DIP Episode 215 - Acetylcholine and The NBME

Okay, welcome. My name is Divine Amma resident. This is episode 215 of the Divine Intervention Podcast. This podcast is going to be a special topics podcast. It's going to be titled Asylokolin and the MDN. Basically I want to talk about a bunch of classic high-yield methodologies that you want to keep at the back of your mind for the USMLA exams. So step one, step two, seek is step three that involve Asylokolin. Right? These are things that pretty much shop on every USMLA exam you take. So you know, just be hopefully a short and sweet podcast and hopefully you get something from this. So first thing is, right? So and most of it is going to be concentrated around like neurons and skeletal muscle. So let's jump right into it. Right? So the thing is we know that whenever we're dealing with muscle, right? You know, muscle needs to be depolarized by some kind of neuron. And if we're dealing with skeletal muscle in this case, it'll be the alpha motor neurons that are the things that depolarize the skeletal muscle. Well, where do we find the alpha motor neurons in the spinal cord? Well, I'll hope you're telling me that it's in the ventral horn of the spinal cord or sometimes it's called the anterior horn of the spinal cord. Now, it is very high yield to know, right? That those lower motor neurons of the spinal cord can be affected by certain things, right?

For example, if the euphoria question about a person that's like an antivaxor or some immigrant from a developing country, that's a kid that has like muscle weakness everywhere, right? Like atrophy of the muscles by literally upper lower extremities. You want to think about polio, right? Polio can torch those lower motor neurons. Another thing that can also torch those lower motor neurons is like the West now virus, but that tends to be transient. People tend to recover from that. And then if you're I guess I think in terms of genetic diseases, you don't want to think in terms of like spinal muscular atrophy, although remember sometimes spinal muscular atrophy is known as red meat, Hoffman disease. So the classic presentation on an MBMI exam will be a six month old kid that has muscle fasts equalizations, right? And he's beginning to lose motor milestones. Please do not forget, right? That it arises from a mutation in the FMN1 gene, the survival motor neuron, one gene, and it's inherited in an autosomal recessive fashion. And for the most part, it arises because chromosome five is all screwed up, right? So those are just all kind of big things. And it's actually credible these these, I mean, the driven is not great, but there is treatment available. Let's just put it that way. So you know, those lower motor neurons, so how do these sent signals ultimately to to the neuromuscular junction to inner vids, skeletal muscle, right?

So the thing that happens is obviously you're going to generate an action potential in those alpha motor neurons, right? So how does this action potential start? Basically, you know, you kind of have cells at the arresting membrane potential. And for the most part, the arresting membrane potential is very high, you know, especially for step one. The arresting membrane potential of cells, right, is around like negative 70 millivolts. And that tends to arise because the cell for the most part is more permeable to potassium than any other iron at that resting state, right? So because it's mostly permeable to potassium, right? And the reason for that permeability is because you have these things called potassium leak channels that just always leak small amounts of potassium out of the cell, right? So that's why the cell membrane potential is, you know, more in the negative 70 millivolts range. That's a USM leak question right there, right? But you know, if for some reason, you know, you kind of like have like something happen and you're like a signal comes and you depolarize, you know, like you become like a little more positive on your membrane potential, right? Votage-gated sodium channels can open. And when those voltage-gated sodium channels open, sodium rushes into the cell. That would depolarize the cell. But at a certain membrane potential that's very positive, that would inactivate those voltage-gated sodium channels.

So the voltage-gated potassium channels within open, when the open potassium will efflux out of the cell, right? And that's essentially a wave of depolarization. And the thing is for the neuron that wave of depolarization keeps spreading, right? From node over environment to node over environment, node over environment, to node over environment, right? In a process that's known as a solitory conduction. And then when you're getting towards the tail end of your neuron, when you're getting pretty close to the synapse, that depolarization will activate a voltage-gated calcium channel, or I'll say voltage-gated calcium channels, right? Because it's a bunch of them. It's not just one. And those channels, right, when they activate it, when they open up, calcium will slip in through the voltage-gated calcium channel. And then it will lead to like some cascade where SNF proteins are activated. And those SNF proteins bring vesicles that continue to transmitter. In this case, acetylcholine to the synapse. And then you essentially square out a ton of acetylcholine. That acetylcholine, right? It can have many feats, right? One feat is it can bind to the nicotinic acetylcholine receptors that you find on the surfaces of those skeletal myocytes. And remember, notice so far I've talked about many voltage-gated channels, right? I've talked about like the voltage-gated sodium channels, the voltage-gated potassium channels, the voltage-gated calcium channels.

Well, do not forget that the nicotinic acetylcholine receptor that's found on the surface of skeletal myocytes, skeletal myocytes, it's an ion channel, but it's a ligand-gated ion channel, right? The ligand that gets. So, voltage-gated ion channel is a channel that opens or closes in response to changes in voltage. On the flip side, a ligand-gated ion channel is an ion, is a channel that opens or closes in response to the binding of ligands. In this case, this ligand is acetylcholine. So, when acetylcholine binds to the nicotinic acetylcholine receptor, that will cause that, it's an ion channel, so the receptor will open and you have sodium flowing down into the skeletal myocytes, and that will cause depolarization of that skeletal myocytes. Well, there's a few more things you need to know there, right? When you have that depolarization, right, you know, that depolarization we've kind of spread along the plasma membrane of that skeletal myocytes, and there is a specialized part of that membrane, plasma membrane of the skeletal myocytes, that's known as the T-tubule, okay? The T-tubule. The thing is the T-tubule itself is a part of the plasma membrane of the skeletal myocytes. So, as the wave of depolarization spreads, you'll then ultimately have a depolarization along that T-tubule. The thing is the T-tubule has a receptor that is literally fixed on it. That receptor is known as the dihydropyredin receptor, okay?

But the thing is that dihydropyredin receptor is managed to someone, okay? The thing it's married to is something called the ryanodine receptor. The ryanodine receptor is actually a receptor that's found on the surface of an organelle in the skeletal myocytes. In fact, if you want to be a little more specific, it's the endoplasmic reticulum of the skeletal myocytes. If you want to be a little more specific than that, it's called the sacroplasmic reticulum, right? So, the thing is you essentially have two structures at play here. You have the T-tubule that's part of the plasma membrane of the skeletal myocytes. You have the sacroplasmic reticulum that sequesters calcium that can be used for skeletal myocyte contraction. And those two structures have receptors for the T-tubule. It's dihydropyredin receptor for the sacroplasmic reticulum. It's the ryanodine receptor, but those two receptors are kind of feathered to each other. So, when that wave of depolarization spreads down a skeletal myocytes and the T-tubule gets depolarized, the dihydropyredin receptor kind of like shakes its body a little, right? And then it's partner shakes its body a little. In this case, it's the ryanodine receptor. And then the ryanodine receptor is essentially a calcium channel. It will open up. And calcium will be released from the sacroplasmic reticulum. And that will promote skeletal myoc different podcast. I'm not going to talk about that here.

And then that acetylcholine that kick started this whole business. One other thing that can happen to acetylcholine is the acetylcholine can be broken down by an enzyme known as acetylcholine esterex into like choline and acetyt. And then that choline and acetyt can be recycled. The choline and acetyt can be recycled. And the choline can get reabsorbed back into the alpha moron neuron. There's a transport that actually makes that happen. And it actually so happens that that transporter is actually inhibited by a drug known as hemicolimium. That's one of those rare things you want to know for the USM Ls. And then that choline can then bind back to like acetyt again. Actually, it doesn't bind back to acetyt. It binds back to acetylcholine. On the reaction of an enzyme known as chat, choline acetylcholine transfer is. And you essentially make acetylcholine again and then you put it in vesicles. And actually that put in acetylcholine into vesicles. You can actually inhibit that process with a drug known as vesemicol. Okay. So again, those are just all things to know about acetylcholine. So notice, I've spent like the first 10 minutes of this podcast literally talking about the physiology of acetylcholine. So now let's go after the fun stuff. I'm sure you guys have all been waiting for which are the pathologies or you can call them the maladies associated with acetylcholine that your friends at the MBM love to test all the type.

The first thing I'll talk about is something called a congenital myestemic syndrome. Right? Congenital myestemic syndrome. Right? It's basically a deficiency of the enzyme known as chat. The enzyme known as choline acetylcholine transfer is. Choline acetylcholine transfer is. Right? Again, it's the enzyme I said that combines choline and acetylcholine to make acetylcholine. Right? So if that enzyme doesn't work, it's kind of a big trouble right there. Right? So you're not going to be able to make acetylcholine. If you're not able to make acetylcholine, well, there's nothing you're going to release for skeletal muscles to contract. Right? So that's something called a congenital myestemic syndrome. And the thing is, because you're not able to make acetylcholine, right? You have like a floppy baby. So if you see like my estenia, my estenia, gravis like symptoms in a baby, think about like a chat deficiency. Although they can also make that into a neuro anatomical question on NV Me exams in relation to Alzheimer's, because remembering Alzheimer's, the basal nucleus of minor is destroyed in Alzheimer's. Right? And that basal nucleus of minor is one part of the brain that produces acetylcholine. Right? I mean, that's part of the reason why you give that's one of the reasons why you give, sorry, that was bad English there. So one of the reasons why you give acetylcholine esterase inhibitors to treat Alzheimer's, right?

So drugs like donepesil, galantamine and rivestigmin, those acetylcholine esterase inhibitors, so they'll prevent the degradation of acetylcholine. So acetylcholine will persist for longer and that can somewhat help with some of the same times of Alzheimer's. But one of the reasons I'm talking about these congenital myestemic syndrome, right? Is because again, if you have a mutation or deficiency of the reclimitin enzyme of acetylcholine synthesis, in this case, chat or colonacidotransferase, right? You're not going to be able to make acetylcholine, so you can have like an Alzheimer's, star phenotype under those circumstances. And then one of the unique things, and this is probably is one of those most handy, dandy questions that pretty much everyone will likely get wrong on the USM at least, but you won't get it wrong because you listen to this podcast, is that if you see a person that has congenital myestemic symptoms from this chat deficiency, if you give them airdrofonial, they will not have an improvement in symptoms, right? Because think about it, right? If you're thinking about the other pathology, I guess in this case, my esteniaegraphis. My esteniaegraphis is when you make auto-antibodies against the nicotinic acetylcholine receptor, that you find out the neuromuscular junction, right? The thing is, those auto-antibodies that you make against this nicotinic acetylcholine receptor, you can outcompete them if you have elevated levels of acetylcholine, right?

So, what am I saying all this stuff? There is an amcino this stuff is because one of the ways you treat, one of the ways you diagnose bacteniaegraphis, although these days, you just check for anti-nicootinic receptor antibodies, anti-nicootinic acetylcholine receptor antibodies or like anti-musk, so like MUSK antibodies, but one test that was used back in the day that you know still makes it sweet to imbim exams, is the tensilent test. The tensilent test is a test that involves the administration of a drug known as adrofolium. The thing with adrofolium is that adrofolium is a very short actinacetylcholine esterase inhibitor. So, if you give adrofolium, you will inhibit acetylcholine esterase, the levels of acetylcholine will go up and then that acetylcholine can essentially outcompete those antibodies that are blocking those nicotinic acetylcholine receptors, so the person will have like a transient improvement in their muscle weakness symptoms, right? But, but that's because at least they are still able to make acetylcholine that oh you can prevent the degradation of, but if you have chat deficiency, you're not even making the acetylcholine in the first place, right? So, if you're not making the acetylcholine in the first place, that's a problem, right? So, you give those people adrofolium and you're not going to get any kind of improvement in the symptoms with adrofolium administration.

That's a very specific, nice high-yout finding on MDM exams with these congenitomy austenics and syndromes, right? And then what if you get a question about a patient that you know, has spoke like two packs of secrets a day for 50 years? And then this person comes to the physician and says that he has trouble rising from a seated position or trouble walking up and downstairs. And then they may tell you that, oh, when the person tries them on over to try to rise from a seated position a few times, you know, the person's, the person is able to get up with relative ease. If you see that, I would really hope you're thinking about like Lambert eating my astenic syndrome. Obviously, this patient I'm referring to has a small cell lung cancer, right? So, what's the pathophysiology behind Lambert eating my astenic syndrome, right? In Lambert eating, you essentially form autoantibodies against that presynaptic voltage-cated calcium channel that I talked about when I was talking about the physiology of acetylcholine in the first 10 minutes of this podcast. So, the thing is, in Lambert eating my astenic syndrome, right? You make autoantibodies against those presynaptic voltage-cated calcium channels. And essentially, right, calcium is not going to be able to rush in. If calcium doesn't come in, you're not going to be able to release those vesicles that, those bugs of acetylcholine essentially that you have in the neuro, right? So, that's something high you'll to know, right?

So, you may ask yourself, oh, so divine, why do those people symptoms improve with continued use of the muscle, right? Well, the reason they are symptoms improve is because as you keep using the muscle, you'll begin to recruit more calcium to those voltage-cated calcium channels. And those things will outcompete those people's those nasty antibodies. And then, you know, you have like an improvement in their muscle weakness. So, I guess it may be very helpful for purposes of the USML Es to be able to differentiate between Lambert eating my astenic syndrome and my astenic gravies, right? The thing is, people that have my astenic gravies, you probably know there's that, oh, the muscle symptoms get worse with use. Well, the thing is, your friends at the MBMED will essentially never put that on an exam, right? Everyone will get that correct, everyone get a 2-ED, which is clearly not the thing that happens on the USML Es. But essentially, when people have my astenic gravies, right? Like, one way they can put that, oh, muscle weakness gets worse with use is they can put it as they can tell you that, oh, the person is observed to have a decrymental response with repetitive nerve stimulation. If you see that, think about my astenic gravies on those circumstances. But on the flip side in Lambert eating my astenic syndrome, those people tend to have more of an incremental. So, an increase, an incremental response with repetitive nerve stimulation.

That's just a fancy 5 way for saying muscle weakness that improves with use. And then another critical difference that I've found to help quite tremendously on the exam, is that, if you know people have theories, people that have Lambert eating my astenic syndrome, they tend to have problems in their appendicular skeleton. So, like, their proximal limb muscles versus people with my astenic gravies that tend to have problems more like their axial skeleton, their bobra muscles, so like their eyes, their head, their neck, their diaphragm. So, those are two nice high-yield differences to keep at the back of your mind for exams. Now, what if they give you a question about a patient? You know that consumed like like convedges that he bought at a store two weeks ago. And now this person is like all floppy and whatnot. If you see that, what are you thinking about? Well, I would hope you're thinking about botulism, right? Botulism. So, in botulism, essentially, you have problems with Clucidium Botolino. Remember, it's a sport form in Boc. So, you kind of become floppy. And I'll talk about the pathophysiology there. One thing that your friends at the NBM is actually want you to know about botulism is differences in mechanism of disease between adult versus kids. So, like, in babies, like infants, right, that have like new needs that have botulism, the reason they get problems is because they actually consume like the actual Boc from like honey, for example.

The thing is normally, Clucidium Botolino is not able to become like pervasive and elaborate like toxin, like a presence GI tract because your GI flora normally suppresses it. But if you're a BB, you have not much in the way of any kind of GI flora. So, that GI flora will not be there. So, C botolino flourishes and blossoms makes a ton of toxin in your GI tract and then become a floppy BB. But if you're an adult, your GI tract is very robust, right? It's robustified. So, it doesn't, I don't think there is a word like robustified but, whatever it's my podcast, I can say whatever I want. So, I have a very robustified GI tract, very good GI flora. So, those can now compete the bug. So, if you consume the bug, no problems. But, if you consume food that contains the preform toxin, you will most certainly run into troubles, right? So, how does the botulino toxin work? Essentially, the way it works is it cleans those step routines that I talked about that helps you bring out bugs of neurotransmitter, right? So, the synapse, right? So, if you clean those step routines, you're not going to be able to release acetylcholine containing vesicles at the neuromuscular junction. So, the bad thing that's going to happen is you're not able to release acetylcholine. So, skeletal muscles are not going to be able to contract. If you're not going to be able to contract, you're going to run into trouble with that, right? So, you're going to become floppy because you have no muscle contraction.

So, that's something that's high you to know for exams, right? And then, I guess, a close cause, but this is not with the neuromuscular junction. This is not a subtle colin, but it's one of those things I figure, and I guess I might as well talk about this, and I'm talking about botulism, is the case of tetanus, right? So, tetanus, also, again, cleavsnare proteins, but cleavsnare proteins in like rendshaw cells, like rendshaw neurons, those are neurons that naturally produce glycine and GABA, which are inhibitory neurotransmitters. So, if you clean those net proteins, you do not release inhibitory neurotransmitters. So, you have like tonic skeletal muscle contraction. So, you get a spastic paralysis, okay? As against the flasid paralysis, that's observed with botulism. So, now, we've kind of talked about those things, right? So, you know, you release this acetylcholine. So, what are some maladies, though, because I said that acetylcholine is broken down my an enzyme, known as acetylcholine esterase. Well, what are some high-yalthines to know with that? Well, maybe let me talk about my estenegravis first. I think that'd be helpful, right? And I've kind of said many things about my estenegravis already, right? So, again, oto antibradies against the nicotinic acetylcholine receptor, yeah, yeah, yeah, yeah, yeah, yeah, right? And then, essentially, you have, you have like a stimulation, you have like a blockade of those nicotinic receptors. So, acetylcholine is not able to bind.

So, you know, you kind of get like problems with, again, your axial scantene like your eyes, your diaphragm muscles, neck muscles and all that stuff. And remember that there's an association between my estenegravis and thymomas. In fact, they may give you a question about a person, you know, you're like, oh, reading this question happy-go-lucky. Oh, this person has my estenegravis. And then, he has for the next step in management. And he may actually be to get like a CT scan of the chest to roll out of thymomas. Remember that's an anterior medias thymomas. So, when I first asked my estenegravis, right, you're like, oh, crap, this sucks. I've talked about how you make the diagnosis. So, let's talk about how you treat, how you essentially get rid of my estenegravis. The way you get rid of my estenegravis is a drug known as by Rido's technique. Because think about this for a second. In my estenegravis, I said, you are making auto antibradies against the nicotinic acetylocolary receptor. Well, what is one way you could fix the problem? You could fix the problem by giving a drug that would maybe bump up your levels of acetylocoline so that you can successfully outcompete those deleteria antibodies and you can relieve the person's symptoms. Well, one drug you can give is by Rido's stigmin, right? So, don't forget that you get rid of my estenegravis with pyridocetin. So, you'll inhibit acetylocolinescerase, you bump up the levels of acetylocoline, right?

And that will allow compitles nasty antibodies and then the person's symptoms get better. That's what. A second thing is with acetylocolinescerase, I guess I need one to mention is what if they give you a question about like a farmer that just sprays these crops or maybe he's child just bleeding a field that was just sprayed with crops, or they can even make this like a terrorist question, right? Where, you know, a person has any one of these exposures and then this person is like bradycardic, has diarrhea, has urinary incontinence, swollen incontinence, sweating, has bilateral pupillary meiosis. If you see that, you want to think about organophosphate poisoning, right? Remember, organophosphates, they work essentially by inhibiting acetylocolinescerase, right? So, you'll have a colineergic toxic oil, right? That's a high-o thing to keep at the back of your mind, for example. And then another thing, I guess I want to see with this is, since we're kind of talking about this nicotinic acetylocoline receptor, remember that we have like, you know, some, let's say you're wanting to beat someone, or you want to do surgery on someone, right? So, this is essentially an anesthesia from a colineer here. The thing you would want to do is you want to anesthetize the patient first with like purple fall or in a dazzle lamp or something like that, but then you'd want to paralyze them, right? It's usually inappropriate to paralyze the patient before and anesthetizing them, right?

That's not ideal, right? Because that will scare the patient, and, you know, that thing can have pretty striking bad memories for the patient, right? So, you know, you're anesthetized the patient first before you paralyze them. And when you paralyze them, right? I mean, you can essentially make your patients floppy in anesthesia, but just giving them a neuromuscular blocking agent, right? And the good thing for purposes of NBM is that there are two classes on neuromuscular blocking agents, right? So, there's like the depolarizing ones, and then there's the non-depolarizing ones, right? So, the depolarizing ones, I think, is like a succino coline. The non-depolarizing ones are those drugs that end in like curium or curonium. So, like the curonium, raccoronium, pancoronium, atracurium, cisatracurium, although remember atracurium, those ones are kind of degraded in a special way, like the Hoffman elimination, like spontaneously, is almost like this, spontaneously just disappear in the bloodstream, right? So, but I'll talk about the breakdown of those agents in a second, right? But if I kind of talk about the breakdown of those agents, I think it may be useful to talk about, you know, what's the difference in mechanism? Because I know some of you may be saying divine. How can something be on your muscular blocking agent, but be a depolarizing your muscular blocking agent? Well, let me give you an analogy here, right?

So, let's say you, let's say I love, I don't know, let's say I love um, broccoli. Actually, I actually do hate broccoli, to be honest with you. But let's say I love broccoli, right? And, you know, let's say you give me broccoli, you know, Monday, morning afternoon, evening, and then on Tuesday, you know, broccoli meal, morning afternoon, evening, breakfast, lunch, and dinner. You know, you kind of do that for a week. I'm like, oh, I love broccoli, I keep eating it. But you know, by like week two week three, I'll be like, you know, I don't want this anymore. I'm tired of this crap. Get this out of my face, right? Like broccoli, right? So, essentially, you've overstimulated your broccoli where I've been like, okay, you know what, that's it. I can't do this anymore, right? I kind of get fed up with broccoli, right? That's essentially what happens with these depolarizing agents, these hyperstimulate the nicotinic acetylcholine receptor, so that after a while, it stops working, right? So, essentially get a blockade that way. Contrast this with the non-depolarizing agents like those curioms and curiomps, those drugs are essentially competitive inhibitors of the nicotinic acetylcholine receptor. And those two drugs are also divided by that mechanism, because it's actually kind of high to know how they are broken down, right? So, succino-polling, I mean, the non-depolarizing ones, right?

So, the curiomps and curiomps are broken down by acetylcholine esteries, so that's kind of good, right? But it's different though for succino-polling. Soxino-polling is actually broken down by drug known as, or you know what, let me put it this way. You know, let me just continue. So, succino-polling is broken down by drug known as pseudo-pollimesteries. It's not broken down, you know what, let me take a step back, let me take a small step back, I feel like I've been spoken here. I actually have been spoken, so just maybe a while, like scratch off what I said for the last like 30 seconds. Soxino-polling is unique in the sense that, because notice it sounds an awful lot like acetylcholine, right? So, succino-polling is actually broken down by, by a enzyme known as pseudo-pollimesteries, and that's pseudo-pollimesteries, it's kind of unique, right? Because there are some people that actually have like no or no, right? So, no pseudo-pollimesteries are decreased activity of pseudo-pollimesteries, and that kind of gets them in trouble, right? Because those people, clearly, right? If you give them succino-pollim, they can have like a prolonged blockade, so be harder for those people to come back from anesthesia, right? But one thing I want to say with the non-depolarizing agent says, those drugs, you can actually reverse them with an acetylcholine esteries inhibitor, right?

So, like, neo-stigling, for example, because the thing is again, if you give an acetylcholineesteries inhibitor, you bump up those people's levels of acetylcholine, and that will outcompete those competitive inhibitors, right? So, they can easily make this amicolism maintained question on that step one example. You will outcompete those non-depolarizing your host blockade agents, and you can reverse those agents that way, essentially, right? So, that's what I'm going to say about succino-pollim. I'm going to say one other thing about succino-pollim, but I'll, you know, see that in a second, right? So, let's assume they give you a question about a person that gets succino-pollim, right? And then this patient, you know, like one hour into the end, like the surgery, the person's temperature is like 105, and the person's white count is like 18,000, the accrediting kind is like, is in the like almost 10,000, and you're like, hmm, what's going on here? Well, I would hope you're thinking along the same lines as myself, that this patient has something called malignant hypertherm. Right? So, malignant hyperthermia is one of those high yield things you want to know for exams, right? It arises from a mutation in one of those T-tubule or succoplastic reticulum receptors I talked about, right?

So, you can arise from a mutation in like ryanidine receptors, we can arise from a mutation in like dihydropyredine receptors, more commonly on nbim exams are actually in the real world, the most common mutation, causing malignant hyperthermia is a ryanidine receptor mutation, right? So, when you have that mutation in the ryanidine receptor, it's almost like the ryanidine receptor is always open, it's like an activity mutation, and calcium will come like flow out of the succoplastic reticulum, you have like super intense contraction of muscle of like skeletal muscle, and you know, that's not good because that will generate a ton of heat, right? So, your muscle cells can die, and all that stuff, so you can get like rubbed out, you can get like hyperchylemia because your muscle cells are exploding, you can get like hyperchylemia, and get like an arrhythmia with those like topic t-waves or sign ways before you system it, you can also get like, you know, like an intranel ekii because the mayoglubein will kind of like clog up your kidneys, but you may then say, okay, so how do I fix this problem? Actually, one thing you should remember, FYI is that it's inherited in an autosomodominant fashion, but how do you fix the problem? You fix the problem essentially by giving, naturally, right? Because I said that you have like an activity mutation essentially in the ryanidine receptor, the ryanidine receptor is essentially a calcium channel, right?

Because it's like a, it's a receptor on the surface of the succoplastic reticulum, which normally stores calcium, you know, although remember that the succoplastic reticulum also produces a ton of a steroid world, right? So, the thing is, if you want to fix the problem, you can essentially give a ryanidine receptor antagonist like dantrulline. So dantrulline, sometimes your friends at the NBME instead of writing like dantrulline as an answer, we can just put calcium channel blocker as an answer and you hopefully know to pick that as an answer choice there. So that's how you treat malignant hypothermia. You can also use dantrulline for neurolithic malignant syndrome, right? Buying this case, the person will take like some kind of anti-psychotic instead of being exposed to like succino-choline, or they're in here, dantrulline aesthetics like halothen or whatever. And then the last thing I want to say, I guess when I talked about organophosphate poisoning, I didn't talk about the treatment, the way you treat organophosphate poisoning, right? The first thing you give is you give um, you give um, atropine, right? Or because again, it's a called allergic tooxidrom, you give a most chronic receptor antagonist like atropine, that will kind of help with, you know, rescuing the patient relatively quickly. And then after that, you give prelydoxin, right? Prelydoxin will regenerate the acetylcholine esterase that has been killed essentially by the organophosphate.

Don't give prelydoxin first. Your patient will probably be long dead before the prelydoxin kicks in, right? So give atropine first and then after that, you give prelydoxin. And then maybe one other thing I should mention, you know those like Votish Kinesodium channels, I say that lie along the surfaces of neurons. So those channels actually blocked by your local anesthetics, right? So like lydocaine, bupivocaine, cocaine and all that stuff. I mean cocaine is not something you probably find in a hospital. So you know like the cocaine derivatives like lydocaine, bupivocaine, remember lydocaine is technically a Class 1 B and terrib make. I mean that's why the, that's why the Class 1 agents are sodium channel blockers, right? So those, you know, those local anesthetics they blocked those sodium channels. And that will prevent the neuron from firing because you essentially stop in solitary conduction, you're stopping the wave of depolarization, right? So that kind of helps with those people's, that kind of numbs up those neurons so that you don't feel big. So I think I'm going to go ahead and stop here. That's all I'm going to see with acetylcholine. As I do at the end of every podcast, I do offer one on one children for a ton of exams, right? Step 1, step 2ck, step 2cs, step 3, pre-clean cool meds, cool exams, 30-ish-off exams, I do booster courses. It's like 15 hours for step 2ck, step 3, 20 hours for step 1.

And then I am going to be studying an online private study group, studying our next, the second week of February, if you're interested. It will just be like two hours, it's 100 per person. And essentially, you'll have like a theme, like, oh, a cardiology theme or a neurology theme, I'll have them, you know, like, every now and then. So if you're interested, just send me an email, if you need to reach out to me through the website, or you send me an email at divine intervention podcast with an Savn.gmail.com. You'll be over Zoom. I'll give more details in a podcast. I'll meet you in the next couple of days. And then, if you need coaching, so for like, if you're a metz-to-the-point to residency, so like an ERAS app or a college center plan to met school, so like an MCAS app, I do like one-on-one like consult, with like personal statements, rec letters, mocking reviews. Again, I have like admissions committee experience at a top-two met school for like a year. And the people have worked within the ERAS process, like the vast majority of them have actually much had their first choices. And then, if you're a college student, and you need to learn from like, Gen CAM, OAM Physics, Bio-CAM Histology, Physiology, basically the MCAT subjects, I feel free to reach out to you. So, I do hope you've got in a lot from this podcast. Please subscribe to the You Tube channel, subscribe to the podcasts. I have it on Apple podcasts, on Spotify, on Google Play. Thank you for listening.

I hope to see you in the next podcast that I'll hopefully meet very soon. So have a wonderful rest of your day. God bless you. I'll see you next time. Thank you for listening.

It is an acetylcholinesterase inhibitor, which increases and prolongs acetylcholine levels at the neuromuscular junction.

LEMS antibodies target presynaptic voltage-gated calcium channels, impairing A Ch release; MG antibodies target postsynaptic nicotinic receptors.

A decremental response (muscle strength decreases with repeated stimulation).

Botulinum toxin, which blocks A Ch release at the neuromuscular junction.

Spastic paralysis (increased muscle tone).

ChAT (Choline Acetyltransferase) deficiency.

The T-tubule depolarization activates the dihydropyridine receptor, which mechanically couples to and opens the ryanodine receptor on the SR, releasing Ca2+.

Pyridostigmine (A ChE inhibitor) or Edrophonium (for diagnostic Tensilon test).

LEMS shows improvement with use (incremental response); MG typically worsens with use/fatigue.

Acetylcholine release at the NMJ; flaccid paralysis.

1. Atropine (muscarinic antagonist) first, followed by Pralidoxime (to regenerate A ChE).

Ryanodine receptor mutation; treat with Dantrolene (a calcium channel blocker/antagonist).

The T-tubule depolarization activates the dihydropyridine receptor, which mechanically couples to and opens the ryanodine receptor on the SR, releasing Ca2+.

Pyridostigmine (A ChE inhibitor) or Edrophonium (for diagnostic Tensilon test).

LEMS shows improvement with use (incremental response); MG typically worsens with use/fatigue.

Acetylcholine release at the NMJ; flaccid paralysis.

1. Atropine (muscarinic antagonist) first, followed by Pralidoxime (to regenerate A ChE).

Ryanodine receptor mutation; treat with Dantrolene (a calcium channel blocker/antagonist).