DIP Episode 472 - Alpha-2 Receptors and the USMLEs (Step 1-3)

Welcome, my name is Divine. This is episode 472 of the Divine Intervention Podcasts. In this podcast, we're going to be continuing with our review of the Adrenergic Receptors. We're going to spend any time today on the Alpha 2 Receptors. So let's just get right into it. So the thing is, as I mentioned earlier on, all the Adrenergic Receptors are G-Protined Coppile Receptors. In the case of the Alpha 2 Receptors, they are in the Hibiteri G-Protined Coppile Receptors. So basically, what do they do? They essentially decrease the activity of Adrenaline Leads Cyclades. If you decrease the activity of Adrenaline Leads Cyclades because you're in the Hibiteri, you'll have less conversion of ATP to cyclic AMP. And with less cyclic AMP being made, you'll have less activation of Protein-Kinase A. If you have less activation of Protein-Kinase A, then obviously that probably tells you that, oh, I'm going to have less phosphorylation. So the Alpha 2 Receptor, when you take something that activates it, you're going to have on the whole net, like a net decrease in phosphorylation. So for example, like things like that depend on phosphorylation, like glycogen phosphorylation. The glycogen phosphorylation is an enzyme that helps you break down glycogen. It's not going to be activated because glycogen phosphorylation is active when phosphorylated. But here, it's not going to be activated. So since it's not going to be activated, it's not going to work as well.

So you're not going to have a breakdown of glycogen. Okay, just the thing is, if you just understand this concept of less phosphorylation, it can help you predict many things in biochemistry. Biochemistry is one of these things. Probably seen from a biochem video where it's based on rules. If you understand the rules, you understand the principles. There are many things that people memorize that you can very easily predict. Like you can, on your own, literally build out the different biochemical actions of the Alpha 2 Receptor. But again, that's not the goal of these podcasts. We're going to go ahead and move on. Now, this Alpha 2 Receptor, one of the critical things about it, and again, I'm going to make integrations with the USML events. Again, because this podcast is intended for putting in step one or the way to step three. But let's just get some quick, basic science things out of the way, right? So this receptor is also presynaptic. It's a presynaptic receptor. Because remember, in the nervous system, we have a synapse. The thing that comes before the synapse is presynaptic. The thing that comes after the synapse is both synaptic. Many times, at the synapse, the presynaptic cell on Neuron will release a neurotransmitter that then acts on the thing that is both synaptic. The thing that's both synaptic can be a Neuron. The thing that's both synaptic can be an organ. So just something you want to keep in mind there. So this Alpha 2 Receptor is presynaptic. It's presynaptic.

And the thing is, because if you think about it, you know, these are the energy synapses. You're going to release calycholamins like Noripinephrine. When you release that Noripinephrine, it does its job. But it's almost like Noripinephrine's self-regulates itself. Because think about it. Noripinephrine is like adrenaline. It's like big time adrenaline. Or, you know, if we're being more accurate, we're going to call it Noripinephrine. So that Noripinephrine, you know, it can really amp you up. So you want to have a little pump the brakes on that. One of the ways you can pump the brakes on that is by that Noripinephrine, as it's been released, self-regulating itself by binding to the Alpha 2 Receptor. When you bind to the Alpha 2 Receptor, it does going to decrease further release of Noripinephrine. It does going to decrease further release of Noripinephrine. So it's almost like a negative feedback inducing receptor. When calycholamine binds to it, it's going to prevent further release of Noripinephrine. Now, one other thing I want to say about the Alpha 2 Receptor is that it actually facilitates cognitive functions of your prefrontal cortex. So I just like to think of it as basically helps you be more focused. It helps you be more attentive. That's something that you're going to see with this Alpha 2 Receptor. So we find it a lot in the prefrontal cortex. So why is this important?

Well, the thing is, decreased activity of the prefrontal cortex has a pretty good, low cortex, has a pretty strong association with ADHD. So it should also surprise you that, hmm, maybe if there's something that activates Alpha 2 Receptors, it will be a good ADHD drug. For example, something like clonidin. In fact, the Alpha 2 agonists, they are used as third-line agents for the management of ADHD. I'm going to talk about that in a little bit more detail as we go along. Because as many of you know, friends at the NBM Es with psychiatry, they love you to know certain neural anatomical associations, right? Like schizophrenia and an increased size of your lateral and third ventricle. You know, just many different things. So like, where are any keys and hemorrhagic infarctions of the mammillary bodies? These things are kind of important to know. So you want to know that ADHD has an association with decreased activity of the prefrontal cortex. So if your prefrontal cortex were to work better, by you giving an Alpha 2 agonist, that would relieve symptoms. Now, some of you may wonder, okay, divine, how this helped? Let me give you a teleological explanation. What do I mean by teleological? This is a concept I learned in college. This, I don't know if what I'm teaching you for this part is factually true. But I think it will just give you like a logical way to reason through this. I just like to think of it this way. When people are really amtop, they make like a lot of mistakes.

They're not able to focus, right? When they're really amtop, their heart is racing, they're not able to focus. But if you're calm, you're able to be more aware of your surroundings. You're able to focus more, focus better. So an Alpha 2 agonist is going to decrease the production of neurobenefery. If you decrease the production of neurobenefery, then you have less of an amp up neurotransmitter. So that's going to calm you down. If you're calmer, you're probably going to be able to focus better and be more attentive. That's the truth, right? Like a person that's driving slowly on the highway is going to be aware of all the speed limits and all those signs, right? But a person that's like super amtop like higher on something, they probably won't see anything. So that's just a nice way to think about it. That's what I mean by my teleological explanation. Now the thing is this explanation I'm giving may actually be physiologically accurate, but I don't know. At least I've never seen anything like that. So take care of what you will. But the reason it should help you logic your way through this business with a prefrontal cortex. Again, I know some people may be like, well, I'll define you really, really spending time with this prefrontal cortex. I promise you, it's not loyal at all to know for, for example. Okay. So now that we've talked about this, then let's start going into integrations, right? I'm sure the people taking step two, step three.

And also step one, you know, they'll be very interested in this in this part. So what if they give you a question about a person and this person, you know, they tell you that they have trouble seeing out of their sides. And this is a person that's like a diabetic or chronic steroid user. Well, the very first thing you want to be thinking about is local memory, local, but one of the things you lose first is your peripheral vision. So one of the things you lose first, especially in, you know, that open angle or common, you're going to lose your peripheral vision first. One of the ways you can fix glaucoma is by giving an alpha to our canist, like aproclonidine or brymonidine. Aproclonidine or brymonidine because the thing is your sympathetic nervous system is utilized in making a cure's humor. So again, if you think about it, if you make a lot of a cure's humor, that's going to increase your intracurricular pressures and that's going to cause glaucoma. Again, the way I think of it, like logically that, oh, why would a sympathetic system make me make more ekeous humor? Well, think about it. When you're in a hyper sympathetic state, one of the things that happens is you're going to help popularize my dry asses. I just kind of think of it like you want your eyes bulging out so you can see whatever lyre that's chasing you better. So if you could dumb down the sympathetic nervous system, because if you think about it, if you made more ekeous humor, your eyes will bulge out more.

If your bulge is out more, you probably have my dry asses from that. So if you were able to dumb down the sympathetic nervous system by giving an alpha to agonist, like aproclonidine or brymonidine, you make less nerve-racking, you have less sympathetic activation in the eye and that would help with glaucoma. And then the second thing I would say here with regards to these alpha to drugs, especially the agonist, focusing on the agonist now, again is this increased activation or increased activity of the peripheral cortex. Again, I kind of explained that already. So this kind of explains why the alpha to agonist can be used as like third line agents for ADHD on exams. Because remember, under USMLE's for ADHD, we tend to use like methylphenidate, Dix-Trumphetamine and whatnot. We can use that to mock the team. That's like a non-stimulant. Obviously methylphenidate, Dix-Trumphetamine, those are stimulants, atomoxetines are non-stimulant. But if you're going third line there, I want you to think more about like an alpha to agonist, like clonidine or close causing known as guanfacin, guanfacin, G-U-A-N, F-A-C-I-N-E. I know some people may be pulling out their hair that divide their other alpha to agonist that are useful to this purpose. But honestly, the USMLE is usually focused mostly on clonidine and guanfacin. But that's not always clonidine. Clonidine is also used to control blood pressure, right? Because again, think about it.

Your sympathetic nervous system has alpha on receptors on blood vessels. When Narbin-Ephrine stimulates those alpha on receptors, that's going to cause a viso-constriction and raise your blood pressure. Well, if you think about it, if clonidine is an alpha to agonist, then it's going to decrease your production of Narbin-Ephrine. So think about it. You're potentially reducing the synthesis of a neurotransmitter that stimulates alpha on receptors. That's going to cause a net viso-dialation, right? And actually believe it or not, there are alpha to receptors literally on your blood vessels as well. There are literally alpha to receptors on your blood vessels. So the lower blood pressure, they're going to cause a lot of viso-dialation. Well, if you think about it, if you're causing viso-dialation, how do you think your heart is going to respond? Your heart is going to ideally respond with a reflex-dialation. Which makes sense, right? Because when you viso-dialate, like that, your blood pressure drops. So your borer receptors are going to be like, wow, why is my blood pressure dropping so much? So they're going to talk to the brainstem and they're going to get a sympathetic discharge to the heart. And that's going to cause you to make your heart go faster, right? Just as a nice general principle, if you're taking a viso-dialiter, you're going to get a reflex. You're going to get a reflex-dialiter as a result of that. Yeah, it's just a general rule. I mean, like think about it.

Like, if for example you want to give a woman a topoletic to try to reduce labor or, you know, shut down labor, especially after 32 weeks, we use my fatty pin, right? Well, my fatty pin is a very, is a calcium channel blocker. It's a dihydroperiodine calcium channel blocker that's going to cause viso-dialation. But again, as you get that viso-dialation, you're going to get a reflex-dialiter from that. And the reflex-dialation sometimes can be quite unsettling to a patient. And then another use for clonidine is we actually use clonidine for opioid withdrawal. Again, the thinnest opioid withdrawal is not fitter, unlike withdrawal from alcohol or benzoes or, you know, barbiturites. But opioid withdrawal doesn't feel good. So one of the ways you can treat it is with clonidine. So you may wonder, divine, why will clonidine help with opioid withdrawal? Well, what we've been here for a second. The first thing to keep in mind here is that is this. How do opioids work? Opioids work on the mu receptor. I mean, there are others, but the one we're going to focus on today is the mu receptor. And that mu receptor, the leveter or not, is an inhibitory-g-protein-copyut receptor. Well, hello. Is there any other inhibitory-g-protein-copyut receptor we've talked about today? Well, I don't know. Maybe the alpha-tore receptor. So the thinnest they are both inhibitory-g-protein-copyut receptors.

And as it so happens, when opioids stimulates the mu receptor, which is an inhibitory-g-protein-copyut receptor, you're actually going to get less release of norepinephrine. I'm going to say that again. You're going to get less release of norepinephrine. So basically, when opioids activates their mu receptors, that decreases norepinephrine release. So if you think about it, if you have less release of norepinephrine, then like I've mentioned earlier in this podcast, you have less sympathetic activation in the eye. Because remember, in the eye, the sympathetic system causes my dryness. Well, if you have less sympathetic activation in the eye, because you're releasing less norepinephrine, you're going to have a necmeiosis. You're going to have public reconstruction. So if you're following along with me in this podcast, you can see why opioids cause pinpoint pupils. They cause pinpoint pupils, because they literally decrease the production of norepinephrine. So there is less sympathetic activation in the eye. But again, as you're seeing, if opioids work by decreasing norepinephrine release, and you're withdrawing from opioids, then it would make sense that maybe you can give another drug that acts almost identically to an opioid, but just works through a different receptor. Voila! You have an alpha to agonist. That's why cloning is very, very helpful in treating opioid withdrawals. Actually, very, very effective in treating opioid withdrawals.

If I'm remembering correctly, I think when I was a medical student, cloning can become a street drug where I went to medical school. Because if you were withdrawing from opioids, it won't feel as bad. Again, just something I want to keep on the back of your mind for exams. So I think I'm going to stop there with clonidine. I think those are kind of like the important things too. No, but the thing is there are just so many USMLE stories that I can bring with clonidine. And honestly, again, I'm just telling those of you prepared for the USMLE exams. Make sure you're learning these stories. The thing is the USMLE is, and all the USMLE is, I integrate the exams. Really try to see if you can see things in multiple dimensions. Again, I'll just promise you, this clonidine and opioid withdrawal, that's a classic concept that can be tested on an exam. Now, let's keep going with these alpha-2-agginess cells. We're almost done with those. Another one is dex-medit-tomidine. Dex-medit-tomidine. It's kind of a fancy sounding drug, a DEX, MEDE, TOMIDI-ini. If you're going into anesthesia, and an anesthesiologist, or you're working an ICU, you're probably familiar with this drug. It's the drug called Precied X. Again, this drug is an alpha-2-agginess, and it's very good for sedation. Again, think about it. If you're not on top, you will calm down. So it would make sense that this can be a very good, useful anesthetic. Actually, there are some anesthesiologists that just love this stuff.

So I see you attending, so just love this stuff. You know, because it's just pretty good. It's pretty well. I just don't think it has as many issues as some of the other things that I used to as sedate people. Okay. And then the final one I'm going to talk about is a methyl-dopa. Methyl-dopa is a drug that you kind of need to know, for example. It's a drug that's a good anti-hypertensive, especially in pregnant women. It's used as an anti-hypertensive in pregnant women. Because remember, some of the classic anti-hypertensive we use like e-synhybitres and arbors that are terrible things. They can cause like renal damage in the fetus. So when you're pregnant, there are certain drugs we love for hypertension. You know, we can use things like hydrozene, methyl-dopa. We can use labidolol. We can use myfetypene. There's a nice moniquid that that hypertensive moms love myfetypene. So the H for hydrozene, the M for methyl-dopa, the alpha labidolol. And then myfetypene, myfetypene. But I'm going to focus on methyl-dopa because methyl-dopa is an alpha-2-agonist. So again, if you're an alpha-2-agonist and you decrease norepinephrine production, again, you've got to have less stimulation of the alpha-1 receptors on your blood vessels. That's going to cause viso-dialetions. It's going to help with your blood pressure. Although to be honest with you, the blood pressure lowering effect of these alpha-2-agonists goes beyond the fact that they just decrease the production of norepinephrine.

There's some other deep pharmacology there that you very likely don't need to know for your exams with like, I mean, the Zolian receptors and stuff. But I wouldn't worry about any of those. But I'm just going to say it out here so that you kind of just have it in your mind that it's not only that decrease norepinephrine production business that results in alpha-2-agonist lowering of blood pressure. But with this methyl-dopa, you know, what if they tell you about a pregnant woman that takes methyl-dopa because she has like gestational hypertension or something or hypertension of any sort. And then you notice that she starts having a joint pain, millerash and all those things. That's going to be drug-induced lupus. That's going to be drug-induced lupus. Drug-induced lupus, remember it's associated with these anti-histone antibodies. Methyl-dopa certainly has an association with drug-induced lupus. Although if you're asking yourself, man, define what are the most common causes of drug-induced lupus? The most common causes of drug-induced lupus are going to be hydrozene and porcane mitre. I just think of HP. That's an easy way to remember those. HP, you know, like the computer-producing company, so like Hylid-Pacard, so the H-think of hydrozene and porcane mitre. Those are the two biggest risk factors in general for drug-induced lupus. They can literally make it a risk factor question. And as many of you know, risk factors are very heavily tested on the USMD exams.

That's where I have so many podcasts on them, right? Like episode 37, 97, and 184. Okay, so go ahead and wrap this series up. Let's go ahead and talk about the alpha-2 antagonist. So the alpha-2 antagonist, there's not as many alpha-2 antagonists, at least that are necessary to know for the USMD exams, as there are agonists. So the antagonist, the first one I'm going to talk about is metasapine. Metasapine, we use it a lot. It's actually a pretty good antagonist present, and it getting worked by being an alpha-2 antagonist. Because remembering depression, there is this thing known as the calycolamine hypothesis of depression, that people that have depression tend to have low levels of neuro-beneferent. So if you give an alpha-2 antagonist, because remember the alpha-2 receptor, I said if you stimulate it, you make less neuro-beneferent. So if you block it, you should make more neuro-beneferent, right? So metasapine in a sense kind of boosts your levels of neuro-beneferent. And you may wonder, divine, like when are we ever going to use this in depression? Well, because metasapine helps with appetite, and it helps with sleep, if a person has depression on the USMD exams, and the person just has really bad insomnia, metasapine is not a bad idea for these people. Or you say a person that has depression, and they have an anorexic component to their depression, they are not eating well, metasapine is going to be a very, very good choice for these people.

The thing is, that's why you see sometimes I tell people this, I can't just blindly memorize stuff as you're preparing for your USMD exams. Again, there's nothing wrong with memorizing, you just again need to have some context. Like, oh, divine, is it every depression question I see on my USMD exams that will make me pick an SSR as an answer? No, even if SSR rides are generally the first life of a contherape for depression, it doesn't mean they always the right answer. The thing is, one of the ways the USMD is creates questions, is they just create a bunch of contraindications, or they create a bunch of extra indications. Like, for example, if a person has depression, and then in the question they're just like, how are you aware how this will have awful sleep? They have like really bad insomnia. Maybe it's better to give them metasapine than any other kind of anti-depressant. And that good claim to fame of metasapine is it doesn't have sexual side effects. Like, we see with some of these anti-depressants like SSR rides, SNR rides, those things can all cause a sexual dysfunction, not so with metasapine. I remember the other anti-depressant that doesn't have that sexual problem is a propion, right? A propion that NDRI, the North American Aferino Paving, reoptica inhibitor.

And then the next problem, I'm going to, series of drugs I'm going to talk about, I'll give you a question about a person that has this episodic headache, hypertension, and the tell you that the metaneference is elevated. This is going to be a few chromosythoma. For patients, a few chromosythoma. Well, one of the critical things you should probably be aware of is that those people should get surgery at some point. But before they get surgery, you want to give an alpha blocker first. An alpha blocker first, and then a beta blocker second, they didn't take them to surgery, right? You don't want to give the beta blocker first, because the alpha one receptor will be wide open. And when you stimulate that alpha one receptor with the caracolomines, being released by the phyocromosythoma, that can cause that on opposed alpha one activation, you'll get like a massive vasoconstriction in your body, massive hypertension, and probably die. You don't want that. So you're going to give an alpha blocker. Well, you can use really any alpha blocker, even something like Prasosin, for example. But many times on the USMLE is they love these drugs, Phentolamine and Phynoxybenzamy. These are nonselective alpha blockers. So they block both alpha one and alpha two receptors. Okay? That's why I'm discussing them under these alpha two antagonists. They block alpha one and alpha two receptors. Phynoxybenzamy is an irreversible alpha one and alpha two blocker.

Phyentolamine is a reversible alpha one and alpha two blocker. Honestly, you know, this alpha two podcast, you know, it kind of sounds like alpha two receptors who cares. But I mean, look at all the things that are potentially testable from this stuff. Again, don't sleep on this material. I promise you these are adrenergic podcasts. They're pretty high, high yield. So I'm going to go ahead and stop here. I also want to want you to rain for step one to step three. I have review courses for step one to step three. You know, I have bio stats classes. I have a social sciences, quality improvement ethics, health care systems class, communications class. That's a five hour class. I have a test taking strategies class. I have a 25 hour step one review on a 20 hour step to step three review. Again, many people have taken these classes and done extremely well. I know that there was this big score dump from the NBM is yesterday. And I got a lot of emails from people taking these that have taken the two of these classes and, you know, got in the 260's very, very high scores. So again, these classes do make a difference. Even if you take them, I mean, I usually try to recommend that you can really take them any time during your dedicated period. I've literally had people take it like they're like, OK, I have been doing audio from my dedicated period.

Let me just try this last ditch effort right before my test to see if anything happens and the took that leap of faith and that faith was very well rewarded. So again, if you're interested, I made like a pretty detailed podcast on that. I believe that maybe a deal to ago just listen to it to give you all the details on the classes. And then I help with applications, you know, airs apps, supplemental apps, personal statements, mocking reviews and things like that. And then I have this podcast on Apple Google and Spotify, the podcast apps for those Apple podcasts, Google podcast, Spotify. And then I have another, I have a You Tube channel, the Vine intervention, USM, Elite podcast and videos. That's where I post the videos that I make. And then finally, I have another website called a divine intervention, life lessons, calm. From a bibliocoperspective, I had dressed certain life lessons. I try to post two podcasts every week, have more than 200 podcasts on there right now. There's actually an Apple podcast associated with that called the divine intervention, life lessons podcast. Again, many people have used that stuff, funny to be really helpful. Basically, here's what I'm going to say. I want to talk about a quick life lesson today. The life lesson I'm going to say, and before I see this life lesson, please, this podcast for test prep purposes only and you might reach me very, and this podcast are not created for clinical decision making.

So my life lesson today is just the importance of focus, the importance of focus. The thing is there are many people in medicine and health care that just very on focus. Just in many things, you see people they go through a dedicated period and that dedicated period is done without focus. I'm like, oh, I see that my desk is studying for 10 hours a day. But if you really check their lives, they only get like four hours of useful study out of those 10 because their phones were there, they're seeing every notification, they're checking every email and everything. The thing is I've said this to many groups of people before, especially some large groups of people that multitasking is actually not a good life scale. That's the truth. Multitasking is almost like the antithesis of focusing. The thing is when you put your heart, your soul and your mind into one thing, you can usually do that thing with a lot of excellence. Again, this kind of sounds counterintuitive, but it's actually kind of important. It's kind of important. Like if you're doing anything, even the Bible says whatever your hands are trying to do, do it with all your heart. Put your focus into that thing you're doing. But you see people, they want to multitask, they want to be driving and checking their phones. They want to be driving and doing this. They want to be driving and doing that. And then they get in a car crash, they don't make it home. Die before they should die. Just things that are not good.

Or you see people in the hospital. To be honest with you, I see this because it's really sad sometimes how inefficient healthcare can be. You see people in the hospital, don't get me wrong. Hospital work is a lot. It's not like kick. It's not easy, easy work. But I can almost promise you that one of the reasons that people are very inefficient in their clinical duties, like residents, some residents are pretty inefficient. And again, I'm not saying this as someone that is just like saying it. This is something I've literally seen with both eyes. So I'm not saying that someone that doesn't know what I'm talking about. I mean, not about many parts of life, but I certainly know a lot about healthcare because I'm a physician as well. So I've seen this in the clinical environment. You see people, they come to work and they don't come to work with any kind of focus. They come to work and they spend all this time on social media, shooting some Tik Tok video, checking all these notifications, blah, blah, blah, blah. But then their core clinical work is just sitting down. And then patients that should be discharged and not discharged on time. You kind of owe it to your patients that if they don't need to be in the hospital, they should be out of the hospital. So just be focused in what you're doing. Like have a list of priorities and therefore each thinning your priority list, just focus on it. Like if for example, you're having leisure, then focus on your leisure.

Like you can have a dedicated period and say that you know what, I'm going to study for seven hours or eight hours. And that's it. It's better to study for a few hours, but really focus in those hours. I mean, it's going from like 10 to 12 hours and you're not focused for most of it. Right? The quality is not just the quantity that matters, but the quality is probably a bigger factor. So if you're in the kitty-pierre, then you say that you know what, I'm going to study till 4 p.m. every day. And then after that, I'm going to enjoy myself. Then that's fine. Study till 4 p.m. And then after that, focus on your enjoyment. Right? But just be, don't be a moment. I feel like there are very few things in life that multitasking is good for. You know, many times you want to walk a narrow way, a narrow way where you know, you're just focusing on one thing to get to where you really need to be. So just FYI, I'm just trying to encourage people because this is something I've seen so much, especially in this social media slash technology age, people are just horrible at focusing. They can focus for a few hours, right? They're like, oh, my attention span is 30 minutes. If your attention span is only 30 minutes, I'm really worried about you on your US Emily exams. Because the US Emily exams, at least step one is like a seven hour exam, step two is an eight hour exam.

If your attention span is only 30 minutes, you can be able to focus on those questions and not lose steam as you're taking your test. Where is enough for the wise? And I really hope you take this to harden kind of applied to your life. Okay, so I'm going to go ahead and stop here. I'll see you in episode 473. Have a wonderful rest of your day. God bless you and bye for now. Thank you.

G-Protein Coupled Receptors (GPC Rs).

It is a $\text{G}_{\text{i}}$-coupled receptor, which decreases adenylyl cyclase activity $\rightarrow$ less cAMP $\rightarrow$ less PKA activation $\rightarrow$ net decrease in phosphorylation.

They decrease norepinephrine release (via presynaptic negative feedback), leading to decreased stimulation of $\alpha_1$ receptors on blood vessels, causing vasodilation.

Apraclonidine or Brimonidine; they reduce sympathetic activity in the eye, thereby decreasing aqueous humor production.

Opioids act on $\mu$-receptors (an inhibitory GPCR), which decreases norepinephrine release. Clonidine mimics this effect by acting as an $\alpha_2$ agonist, reducing sympathetic outflow and stabilizing the patient.

Hydralazine and Procainamide (HP).

Inhibitory G-protein coupled receptor ($\text{G}_{\text{i}}$); decreases cAMP and phosphorylation.

Apraclonidine or Brimonidine (Alpha-2 agonists).

Opioids activate inhibitory $\mu$-receptors, decreasing norepinephrine release, which reduces sympathetic activity in the eye.

Methyldopa.

Hydralazine and Procainamide.

Dexmedetomidine.

Inhibitory G-protein coupled receptor ($\text{G}_{\text{i}}$); decreases cAMP and phosphorylation.

Apraclonidine or Brimonidine (Alpha-2 agonists).

Opioids activate inhibitory $\mu$-receptors, decreasing norepinephrine release, which reduces sympathetic activity in the eye.

Methyldopa.

Hydralazine and Procainamide.

Dexmedetomidine.