Transcript for:
Adrenergic Antagonists

What's up Ninjerners? 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 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 you want to subscribe to our channel, please do. makes sense, please support us.

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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 gonna be releasing neuroepinephrine.

Now, when neuroepinephrine is released, you have to know particularly how it's made. So we start off with a very, 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 gonna be norepinephrine that's getting released out into the synaptic cleft here, right? So all these neurotransmitters here are primarily norepinephrine. Now, when tyrosine gets taken up, in order for it also to be brought in, it has to be brought in via a 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 metabolize dopamine and convert it into neuroepinephrine.

So that's kind of the process by how we make the neuroepinephrine within these nerve terminals that release neuroepinephrine. Now, how does the neuroepinephrine in this vesicle fuse with the actual cell membrane to release the neuroepinephrine out into the cell? 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 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. Now once the norepinephrine is out in the synaptic cleft it has a couple different options or a couple different pathways that it can go. One is that it can go and bind onto all these different types of receptors here that do a lot of different things. So it can bind onto 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 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 onto these particular receptors, it exerts a particular physiological response. All I really want you to know 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 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 levels 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 gonna increase or stimulate this contraction of smooth muscle. On the alpha-2 receptors though, it works via something called 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'll also increase potassium efflux. This can really inhibit particular types of processes. It actually can cause hyperpolarization of particular neurons or cells. And really what ends up happening is that these 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, the beta receptors is really interesting because all of these beta receptors... just 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 what happens here is for beta 2 and beta 3, it's the same thing and so is it for beta 1, 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. 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 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 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 as a stimulatory. Beta 2, beta 3, they're kind of a little bit a weird way, more of an inhibitory kind of function, 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 it activates 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 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 when norepinephrine norepinephrine is actually done doing its work.

Another thing that it can do is it can actually be metabolized. So you know there's an enzyme out here called catechol-ol-methyltransferase. And what it does is it takes norepinephrine and actually breaks it down.

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. And this is, so let's put here... this is one particular pathway. Another pathway is that norepinephrine may bypass that enzyme and then via a special transporter get taken back up in to the actual synaptic vesicle. So here's our norepinephrine getting taken back up into the vesicle.

This is via a norepinephrine reuptake transporter. And by this transporter, we get norepinephrine to be recycled so that it can be utilized again. But that's not always the case.

Sometimes the norepinephrine, 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 reutilized. But sometimes this norepinephrine 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. metabolite and that is via this monoamine oxidase is So that's the basic concept that I want you guys to understand about 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 would bind so that receptor it produces then when it's done exerting its effect, how does it actually get broken down or Recycled and reutilized that's an important concept now The next thing that I want us to talk about here is that in our sympathetic nervous system, our adrenergic system, norepinephrine is not the primary neurotransmitter. There's another one, epinephrine.

And so we have sympathetic nerve fibers that actually, very interestingly, 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% that the adrenal medulla pumps out. The other is epinephrine, and that accounts for 20% that the adrenal medulla pumps out. But either way, these suckers get into the bloodstream. and when they get into the bloodstream, they can actually move and then bind onto these different receptors here on their targets.

And so that's an interesting concept here because when you really look at the actual interesting aspect here of epinephrine and norepinephrine, obviously we know... Morphinephrine prefers the alpha receptors more than it does the beta receptors. We talked about the agonist lecture.

And epinephrine prefers the beta receptors over the alpha 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? 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 OH, and also has an NHCH3 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 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, combine onto these receptors. So when we talk about giving blockers, antagonists to epinephrine and norepinephrine, 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 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 what 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 gonna do next so let's now talk about some of the 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 alright 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 gonna do is block that effect do the exact opposite all a beta blocker is gonna do is oppose that effect so think about this 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 receptor, 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 systemic vascular resistance, you're going to increase the patient's blood pressure. So 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-1 receptor, blocker what do you think an alpha blocker is going to do an alpha blocker I'm just gonna 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 systemic vascular resistance because 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 1 receptors are hit they're also present on the internal urethra sphincter 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 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 work work potentially on the pupil muscle.

So the pupil muscle, it's actually going to do what? It's gonna stimulate pupils to contract. And whenever the pupil contracts, what happens is it actually stimulates the dilator pupillae.

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 pupil from contracting and instead you'll subsequently lead to pupil constriction. And this can actually be a side effect of alpha blockers. We'll talk about that later. It's called intraoperative floppy iris syndrome.

Really weird one, right? Alright, alpha-2 receptors. Now naturally what happens is, norepinephrine, when it's released from this, this is actually at a presynaptic nerve terminal. So presynaptic nerve terminal. And all this puppy does is it pumps out norepinephrine.

So we're going to release norepinephrine, have it work on this neuron, and then again increase the sympathetic tone. So this is all about 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, we'll cause the heart rate to increase, we'll cause the contractility to increase, all of that stuff. But when we give, what happens is 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. When norepinephrine is done exerting its effect, it actually acts on a alpha-2 receptor.

And what it does is it actually inhibits for the norepinephrine release. So it drops the norepinephrine production and then decreases the sympathetic tone. the natural type of response, right? That's our natural response to be able to prevent this process. If I give a drug, like an alpha two 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 bind onto the alpha two 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 two 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 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.

Well, whenever you actually do this particular process here, you're inhibiting that. So if you inhibit 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. insulin and then drop the blood glucose 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 myocardial 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 we're gonna give a drug that's going to block that and increasing the release of the blood glucose levels. of norepinephrine increasing the release of insulin and 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 or epinephrine it binds onto 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 contraction contractility because it's gonna bind on to the beta-1 receptors in 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 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 hearts already squeezing, squeezing, squeezing so much that there's a high demand and maybe they have a plaque in their vessel and it's not giving a lot of blood flow. So then they potentially have angina or MI, things like that, we can use to kind of treat those particular processes.

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 and angiotensin aldosterone system, which will pump up your blood pressure.

It'll squeeze your blood vessels, it'll increase aldosterone ADH, which it 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 renin 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 the conduction, inhibiting the secretion. The next thing is your beta two receptors. Now we do have beta two receptors.

beta-2 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 beta-2 receptors on the blood vessels in the brain near the dura.

We'll talk about that a little bit later because it's actually a clinical point to that. But what happens is when you give a beta-2 receptor, when you hit a beta-2 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 and 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 a bear or whatever it is in a sympathetic situation. So it 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 beta 2 blocker, it will inhibit this process. So it may actually increase the resistance a little bit and increase the blood pressure a little bit.

So that's another effect of this as well. Very minor in the overall scheme of things with blood pressure. The next thing is the bronchi. smooth muscle.

So you have bronchial smooth muscle, lots of beta two receptors there, right? When we have lots of beta two receptors here, what is it going to do? It's going to, again, what's the overall concept of hitting the beta two receptors? What do we do?

We increase the glycanin P to actually cause increased phosphorylation of particular kinases that inhibit. Smooth muscle contraction. So here the smooth muscle is not contracting.

It's dilating but we give a beta blocker to increase it here It's causing again real bronco dilation. 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 bronco 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 actually cause bronchoconstriction all right 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 baby...

beta blocker, what we do is we inhibit the liver from being able to do gluconeogenesis and glycogenolysis, which helps to increase glucose levels. So instead it will 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 unawareness. We'll talk about that a little bit later. But that's the effect here.

So we know that naturally it's to inhibit smooth muscle contraction and All right, so to cause it to relax or inhibit secretion of particular types of and then we're 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 and it'll actually do what inhibit the secretion of Glucagon and inhibit the glycogen analysis and gluconeogenesis by the liver and help to drop the blood glucose 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 that, the detrusor 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, 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, all 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 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 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 would inhibit 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 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 or norepinephrine binds to these receptors, what do they do? And now we talked about, well, oppose everything of those actions with alpha-bloc. blockers or 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 antagonists. We're going to kind of use that synonymously. This is the same thing, alpha blockers, alpha antagonists. We talk about these, let's first say, what are the different types of drugs? So these are specifically, so when I say specifically, Basically they're more selective.

So remember I told you that we have an alpha blocker that can bind onto an alpha receptor and prevent epinephrine and 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. 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 Prazosin. Another one is called Tarazosin.

Another one is called doxazosin. So there's a lot of these particular drugs that you're going to see, particularly on your exam. So think about these particular drugs.

Oftentimes you can kind of see that they often end in osin. 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 drug, and then what's an adverse effect, right? So first thing is you have alpha-1 receptor. receptors 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-1 receptors, increase the resistance and increase the blood pressure. I'm opposing all of these actions.

So I'm going to, for the 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 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 bit. Now if you block that even more you significantly reduce their this 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 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 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 in 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 first-line. And that leads me to the second situation.

It's often good in patients with an underlying... comorbidities 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 urethral sphincter. So if I give a drug that is going to block the alpha-1 receptor here at the internal urethral sphincter, what am I going to do? Well, if I inhibit the alpha-1 receptor at the internal urethral 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 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 secondary to BPH so that would be an indication for this particular drug categories okay Tamsulosin, Prazosin, Tarazosin, Doxazosin and all of those things so because of that I want you to remember that you can utilize the 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 that we have some more room. But one of the other big things that I want you guys to think about here is 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 you're dropping their blood pressure, what does it do to those chemoreceptors, I'm sorry, the baroreceptors 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. heart rate. 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, increase the heart rate, which is a reflex tachycardia. So watch.

Watch for reflex tachycardia as another effector. 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 interesting kind of thing here.

So you think, what does that have to do with anything? Well, when we think about this, normally what do we know? We know that we have alpha-1 receptors that are present here on this pupil.

And normally when you stimulate them, it's supposed to do what with this sympathetic? To 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, 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-1 blockers, such 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 in from a different position to a standing position. It also can cause reflex tachycardia because it drops the systolic blood pressure.

I'm sorry, it drops your blood pressure in general, your diastolic blood pressure. So it can cause reflex tachycardia. And on top of that, because it can cause pupil constriction, if you have this patient utilize that during a cataract surgery, it can actually cause prolapse of the iris, which can lead to intraoperative floppy iris syndrome. So watch out for that as well. One other indication that you can throw in there if you want to remember is prazosin.

Prazosin can actually be utilized in PTSD related nightmares because it can actually reduce the alpha alpha-1 mediated stress response to a patient who's sleeping. So if you want to remember that one, prazosin can also be utilized in PTSD-related nightmares, but I'm not gonna put that in here in this lecture. All right, now that we covered the selective alpha-1 antagonists, let's come down and talk about the interesting drugs that are pretty much alpha-1, but they have this really interesting alpha-2 antagonistic activity as well.

All right, my friends, so the next drugs, the alpha-1, alpha-2 antagonists are really interesting. So this drug category is called phytolemy. and phenoxybenzamine.

So there's two particular drugs here. One is called phentolamine 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 phentolamine and phenoxybenzamine are definitely really interesting drugs. little kind of piece of it on their pharmacodynamics though.

So when you look at how phenoxybenzamine and phentolamine work, they definitely work to block the alpha receptor, but the activity, when you get to the biochemical level, it's a little bit different. So So let's say 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 gonna have maybe a drug like epinephrine, I'm gonna just put norepinephrine.

So here's gonna be norepinephrine. Now, norepinephrine wants to bind onto this alpha receptor, so let's say that I'm just gonna put here this is an alpha receptor. Here you're gonna have a alpha receptor.

Phentolamine is interesting in the sense that it actually does bind to the active site where norepinephrine will bind. Phenolamine will also bind and inhibit norepinephrine from being able to bind there. And then it'll exert its inhibitory type of effect here, right?

Phenoxybenzamine is a little bit more interesting. It actually binds onto this little site here. So it binds on to what's called the allosymbionic.

Steric site. So the allosteric site. And what it does is it actually kind of changes the shape of this alpha-1 receptor.

And now this alpha-1 receptor, when you change its shape, it's no longer able to bind to norepinephrine the same way. 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 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, it's an active site 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 pharmacodynamics of these two drugs. So again, you have Phentolamine active site inhibitor, kind of has a shorter duration because of that.

Phenoxybenzamine 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 Phentolamine. All right. So that's one of the interesting things.

Now, when we talk... 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 vasodilation and when you vasodilate you decrease systemic vascular resistance and you decrease the blood pressure. With the alpha-1 receptor though, you cause vasoconstriction.

And when you vasoconstrict, you increase systemic vascular resistance and you increase blood pressure. What we know is that Phentolamine and Phenoxybenzamine definitely bind onto the alpha-1 receptors. They won't bind to the beta-2, they'll bind to the alpha-1 receptors. And so because these drugs will definitely bind to the alpha-1 receptors, this is their primary site of action on blood vessels. So this would be both of these drugs, phenoxybenzamine and phentolamine.

And they'll inhibit the alpha-1 receptor. receptors. So they will decrease vasoconstriction, they will decrease systemic vascular resistance, and they will decrease the patient's blood pressure.

And so 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. So it's going to inhibit that type of action.

That leads to a really interesting type of effect here, where we can think about particular diseases where where there is just massive amounts of norepinephrine and epinephrine. And one disease is called a pheochromocytoma. In pheochromocytoma, 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-2 receptors. Think about why this drug is perfect.

like phytolemin and phenoxybenzamine. 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 inhibition of vasoconstriction, inhibition of systemic vascular resistance, systemic vascular resistance that's increasing and then drop their patient's blood pressure. Because think about it, if you didn't have this alpha-1 blocker, what's norepinephrine, epinephrine going to do in 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 systemic vascular resistance to 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 Phentolamine and Phenoxybenzamine.

Phenoxybenzamine 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 because it's a little bit shorter acting. Phenoxybenzamine 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 gonna 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 onto the beta-2 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 to 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 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 reuptaken, right? It can be recycled. It can also be metabolized via the monoamine oxidase.

And And then there's another drug called catechol-omethyltransferase that also metabolizes it, right? Now, what I want you to understand is that when patients take particular drugs, all 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 don't break down norepinephrine. If I inhibit the reuptake, uptake 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 re-uptake 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 alpha-1 receptors, produce again their effect. In this case, they're going to squeeze the hex.

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 monoamine 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 plus tyramine it really really inhibits this monoamine oxidase and if you inhibit this you keep a lot of more 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. by increasing the norepinephrine release.

If you give a drug like phytolemin or phytoxibenzamine, 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 indication is a hypertensive crisis due to a Pheo or hypertensive crisis due to cocaine, and as well as a monoamine oxidase inhibitor plus tyramine. One thing I would say is cocaine, if you're 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 to think about here is whenever a drug, let's say that you 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 have an IV in, all 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 extravasated the norepinephrine and the epinephrine.

out into the subcutaneous tissue. So now it got out, it extravasated 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 and epinephrine can bind on. to 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 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 in a situation of vasopressor. extravasation there was one patient I had he was on a little bit of norepinephrine and for some reason the 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 then norepinephrine requirements went from 30 down to about 4 within a very short amount of time so something was odd because the patient did not actually required that large amounts of norepinephrine that we thought it did.

What we found is that one of the IVs that was actually in 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 of that, they were at risk of cutaneous vessel vasoconstriction and potential necrosis.

So that was one time that I actually had to push ventolamine into the actual IV and around the area to prevent it from really kind of blocking that norepinephrine from squeezing on the cutaneous vessels. So to prevent the extravasation necrosis that you could see from this. So remember, phentolamine, particularly for vasopressure extravasation, but both of them good for pheochromocytoma and hypertensive crisis. Cocaine, monoamine oxidase inhibitors with tyramine, hypertensive crisis, better with phenoxybenzamine. So again, I want you to remember that phenoxybenzamine is actually preferred 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.

You probably did. You guys are really good. smart so we talked about alpha-1 a lot but I told you that this is an alpha-2 again antagonist blocker so on these presynaptic nerve terminals that release norepinephrine guess what is also present there my friends an alpha-2 receptor And if I give something like Phenoxybenzamine or Phentolamine at this Alpha-2 receptor, what would this do? It would block the effect.

What's the normal effect? To inhibit neuroepinephrine 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 release. You're probably like Zach, that doesn't make any sense. because I thought the whole point was to 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 the drug. of that sympathetic tone on the alpha-1 receptors. So norepinephrine, epinephrine, when it's being released, yes, it'll bind to the beta-2, which will produce vasodilation, drop their pressure, but will block the alpha-1 receptors, so it won't be able 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. And this norepinephrine that is in increasing amounts, or epinephrine in increasing amounts, could stimulate the hex. 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. And this adverse effect here is called a reflex tachycardia. That is an adverse effect of phenoxybenzamine or phentolamine.

They will increase the sympathetic tone because they're going to inhibit the alpha-2 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, if an open epinephrine release is going to increase, you block at least the effect on the alpha-1 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 phentolamine and phenoxybenzamine. Now that we've covered the alpha blockers, alpha one selective and alpha one and two, let's now go on to the beta blockers and talk first about the cardio selective ones, the beta one blockers. All right, my friends, so now beta blockers. Beta one antagonists are beta one blockers if you want to think about it.

So these are really interesting because they're cardio selective. Now, the way I remember the drugs in this category is... to figure out the first beta receptor. So think about some of the first letters of the alphabet. The first day that 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 those letters in there, it's likely going to have an O-Law at the end. So first one is Atenolaw. Then, Atenolaw.

Then, Bbisoprolaw. Then we would go to the next one. So we're going to skip a couple because there are these other ones, Carvata Law and things like that.

They're actually in other ones. We'll talk about those a little bit later. They're beta and alpha.

Then we get to E, Esmol Law. And then we get into M, metoprolol. And this is gonna be probably out of all of them, the most commonly utilized one.

So out of all of these, again, you can actually remember this if you had A to M. So A to M, where it's atenolol, acebutyrolol, bisoprolol, esmolol, and metoprolol. These are going to be the most common beta-1 antagonists 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 beta-2 receptor. They have very, very little affinity for the beta-2 receptor.

Very little affinity. That's why I'm going to really keep them for simplicity sake, that they are primarily a beta-1 antagonist or beta-1 blocker. Now what are the indications of these drugs? 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 want to think about them beta-1 blockers they're reducing heart rate they're reducing contractility. Alright that's a great situation.

One of these particular scenarios where I would say it 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 reentrant circuits to occur or maybe you have like this reentrant circuit and again they're 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 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 it.

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 effect?

Well, again, if I'm giving drugs like metoprolol, esmolol, bisoprolol, acebutylo, atenolol, 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. Alright, of all of these electrical foci, which is going to decrease the heart rate in a 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 or flutter. And it would also be great in another type of situation where maybe the re-intra-circuit is actually present in the AV node. So another one could be supraventricular tachycardia.

So these are two particular indications, in particular tachyarrhythmia. where I'm going to inhibit this tachyarrhythmia. So this is why I'm gonna utilize these particular drugs. I'm going to inhibit these particular supraventricular tachyarrhythmias, such as atrial fibrillation, atrial flutter, and SVT, like an AVRT or 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 AVNRT 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. effect. It's going to inhibit the AV node conduction and inhibit the SA node as well.

That's a great situation where I would love to utilize this drug. The next situation, let's say that I have somebody who we look at it like this. Okay.

Here we have a blood vessel. Alright, I'm going to look at it like this. Here I have a blood vessel. And in this blood vessel I'm going to 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. 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, in some cases, you're going to have a more severe increase in demand for whatever that reason may be.

certain situations what I can potentially do is I can potentially help out because there is 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 O2 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 demand and increase supply.

That's kind of the natural kind of thing that you want to have here. So what 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 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 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 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 gonna 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'll also reduce the oxygen demand.

Well guess what? I have drugs that can actually do that. Metoprolol, Esmolol, Bisoprolol, Acebutyrolol, and Atenolol. 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 block. blocking them and it's 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 beta ones is an atrial flutter Atrial fibrillation SVR SVT to inhibit the AV node conduction.

I have angina and coronary artery disease because it's going to decrease the O2 demand by decreasing heart rate 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 tiny? That's called a left ventric. 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 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 is your septum. When the muscle is kind of bulging out like this, it's because it's intensely contracting. So when it's bulging out like this, it's going to increase the left ventricular outflow 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 ...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 contractility.

And if I inhibit contractility, what am I going to do? I'm going to decrease the effect of the left ventricular outflow tract 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 opened up more now. And now that that thing's opened 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 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 tracts 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 a second to fill, it might fill 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 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, 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 to 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 tract obstruction and improve the the 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-1 blockers, selective ones, cardio-selective, and reducing supraventricular tachyarrhythmias, 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 in tachyarrhythmias, such as AFib, AFlutter, SVT. In situations where patients have reduced supply due 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 the cardiac output. And so their oxygen demand decreases and you can still help to prevent that patient's chest pain. 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 longer filling time.

These both... relieve the obstruction and help with hypertrophic cardiomyopathy. Alright, now let's come on to the last indication here which is heart failure and post MI. Alright my friends, so now last situation here that I want you guys to think about.

If a patient 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 muscle is 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 that there may be a reduction in cardiac output, right? That's the overarching theme. A reduction in cardiac output due to heart failure, 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. If I don't perfuse the kidneys very well, they pick up on that sense.

And they say, hey, hey, 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 that this is going to work to increase the patient's blood pressure via angiotensin II. We know that all of this is going to increase blood pressure. couple different ways.

One is angiotensin 2 because it 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 what does that do to the actual left heart?

The left heart's like, oh, dang it, 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 to think about. about it increases your systemic vascular resistance which could increase your blood pressure but it also increases your afterload because that this can lead to left ventricular hypertrophy so now the left ventricle is gonna get all thickened up now so because that if I 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 afterload due to the Renin-Age-Attention-Adustrin system is gonna cause left ventricular hypertrophy. The other concept here though, which is really interesting, is that the renin-angiotensin-aldosterone system also increases preload.

And the way it does is by increasing sodium and increasing water. And if you increase 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 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.

Alright, so here we're going to have dilation. Now, the other aspect behind this is that whenever you have a reduction in cardiac output, you act on those chemoreceptors. I'm sorry, baroreceptors.

I apologize. Baroreceptors. And when you stimulate the baroreceptors, I'm going to put stimulate the baroreceptors, 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 and then your sympathetic nervous system will then activate the sympathetic nervous system 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 onto 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 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 dilation. in particular hypertrophy as well.

So it's important to be able to understand that this can also cause changes, a remodeling of the heart if you will. The other thing is that it's gonna 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 mass... sympathetic surgeon, renin angiotensin, aldosterone system, 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?

When I gave a beta-1 antagonist or a beta-1 blocker, I'm going to do what? Patient has heart failure, post-MI, reduce their cardiac output. They have less effect on the baroreceptors, they stimulate the baroreceptors.

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 ranonidriotansin aldosterone system.

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 left 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 hyper chafin dilation and I'll also again not as much here on the alpha-1 receptors but again you get You get the point that 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.

So beta blockers are actually great in patients who have heart failure. or a 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, carvedilol, but the commonly utilized ones in these particular diseases are going to be like metoprolol.

Metoprolol, Esmolol, 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 antagonists. Now, what could be an adverse effect that I want you guys to think about? Since these affect the cardiac output, they affect the heart rate, 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 a potential side effect out of this?

A potential adverse effect could be bradycardia. The other thing is you should reduce cardiac output potentially, right? 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 and 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 decompensated heart failure and they're already and 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 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 who's super bradycardic as well. because that might be an adverse effect. Decrease the drug dosage or hold the drug dosage, 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, Zach, 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 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 the 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 acebutylo, atenolol, esmolol, bisoprolol, and then metoprolol. Those are the big ones. So A to M. For these ones, you can think about those from N to Z if you want to.

So this includes particularly natolol. So natolol. This also consists of another drug called temotrolol.

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 can think about this from if you really want to in to Z. So again, we got natalol, temolol, propanolol, with the most commonly utilized ones you're going to see on this board here being propanolol. Now, with these drugs, you got to think about, again, some of the receptors.

So the beta-1, beta-2 receptors, 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-1 receptors on the pupil. So that's not going to be the particular fan here. It's going to be the beta-2 receptors on the ciliaris. Now the ciliaris has little processes that actually secrete aqueous humor, right?

So if we have a beta-2 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 dec... ...crease the aqueous humor 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.

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. 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 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 Timolol as the primary one that is utilized in what type of situation here we primarily use Timolol 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 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 is this disease here called 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 large amounts of T3 and T4. lots of that hormone. Now we know that there's a lot of other effects that we've talked about in the hyperthyroidism lecture, but one of the 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, cardiac cells, what I want you to do is I want you to increase the sensitivity and the number. of beta 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 response.

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 one 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 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 propranolol. 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 this situation of propranolol. Because not only... does thyroid storm really increase the amount of sensitivity of just the beta 1 receptors that increase the sensitivity of a lot of the beta receptors and alpha receptors and so giving propanolol 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 during thyrotoxicosis so we can give what type of drug we can give a drug here such as propanolol because what perpantelol is going to do is perpantelol 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. And so that's another potential benefit.

Okay, the next concept. So we got propanolol 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.

In a disease called portal hypertension, which can have a lot of different etiologies like cirrhosis or 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 rupturing.

All right, so these are called varices. And so we don't want 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.

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 propanolol comes into play. So propanolol is really really cool because it does a couple different things. One of the benefits of Propanolol 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 gonna reduce the blood flow or the perfusion to different particular organs. And one of the best situations here is 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 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 that does is by reducing the splanchnic blood flow, you reduce the portal. vein blood flow. And 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 about propranolol. Propranolol 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 vasoconstriction. So if I cause vasoconstriction of these blood vessels, I increase systemic vascular resistance, and therefore reduce splanchnic blood flow. Reducing more flow through the actual splanchnic arterial system and subsequently, less blood flow through the portal venous system, less blood within that circuit is gonna reduce the portal venous pressure.

So this is a prophylactic therapy in portal hypertension. So remember, it's primarily prophylactic. All right, another benefit of perpantelol, you're going to see that pretty much perpantelol is going to be for one, two, three, four. All right, here's another thing. We have beta-2 receptors that are present on some of the blood vessels that go to the circulatory system in the brain, right?

So let's say that this is going to 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 denote these here in like this purple color here. 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 overstimulate the pain receptors within the dura mater, the meninges.

And one of the reasons is these blood vessels could be a little bit dilated. All 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. If you're stimulating the pain receptors, that's going to produce pain, therefore migraines. If I give a drug like propranolol, 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 Imagine it like this. Here you have your blood vessel. Here's 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 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 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 propranolol.

So don't forget perpanolol 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 beta-2 receptors?

And so we have these beta-2 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 going into your muscle and cause it to contract.

And that can produce tremors. So the effect here is that it actually may cause a little bit of a tremoring activity if you over-stiffen. 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 that beta-2 stimulation, we can give a particular drug to block the beta-2 receptors, inhibit the excessive contraction, reduce the afferent signals, reduce the efferent signals, and reduce some of the tremoring effect. And so if I give a drug like propanolol, 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, natilol, temilol, propanolol.

Most commonly utilized one within this category is gonna be propanolol. 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-1. That was just one of the examples.

It can inhibit a lot of the other beta-2 receptors. Guess what else patients have during thyroid storm? Tremors. So guess what else propranolol could also do if a patient has thyrotoxicosis? Reduce some of the tremor effects because it can hit the beta-1 receptors in the heart and the beta-2 receptors in the muscle spindles.

So you see the whole point. That's why propranolol 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.

tension. It also can be utilized in migraine prophylaxis, and it also can be utilized to reduce essential tremors. And then lastly, don't forget Tenolol because it can reduce aqueous humor 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 one and beta two. 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 heart rate so they can really cause bradycardia these can do that as well but they also hit the beta-2 receptors and so because they hit the beta-2 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 gonna see more bronchospasm with these particular drugs then you would with the beta-1 receptor because they are gonna hit beta 2 and so they're gonna block block those and cause bronchoconstriction. 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 agonists 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 those love both beta-1 and beta-2, 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 labetalol. This is a pretty commonly utilized drug and another one is called Carvada Law. Now there's another drug, I'm just going to briefly mention it.

It can actually be kind of considered to be utilized or kind of considered similar to these particular drug categories. I'll talk about it in just a little bit. And it's called Nabivalol.

Nabivalol doesn't actually have alpha blockade, it's a weird one. Nabivalol, I want you to associate with nitric oxide, nabivalol 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 nabivalol. So remember it increases nitric oxide so it does have beta blockade and increased nitric oxide which causes vasodilation.

but it does not have alpha blockade. So just remember that one. All right.

Coming back to LaBetaLongCarbetaLong. 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 one receptors on the heart. And you also have alpha receptors that are present here, my friends, on the veins and alpha receptors present on the lungs.

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 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 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 or 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 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 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 actually seems that labetalol may be more superior. So labetalol may be more superior in the comparison between these two. So labetalol may be greater in efficacy than carvetalol. 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 carvetalol. Carvetalol is actually preferred over over labetalol as compared to in a patient who has hypertension labetalol 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 is a reduction in cardiac output the 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 renin-angiotensin-aldosterone system, what does that do? It increases your systemic vascular resistance and 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, you're increasing afterload, you're increasing preload.

We already talked about this a little 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 is low because remember it activates the...

the baroreceptors. So the baroreceptors 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 GG 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. And then again, increase the systemic vascular resistance. And we already know what that did. We already talked about it up there.

So it'd just be the same as a... It's going to increase afterload causing left ventricular hypertrophy and increase blood pressure causing left ventricular hypertrophy. 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. I give a drug like labetalol or carvetalol, what am I doing?

I'm blocking the beta receptors that are present on the JG cells. Therefore I will inhibit the renin-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... to stretch out. I'll also inhibit the beta receptors on the heart, which is going to cause, again, this 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 then over time, dilated. And then 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 actually increase mortality. So giving these drugs have been shown to decrease mortality, and that's why we give these particular drugs. this scenario. All right, my friends.

So we got hypertension. Oh, and then really good here. What do you think a libido law would be preferred 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. Labetalol is also a good one for preggers, for patients who are preggo and hypertension type of situations as well as hydralazine and nifedipine.

Alright, 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 situation is Carvetalol.

Now let's quickly get to the point here. to the point here. Carvatalol 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 arterioles. 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 decrease heart rate. You decrease cardiac cardiac output, you decrease the splenic 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 beta-2 is supposed to relax them. You're going to block that effect. And that is going to, again, reduce the splanchnic 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, 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 Labetilol, interestingly, but Propanilol, Carvedilol, we utilize these as a prophylactic therapy in patients who have portal high hypertension to prevent esophageal varices, and subsequent upper GI bleeding. Carvedilol would actually seem somewhat superior though if you think about it, because you hit both beta receptors to reduce splanchnic 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 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 drugs libator law carvator law now Now, and then we also briefly talked about nabivalol, which again is similar to them, but it doesn't actually block alpha receptors. It has nitric oxide synthase types of activities where 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 one receptor, 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 beta two receptors that we talked about above. So because of that, you can see bronchospasm, you can see hyperchloroquine, You can see hypoglycemia and hypoglycemia unawareness. But the other thing is that you block alpha receptors.

So you're going to get some of the effects of the alpha blockade. What 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 the venous return, and that can actually drop the patient's blood pressure when they go from a kind of like abrupt seated to a standing position or laying down flat to a seated position. 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 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 whiteboard and talk about that all right so with the beta blocker overdose 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 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 metoprolol, asmolol, bisoprolol, propranolol, 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 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 that 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 drop that. cardiac output it 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 antagonists okay next situation here the lungs which kind of receptors are here being a two receptor so you're gonna You're going to see this more with the propranolol, the natalol, temolol not so much, but you can also see this with the betaloncarbetolol. Now the reason why is because those hit both beta-1 and beta-2.

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. And if I cause intense bronchospasm, that's a terrible situation, especially in particular diseases.

So I'd really want to be careful in utilizing drugs that have beta-2 blocking systems within COPD, and I'd really want to be careful in utilizing this in patients. patients who have asthma, some type of reactive airway disease, because if I bronchospasm them 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 and the pancreas, especially with the glucose system. So there's two-fold 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 blockers, blocking type of activity, you're going to see a natural potential, very minor, not significant, but 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 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 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 in 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? 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 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.

All right, the next thing which is also really important is we have beta two receptors on pretty much every single cell in our body that is regulating the act 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 beta-2 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 one. If it inhibits the beta-2 receptor, I inhibit the sodium potassium pump.

If I inhibit the sodium potassium pump, I don't pump potassium into the cell. So potassium won't go into the cell. If potassium doesn't go into the 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 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 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 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 patient becomes extremely hypotensive and bradycardic to the point of cardiogenic shock, you need to have some something that's 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 couple. All right, my friends, let's do some cases here on adrenergic antagonists. So the first one that we have here is a 60-year-old patient started a new antihypertensive medication.

His blood pressure is well-controlled. 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, guys.

So big thing here is that with orthostasis, we talked about this primarily with the alpha 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 postures.

changes when they get up out of bed. So it's oftentimes going to be an alpha-1 receptor blocker or antagonist. In this situation, which one do you think is an alpha blocker? Rheumatoprolol is primarily a beta-1. For Pantolol, it's non-selective, so beta-1 and beta-2.

Prazosin is an alpha-1 receptor blocker, selective. And then alphazosin, I wouldn't worry about this one. So again, it is definitely prazosin.

So prazosin 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 increase norepinephrine release from presynaptic nerve terminals and increase that flood of norepinephrine to the heart and the blood vessels.

So they're going to get hypertension. They're going to get tachyarrhythmias. They're going to get increased contractility. 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? 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, 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 nothing to oppose them. Because if you hit the beta 2 receptors, that's causing vasodilation. You're blocking those now. Now you can...

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 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 and phentolamine. We talked about that in situations of cocaine.

Usually it's second line or amphetamines, it's usually second line. But in this situation, prazosin is there, right? It's an alpha-1 blocker, right? But I didn't talk about prazosin and these kind of hypertensive crises related to a particular drug over time.

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 labetalol. Labetalol 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 labetalol is that it has a lot of alpha blockade, so it can really work to hit those alpha receptors. So I think really the best option here out of all of these.

Wouldn't be metoprolol because that's primarily beta-1. Prazosin, 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 phenoxybenzamine or phentolamine.

And then nabivalol, 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 because it can actually increase nitric oxide synthase. But there's no specific indication for that one that we discussed on the whiteboard. Labetalol 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. Alright, a beta blocker was prescribed for hypertension in a patient with asthma after a week of treatment to asthma attacks got worse and the patient 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 2, is remember we talked about these are your atenolol, asputolol, bisoprolol, azmolol, metoprolol. Those are the preferred ones. Propanolol, is definitely going to love the beta-1 just as much as it loves beta-2.

And labetalol and carvetalol also like the beta receptors as well. They can also hit beta-1 and beta-2 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 metoprolol has pretty much beta-1 and almost no beta-2. So metoprolol would probably be the best option here 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.

He complains of dizzy spells while getting up from the bed at night. 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 at the alpha blocker. So that leaves Tamsulosin and Terazosin. Phentolamine is not really one of those that we utilize for BPH and neither is Propanolol.

So it's definitely Tamsulosin and Terazosin. The question is, is which one of these has less of the significant effect of Tamsulosin? 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 type of orthostasis with Tamsulosin compared to the other types of Alpha-1 blockers. So Tamsulosin would be the preferred. All right. 50-year-old male was in anaphylactic shock after being stung by a hornet.

The medical team tries to reverse the bronchoconstriction hypotension using epinephrine. However, the patient is not able to do so. 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 that contributed to reduce 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 hit beta-2 receptors and block those.

And we need drugs that can block potentially the beta-1 receptors. also on the heart. So maybe it blocks the beta-1 receptors on the heart, and maybe it even hits a little bit of 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-1. Propanolol 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. pressure. It also has beta-2 receptor blockade, so it can actually 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 propanolol 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 acebutyrolol, it's primarily beta-1. So that leaves me with propanolol is the likely option here. All right, next question, which of the following is 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 prosthetic hyperplasia that's definitely true the reason why is if we think about these again this is your tansylosin Prazosin, prazosin, 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 the internal urethra sphincter constricted and tight, which prevents us from being able to 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 actually. untrue.

It actually can cause reflex tachycardia. And alpha-asinogenic blockers reduce the frequency of urination. That's actually untrue.

It actually increases the frequency of urination because, again, you're relaxing the urethral sphincter and allowing for urination to potentially occur. So I would say that the correct answer here would be would be B. All right, next one.

Which of the following is correct regarding beta blockers? Treatment with beta blockers should not be stopped at abruptly. That's 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, if you stop it, let's say that you have 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 heart rate, increase your blood pressure. And so because of that, these patients would develop a rebound tachycardia and hypertension. So that's definitely true.

Propanolol is a cardioselective. That's not true because remember it loves beta one and beta two. So it's a non-selective beta blocker. Cardioselective beta blockers worsen asthma. That's not true because if it's cardioselective, it's beta one.

So it can't worsen asthma because the bronchioles are beta two. And beta blockers decrease peripheral. resistance by causing vasorelaxation.

Technically, there's beta-2 receptors on the blood vessels, right? So if you give a drug and beta-2 receptors on 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 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 is commonly used topically in the treatment of glaucoma? Remember I told you that this is the answer. specifically going to work on the beta-2 receptors on the ciliaris to help to, generally, what do these things do? Generally, whenever you give these drugs, beta-2 receptors on the ciliaris, whenever they're stimulated, they help to increase the aqueous humor production.

If you give a drug that blocks the beta-2 receptors, you won't make aqueous humor. You'll decrease its production, which can 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 ortho? orthostatic hypotension when given together with prazosin?

That's a great question. So prazosin 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, 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.

Propanolol, beta one, beta two. Atenolol, primarily beta one. Labivolol, it's beta 1, beta 2, but it doesn't actually hit the alpha receptors. Remember, it increases nitric oxide and synthase, which can cause vasodilation.

But that's not specific to the actual veins. It's more specific to arterioles. Labetalol does have beta and alpha blocking effects.

So it would hit the alpha receptors on the veins as well. So labetalol is definitely the likely alpha blocker here. That's the only alpha blocker. So I'd say labetalol would be the correct answer. All right, my friends.

So that covers this video here. here on adrenergic antagonists. I hope it made sense. I hope that you guys liked it. And as always, until next time.