuptake and it also can inhibit some of these monoamine oxidases if i inhibit these monoamine oxidases i
41:56
don't break down norepinephrine if i inhibit the reuptake transporter i keep norepinephrine in the synapses for longer amounts so if i don't break it down i allow for more of it to be recycled so if i don't break it down i increase the amount that's in the vesicle to be recycled and if i don't reuptake it i keep more of the norepinephrine in the synapses so either way the end result is i'm releasing more norepinephrine more norepinephrine can do what go and bind on to beta-2 receptors or
42:24
alpha-1 receptors produce again their effect in this case they're going to squeeze the heck out of the vessel and increase the blood pressure and cause hypertension right so that's one type of effect here the other one is we can give a drug called a mono amine oxidase inhibitor plus we have them take that and they're eating particular cheese and wine products that contain lots of tyramine and whenever you do this whenever you give something like a monoamine oxidase
42:52
plus tyramine it really really inhibits this monoamine oxidase and if you inhibit this you keep a lot of norepinephrine to not be broken down and so you really really inhibit this particular process and you really up the norepinephrine release so lots of norepinephrine again can bind onto these particular situations so again we can also say that this could be drugs that induce a hypertensive crisis so you can still utilize these drugs because what do they do they induce a hypertensive crisis
43:22
by increasing the normal epinephrine release if you give a drug like phentolaminophenoxybenzamine they block the alpha interceptor which helps to prevent norepinephrine and epinephrine from binding onto these preventing the vasoconstriction response and allowing for them to bind to the beta-2 receptors and allow for what the vasodilation that's the cool benefit of these drugs the other thing i think that's really important about this so that would be the primary indications of hypertensive
43:48
crisis due to a fio or hypertensive crisis due to cocaine and as well as a monoamine oxidase inhibitor plus tyramine one thing i would say is cocaine um if your cocaine induced hypertension it's usually second line it's not first line believe it or not we actually prefer benzodiazepines and calcium channel blockers first line it would be more of your second line to use an alpha blocker just so you know okay now the next thing we think about here is whenever a drug let's say that you
44:14
have epinephrine and norepinephrine running through your circulation so you have a patient and this is the only time i've ever had to use these drugs let's say that you're you have an iv in right so here's the iv and it was in the vessel and it was pushing this epinephrine and norepinephrine into the bloodstream to increase the patient's blood pressure right but for whatever reason something happened with the iv and it got displaced or it extravazated the norepinephrine and the epinephrine out
44:43
into the subcutaneous tissue so now it really got out it extravazated out of the actual blood vessel and into the subcutaneous tissue when it gets released into the subcutaneous tissue guess what that norepinephrine and epinephrine can do the norepinephrine epinephrine can bind onto these small subcutaneous vessels and squeeze the living heck out of these subcutaneous vessels if they squeeze the heck out of these subcutaneous vessels what do you think is going to happen here it's going to
45:13
cause intense cutaneous vasoconstriction and guess what these patients can actually start causing necrosis of their skin so this will actually lead to necrosis so another indication for these drugs especially phentolamine is you can utilize this to inhibit this necrosis process and so the way that we would use this is we could use it as in a situation of vasopressor extravazation there was one patient i had he was on a little bit of norepinephrine and for some reason the
45:50
norepinephrine requirements started going up and up and up and up and up eventually they were on 30 mics of norepinephrine couldn't figure out why and i'm like what's going on here okay so i go to the room we end up having to put a central line in when i put the central line in the norepinephrine was now running through the central line and the norepinephrine requirements went from 30 down to about four within a very short amount of time so something was odd because the patient didn't actually
46:12
require that large amounts of norepinephrine that we thought it did what we found is that one of the ivs that was actually the basilic vein had extravasated all of the norepinephrine into the patient's arm and so the actual arm was starting to look a little bit kind of like nasty now and so because that they were at risk of cutaneous vessel vasoconstriction and potential necrosis so that was one time that actually to push phantolamine into the actual iv and around the area to
46:34
prevent it from really kind of blocking that norepinephrine from squeezing on those cutaneous vessels so to prevent the extravazation necrosis that you could see from this so remember ventolamine particularly for vasopressure extravasation but both of them good for theochromocytoma and hypertensive crisis cocaine monoamine oxidase inhibitors with a tyramine hypertensive crisis better with phenoxybenzamine so again i want you to remember that phenoxybenzamine is actually preferred
46:59
for the hypertensive crisis due to these particular situation all right one last thing that's actually really interesting about these drugs i bet you didn't think about this yeah you probably did it's really smart so we talked about alpha one a lot but i told you that this is an alpha two again antagonist blocker so on these presynaptic nerve term is the release norepinephrine guess what is also present there my friends an alpha 2 receptor and if i give something like phenoxy
47:32
benzamine or phentolamine at this alpha 2 receptor what would this do it would block the effect what's the normal effect to inhibit norepinephrine release that's the normal effect but if i'm giving a drug like an alpha 2 blocker i will no longer allow for the inhibition of norepinephrine i'm going to stimulate norepinephrine production and i'll increase norepinephrine at least your parel exact that doesn't make any sense because i thought the whole point was to
48:07
prevent norepinephrine from being able to bind to these receptors well guess what that's one of the interesting things about this drug yes it may cause a slight increase in the sympathetic tone but it's going to block the effect of that sympathetic tone in the alpha one receptors so norepinephrine epinephrine when it's being released yes it'll bind to the beta two which will produce vasodilation drop their pressure but we'll block the alpha one receptor so it won't be able
48:31
to increase their blood pressure what is one thing that norepinephrine could do or epinephrine could do it could bind onto the beta-1 receptors of the heart so there's beta-1 receptors that are present on the heart in this norepinephrine that is an increasing amounts or epinephrine and increasing amounts could stimulate the heck out of these beta 1 receptors and what would that do to the patient's heart rate increase increase increase increase their heart rate this is an adverse effect
48:58
and this adverse effect here is called a reflex tachycardia that is an adverse effect of phenoxybenzaminophentolamine they will increase the sympathetic tone because they're going to inhibit the altitude receptors and if you inhibit the alpha-2 receptors you actually will allow for norepinephrine to be released because normally it inhibits norepinephrine release but you're now going to stimulate it so norepinephrine release is going to increase you block at least the effect on the alpha-1
49:22
receptors but you can't block the effect on the beta-1 receptors because it's not a beta receptor blocker so because of that it'll hit the beta receptor and increase the patient's heart rate so watch out for reflex tachycardia as a very common side effect of these particular drugs all right that covers fintolaminophenoxybenzamine now that we've covered the alpha blockers alpha 1 selective in alpha 1 and 2 let's now go on to the beta blockers and talk first about the cardioselective ones the beta
49:47
one blockers all right my friends so now beta blockers beta one antagonists are beta one blockers if you wanna think about it so these are really interesting because they're cardioselective now the way i remember the drugs in this category is different about the first beta receptor so think about some of the first letters of the alphabet the first day the usmle actually talks about this that we can remember them via a to m so anything from a to m if i kind of throw one of
50:12
those letters in there it's likely going to have an o law at the end so first one is antenna law then ace butyl law then b bisopra law
50:29
then we would go to the next one so we're going to skip a couple because there are these other ones carved law and things like that they're actually in other ones we'll talk about those a little bit later the beta and alpha then we get to e esmo law and then we get into m metopr law and this is going to be probably out of all of them the most commonly utilized one so out of all of these again you can actually remember this via a to m so a to m where it's atenolol acebutylol
50:58
bisoprolol esmalolol and metoprolol these are going to be the most common beta-1 antagonist or beta-1 blockers now when i say that these are beta 1 that's partially true if you really want to look at it these guys their affinity for the beta 1 receptor is insanely higher than their affinity for the beta2 receptor they have very very little affinity for the beta2 receptor okay very little defendancy so that's why i'm going to really kind of keep them for simplicity's sake that
51:32
they are primarily a beta 1 antagonist or beta 1 blocker now what are the indications of these drugs with i would want you to put most stress on the most commonly utilized one in practice that being metoprolol this is going to be the most commonly utilized one that you'll see one of the particular situations here is you wanna think about the beta one blockers they're reducing heart rate they're reducing contractility all right that's a great situation one of these particular scenarios where
51:58
i would say would be really really good is let's say you have a disease here where maybe there's like this ectopic foci and it is causing lots of re-entrant circuits to occur or maybe you have like this re-entrant circuit and again they're causing all of these like lots of electrical activity to originate from the atria and they're sending all of this massive electrical activity to the av node to increase conduction down the av node and subsequently really really really
52:24
increase the patient's heart rate well if i give a drug that could potentially block the effect of the av node i can inhibit all these electrical activities that are coming from this reentrant circuit here or these multiple ectopic foci over here i can potentially fix this and block that effect that's what i'm going to do i'm going to give a drug that's going to inhibit this particular effect so what kind of drug what kind of situations would i want to do that where i'd want to block that
52:49
effect well again if i'm giving drugs like metoprolol esmol bisoprolol acebutyl a tenelolol this would be great because what i'm going to do is i'm going to give these drugs and they're going to inhibit the av node conduction right of all of these electrical foci which is going to decrease the heart rate and attack tachyarrhythmia particular tachyarrhythmias that i would want to utilize this in is this would be great in situations of atrial fibrillation or flutter so atrial fibrillation
53:26
or flutter and it would also be great in another type of situation where maybe the re-insurance circuits actually present in the av node so another one could be supraventricular tachycardia so these are two particular indications in particular tachyarrhythmias where i'm going to inhibit this tachyarrhythmia so this is why i'm going to utilize these particular drugs i'm going to inhibit these particular supraventricular tachymias such as atrial fibrillation atrial flutter and svt like an avrt or
53:56
avnrt okay so that's what i want particularly avnrt i would actually really kind of say here if we really really wanted to talk about it this is particularly an a v and r t that i really would want to block so this is the kind of indications where i would use this because it's going to have a negative chronotropic effect or a negative dromotropic effect it's going to inhibit the av no conduction inhibit the sa node as well that's a great situation where i would love to utilize this drug
54:21
the next situation let's say that i have somebody who we look at it like this okay here we have a blood vessel all right i'm gonna look it like this here i have a blood vessel and in this blood vessel i'm gonna have a big old plaque okay but it's a stable plaque it's a chronic plaque it's a plaque that the patient has had for a decent amount of time okay not a lot of really a lot of blood getting into the muscle at this point right so here i'm going to draw some of the cardiac muscle cells
54:50
here's my cardiac muscle cells so what i know is that this patient at baseline is going to have very little blood flow getting to this cardiac muscle so i can say that there is going to be naturally a chronic decrease in oxygen supply this is a chronic particular situation right now what if i have a patient who maybe they have an increase in demand for whatever particular reason so if you give a less oxygen supply and you have an increase in oxygen demand for whatever that reason may be
55:24
in certain situations what i can potentially do is i can potentially help out because there is a a particular kind of balance that you want to be able to maintain here to making sure that you don't cause damage to the heart so whenever you maintain this balance to prevent damage to the heart it's really 02 supply so i'm going to put supply here and demand you really want to maintain a nice balance between these two where you want to decrease supply and decrease demand
55:53
and increase supply that's kind of the natural kind of thing that you want to have here so what i can't i can't do is i can't increase supply with drugs i'd have to go in there and remove this plaque or stent open the vessel i can't do that with a drug what i can do with drugs is i can try to decrease the demand because if i hope to be able to maintain because right now this this part of the equation isn't working i can't fix this part i just can't i can't do it with a drug i
56:19
can do it with a procedure like a percutaneous intervention but i can't with a drug what i can do is i can give drugs to be able to fix this that's what i can do i can decrease the demand how do i decrease oxygen demand well the big thing here is that naturally if you decrease the patient's heart rate you're going to decrease the oxygen consumption okay actually let's do it a little bit different way so if i give drugs that decrease the heart rate that'll help to
56:50
be able to do what decrease the cardiac output and that'll reduce oxygen demand right so we can kind of look at it like that if your heart isn't beating as fast you're not going to be utilizing as much oxygen for it to beat the other way that i can think about this is if i give a drug that blocks the contractility if i decrease the contractility that also will reduce the cardiac output and that will also reduce the oxygen demand well guess what i have drugs that can actually do that
57:18
metoprolol asthma albus overall asp law and antenna law so if i can reduce oxygen demand this would be great in situations where i have plaques and patients who have angina or some type of like coronary artery disease this would be a great indication for these because they have these plaques in their vessels and if i give them a beta blocker it's going to do what it's going to stimulate a reduction in their heart rate by hitting the beta 1 receptors and blocking them and it's
57:47
going to inhibit a contractility by hitting the beta 1 receptors in the heart leading to a reduction in cardiac output reducing the oxygen demand even though they have a decreased o2 supply so if i reduce the demand i help out even though i have very little supply and if that doesn't work and it gets worse guess what then you go to a cath and you put in a stent and help that situation there as well but that's one of the indications as well so i have so far situations here where i would use these
58:14
beta ones is an atrial flutter atrial fibrillation sbr svt to inhibit the av node conduction i have engine on coronary artery disease because it's going to and decrease the o2 demand by decreasing heart and decreasing contractility pretty cool right what's another indication another situation here is in a patient who has a disease here called hypertrophic cardiomyopathy and hypertrophic cardiomyopathy their problematic issue with this disease is this part here you see how it's so dang
58:45
tiny that's called a left ventricular outflow tract obstruction a lot of words but that's literally what it's called it's called a left ventricular outflow tract obstruction whenever patients want to try to get blood out of their heart so here's some blood sitting in their heart they want to contract they got to squeeze that blood through that tiny little guy right there okay that's a problematic issue because that can lead to a reduction in cardiac output what i want to do is
59:11
is i want to try to figure out a way that i can reduce that obstruction that's really what i want to do in hypertrophic cardiomyopathy and the best way to do that is to reduce contractility because if i don't contract this muscle as much i won't bulge it in as much so i want you to think about this when the muscle is like this when the muscle is let's say here is your septum when the muscle is kind of bulging out like this it's because it's intensely contracting
59:39
so when it's bulging out like this it's going to increase the left ventricular alpha tract obstruction that's if you increase contractility we know that so if you increase contractility you increase the left ventricular outflow tract obstruction it bulges it in more but if you decrease the contractility you'll decrease the bulging of the septum and reduce the left ventricular outflow tract so i want to give drugs that are going to do what i want to give drugs that are going to inhibit
1:00:08
contractility
1:00:15
and if i inhibit contractility what am i going to do i'm going to decrease the effect of the left ventricular outflow attract obstruction i'm going to open it up more and so if i'm not bowing that septum in as much because i'm not contracting that septum as hard now look what happens oh baby that thing's open up more now and now that things open up more now i can get more blood out and improve the patient's cardiac output so you can actually improve the patient's cardiac output by actually
1:00:41
giving them a negative inotropic drug which seems counterintuitive but the problem is that the more you contract the more you bulge the septum in and block the outflow tract the less contractility the less bulging the more the outflow tracks open the more blood you can get out of the heart the other thing here is the way that more blood goes into the heart is if you give it more filling time so if you prolong the filling time so imagine if i only give my heart about
1:01:06
a second to fill it might feel to this point right if i gave it like four seconds to fill i'm just making these numbers up i'm going to allow for more time for it to fill up with blood the more i fill up the heart with blood the more i stretch that outflow tract open so the other thing that i want to do here is i want to give drugs that actually do what they reduce the heart rate because if i reduce the heart rate what i do is is i increase the filling time and if i increase the filling time
1:01:34
i stretch the outflow tract the left ventricular outflow tract obstruction open and therefore decrease the left ventricular outflow tract obstruction both of these things are great in hypertrophic cardiomyopathy and by giving beta blockers what i do is beta blockers will work too stimulate this part inhibit the contractility and they'll also work to drop the heart rate and both of these things will do what reduce the left ventricular outflow attract obstruction and improve the
1:02:07
cardiac output improve the filling that is the overall process that i want you to understand from this so so far we have that we can use these beta one blocker selective ones cardioselective and reducing supraventricular tachyrhythmias things where they're trying to go through the av node or originating the av node you're trying to block the av node from conducting these excessive action potentials and tachyrhythmia such as a-fib a-flutter svt in situations where patients have reduced supply due
1:02:32
to a coronary plaque that's relatively stable such as in coronary artery disease or angina pectoris where they have a reduced supply you can't fix the reduced supply unless you go in and open up the vessel what you can do with drugs is decrease their demand because if you reduce their heart rate you reduce their contractility they don't utilize as much oxygen to maintain a cardiac output and so their oxygen demand decreases and you can still help to prevent that patient's chest pain
1:02:55
and last one i can relieve the obstructive outflow tracts due to this big thickened septum by reducing the contractility opening up more don't bulge in as much and reduce the heart rate because it allows for a longer filling time these both relieve the obstruction and help with hypertrophic cardiomyopathy all right now let's come on to the last indication here which is heart failure and post mi all right my friend so now last situation i don't want you guys think about if a patient
1:03:16
has heart failure or a myocardial infarction either way there's some disease process of their ventricle right so let's say here's their disease process either there is heart failure so their muscles just weak in general or there's an infarction that destroyed the heart tissue but either way there is a reduction in the ability of the heart to generate good systolic forces so because of that we know that in these situations here such as in heart failure or post myocardial infarctions we know
1:03:53
that there may be a reduction in cardiac output right that's the overarching theme reproduction of cardiac output due to heart failure they reduce they lose their systolic function post mi they lose their systolic function but there's a reduction in cardiac output if there is a reduction in cardiac output that leads to less perfusion to particular organs right so if you reduce cardiac output you don't perfuse particular organs as well okay what happens with this is something very interesting
1:04:22
if i don't perfuse the kidneys very well they they pick up on that sense and they say hey i don't like this the cardiac output's low what i need to do is i need to work to cause an increase in the renin angiotensin aldosterone system and what that does is is that this is going to work to increase the patient's blood pressure right via angiotensin ii we know that all of this is going to increase blood pressure does it a couple different ways one is angiotensin too because it
1:04:54
squeezes the vessels the other one is it increases water and sodium via adh and aldosterone the other thing is that it can actually cause an increase when you squeeze the vessels right you do increase blood pressure so they'll become hypertensive right but the other thing is that you increase afterload because when you squeeze the arteries it puts a lot of stress on the heart and when you put a lot of stress on the heart that leads to the heart having to compensate for that high afterload so
1:05:22
what does that do to the actual left heart the left heart's like oh dang i can't i can't overcome all of this increase in afterload because you're squeezing the vessels so what it does is here's what i want you think about it increases your systemic vascular resistance which could increase your blood pressure but it also increases your afterload because of that this can lead to left ventricular hypertrophy so now the left ventricle is going to get all thickened up now so because if i
1:05:47
were to draw here the left ventricle now now it's super thickened up because of why because of all that high afterload so that's one thing the high after load due to the renin angiotensin adoption system is going to cause left ventricular hypertrophy the other concept here though which is really interesting is that the random angiotensin aldosterone system also increases preload right and the way it does is by increasing sodium and increasing water and if you increase
1:06:19
preload way too much what do you do to the ventricles you actually cause left ventricular dilation because now you're going to cause them to become volume overloaded so on top of left ventricular hypertrophy due to thickening up the muscle so this is hypertrophy so you're thickening up that muscle you also can cause left ventricular dilation so now the left ventricle can get all kind of like huge as well so you see how like this negative effects happen whenever a patient has an
1:06:47
mi or they have kind of heart failure that the overarching theme here is that they can really mess up their heart so either way we can either cause it to become thick or we can cause it to become dilated all right so here we're gonna have dilation
1:07:03
now the other aspect behind this is that whenever you have a reduction in cardiac output you act on those chemoreceptors i'm sorry bear receptors apologize bare receptors and when you stimulate the bare receptors i'm going to put stimulate the baro receptors they respond to that low cardiac output low blood pressure baroreceptors and what they do is they send this information to your central nervous system your central nervous system will then activate the sympathetic nervous system
1:07:32
and then your sympathetic nervous system when it's stimulated guess what it does it goes and releases norepinephrine onto the beta 1 receptors on the jg cells which increases this whole negative process here on top of that it also releases norepinephrine on to a bunch of other areas here it'll release it onto the heart and it'll release it onto the blood vessels the blood vessels aren't as important here but i want you to understand here that when it works on the heart it works
1:08:10
on the beta 1 receptors of the heart and that is going to increase the patient's heart rate it's going to increase the patient's contractility and that's going to make that patient's heart have to work hard and hard and hard and difficult over time this can also lead to potential changes of maybe left ventricular dilation as well as maybe even cause left ventricular hypertrophy as well so it's important to be able to understand that this can also cause like changes or remodeling of the heart if
1:08:41
you will the other thing is that it's going to squeeze the heck out of the vessels so if you squeeze the heck out of the vessels that's via the alpha-1 receptors and the alpha-1 receptors will increase the systemic vascular resistance they'll increase afterload we already know all this junk here and again that'll cause left ventricular hypertrophy you get the whole point here is that with all of this massive sympathetic surgeon rent an angiotensin aldosterone system
1:09:08
the problem is that you get maybe a combination of both of these and the combination of this hypertrophy and dilation can lead to what's called cardiac remodeling and believe it or not when you remodel the heart in this particular way where you cause a combination of left ventricular hypertrophy and left ventricular dilation this really increases mortality of the patient who has heart failure or post mi so you're probably like what in the world does all of this have to do with anything
1:09:38
when i give a beta 1 antagonist or a beta 1 blocker i'm going to do what a patient has heart failure post to my reduce their cardiac output they have less effect on the bare receptors so they stimulate the bare receptors sympathetic nervous system becomes increased releases norepinephrine onto the beta 1 receptors here what am i going to do when i give a beta 1 receptor i'm going to inhibit this therefore i'm going to inhibit the random angiotensin aldosterone system
1:10:03
i'll inhibit this increase in resistance this increase in blood pressure i'll inhibit the increase in afterload inhibit the left ventricular hypertrophy i'll inhibit the preload due to increase in sodium and water and i'll inhibit the ventricular dilation i'll also inhibit the norepinephrine release onto the heart which will help to prevent the increase in heart rate increasing contractility would also inhibit the left ventricular hypertrophy dilation and also again not as much here
1:10:27
on the alpha-1 receptors but again you get the point that i won't i won't have much effect here but all of this is going to be inhibited and so because of that if i'm inhibiting the beta 1 effect on the renin angiotensin aldosterone system and i'm inhibiting the excessive beta effect on the heart all of these things are causing hypertrophy and dilation which causes cardiac remodeling i'm inhibiting cardiac remodeling and i'm essentially doing what decreasing mortality
1:10:55
so beta blockers are actually great in patients who have heart failure or post mi because it's potentially shown to reduce the mortality of these diseases by reducing cardiac remodeling and that's a really important concept that i really want you guys to understand here with the beta blockers and again preferably out of all of these diseases the most commonly utilized ones are going to be things like metoprolol okay you can also use another drug we'll talk about later um bisoba or carvadalol
1:11:25
but the commonly utilized ones in these particular diseases is going to be like metoprolol esmola bisoprolol those will probably be the only ones that you might commonly see out there but again overall if you think about it all of these will have the same effect we just might prefer one of those drugs up above in comparison to another and oftentimes it's metoprolol all right that covers the overall indications effects of beta-1 antagonist now what could be an
1:11:51
adverse effect that i want you guys to think about since these affect the cardiac output they affect the heart rate what could be a potential negative thing out of utilizing these drugs you could potentially block the heart a little bit too much and cause bradycardia if you block the heart rate a little bit too much what's the potential side effect out of this a potential adverse effect could be bradycardia the other thing is you can reduce cardiac output potentially right
1:12:14
and that might be bad if a patient has decompensated heart failure so one of the things i would actually urge you guys to understand here is really try to avoid these drugs really stay away from them in decompensated heart failure because these patients already have a super low cardiac output if you give them a drug that drops their cardiac output even more you could potentially kill them okay so one of the things i would say to avoid with beta blockers if a patient is an acute
1:12:42
decompensated heart failure and they're already in cardiogenic shock or hypotensive stay away from a beta blocker because you could actually make them worse drop their cardiac output even more also if you've got a drug you're giving it to a patient to slow their heart rate down if they're super super bradycardic what would i do i'd probably avoid this drug in a patient with super bradycardic as well because that might be an adverse effect decrease the drug dosage or hold the drug dosage
1:13:02
whatever it may be all right let's move on to the next category which is the beta 1 and beta 2 antagonists all right guys so you're probably wondering exactly what the heck happened you're in a different shirt we had to take a little break sorry but we're back at it we're going to finish this video off strong so when we talk about beta blockers we've gone through the beta 1 antagonists or the beta 1 specific blockers now what i want to do is i want to hit some of the
1:13:24
ones that actually have a lot of love for the beta 1 and beta 2 receptors so they block both of them and what's a potential benefit and also a downside to that so one of the big things is that we have to talk about some of the drugs within this category so we talked about you know within the beta 1 primary antagonists or blockers it was acebutel atanalol esmela bisopra law and then metopr law those are the big ones so a to m for these ones you can think about
1:13:48
those from n to z if you want to so this includes particularly natalololol so nanolaw this also consists of another drug called temolol and then the last one which is probably going to be the most commonly utilized one which is going to be propanolol now with these particular drugs again you can think about it from that was from a to m and for the beta 1 and beta 2 you could think about this from if you really want to n to z so again we've got natalololol templo per panel with the most commonly
1:14:20
utilized ones you're going to see on this board here being propanol now with these drugs you got to think about again some of the receptors so the beta 1 beta 2 receptors you're going to notice a lot of this is the beta 2 love though so we're going to be looking at a lot of the beta 2 receptor effects within these drugs so you know within the eye we have what kind of receptors well we have alpha one receptors on the pupil so that's not gonna be the particular fan here it's
1:14:44
gonna be the beta2 receptors in the ciliaris now the ciliaris has little processes that actually secrete aqueous humor right so if we have a beta2 receptor there if we generally when you stimulate that it actually helps it to make aqueous humor right but if we block that we're going to decrease the aqueous human production meaning that all that fluid that we make less of it that can really decrease the pressure inside of the actual eye so the intraocular pressure it's really good at reducing it
1:15:11
so a particular drug that would be great in this scenario is inhibiting the beta 2 receptors present on the ciliaris because what that's going to do is that's going to decrease the aqueous humor production that's going to reduce intraocular pressure guess what that's great for diseases where there's already high intraocular pressure glaucoma now out of all of these drugs up here on the top which is only a big whopping three of them one of them is the only primary one that is utilized
1:15:40
and because it's more topical on the eye you don't really get a lot of the systemic adverse effects from this drug it's going to be timolol so i want you to think temelol as the primary one that is utilized in what type of situation here we primarily use temelol in situations of glaucoma all right beautiful a couple other things which are really interesting but kind of slightly weird so in a situation where a patient has what's called thyrotoxicosis or thyroid
1:16:06
storm what they do is in this disease they pump out large amounts of t3 and large amounts of t4 thyroid hormone so again what does this disease here call whenever you make lots of this t3 and t4 this is called thyroid storm if you really want to another name for it is thyrotoxicosis either way this is the situation when you're pumping out lots of that hormone now we know that there's a lot of other effects that we've talked about in the hypothyroidism lecture but one of the
1:16:35
big things that thyroid hormone does to the heart is it increases the sensitivity and the number of beta receptors that are present on the heart so in other words if i were to take a piece of this heart tissue this includes the nodal cells the other ones that send action potentials and the ones that contract so it's going to go to this particular cells here and say hey you know cardiac cells what i want you to do is i want you to increase the sensitivity and the number of beta
1:17:00
receptors that you're producing so it's going to increase the activity or the sensitivity of these beta 1 receptors on the heart now why is that important if i increase the number of them and i increase the sensitivity of them so they're just ready to be stimulated whenever a patient releases just a little bit of norepinephrine which we naturally do or epinephrine that molecule is going to bind onto here so norepinephrine or epinephrine and it is going to produce a profoundly increased
1:17:28
response way beyond normal and what that'll do is is that'll really cause an intense amount of cardiac stimulation and so that cardiac stimulation can look like what well if i'm stimulating the heck out of these beta receptors on the heart which ones the beta 1 receptors then i'm going to see a lot of cardiac stimulation so i'm going to see an increase in the patient's heart rate i'm going to see an increase in their contractility and that's going to increase their
1:17:54
cardiac output right but we're going to see a lot of tachyarrhythmias and a lot of squeezing of the heart so what i can do is i can give a particular drug that will inhibit the beta-1 receptors in the heart and that would be what that would be propanol but you know what else is nice is that there's also a lot of beta-2 receptors too in other areas and that's one of the other benefits of the situation of propanol because not only does thyroid storm really increase
1:18:18
the amount of sensitivity of just the beta-1 receptors it increases the sensitivity of a lot of the beta receptors and alpha receptors and so giving propanol is going to be great to be able to block all the different types of beta receptors not just the beta receptors in the heart the beta receptors all over the place and so that's one of the benefits i just think one of the most important ones think about that it can reduce cardiac stimulation and the cardiotoxic effects
1:18:40
during thyrotoxicosis so we can give what type of drug we can give a drug here such as propanol because what propanol is going to do is perpendilol is going to inhibit these beta 1 receptors and that's going to shut down the cardiac stimulation so it'll help to be able to reduce the excessive increase in heart rate and reduce the excessive contractility but also don't forget it's going to reduce the activity or the sensitivity number of beta 2 receptors in different areas of the body as well
1:19:11
and so that's another potential benefit okay the next concept we've got for panel law for thyrotoxicosis the other thing is really interesting here so you know in diseases which we call portal hypertension so portal hypertension let's write that up here portal hypertension so this is basically the portal blood vessels the hepatic portal system that runs through the liver and a disease called portal hypertension which can have a lot of different etiologies like cirrhosis or
1:19:37
some other different kinds of causes but the pressure within this portal system is high the problem with having high portal blood pressures is with portal hypertension one of the potential complications that is the most feared is it can balloon out some of these branches that come off the portal system and these are called the esophageal veins and they can really balloon them and increase the risk of risk of rupturing all right so these are called varices and so we don't want
1:20:03
these things to rupture because they can cause massive upper gi bleeding so whenever portal hypertension occurs it increases the risk of these varices and therefore increases the risk of upper gi bleeds pretty significant ones so what i want to do is i want to give drugs that reduce prophylactically reduce the portal blood pressures reduce the risk of varices and reduce the risk of an upper gi bleed how do i do that that's where propanol comes into play so propanol is really cool because it does
1:20:30
a couple different things one of the benefits of perpendible is that when you give this drug it inhibits the beta-1 receptors that are present on the heart isn't that a cool concept here and that's going to reduce heart rate reduce contractility if you reduce both of these things the combined effect of these two is you're going to reduce cardiac output that's going to reduce the blood flow or the profusion to different particular organs and one of the best situations here is
1:21:01
it's going to reduce what's called splanchnic blood flow so splanchnic vessels are the vessels that go to your git so there's going to be less blood flow running through the splanchnic arteries that means that there's less blood flow going to these actual organs and then less of it is actually being getting picked up by the portal venous system so if less blood is going through the arterial system less blood will actually go through the venous system and what
1:21:24
that does is by reducing the splanchnic blood flow you reduce the portal vein blood flow and that if you have less blood within that portal system you can potentially reduce the pressure so that's a benefit to that here's another cool thing upper panel law propanol also hits the beta-2 receptors so it inhibits the beta-2 receptors that are present on the splenic blood vessels what do beta-2 receptors on blood vessels do they cause vasodilation if you inhibit vasodilation you'll cause
1:21:52
vasoconstriction so if i cause vasoconstriction of these blood vessels i increase systemic vascular resistance and therefore reduce splenic blood flow reducing more flow through the actual splenic arterial system and subsequently less blood flow through the portal venous system less blood within that circuit is going to reduce the portal venous pressure so this is a prophylactic therapy and portal hypertension so remember it's primarily prophylactic all right another benefit upper panel
1:22:22
you're going to see that pretty much where panel is going to be for one two three four all right here's another thing we have beta two receptors that are present on some of the blood vessels that go to the um the circulatory system in the brain right so let's say that this is gonna be up above this bone is the cns and then here's going to be bone and then here this blue tissue is the dura and you know within the dura there's lots of pain receptors let's actually
1:22:45
denote these here in like this purple color lots and lots of like pain receptors connected to the trigeminal nerve now in diseases like migraines or headaches and things of that nature the theory is that you over stimulate the pain receptors within the dura mater the meninges and one of the reasons is these blood vessels can be a little bit dilated right that's one of the theories behind it so if the blood vessels are dilated they're stimulating these actual what these pain receptors
1:23:13
if you're stimulating the pain receptors that's going to produce pain therefore migraines if i give a drug like propanol what it's going to do is it's going to inhibit the beta 2 receptors on these cerebral blood vessels and cause them to just squeeze a little bit so it may actually just cause a little bit of vasoconstriction of these blood vessels not crazy but just a little bit if it squeezes the vessels a little bit now imagine it like this here you have your blood vessel here is
1:23:43
going to be the hole that it's actually running through and then around it is going to be those pain receptors if the vessel right if the this is running through that area here where the dura is if you constrict the vessel a little bit and you make it a little bit smaller you can kind of think about it now it's going to have less stimulation of those pain receptors nearby and so that's the whole kind of concept is when you squeeze the particular vessel you make
1:24:03
it smaller and by making it smaller you're going to have less stimulation of those pain receptors and so that may actually help to play a role within reducing migraines particularly like a prophylactic therapy so it's more utilized in decreasing the cerebral blood flow inhibiting pain receptors and that's great in situations such as migraines so we can use this in migraine prophylaxis and that is which drug again that can perform this function well the one that inhibits these is going to be
1:24:38
propanol so don't forget propanol is the primary one that's working here as well all right the last one here is going to be the muscle spindles you know your muscle spindles also have beta2 receptors and so we have these beta2 receptors that are present on the muscle spindles and what they do is whenever you stimulate them they squeeze the spindles increase the signals via the afferent fibers to your spinal cord and then via that reflex arc they increase the efferent fibers
1:25:05
going into your muscle and cause it to contract right and that can produce tremors so the effect here is that it actually may cause a little bit of a trimmering activity if you over stimulate those beta 2 receptors so in certain disease processes where patients have what's called essential tremors they have just a little bit too in the beta 2 stimulation we can give a particular drug to block the beta2 receptors inhibit the excessive contraction reduce the afferent signals reduce the efferent
1:25:31
signals and reduce some of the tremoring effect and so if i give a drug like propanol what it's going to do is is it's going to inhibit these beta 2 receptors it's going to inhibit the afferent signals efferent signals and decrease the tremors and essential tremors so that's another particular indication for these drugs so when it comes to talking about beta 1 and beta 2 blockers or antagonists remember n to z nadolol temolol per pentalol most commonly utilized one within this category is
1:26:00
going to be propanol what can we use it for again to remind you reducing the cardiac stimulation during thyrotoxicosis or thyroid storm you're probably like well it only inhibited the beta one that was just one of the examples it can handle inhibit a lot of the other beta2 receptors guess what else patients have during thyroid storm tremors so guess what else per panel could also do if a patient has thyrotoxicosis reduce some of the tremor effects because it can hit the beta 1 receptors
1:26:25
in the heart and the beta 2 receptors and the muscle spindles so you see the whole point that's why the panel is a little bit better because it can really block multiple different beta receptors so again it can be used in that situation okay it also can be utilized as a prophylactic therapy and portal hypertension it also can be utilized in migraine prophylaxis and it also can be utilized to produce essential tremors and then lastly don't forget temelo because it can reduce aqueous human
1:26:49
production and then reduce intraocular pressures in situations like glaucoma now the thing i would want you to think about though when it comes to adverse effects of these drugs is that these puppies hit the beta 1 and beta 2. so not only with beta one you could see decreased heart rate you could see decreased cardiac output which could be disastrous in patients who have decompensated heart failure that's why we try to be careful with those and also they can drop patients hearts so they
1:27:13
can really cause bradycardia these can do that as well but they also hit the beta2 receptors and so because they hit the beta2 receptors what kind of effect would you see more of with these particular drugs guess what i would see more of with these drugs i see more particular bronchospasm you're going to see more bronchospasm with these particular drugs than you would with the beta-1 receptor because they are going to hit beta-2 and so they're going to block those and cause bronchoconstriction
1:27:41
you also may see a little bit more of a hyperkalemia effect and you also may see more of the hypoglycemia and hypoglycemia unawareness with the beta 1 and beta 2 agonist as compared to the beta 1 antagonists okay all right beautiful that's these let's now come down to the last group which is a group of drugs two particular that actually block beta 1 beta 2 and alpha receptors as well all right so now beta and alpha blockers so again we already talked about how
1:28:10
those love both beta 1 and beta2 so they have an affinity for both beta 1 and beta 2 equally this one again it loves beta 1 beta 2 and alpha so the drugs in this particular category is going to consist of labatalol this is a pretty commonly utilized drug and another one is called carvatal law now there's another drug i'm just going to briefly mention it can actually be kind of considered to be utilized or kind of considered similar to these particular drug categories i'll talk
1:28:36
about it just a little bit and it's called nabiva law nabivi law doesn't actually have alpha blockade it's a weird one nabiville i want you to associate with nitric oxide nebula nitric oxide it actually increases nitric oxide levels which has a vasodilatory effect so it may act similar to these drugs but realize it does not have alpha blockade it's called nabivolol so remember it increases nitric oxide so it does have beta blockade and increased nitric oxide which causes vasodilation but it does
1:29:04
not have alpha blockade so just remember that one all right coming back to the beta long carved log again we know that they have an affinity for the beta receptors they also have an affinity for the alpha receptors so they can block both of these so think about that for a second one of the really beautiful things is that you have beta receptors so it's going to inhibit the beta 1 receptors on the heart and you also have alpha receptors that are present here my friends
1:29:31
on the veins and alpha receptors present on the arteries so what's the overarching effect out of all of this well if i inhibit the beta-1 receptors in the heart both of these drugs will do what well they'll reduce the heart rate they'll reduce the contractility if both if it does both of those things then the combination of that is it can reduce cardiac output and can reduce your systolic blood pressure a little bit so it can be great in reducing blood pressure the other thing though
1:30:00
is that it also helps to block the alpha-1 receptors on veins now remember what do alpha-1 receptors do whenever epinephrine hits this norepinephrine it squeezes and pushes blood flow up into the right heart well you're going to block that effect and so you're going to get a decrease in venous return if you get less venous return to the heart what does that do to your preload my friends it drops your preload if you drop your preload what does that do to your stroke volume and cardiac output it
1:30:29
drops your stroke volume and cardiac output and guess what that is going to do it's going to reduce your systolic blood pressure so it's good at reducing blood pressure the other thing here is that whenever we stimulate alpha 1 receptors on the vessels of the arteries they squeeze those like a son of a gun and then increase resistance and increase your diastolic blood pressure well now we're going to inhibit that so we're going to do what reduce the systemic vascular
1:30:53
resistance and we're going to do what we're going to reduce the diastolic blood pressure but the combination of both of these is that it's reducing your blood pressure in general well if it reduces the blood pressure it'd probably be good to give this to a patient who has a high blood pressure right that's the indication so the indication of these particular drugs is they're very very favorable in hypertension but if i had to pick between one of these which is better it
1:31:18
actually seems that lebado law may be more superior so the beta law may be more superior in the comparison between these two so the beta law may be greater in efficacy than carvadal law now that actually flips when we get to the next one though so the next indication of these particular drugs is in heart failure so you know patients who have heart failure we actually prefer the opposite now so now we actually prefer carvado law carvedo law is actually preferred over label law
1:31:50
as compared to in a patient who has hypertension the beta law might be more preferred now let me explain why we already talked about this a little bit someone has heart failure maybe they have a reduced systolic function maybe they have a reduced diastolic function the whole point of the matter is is that in heart failure there is a reduction in cardiac output that's the whole overarching theme is that this thing is not pumping blood out because it doesn't pump blood out there
1:32:16
is a reduction in cardiac output the problem with that is that whenever there is a reduction in cardiac output so less blood flow going to particular organs that leads to a very important type of effect here one is we know it acts on the kidneys to increase the activity of the renin angiotensin aldosterone system we already discussed how this is a particular problem when you increase the renal angiotensin aldosterone system what does that do it increases your systemic vascular resistance and
1:32:44
increases your blood pressure it also is going to do what else it increases afterload it also is going to do what else besides doing that it's also going to increase your sodium and water retention and if you increase sodium and water retention that increases blood volume and that can actually increase your preload but the whole concept here is that you're increasing the patient's blood pressure increasing afterload you're increasing preload we already talked about this a little
1:33:15
before this may sound similar right increasing afterload can cause left ventricular hypertrophy increasing blood pressure can cause left ventricular hypertrophy increasing preload can cause left ventricular dilation you're kind of changing the shape of the myocardium all over the place you're remodeling that son of a gun same concept here is that you stimulate the sympathetic nervous system whenever your cardiac output's low because remember it activates the baroreceptors
1:33:38
so the bare receptors will pick that up and say oh sympathetic nervous system get going and that'll actually increase the outflow of the heart and so what that'll do is that'll send information and stimulate the beta 1 receptors that are present on the renin angiotensin aldosterone system the jg cells it'll also go to the heart and it'll try to increase heart rate it'll try to increase cardiac output by causing contractility it'll also act on the blood vessels
1:34:06
and then again increase the systemic vascular resistance and we already know what that did we already talked about it up there so just be the same as above it's going to increase afterload causing left ventricular hypertrophy and increased blood blood pressure causing left ventricular perturbing but again it's going to do it on the heart via the beta 1 receptors and it's going to do it on the vessels via the alpha 1 receptors if i give a drug like lebado labatalol or carvada law what am i doing
1:34:35
i'm blocking the beta receptors that are present on the jg cells therefore i will inhibit the random angiotensin aldosterone system i'll inhibit all of these particular changes causing left ventricular hypertrophy due to the increased afterload and blood pressure i'll inhibit the left ventricular dilation via causing a lot of sodium and water retention causing the heart to stretch out i'll also inhibit the beta receptors on the heart which is going to cause again this
1:35:04
entire degree of stress on the heart this is going to stress the heck out of the heart when you're having to beat hard and having to contract too hard eventually it will fail and weak become more hypertrophic and over time dilated and i'm also going to inhibit the alpha 1 receptors and not squeeze on the vessels to increase after the whole point is i'm reducing cardiac remodeling because the combination of hypertrophy and dilation to the heart can be catastrophic can remodel the heart and
1:35:30
actually increase mortality so giving these drugs have been shown to decrease mortality and that's why we give these particular drugs in this scenario all right my friends so we got hypertension oh and then really good here what do you think a little beta law would be preferred for for i talked about this prior with remember when we talked about in the agonist lecture how alpha methyl dopa is one of those that actually is good for hypertension and high blood pressure
1:35:55
labatalo is also a good one for pragers for patients who are prego and hypertension type of situations as well as hydrolyzing and fetapine all right the last one here is very similar to what we've already discussed here which is portal hypertension so this mechanism we can already kind of like quickly get to the point here that with portal hypertension you increase the risk of varices upper gi bleeding we want to prophylactically prevent that the primary drug utilized in this
1:36:20
situation is carved law now let's quickly get to the point here carved law has beta and alpha it's not hard to imagine you inhibit the beta 1 receptors in the heart you inhibit the beta 2 receptors present on the splenic arteries and you also have alpha 1 arterials and in this situation here you have alpha 1 receptors present on the venous circulation of the portal venous system so i'm going to inhibit them as well what's the overarching effect of all of these we already know this one you
1:36:52
decrease heart rate you decrease cardiac output you decrease the splanchnic blood flow the blood flow that's going through the actual gi circulation so less running through the arterial system less will actually get picked up by the venous system less portal venous blood flow will be the overarching theme from that right and you get the same effect here when you inhibit the beta-2 receptors you have a increase in systemic vascular resistance you squeeze the vessels because normally beta2 is
1:37:20
supposed to relax them you're going to block that effect and that is going to again reduce the splenic blood flow here's another thing if i also inhibit the alpha-1 receptors these are generally kind of causing a lot of resistance so what they do is they naturally cause an increase if you squeeze this portal vein imagine a lot of blood having to run through a very narrow vessel if you increase the resistance of blood flow you're going to increase the pressure within that circulation
1:37:46
especially the portal venous system i don't want that so if i inhibit the alpha-1 receptors i decrease the systemic vascular resistance and what do i do i actually inhibit the increase in portal blood pressure so that's the beauty of carvedilol in this situation which we don't see much of a benefit from lebado law interestingly but perpendilon carved a law we utilize these as a prophylactic therapy in patients who have portal hypertension to prevent esophageal varices and
1:38:14
subsequent upper gi bleeding carved law would actually seem what's somewhat superior though if you think about it because you hit both beta receptors to reduce flanking blood flow and alpha-1 receptors to reduce the actual portal venous constriction and then allow for it to be dilated increasing the blood flow through there as well as well allowing it easier for blood to flow through there and reducing the pressure within that circulation because again if i constrict a vessel the narrower it is
1:38:41
the more pressure it's going to undergo so if i dilate it i'll have less of that actual pressure because again there's going to be less resistance to blood flow and so that's the beauty of this particular drug all right so that covers these three particular drug labatalog carvatalol now and then we also briefly talked about nabivolol which again is similar to them but it doesn't actually block alpha receptors it has nitric oxide synthase types of activities where
1:39:06
it increases nitric oxide levels which can cause vasodilation the last thing i want to talk about some of the potential adverse effects from these you get the same thing with the beta receptors you're blocking beta 1 receptors so you can drop their heart rate you can drop their cardiac output right that's the same kind of concept you can block the beta2 receptors that we talked about above so because that you can see bronchospasm you can see hyperkalemia you can see hypoglycemia
1:39:28
and hypoglycemia and awareness but the other thing is that you block alpha receptors so you're going to get some of the effects of the alpha blockade would be the alpha blockade well if i block this puppy right here what am i doing i'm increasing the risk if i have this one here i'm increasing the risk of orthostasis because i'm relaxing the blood vessels in the venous circulation reducing poor the venous return and that can actually drop the patient's blood pressure when they go from a kind of
1:39:56
like abrupt seated to a standing position or laying down flat to a seated position again same thing like alpha blockers because it has alpha blocking activity so watch out for that in combination with all the other beta blocking effects so now let's talk about that in a worst case scenario a patient takes one of these three categories of drugs they take a pure beta 1 blocker what are the potential adverse effects they take a beta 1 beta 2 antagonist blocker what's the adverse effects or
1:40:22
they take a drug that has both beta 1 beta 2 and alpha blocker let's think about these in the worst case scenario and get to the white board and talk about that all right so with the beta blocker overdose we're kind of talking about adverse effects here right so thinking about the different types of beta receptors beta 1 beta 2 right all of those situations here we already talked a little bit about the alpha blockers obviously the complications associated with that well beta blockers
1:40:43
what i really want you to think about here is what if i block the beta 1 receptors in the heart a little bit too much i take too much of metoprololar asmolal bisopralop one of the drugs i take too much of it what's the potential adverse effect of that well because i'm blocking the beta 1 receptors on the heart if i really block these really intensely i can really really drop the heart rate and so watch out for potential like bradycardia that might be one potential complication like pretty
1:41:06
low and sometimes you can even cause like an av block so that's a potential complication you want to watch out for the other thing is if i reduce the contractility so if i really really drop the contractility of the heart and i really prevent it from being able to squeeze blood out that could really be catastrophic in a patient who has decompensated heart failure it could actually cause them to die but on top of that it could really drop their cardiac output and i would
1:41:29
drop that cardiac out but i could actually put a patient into cardiogenic shock so watch out for potential complications such as cardiogenic shock so the patient actually may become extremely hypotensive and bradycardic so watch out for that as well all right that would be particularly with what type of drugs all of them you could see that with any of the beta blockers whether that be the primary beta 1 whether it be the beta 1 beta 2 or whether that be the beta and alpha antagonist okay
1:41:55
next situation here the lungs which kind of receptors are here beta 2 receptors so you're going to see this more with the propanolol the nanolaw and timolol not so much we can also see this with the betalone carvada law now the reason why is because those hit both beta 1 and beta2 the beta 1 antagonists don't really have much of an effect here so if that happens what am i going to cause i'm going to cause intense bronchospasm now that causes intense bronchospasm that's a terrible
1:42:18
situation especially in particular diseases so i'd really want to be careful in utilizing drugs that have beta2 blocking systems within copd and i'd really want to be careful in utilizing this in patients who have asthma some type of reactive airway disease because my bronchospasm and they already have a degree of bronchospasm it can make them worse so i don't want to exacerbate that particular situation the next thing is i want to think about what could this do to the actual liver
1:42:41
in the pancreas especially with the glucose system so there's twofold kind of concept here which is really cool really interesting so we know that we have beta-2 receptors that are present on both of these and if we inhibit these we'll obviously see that potential effect now we can see this effect in two ways i'm going to talk to the first one with those drugs that have beta 2 blocking type of activity you're going to see a natural potential very minor not significant but
1:43:04
a minor drop in the blood glucose levels and the reason why is you're inhibiting the liver from being able to produce glucose via gluconeogenesis glycolysis so that'll drop the glucose levels and you inhibit the pancreas from releasing glucagon so you drop the glucagon levels and because of that that's actually going to drop the glucose levels so you may see this as a potential complication of hypoglycemia but here's where the other drugs come into play whenever you have hypoglycemia what this
1:43:31
is supposed to do is it's supposed to stimulate your sympathetic nervous system so hypoglycemia naturally will stimulate the sympathetic nervous system and this will come and then go to your heart it'll also go to your sweat glands do a bunch of other things and what's the effect here is that it'll cause maybe your heart to beat a little bit faster so you may get tachycardic you may get palpitations it may go to your sweat glands and so if i were to just go draw a piece of skin
1:43:56
here it may go to the sweat glands and increase diaphoresis and the effect there could be on a lot of different types of beta receptors especially the heart rate and a lot of these but the whole point is that you're causing the sympathetic nervous system to be increased whenever the sympathetic nervous system is increased and you're having these act on particular beta receptors so maybe this is some type of beta receptor here this is a beta receptor here guess what happens
1:44:21
if a patient has hypoglycemia it's supposed to stimulate the sympathetic drive to cause you to become aware so it'll produce particular manifestations and basically the hope is that if it makes your heart rate goes up makes you sweat makes you a little bit pale makes you a little bit kind of confused etc that's supposed to induce awareness of low glucose so that you go check your glucose oh okay it's really low i better give myself some glucose if that's the case this could be blunted
1:44:51
because now if i give a beta blocker not only do i cause a twofold problem here one situation is that i can lower the glucose directly the other situation here is i block all of the sympathetic effect from the low glucose levels and so now me being aware of my low glucose via the sympathetic effects is gone and this is called hypoglycemia unawareness and you can potentially see this with any beta blocker so that's the potential complication to watch out for here
1:45:21
all right the next thing which is also really important is we have beta 2 receptors on pretty much every single cell in our body that is regulating the activity of these pumps called sodium potassium pumps and they pump potassium into the cell and they pump sodium out of the cell right that's the whole job of it and the beta2 receptors are supposed to stimulate that pathway well if i give a beta blocker especially one that has beta 2 blockade what is it going to do it's going to inhibit this
1:45:47
one if it inhibits the beta2 receptor i inhibit the sodium potassium pump if i inhibit the sodium potassium pump i don't pump potassium into the cell so potassium will go into the cell if potassium doesn't go into the cell it stays out in the extracellular space especially within the blood and bumps the potassium levels to high levels and this can lead to hyperkalemia okay so that's another potential complication of these particular drugs more specifically watch out for beta-2
1:46:18
blockers the last thing if you really wanted to consider this would be it does have some degree of effect on the central nervous system there's a lot of like norepinephrine and neurons that are involved in a lot of like activity within the brain think about it whenever your fight or flight situation is on you want to be have a certain degree of kind of like you know acknowledgement maybe a little bit anxious maybe a little bit irritable you're more aware of things if you have
1:46:42
somebody who you're blocking a lot of those sympathetic effects in the brain you're really kind of shutting things down slowing them down a little bit you're going to make them pretty much fatigued and left lethargic so watch out for some degree of fatigue and lethargy that also may be potential complications from beta blockade but that's the concept so if you give somebody a beta blocker and they develop some of these particular effects and i'd say the most worrisome is the cardiac effects if a
1:47:05
patient becomes extremely hypotensive and bradycardic at the point of cardiogenic shock you need to have some things we're going to be able to reverse that and the drug that's usually most commonly given to try to reverse especially with the cardiogenic effects here is going to be a drug called glucagon so that's important to be able to remember and that kind of wraps up this lecture here on the whiteboard with talking about adrenergic antagonists let's get to the actual cases and do a
1:47:30
couple all right my friend so let's do some cases here on adrenergic antagonist so the first one that we have here is a 60 year old patient started a new hyper antihypertensive medication his blood pressure is well controlled but complains of fatigue drowsiness and fainting when he gets up from bed so orthostasis which of the following drugs is most likely the one that he's taking so think about this guy so big thing here is that with orthostasis we talked about this primarily with the alpha
1:47:56
blockers because remember when you block the alpha 1 receptors you block it on the veins and on the arteries so when you block it on the veins you reduce their preload their venous return to the right heart and therefore you can drop their blood pressure whenever they have these postural changes when they get up out of bed so it's oftentimes going to be an alpha one receptor blocker or antagonist in this situation which one do you think is an alpha blocker well metoprolol is primarily a beta one
1:48:23
propanol is non-selective so beta 1 and beta2 prasasin is an alpha-1 receptor blocker selective and alpha-zosin i wouldn't worry about this one so again it is definitely processing so practising should be the answer in this one all right 30 year old male was brought to the emergency department with an amphetamine overdose he presented with high blood pressure and arrhythmias and again that's because amphetamines increased norepinephrine released from presynaptic nerve terminals and increase
1:48:46
that flood of norepinephrine to the heart and the blood vessels so they're going to get hypertension they're going to get tac arrhythmias they're going to get increased contractility and so because of that what are we thinking here which drug is the most appropriate to treat the cardiovascular symptoms of amphetamine overdose in this patient well remember i told you you can't use a sole beta blocker if you use a beta blocker you will block the beta receptors which is the beta 2 receptors
1:49:07
right which is going to allow for vasodilatory effect and then all the norepinephrine will saturate the alpha-1 receptors and when you saturate the alpha-1 receptors it'll squeeze the heck out of them and they have no nothing to oppose them because if you hit the beta-2 receptors that's causing vasodilation you're blocking those now now you can't vasodilate so if all the norepinephrine is hitting is the alpha-1 receptors it's going to squeeze the heck out of the vessel and shoot the pressure
1:49:29
up even more so because of that i think it's important to be able to remember that we want to give a drug that either is primarily alpha but generally the one alpha that we prefer in this situation is phenoxybenzamine infantillamine we talked about that in situations of cocaine usually it's second line or amphetamines it's usually second line but in this situation processing is there right it's an alpha one blocker but i didn't talk about prazisin in these kind of hypertensive crises
1:49:57
related to a particular drug overdose the only one that i know has some type of alpha blockade and it can use specifically to treat blood pressure here is going to be lebado law labanol is great because yes it does have beta receptor activity so it will actually hit the beta 2 receptors and have a little bit of opposition there but the other beautiful thing about the beta laws that has a lot of alpha blockade so it can really work to hit those alpha receptors so i think really
1:50:26
the best option here out of all of these wouldn't be metoprolol because that's primarily beta 1. prasasin it's a good one because it does block the alpha receptors but it's not a part of the indications of that drug it's mainly bph hypertension right not related to this the main one is phenoxybenzaminophentolamine and then the bibliolaw we didn't talk about this one but we only mentioned a little bit that it actually does have a little bit of vasodilatory action
1:50:50
because it can actually increase nitric oxide synthase but there's no specific indication for that one that we discussed on the whiteboard metal beta law we know helps to be able to reduce blood pressure and because it has alpha blockade it would probably be the best choice here not the most ideal but probably the best in this situation all right a beta blocker was prescribed for hypertension and a patient with asthma after a week of treatment the asthma attacks got worse and the patient
1:51:14
was asked to stop taking the beta blocker which beta blocker would you suggest as an alternative that is less likely to worsen the asthma so in other words we need to give them a beta blocker that is selective it avoids the beta 2 receptors i think that's the key thing and the most particular ones that are selective in other words they prefer the beta 1 they don't really like the beta two as remember we talked about these are your atenolol acebutyl law besopro law esmola metoprolol those are
1:51:42
the preferred ones propanelaw is definitely gonna love the beta one just as much as it loves beta two and labatalon carvada law also like the beta receptors as well they prefer they can also have beta one and beta two as well and they hit the alpha receptors so i think the big thing to think about here is that because of that i think the best one here is going to be metoprolol because metopr law has pretty much beta 1 and almost no beta 2. so metoprolol would probably be the best option here
1:52:09
because it's not going to have anywhere near as much beta 2 activity as all the other that we just mentioned all right a 70 year old male is treated with doxazosin for overflow incontinence due to his big old prostate complains of dizzy spells while getting up from the bed at night um which drug would you suggest as an alternative that may not cause as much dizziness well generally when we think about these we are looking primarily the alpha blocker so that leaves tamsulosin and terazycin
1:52:34
phentolamine is not really one of those that we utilize for bph and neither is for panel also it's definitely tamsilos and it's arazosin the question is which one of these has less of the significant effect of dizziness when getting up from bed at night in other words which one causes less of that kind of orthostasis kind of effect and we didn't mention this a lot but tamsulosin actually is preferable in those situations because there is less significant types of orthostasis with camsyllosin and
1:53:00
compared to the other types of alpha-1 blocker so tamsulosum would be the preferred all right fifty-year-old male is in anaphylactic shock after being stung by a hornet the medical team tries to reverse the bronchoconstriction and hypotension using epinephrine however the patient did not fully respond to the treatment the patient's wife mentioned that he is taking a prescription medication for blood pressure which medication is most likely taking uh most likely taking that kind that contribute
1:53:24
is he most likely taking that's contributed to a reduced response to epinephrine so we have to think about this in a very interesting way where we need a drug that can block if it's not reversing the bronchoconstriction we need a drug that can have beta-2 receptors and block those and we need drugs that can block potentially the beta-1 receptors also on the blood vessels those are on the heart so maybe it blocks the beta-1 receptors on the heart and maybe it even hits a little bit of
1:53:48
the beta-2 receptors on the blood vessels so we're looking for beta-2 receptor and beta-1 receptor blocker so which of these drugs is primarily a beta 1 and beta 2 loving antagonist well doxazosin is an alpha one propanol is a beta 1 and beta 2. so it likes to hit the beta 1 so it'll help to be able to drop the patient's heart rate contractility and then also drop their overall cardiac output which can drop their blood pressure it also has beta-2 receptor blockade so it can actually
1:54:14
cause bronchoconstriction and vasodilate the blood vessels and so because of that it would be blocking epinephrine from being able to bind to those receptors so i'd say propanol is pretty much the best option here metoprolol doesn't have any effect on the beta-2 receptors because it's primarily beta-1 and the same thing for asbuto law it's primarily beta-1 so that leaves me with propanol as the likely option here all right next question which of the following is
1:54:38
correct regarding alpha adrenergic blockers so they're used to treat hypotension and anaphylactic shock that's not true that's epinephrine alpha adrenergic blockers are used in the treatment of benign prostatic hyperplasia that's definitely true um the reason why is if we think about these again this is your tamslosan terrazism prazasin doxazosin they're blocking the internal urethra sphincter right so i mean that's the job of the alpha receptor they help to be able to keep
1:55:07
the internal urethra centers constricted and tight which prevents us from being able to you know make urine okay undesirably but if a patient has some type of urinary retention or bph and we want to dilate or open up that actual urethra so that we can eliminate urine especially in situations where it's being crowded by a big old prostate like bph this is a great drug category to utilize okay so i'd say bph for sure alpha adrenergic blockers may cause bradycardia it's
1:55:35
actually untrue it actually can cause reflex tachycardia and alpha adrenergic blockers reduce the frequency of urination that's actually untrue it actually increases the frequency of urination because again you're relaxing the urethra sphincter and allowing for urination to potentially occur so i would say that the correct answer here would be b all right next one which of the following is correct regarding beta blockers treatment with beta blocker should not be stopped at abruptly that's
1:55:59
true because anytime you remove a drug that you've been on and it's potentially blocking those beta receptors it's blocking the norepinephrine from being able to hit those beta receptors again you're preventing it from leaking me if you stop it let's say that you have these these beta blockers they're preventing norepinephrine from binding on the beta receptors on the heart you go ahead and take that away now the norepinephrine is going to hit those receptors very powerfully increase your
1:56:23
heart rate increase your blood pressure and so because of that these patients will develop a rebound to tachycardia and hypertension so that's definitely true perpendicular is a cardioselective that's not true because remember it loves beta 1 and beta 2. so it's a non-selective beta blocker cardioselective beta blocker is worse than asthma that's not true because beta if it's cardioselective it's beta one so it can't worsen asthma because the bronchioles are beta two and
1:56:48
beta blockers decrease peripheral resistance by causing vasorelaxation technically there's beta2 receptors on the blood vessels right so if you give a drug and beta-2 receptors in the blood vessels cause vasodilation if you give something that blocks that it's not going to vasodilate it's going to vasoconstrict so it actually increases resistance cause by causing vasoconstriction if you give a beta-2 blocker all right so the correct answer here has to be a all right which of the following drugs
1:57:17
is commonly used topically in the treatment of glaucoma remember i told you that this is specifically going to work on the beta-2 receptors on the ciliaris to help to incre well generally what do these things do generally whenever you give these drugs beta-2 receptors on the siliers whenever they're stimulated they help to increase the aqueous humor production if you drive give a drug that blocks the beta-2 receptors you won't make aqueous humor you'll decrease its production which can
1:57:39
decrease the intraocular pressure that's great in situations of glaucoma and the primary one there is temelol all right which of the drugs has the highest potential to worsen orthostatic hypotension when given together with parasin that's a great question so processing is an alpha blocker so if i give a drug that also is an alpha blocker that's also going to worsen the patient's orthostasis because i'm going to significantly reduce their venous return to the heart reduce their preload
1:58:06
reduce their cardiac output and then potentially cause them to have an orthostatic event because they'll drop their pressure whenever they have postural changes so i need another drug that has an alpha one blocker effect for panel beta one beta two antenna law primarily beta 1. nabivi law it's beta 1 beta 2 but it doesn't actually hit the alpha receptors remember increases nitric oxide and synthase which can cause vasodilation but that's nowhere that's not specific
1:58:31
to the actual veins it's more specific to arterials libado law does have beta and alpha blocking effect so it hit the alpha receptors on the veins as well so the beta law is definitely the likely alpha blocker here that's the only alpha blocker so i'd say label law would be the correct answer all right my friend so that covers this video here on adrenergic antagonist i hope it made sense i hope that you guys liked it and as always until next time
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