DIP Episode 471 - Alpha-1 Receptors and The USMLEs (Step 1-3)

All right welcome my name is divine this is episode 471 of the divine intervention podcasts into these podcasts. We're gonna be going over the Agrenergic receptors for the US Emily exams. The Agrenergic receptors honestly these things are pretty high-yield. This podcast who's gonna benefit from it's gonna be people that are taking step one, people that are taking step two and step three. In one way or the other, Agrenergic receptors are kind of important. They're kind of useful for like a lot of stuff. So it's just one of those things where you pretty much be shooting yourself in the foot. If you don't understand them, many people think that step two and step three have like no basic sciences in them. That could not be further from the from the truth. So you need to make sure you kind of understand these things. If not, you're putting yourself in a very tough spot. Okay so let's just go ahead and get right into them. So the thing is in terms of our Agrenergic receptors, the ones that we're really gonna care about today are the alphas and the betas. That's it. The alphas and the betas. Now the good thing about those is that they all have... There's five total that we really care about. There's alpha one, there's alpha two, and then there's beta one, beta two, and beta three. Beta three has a very limited role, but we'll discuss what that a limited role is in terms of the USM and the exams. So let's maybe go straight into the alpha one receptor.

So the alpha one receptor, the thing is for these receptors, I guess maybe if I jump into that, the critical thing to know is how do these receptors work? Where they found and what are their major functions and what are like some key pharmacology times you may want to take away with you for your exams. So that's how I'm gonna approach each and every one of these ones. So number one, alpha one receptors. Alpha one receptors, right? They're kind of a G protein cup holder receptor. In fact, let me tell you this right now. A nice generalization for all the Agrenergic receptors is that they are all G protein cup holder receptors. Okay? And the thing about them is that... And you know, I'm trusting God that in the future. I'll be able to make a podcast where I just talk about receptors like those G protein cup holder blah blah blah blah blah. Because those things are also pretty, pretty high on. Well, that's probably more for a step one of the purpose. But basically, if you want to categorize these things, they're all G protein cup holder receptors. All the better receptors are stimulatory G protein cup holder receptors. Literally all of them. So they all increase the activity of a DNA-lil cyclase. And then the alpha one receptors are in GQ cup holder receptors, the alpha two receptors are GI cup holder receptors. Those are the ones that are kind of funky. So the alpha two decrease the DNA-lil cyclase activity. And then the GQ, right?

Alpha one works through that forceful IPC business. Again, we'll talk about that in the in the future. So alpha one receptors. So again, they're GQ G protein cup holder receptors. What are like the big, big, big uses you're going to find with these things? Well, or where would you, where would you say we'll find them? For USMD purposes, the ones that are the most important to know are one, your smooth muscle. Smooth muscle, super, super, super, super important. And then another place where you find out for receptors is the bladder neck, the prostate. There are many other places you can find them, but to be perfectly honest with you, the ones that you really, really need to know is the smooth muscle, which obviously that means they're going to affect blood vessels a lot. And the bladder neck slash the prostate. In the smooth muscle, what do these things do? Well, if you activate them, then that's going to cause you to have viso construction. If you have viso construction, it is pretty obvious that your systemic vascular resistance is going to increase. And think about it. If you raise your systemic vascular resistance, how exactly do you think your cardiac output is going to respond? It's not going to respond well. Your cardiac output is going to go down because you're literally increasing after load. You're making it very, very difficult for stuff to literally leave the heart. That's a very important concept and principle to keep a debacle of your mind, for exams.

So drugs like phenol effring and effedering, the alpha one agonist for that reason. They're very helpful for that purpose because many times they test them in the context of, ooh, a person gets a person gets an aesthetics on the exams. And right after induction, the blood pressure just tanks, tanks, tanks, significantly. Well, in those circumstances, what are you going to do? Usually an alpha one agonist is exactly what you're going to be jumping for, exactly what you're going to be reaching for in these folks. Because by giving that alpha one agonist, your cause viso construction, you jack up the blood pressures, and that's going to be very helpful for those people. Okay? That's going to be very, very helpful for those people. Another situation when you may see alpha one agonist is a person that has like right in a rear, you know, has like nasal, you know, right in a rear, and all those things, you can give an alpha one agonist like pseudo effedering, like pseudo fed. What do you think? How do you think pseudo fed works? Well, pseudo fed is in fact the alpha one agonist. So because the alpha one agonist is going to cause viso construction of the vessels that feed the nose. So there'll be less blood fed to the nasal mucosa. You have less runorrhea. You're going to feel amazing. So if there's alpha one agonist, then obviously it's going to be alpha one blockers. Alpha one blockers. Again, if you give an alpha one blocker, you're going to get viso dilation.

If alpha one activation got got as viso construction, alpha one blocker will give us viso dilation. That viso dilation, you're going to get that, um, will draw like tamso losen, although tamso losen I'll talk about it's special role. Tamso losen, prazo sen, doxazosen, alfuzosen, many of them end in zosen. Tamso losen is kind of weird in the fact that it ends in losen instead of zosen like the others. So it's pretty, it's pretty, pretty helpful for viso dilatory purposes. So occasionally you can use these drugs for blood pressure purposes, but they're really, really used. I will tell you this. Alpha one antagonist are not first line for managing hypertension. The drugs you want to think about as first line for managing hypertension on your exams are thazidei redics, ACE inhibitors, AR Bs, and calcium channel blockers. For presion has any kind of hypertension thazidei redics, ACE inhibitors, AR Bs, calcium channel blockers. That's where it's at on the USMID exams, in terms of first line for for hypertension. The only reason why something else maybe first line is if for some reason, people have some weird comorbidity that may make some other drug just more useful for them. So let's say for example, a presion hypertension is from Havane con syndrome. They have like primary hyper-adjusteurysm. Then yeah, those circumstances, the hypertension probably respond pretty well to an auto-stron antagonist like Spurnolactone or a Plurino.

But again, those situations tend to be few and far between. So I'm going to repeat this again because this is not something here in many places, but it's actually pretty important for exams. When a presion has high blood pressure, when a presion has high blood pressure, the first line series you should use on your exams is you're going to thazide, an ARB or an ACE inhibitor, or a calcium channel blocker. That's it. That's it. That's it. And African Americans, we don't just usually jump to ACE inhibitors or AR Bs in those folks. We only do that if whatever reason they have an indication for being on an ACE inhibitor and ARB. Let's say for example, they have diabetes, right, or they have heart failure or something like that because in diabetes, the ACE inhibitor and ARB is going to be very non-protective. In heart failure, the ACE inhibitor or ARB is going in per survival. That's the thing. That's why, again, I tell people this, you can just like linearly memorize things for the USML Es. Usually, it doesn't pan out very well for people. You need to understand many of these things in context. You need to understand many of these things from a pathophysiological perspective. So we're going to continue. So these alpha one blockers, again, they can lower blood pressure. They're pretty good, but again, like I said, they're not first life for blood pressure.

One situation where you may want to use them for blood pressure purposes is usually when a person has an intoxication or they have some disease, where caracolamines are in excess. Like for example, if you have cocaine intoxication and they're trying to say, oh, which one should you give? An alpha blocker or a bit of blocker first? Well, obviously, they're going to give an alpha one blocker first. Why do you want to do that? Well, you want to do that because cocaine increases the release of caracolamines at the adrenergic center. So because cocaine increases the release of caracolamines at the adrenergic center. If you give a bit of blocker first, as you'll see when we talk about the bit of receptors, as you'll see, if you give a bit of blocker first, then your alpha one receptors will be left wide open. And those caracolamines that have been increased in terms of release, they'll stimulate those alpha one receptors and cause a very gnarly hypertension. So typically in those circumstances, we want to give an alpha one blocker first. Like again, like a prazo scene or doxazo scene or fuzo scene, something along those lines. And then another situation where you want to keep this alpha one on opposed alpha business in mind is if they give you a question about a person that has a few criminal cytoma, right? So if a person has a feel, you probably want to do surgery to fix set feel. Well, that's all well and good.

The only problem that you kind of run into there is you cannot just take them to surgery because as you are manipulating the tumor, you can release astronomical amounts of caracolamine and that can literally kill the patient from like a hypertensive crisis. So you don't want that. So what are you going to do in those circumstances on your exams? So what you're going to do is you're going to give an alpha blocker first, an alpha one blocker first. Again, you can give something like prazo scene or doxazo scene. Although alternatively you can also use other alpha one blockers like phentolamine or phynoxybenzamine. Phentolamine is reversible alpha antagonist. Phynoxybenzamine is more of an irreversible alpha antagonist. So it's pretty helpful in those circumstances. But those are in general honestly, those two situations I've mentioned are probably the only situations where you should use alpha one blockers for blood pressure purposes. Another like remote scenario, I could think of that me pop up on a USML exam. It's for example, a person that has PTSD. Well, people that have PTSD, one of the problems they tend to have are nightmares. Those nightmares can be treated very effectively with prazo scene. So let's say for example, you get this bizarre scenario of a person that has PTSD having a ton of nightmares and the person has hypertension. You can literally kill those two birds with one stone. You can literally the nightmares and the high blood pressure.

You can target both with an alpha one blocker. Prazo scene is the drug of choice for nightmares and people that have PTSD. In fact, honestly, the might continue this podcast. The mom like, ah, divine, maybe you should make separate podcasts on each of these adrenergic receptors. So honestly, I'm just going to limit this podcast to the alpha one adrenergic receptor. I think it's just something that's kind of important because if I leather you with so much detail all in one podcast, it's going to kind of be a lot to to to to a monster. Okay. Now what's under big thing with alpha one receptors that you need to know for example, so we kind of talked about that you find them in the bladder neck and the prostate. So obviously if they give you a question about some really old man, right, with urinary problems, um, renal failure, whatever, right? Obviously thinking of BPH. Maybe like, wow, divine. BPH causes renal failure. Ah, yeah, it does. Right? Because if you think about it, how can you get renal failure from BPH? We can get renal failure from BPH because that BPH benign prostatic hyperplasia is going to make make it really, hard for your bladder to drink. Well, if your bladder does not drain, then your urinary there's another drain. If your urinary do not drain, then you literally jack up the hydrostatic pressures in your woman's space.

If you increase the hydrostatic pressures in your woman's space, that's going to disfever, disfever filtration at the level of the glomerular capillaries. Well, if that disfever, if you disfever filtration, your GFR is going to plummet. If your GFR plummet, your creatinine is going to go up. So they can dial, they can basically have an obstructive neuropathy. That may cause renal failure. So again, if you see, again, an old man with, uh, diluted urators, especially if it's bilaterally diluted ur- ur- urators, bilateral hydrolyphrosis, you generally want to think about BPH. Um, if you see that in a young female, uh, I usually be more unilateral, young female, it's unilateral. And you notice that, um, you know, she's been losing weight. That's cervical cancer right there. Actually, the most common cause of death in cervical cancer is renal failure because the thing can basically spread to the pyrimidium, uh, clog up your urators and cause a cause of a bunch of problems. Um, obviously, if you see, you know, hydrolyphrosis in a child on your exams, there are many different ways you can go with that. Uh, you may be thinking of something like, um, uh, vesically uratory flux, right, maybe thinking of a posterior erythrovalves, those things can all cause hydrolyphrosis. Uh, if you see a toner syndrome patient, right, horseshoe kidney can cause those problems, right. So there are many things that can cause those issues on on exams, right.

Or if you see a person that has a history of right-elf styroiditis, maybe thinking of retroperitoneal fibrosis as the cause of their hydrolyphrosis. I know for whatever reason why it's sad to stream to talk about hydrolyphrosis, but it's a pretty high-yield concept to know for, for exams. But again, I'm going to go ahead and, uh, pause with with that, right. But if a person has BPH, well, what can you do? Well, what you can do is you can try to open up the bladder neck so that the prostate can drain, uh, you can open the, the, the, the, the, you can try to dilute out that bladder neck by giving an awful unblocker. It can give something like prazocin, doxazocin, refusalcin, timesulocin, uh, many times we prefer timesulocin for that purpose. Well, why is that? Well, the reason we prefer for that purpose is that when you give, uh, timesulocin, timesulocin in general acts more on the alpha one AD receptor, ADS and Anthony Davis, if you're a Laker fan, uh, blocks the alpha one AD receptor, that's the alpha one receptor that is localized very heavily to the bladder neck. So it's very helpful. So it doesn't have many visual active effects, like you would see with the other alpha one blockers. Okay, so that's something to keep in mind. Although I'm not going to say that, uh, timesulocin has like zero visual active effect, it does not have zero visual active effect. It does have some visual active effect, but it's certainly not in league with the others like prazocin and what not.

I kind of wonder if that's why it has a different ending, like lousin, instead of zousin, like the others. And then remember, obviously, right, uh, just maybe finishing up this BP story for person has BPH and, um, we know that, uh, you know, we're like, okay, short term, we're giving an awful unblocker. But long term, you can give them a five-hour for adoptees inhibitor. So something like a phenesteride or deutastoride, because DHT is the thing that dihydrothestosterone is the thing that makes your prostate grow. Um, and five-hour for adoptees converts testosterone to DHT. So if you shut down five-hour for adoptees, then you can really, really help in a person that has a, uh, uh, uh, prostita prostitutes issues. Actually, you can shrink the prostitutes in really good size by doing that. And then don't forget that if all of that, if all these pharmacotherapies don't work, you can consider presidenonous chirp, uh, trans-urithral resection of the prostate, chirp trans-urithral resection of the prostate. That can be a way to treat a BP, BPH. But again, honestly, again, there are other things you can know about alpha-1 receptors. Well, many of those other other things, one, a pretty low yield, two, don't have much clinical significance to them. So how likely is it that our friends at the USM Ds who go after those, not much, right? But as you can see, there are many different ways you can go after the alpha-1 receptor.

And I know what I was thinking, thinking that I'll cover all the alpha-1-bit receptors in one, in one podcast. I mean, literally alpha-1 is just 60 minutes already. Okay. So, and again, I know some pull maybe annoyed, like, define why do you keep straining off in these directions? But again, that strain is part of the benefit of this podcast. Because again, I've told you this, many people are beginning to see this with the newer MBM Es, like the MBME 13s, 14s. If you're the step two test-taker, or the MBME 31s, I won't know if you're the step one test-taker. The MBM Es these days are not linear exams. Like, many of the, many of the questions are like very integrative. Well, you have to think in multiple dimensions. So I'll just say again, all these added stories that I'm adding on. Like, for example, we talked about alpha-1 today. But then we ended up talking about hydrogen at first, and a bunch of other weird stuff. Again, I promise you, like knowing these added stories while we're deep in your understanding, too, will help you see things in many dimensions. So when you see a USM Ly question, you don't feel like a deal in the headlines. Just FYI, these things, I'm not just doing them for the fun of it. I'm not sure you're doing them because it actually matters for you doing well on your USML Is. And again, obviously, this podcast is not for medical decision making, but you want to be a doctor that is able to think like this.

Because again, you'll be able to catch things that may not be otherwise caught by most people that are just linear thinkers. But I'm going to go ahead and stop here. Again, I offer review courses for the USML Is. I have literally one starting today, the test-taking class. I have one today. I have a different one tomorrow, bio stats. I have a different one on Saturday, social sciences. And then I have, and those are all for step one, just step three. And the next week, one day, I have a step two, and step three, one, that's 20 hours long. If you're interested, shoot me an email. I'll throw one on one, two, three, for all the USML exams and medical exams. I have these podcasts on the major apps, Google, Spotify, Apple. I have a You Tube channel, Divine Intervention, USML podcasts and videos. Just check that out. That's where I post the videos I make. I have a website Divine Intervention Lifelesses.com from a biblical perspective. I post two life lessons a week. They're about 10 to 20 minutes long. I actually have like 200 podcasts on there right now. There's actually an Apple podcast associated with that. But from a biblical perspective, I try to address a common problem that's faced by humanity. And then, final thing I'll say is if you need help with your ERAS applications, recommend additional letters, personal statements, mock interviews, plan them out to your ERAS cycle, I do all these things with people. So if you're interested, shoot me an email.

I'll give you some more information. Thank you for joining me. God willing, we'll continue with this adjunctual receptor story in the next podcast. So God bless you. Bye for now. Thank you.

Alpha-1 ($\alpha_1$), Alpha-2 ($\alpha_2$), Beta-1 ($\beta_1$), Beta-2 ($\beta_2$), and Beta-3 ($\beta_3$).

$G_q$. Activation leads to increased intracellular calcium.

Thiazides, ACE inhibitors, AR Bs, and Calcium Channel Blockers (CC Bs).

To prevent the massive release of catecholamines from adrenergic centers that would otherwise stimulate open $\alpha_1$ receptors, causing severe hypertension.

Obstructive uropathy leads to increased hydrostatic pressure in Bowman's space, which reduces glomerular filtration rate (GFR).

Tamsulosin.

$G_q$. Causes vasoconstriction (increased SVR).

Cocaine intoxication or Pheochromocytoma crisis/surgery.

Finasteride or Dutasteride; they inhibit 5-$\alpha$-reductase.

Prazosin (an $\alpha_1$ blocker).

Obstruction $\rightarrow$ Increased hydrostatic pressure in Bowman's space $\rightarrow$ Decreased GFR.

An aldosterone antagonist (e.g., Spironolactone or Plurinolone).

$G_q$. Causes vasoconstriction (increased SVR).

Cocaine intoxication or Pheochromocytoma crisis/surgery.

Finasteride or Dutasteride; they inhibit 5-$\alpha$-reductase.

Prazosin (an $\alpha_1$ blocker).

Obstruction $\rightarrow$ Increased hydrostatic pressure in Bowman's space $\rightarrow$ Decreased GFR.

An aldosterone antagonist (e.g., Spironolactone or Plurinolone).