DIP Episode 40 - Neuro Pharmacology Part 3 (Anesthetics and Opioids)

Okay, welcome. My name is divine. This is a fourth year episode of the Divine Intervention Podcast. I'm a PGY one resident. So let's begin. So today we're going to continue a topic of neuro from ecology. But with this section I'm going to be talking about a lot of anesthesia meds and some other like weird stuff here and there. So let's see how do I want to do this? Okay. So let's start with the inhaled anesthetics. The inhaled anesthetics. So I just want to establish a few concepts for starters. So let's talk about general anesthesia. Let's start with the onset of action. So the thing is when you pump a gas into an liquid. The first thing that happens is it has to dissolve in the liquid until the liquid is then saturated. When the liquid is saturated then you begin to have the gas remaining as like persisting in the gicious form. So it's like oh feel liquid first before you then have some stuff left over in the gicious form. So if a gas is very soluble in the liquid, right? That means that liquid will keep taking more and more and more of it and it will take a much longer time for that liquid to saturate, right? And conversantly it will take a much longer time for that gas for you to begin to have some left in the gicious form. So the thing you have to remember again anesthesia has to work as a free gas. So the less soluble it is in blood, okay? The fast rate works, okay? And the concept that connects these things is something known as the blood gas partition coefficient.

You basically want this low, right? So it's like blood gas, right? So you want your anesthetic to be in the gicious form. So you want the denominator to be as high as possible and the numerator which is blood to be as low as possible, okay? So a lower blood gas partition coefficient means that most of the anesthetic is in the free gas form, okay? And with that you have a shorter onset of drug action because most of the drug is in the gicious form. So a low blood gas partition coefficient means quicker onset for an anesthetic, a high blood gas partition coefficient means longer onset for an anesthetic. Then the second concept I want to discuss is potency, okay? So the thing is the blood brain barrier is more permeable to lipid soluble drugs, okay? So there's a few things you want to keep in mind here. That's like the general principle you want to understand. So the first thing I want to talk about is something known as the minimum anesthetic concentration on MAC, okay? So if you hear me say MAC, I mean minimum anesthetic concentration. So the thing is in general for anesthesia you want something with a low MAC and here's why. Lipid solubility is inversely related to MAC, right? So if something has a low MAC, it means it has a high lipid solubility and if something has a high lipid solubility, that means it can cross the blood brain barrier really well, okay?

And obviously an anesthetics, a lot of the work, I mean they do some peripheral work but a lot of the work is in the brain. So you want them to be as lipid soluble as possible, okay? So low MAC means high lipid solubility which means high potency, okay? So it means that you don't have to give much of the anesthetic to achieve an effect because you give a very low amount, right? So that means oh, you need like a very small amount of the anesthetic to knock out 50% of people, right? So low minimum and aesthetic concentration. You give that low amount, it's very tiny, crosses the blood brain barrier in certain effect. So the potency of an anesthetic is related to the minimum of your concentration, the lower the MAC, okay? The higher the potency, the lower the blood gas partition coefficient, the quicker the onset of action. So remember these rule of laws for anesthetics. If you have low BG coefficients, you have quicker onset of action. If you have low MAC, you're more potent. Nitroxoxide is an example of an anesthetic with a low blood gas partition coefficient. So it's onset of action is like almost instantaneous, okay? Versus a hollow thing, for example, hollow thing, although no one uses it anymore because it's hepato toxic and it can also trigger a malignant hyperthermia, but it's a very high potency and a little amount for you to achieve an effect. Okay, so the inhaled anesthetics, right?

So a lot of them end in like thin or flurring and then there is mitroxoxide, which like I said has a low blood gas partition coefficient. So, mitroxoxide again, I said it has a low blood gas partition but it actually has a high minimum anesthetic concentration. So it takes a large doses of mitroxoxide for you to achieve an effect. Hollow thing has a low minimum anesthetic concentration, okay, but it actually has a high blood gas partition coefficient. So it takes a while for hollow thing to begin to work, but you need just a little dose of hollow thing to observe some kind of effect. Okay, so like I said, hollow thing triggers malignant hyperthermia, you treat that with a denture link, right? So, denture link is a calcium channel blocker, if you really get down to it, it's a ryanidine receptor antagonist. Now, for the IV anesthetics, right? So the first one I'll talk about is proper form. This is classically known as the milk of amnesia, okay? It's usually given as a lipidemotion, okay? It's an IV anesthetic because it's dissolved in liquids. Key things you want to know about proper form, it can cause severe respiratory depression, okay? And it can cause profound decreases in blood pressure. If you get an example question about a person that has like a profound decrease in blood pressure with the administration of proper form, okay? One way you can reverse that is to give an alpha one agonist, like effedrine or phenyl effort.

Now, it can also cause hypertraglicereidemia, right? Again, think of it because you're giving something, you're basically giving an infusion of lipid, okay? In fact, there's something known as proper form infusion syndrome. The big thing you just want to know about that is if you tell you about, if you give your question about a person that's getting proper form, and then they have a lactic acid dosis and a hyper-kilemia, okay? Think about proper form infusion syndrome. Now, next drug I'll talk about is keramine, okay? It's another IV anesthetic, it's an NLG receptor antagonist, okay? It's classically known as the dissociative anesthetic, okay? So the patient may be awake and like morning, but they're actually like completely out, okay? So their eyes may be open, but you if you ask them about like events after the keramine wears off, they will remember a thing, okay? That's what's called the dissociative anesthetic. It's actually kind of analogous to PCP, right? Don't forget that side drug that makes people go crazy, makes them violent, makes them have like VV dreams and hallucinations, and also like mastagmas. And so keramine does in fact have the ability to cause those kind of VV dreams as well, it can cause hallucinations. Don't forget though that there are certain drugs, other drugs that you need to know for bored exams, right? That have that VV dream association, right? So effaburant, right?

It's an anti-HIV med, causes VV dreams, remember it's a tear averaging, so you don't want to give it to a pregnant female. And then malaronis, an anti-malarial, that's like the branding, it also has the ability to cause a VV dreams. And then the last IV anesthetic I want to talk about is it tomidate. It tomidate, the big thing you just want to know is it's used quite commonly for rapid sequencing to be seen, but there's just one weird factoid you want to remember about it tomidate. The weird factoid is that it can actually cause adrenal suppression. So if a patient has a history of adescent disease, you probably do not want to put place them on it tomidate, okay? Because it actually has the ability to inhibit 11 beta hydroxylis, which is part of the pathway for the synthesis of cortisol. Now for local anesthetics, right? Slash opioids for the most part, right? So these drugs all end in K, okay? The longest active, very high you to know this. The longest active local anesthetic is bupiva king, okay? And these drugs for the most part, they kind of work like class 1, the entire rhythmic. They are sodium channel blockers, okay? And one thing that's classically done when these drugs are given is they're giving with Norepinephrine. Remember Norepinephrine has very powerful alpha one activity, right? So by doing that, you increase the effectiveness of the drugs because Norepinephrine causes visual constriction.

So the drug doesn't go away from the local spots that you want it to work at, okay? I remember Norepinephrine works on all alpha receptors and works on all beta receptors with the exception of beta 2, but its strongest effect is on alpha one receptors. And just as a quick sidebar here, remember, if a patient has sepsis, they have seculatory collapse, right? They have very diluted veins. If a patient has anaphylaxis, they have diluted veins, but they also have bronchoconstriction, that's a beta 2 effect, okay? So beta 2 blocky, beta 2 effect is, like if you block beta 2 receptors, you have bronchoconstriction. So this is why in sepsis, because at least one of your primary problems is seculatory collapse. You give something that has very powerful alpha one agonist activity, like epinephrine. Epinephrine is the drug of choice for the management of anaphylaxis. Sorry, sorry, sorry, sorry, whoops. So for sepsis, right? You have seculatory collapse, whoops, sorry about that. So for sepsis, seculatory collapse, you have massive vasodilation. So you want something with powerful alpha one agonist activity, that's why you give Norepinephrine. Norepinephrine is the drug of choice for the management of septic shock. Contrast that with anaphylaxis, where yes, you have peripheral vasodilation, but the thing that can kill you immediately is hypoxic respiratory failure from the bronchoconstriction.

So you want to give something that can cast powerful bronchoctyletri activity, something that has powerful beta 2 receptor agonist activity, okay, like epinephrine. That is why epinephrine is the drug of choice for the treatment of anaphylaxis shock. Epinephrine for the most part has very strong beta 2 effects. Now, one other thing you need to is that for the local anesthetics to actually block sodium channels, they actually have to be in the charged form inside the cell, okay? But the thing is for it to have the ability to enter the cell, remember if anything is charged, it cannot cross cell membranes very well. So we know it needs to be charged inside the cell, but another thing we know is that it needs to be uncharged, okay, to cross the cell membrane. So how does this work, right? So, or why is this relevant to our discussion? The thing is, it generally takes more anesthetic to work in injured tissue, right? Because injured tissue has a more acidic environment, okay? From all the cell death and all that crap, you have a more acidic environment, so it's much harder for those anesthetics to work in that injured tissue. And just another like sidebar here, and the reason it's more, it takes more anesthetic to work is that those anesthetics become charged much earlier, okay? So they have reduced ability to cross cell membranes. Another sidebar here is, don't forget, period xenomite.

Period xenomite is a TB drug that works really well in the acidic environment that surrounds a TB granuloma. Now, next major concept with these local anesthetics is what kinds of fibers are blocked by these local anesthetics, right? So the big overarching principle you won't remember is that smaller nerve fibers are affected first, okay? So smaller nerve fibers are affected first, okay, before bigger fibers. So size actually matters here more than my initial. So because sort of think about it this way, right? In, for example, you're given, I don't know, let's say you have two countries, right? So let's say you have country A that has a population of 10,000 people, country B has a population of 1 million people, but you give 10 million dollars to each country, right? You get higher concentrations of money in the smaller population compared to the bigger population for the same amount of money, okay? So just think of that as the reasoning behind why smaller fibers are affected first by anesthetics compared with larger fibers. And again, size is more relevant than my linearization. However, my linearized fibers actually affected first compared to on my linearized fibers, okay? So let me give you a few scenarios here. If you're comparing a small on my linearized fiber and a large my linearized fiber, which one would transmit and which one would be anesthetized first? Remember, I said size is more important than my linearization.

So the answer is small on my linearized fiber, okay? And in general, like pin and temperature modalities go away first before vibration and perception. And then let's see some other weird things about some of these anesthetics, right? And also I'll give some of these sidebar stories because they are just high-yield things that we love to test. So benzokin, benzokin is a local anesthetic, okay? But one of the things you need to know about benzokin is that it's a powerful oxidizing agent, okay? And because it's a powerful oxidizing agent, it can actually convert Fe2 plus, right? So that's like a Ferrous iron, which has the ability to bind oxygen to Fe3 plus, which is ferric iron, which has no ability to bind oxygen, okay? In fact, that process is known as the induction of methemoglobinemia, so benzokin has that ability, nitropercylate, a drug that's used for hypertensive urgency and emergency also converts Ferrous iron to ferric iron, right? So you're basically inducing meth because hemoglobin that contains a high concentration of Fe3 plus iron is known as methhemoglobin. So methelymoblu, right? It's what you can use for methemoglobinemia. You can give methelymoblu in activate methemoglobin reductase and that helps you convert Fe3 plus to Fe2 plus, okay? Because Fe2 plus is the only form that can carry oxygen. Now, a related concept to that is cyanide poisoning, right? So the thing is, remember cyanide inhibits complex form of the electron-transport chain, right?

So it basically inhibits aerobic metabolism. Now, the thing is, if you want to treat cyanide poisoning, right? So the classic example is the person that has been on like an nitropercyte drip and then they tell you the patient has like ultra-mental status and a lactic acidosis, okay? Think about cyanide poisoning because remember nitropercyte has a ton of cyanide. So that cyanide poisoning is actually treated pretty well by inducing a methemoglobinemia because Fe3 plus iron actually has the ability to bind cyanide very well. So inducing a methemoglobinemia, you bind cyanide better, okay? And then that cyanide, like the cyanide that has been bound to the methemoglobin, you then give thiosophids, that thiosophids will then complex with a cyanide to form thiosanide and that can be excreted fairly well, okay? So usually you give a nitrate, okay, to induce a methemoglobinemia like immonal nitrate, for example, and then you give thiosophids to convert that cyanide to thiosanide and then you can excreted pretty well. So that's all I think I'm going to see with an aesthetic. So let's jump to the headache syndromes, okay? These are very high yield to no-forborn exams. So they are three headache syndromes, right? So they're attention headaches, there's migraine headaches and there's cluster headaches, okay? Now attention headaches, they are the most common, right?

If you're studying for any board exam and you've been studying too hard for too many days or something, the third person probably will get attention headache, right? So it's the most common headache, it's usually bilateral, okay? High yield to know that, it feels like a band around the head and it's classically worse in the evening at the end of a long day's job, like studying for step one or step two. Now, again, it's usually due to like a monthly taxing activity and for the most part you actually treat attention headache with NSAI Ds, okay? You don't need to give like a summer trip time, for example. Now, let me just establish a concept here, although there are studies that agree with this and studies that do not agree with this, okay? So this is still kind of in flux at the moment, at least last night checked. Now, the thing is, viso-construction is good for headache, okay? Viso-construction makes headache better, that's the concept you want to, like sort of put in your mind. Think of it as a teleological concept, so you may not exactly be fully proven, but it helps you understand some stuff relating to headache. Viso-construction is good for headache, but viso-dilation is bad for headache, okay? So just think about the treatment of tension headaches. You are given NSAI Ds, which are coxine habiters, by giving a coxine habitter, you're decreasing the synthesis of Prostaglandins.

We know that Prostaglandins are viso-dilators, so by giving something that decreases the synthesis of viso-dilators, you actually the Cosmo-net viso-construction and you relieve the headache symptoms. Now, if we go to a migraine headache, right? So a migraine, it's usually like unilateral, but it could also be bilateral, so don't be swayed off by that on an exam question. Usually they'll tell you that it's worsened by loud noises, right? So that's a phonophobia, or bright lights, that's a photophobia. And migraines actually inherit it in an autosomal dominant fashion. It's very high up to know that, but they generally have multifactorial inheritance. Now, how do you treat migraines? You need to be careful here. This is how they'll try to get you on a step-on or step-toe. Migraines, there is such a thing as an acute treatment of a migraine, and there is such a thing as a chronic treatment of a migraine. If you want to treat migraines acutely, you can give drugs that belong to the triptan class. So, for the acute treatment of a migraine, right? You want to give a triptan, right? So triptans, they all end in triptan. There's like zomy triptan, risatriptan, so much triptan, that's probably the poster child one. And the mechanism of action is that they're serotonin 5 HC3 receptor agonists, okay? And by activating those serotonin receptors, you cause viso-construction. So, so much triptan, right?

Again, on all of the triptan, they're used for the acute, not chronic, the acute treatment of migraines, okay? You don't want to use them daily because there's an increased risk of stroke, right? Because again, think of these drugs as things causing cerebral viso-construction. Now, a few high-yield things you want in a relation to somatriptan, right? Is that you do not want to give it to patient with a histro-like coronary visospasm, right? Like prince metal angina, or I guess the newer term is a variant angina, or crest syndrome, because these people have visospastic disease, okay? You don't want to give them a triptan, because that can worsen your condition. Alternatively, also don't want to give somatriptan, right? I know it's in the hospital, I believe it's known as imitrex, to a patient that's on an SSRI, or on lignisolid, or on an MAOI, or TCA, because again, because somatriptan has serotonin receptor agonist activity, it can actually trigger serotonin syndrome. So, you want to be careful of that. Now, for chronic treatment of a migraine, right? You don't give a triptan, you can give propranolol, which is a bit of blocker, okay? Or you can give like a topyramid, right? Topyramid also works, or you can give like a tricyclic antidepressant.

And again, I believe I mentioned this in a previous podcast, relating to topyramid, but you know, you do know it's a seizure medication, but you can actually use it for chronic migraine treatment, and don't forget the two high ill side effects. It causes mental slowing, actually three high ill side effects, causes mental slowing, okay? It can cause kidney stones, so it increases the rates for nephrolethyases, and the third thing is that topyramid can actually cause weak loss. So, just one of those weird things you want to keep in mind. Now, for a cluster headache, right? So, cluster headache, the classic presentation is like a guy in his 20s to 30s that smokes, and it's usually a unilateral, so it's not bilateral. It's usually a unilateral headache on exams, and the thing is, on the exam, they will tell you that the patient has like toses and maiosis. So, what does that sound like? That sounds like honours syndrome, right? Well, it's a partial honours syndrome because we don't have the anhydrosis part of things, okay? And classically, they'll also see that this patient has like rinorrhea, right? That's a fancy term for runny nose, and really, the way you treat a cluster headache acutely, right? You want to give 100% oxygen. That's probably the most common exam answer you'll find on a on a boy's exam, right? So, you give 100% oxygen and a botched the headache very quickly, okay?

But other things you could give, you could give a trip 10, like so much trip 10, or you could give an Urgot alcaloid, like Urgotamine. I will talk about Urgotamine in the future when we talk about provocative testing for variant engine, but that's a topic for another day. Now, let's say some things about the neuromuscular blocking drugs, okay? So, a few things you want to keep in mind, right? So, all these neuromuscular blocking agents I'm going to talk about, they all work by blocking nicotinic, not moscorinic, nicotinic acetylcholine receptors. And we know that these receptors, at least across many podcasts, I've talked about places where you could find these receptors. You can find them at the cell member on the cell membranes of post-gangryonic neurons in the sympathetic and parasympathetic nervous system, okay? You can find them on the surfaces of the chromophine cells in the adrenomidol, remember those chromophine cells in the adrenomidol are derived from neurocrest and they're just like modified post-gangryonic sympathetic neurons. And then also the alpha-muron neurons. Actually, the the skeletal myocytes that receive innervation from alpha-muron neurons from the ventral form of the spinal cord also have nicotinic acetylcholine receptors on their surface. So, for an anesthetic to work, right? We need to do two things, right?

One, we need to put the patient to sleep, which is what I've talked about already with proper fall and ketamine and benzoes and all that fun stuff. And then the second thing is you need to paralyze the patient, right? If a patient has like increased muscle tone, those patients are very hard to intubate. So, your muscular blocking drugs, they help us accomplish the second purpose, their parallelics, their block nicotinic acetylcholine receptors. Now, these drugs fall into two categories. They're the depolarizing neuromuscular blocking drugs and they're the non-depolarizing neuromuscular blocking drugs. Now, the depolarizing agents, the thing is they actually activate nicotinic acetylcholine receptors. Okay? So, here's the way I want you to think about these drugs. The way these drugs work for the most part is that let's assume I cast a spell on someone and I tell them to lift like 500 poundweets constantly, like with no rest, no bricks, nothing, right? After a while, that person will probably like crop out and like die or something, right? I mean, obviously I'll never do that to another human being, but that would happen. So, that's the same thing with neurons. These depolarizing agents, the way I think about them is that you make them activated all the time, but if you think about it, right? Many times if you trigger an action potential, you want the neuron or the cell that has depolarized to like repolarize before it fires again, right?

So, if you just keep depolarizing depolarizing, it's like you basically don't get to a point where you can like repolarize and then have the ability to fire again, right? So, ultimately you can see how that can sort of quieten down that cell and prevent it from firing. That's really how these depolarizing your muscular blocking drugs work. So, again, they activate nicotinic acetylcholine receptors. Okay? And don't forget that nicotinic acetylcholine receptors are like and gated ion channels. And these drugs, there is a way to work well, is that they're actually not broken down by acetylcholine estaries. They're actually broken down by an enzyme known as pseudo-choline estaries. Okay? Sudo-choline estaries is so happens for the most part, it only exists in the bloodstream. It actually does not exist at the neuromuscular junction. Okay? And this is why these drugs they have a fairly long duration of action, although it's not really long if you sort of like check out the exact pharmacology. But for purposes today, right? So, this is not an anesthesia lecture because really these drugs that I'm talking about, I'm just giving you like surface level knowledge. If you actually dig a little deeper and try to like really understand these drugs, there's a lot of facts that I'm not going to mention today. That's more for like anesthesia boards or something. Or them fascinated by itself, studied it up before, but not for our purposes today. So, these drugs in general, you cannot.

So, this is look again, this is not completely true, but in general for these drugs, you cannot reverse them with an acetylcholine estaries inhibitor, right? Because the thing you want to think is, oh wait, so these drugs are blocking nicotinic acetylcholine receptor. So, if I boost the levels of acetylcholine at the neuromuscular junction, I could overcome the effects of these drugs. That is true and that is not true at the same time, okay? But in general, classically, these drugs cannot be reversed by acetylcholine estaries inhibitors. Because remember, acetylcholine estaries inhibitor, when inhibitor acetylcholine estaries, you reduce the breakdown of acetylcholine, acetylcholine builds up and you can outcompete these agents, okay? So, in general, these drugs, the acetylcholine estaries inhibitors, okay, they have no ability to reverse the effects of the depolarizing neuromuscular blocking agents, okay? That principle is known as a phase one blockade, okay? In a phase one blockade, you cannot reverse these depolarizing neuromuscular blocking drugs with an acetylcholine estaries inhibitor. However, there's something known as a phase two blockade. In a phase two blockade, okay? You actually can reverse the depolarizing neuromuscular blocking agents with an acetylcholine estaries inhibitor. So, what is the classic poster child acetylcholine depolarizing neuromuscular blocking agent? We have a succinocholine, okay? succinocholine is an acetylcholine receptor agonist, okay?

That's why I said it's a depolarizing drug, okay? And the big thing you want to know about this drug is that it can trigger malignant hypothermia, okay? And that's why you treat this with dantrolym. And again, remember, this is subject to phase one blockade and phase two blockade. In fact, if you actually give a phase one block, you can actually make the paralysis. Let's say you're in phase one blockade for succinocholine, for example, if you were to actually give that patient an acetylcholine estaries inhibitor, you could actually make the paralysis that they already have worse, okay? Versus a phase two blockade, like I said, which is reversible with an acetylcholine estaries inhibitor. If you want to know more about these phase one and these two blocks, just shoot me a message or post a comment and I'll be happy to walk you through this. It's a very complicated thing. Yeah, but that's not necessarily for body exam purposes, at least not step one and step two. Now, the non-de polarizing agents, right? So these drugs essentially work as competitive inhibitors of nicotinic acetylcholine receptors, right? So they don't change the V-max, but they do increase the K-M, right? So the affinity for acetylcholine for these receptors decrease. And these drugs for the most part, they all end in coronium and in curia, okay? And the thing is, they can actually be excreted by the kidney of the liver.

Now, anything that increases the amount of acetylcholine in the synapse will actually reverse these agents, okay? So what do I mean by that? Essentially, I mean that acetylcholine estaries inhibitor can reverse the effects of these non-de polarizing, your muscular blocking drugs. So, an acetylcholine estaries inhibitor like NIO stigma, okay? Can be given and that can reverse these effects. But let me talk about something that may potentially be an experiment-based question on any of these board exams, particularly the USML-E Step 1 exam. The thing is, if you give a patient NIO stigma, right? NIO stigma cannot decide within itself that, oh, you know what? I'm just going to go to nicotinic acetylcholine receptors, I'm not going to do any effect at most curinic acetylcholine receptors. We know that's not possible because there's acetylcholine estaries at all those acetylcholine receptors. So, if you give a patient NIO stigma, you're like, oh, wait, don't reverse the curinium, for example. The curinium, the curinium will paralyze the person by blocking nicotinic acetylcholine receptors. But, you know, like, okay, let me reverse this by giving NIO stigma. If you give NIO stigma, NIO stigma will inhibit acetylcholine estaries. When NIO stigma inhibits acetylcholine estaries, it will actually increase the levels of acetylcholine both at nicotinic synapses, okay, and at musculinic synapses, okay? So, even if you're reversing the nicotinic effects, right?

So, the anti-nicotinic effects of the non-di polarizing your muscular blocking drugs, okay? You actually begin to create pro-parasynpathetic effects at musculinic acetylcholine receptors because you are not specifically increasing the amount of acetylcholine at all these receptors, okay? So, classically, on at least in the real world, if a patient is being reversed with NIO stigma, for example, you actually add drugs like atropin or glycopyrolit. More classically, glycopyrolit is what is given, because glycopyrolit and atropin are musculinic receptors and antagonists. So, as you are boosting the levels of acetylcholine, add those like synapses that involve musculinic acetylcholine receptors because you're giving NIO stigma, you're preventing those musculinic effects, okay? While you're trying to take away the nicotinic effects from blocking nicotinic acetylcholine receptors with non-di polarizing your muscular blocking drug. So, I feel like that was confusing. So, let me just state it again. If you give, so, I'll state it again. So, a drug like the corollum, for example, is a non-di polarizing your muscular blocking drug, okay? It's a competitive antagonist at nicotinic acetylcholine receptors. If you want to reverse those effects, you give at acetylcholine receptors inhibitor because that will increase the levels of acetylcholine and that will bump the drop off the nicotinic acetylcholine receptor.

However, when you give an acetylcholine receptors inhibitor, acetylcholine receptors exist both at nicotinic synapses and at musculinic synapses. So, the levels of acetylcholine will rise to outcompete the non-di polarizing your muscular blocking drug at the nicotinic synapses, but the levels of acetylcholine will also rise at the musculinic synapses. So, to prevent those promoscaryneic effects, while you're giving the new steaming, you also give a musculinic receptor antagonist, like glycopyrolites or atropine, so that you don't get those promoscaryneic effects from reversing the non-di polarizing your muscular blocking drug with an acetylcholine estuaries inhibitor. So, you see, this is convoluted. This is why your friends at the NBM will love to test something like this, so make sure you understand this. If you need to rewind and listen to it again, I would certainly recommend that. Now, don't forget your other acetylcholine estuaries inhibitors, right? I already talked about these in previous podcasts, like phyzo-stigmin, pyrido-stigmin that's used for myastinia. Phyzo-stigmin is classically used to fix an atropine overdose, okay, an adrophonium, which is used as a component of the tensileant test for the diagnosis of myastinia gravis, okay? And then, don't forget that pretty doxine is a regenerator of acetylcholine estuaries, right? So, if a patient has like an organophosphate overdose, organophosphates, right?

They're acetylcholine estuaries inhibitors, so for that you give atropine, okay, because atropine will block most scryneic receptors. So, atropine will have like all these central effects. It doesn't have skeletal effects because for the most part, atropine does not work at nicotinic acetylcholine receptors, and then the pyridoxine will help you regenerate the acetylcholine estuaries so that you can have central and peripheral effects, because that pyridoxine will help you regenerate the acetylcholine estuaries so you can start breaking down the acetylcholine so that you can sort of dumb down the effects of organophosphate poisoning. Now, one special, actually I want to mention two special cases before we're on the off with these anesthetics. Cisatrochureum is a special, is a special case, okay? The thing is it spontaneously decomposes in the blood, okay? It's actually degraded by something known as Hoffman elimination. I'm not going to bring back bad memories for many of you from organic chemistry in college, although I kind of like organic chemistry, obviously, because I feel like organic chemistry helps you understand so many things in this world, but that's a different, different discussion. But Cisatrochureum just think of it as it sort of just falls apart in circulation, okay? And that's the process behind that is something known as Hoffman elimination, so it's actually not degraded in the liver of the kidney.

Now, another special thing you want to know is, so I don't believe this drug is in first aid, okay? But it's blockbuster enough to where I feel like it may show up on USMLA exams in the future, and this drug is known as Sugama Dex, okay? Sugama Dex is like the golden boy of anesthesia right now, okay? It's a very good drug with very few side effects, and the way it works is that it's a very strong binder of Rockureum. That is all I'm going to say about Sugama Dex, but watch out for Sugama Dex in the future. One of those things I can almost predict will shop on board exams in the future. Now, next set of drugs I want to talk about are the opioids, and this will be the last set, and the next podcast I'll probably talk about like Ipharmacology. Okay, although I mean fused out with a neuro podcast, but we'll see. So opioids, right? So opioids are a mere receptor agonists, okay? And the thing is when we bind to these mere receptors, they actually cause a decrease in the release of neuropenefrein, okay? So when you activate mere opioid receptors, you cause a signaling cascade that causes a decrease in the release of neuropenefrein. Is there a particular adrenergic receptor that kind of works the same way? Well, I hope you're thinking of alpha-2 receptors. Alpha-2 receptors, if you gave an alpha-2 agonist, remember alpha-2 receptors are GI coupled, you have a decreased release of mere penefrein.

So this is why drugs like clonidine, which are alpha-2 agonists have become like street drugs because they can actually make the, we draw from opioids, feel better because they essentially work like opioids, right? Because we said opioids decrease the release of neuropenefrein, alpha-2 agonist also decrease the release of neuropenefrein, right? So that's why clonidine is like a street drug now. So it's now like very tightly controlled, at least in a hospital circles. Now, there are other endogenous opioid receptors that you want to know for step one and step two, believe it or not, these things show up, right? So the mere opioid receptors, the endogenous opioid that we make in our brains that activates mere opioid receptors is beta-endorphine, okay? And then if you're thinking about the coupled opioid receptors, the endogenous for those is dynorphine. And then if you're thinking about delta-opered receptors, the endogenous agonist for that is in kephaline, okay? So just wear things, those wear things you want to keep in mind for the future. Now, the thing is mere receptors, you actually find them in the GI tract, okay? And the thing is they actually decrease GI motility. So you could see how you could use this to your advantage. If a patient has diarrhea, you can give a mere opioid receptor agonist like lopairamide or diphenoxylate, okay? Lopairamide, I believe that's the consequence of immodium, okay? Immodium contains lopairamide.

That's a mere opioid receptor agonist, so that decreases GI motility, so that can decrease the symptoms of diarrhea. Now, the thing is in general opioids, right? So I said that they decrease the release of neuropinephrine. So if you're decreasing the release of neuropinephrine, are you supposed to find meiosis or mydriasis? Well, I'm hoping you're thinking meiosis, okay? Because if there's less neuropinephrine around, there's less activation of alpha-onoreceptors in the GI, so there's less mydriasis, so there's more meiosis. So, high yield thing you want to know here is that opioids cause meiosis, okay? And again, because they decrease GI motility, they also cause constipation. Now, why am I mentioning these two things together? The reason I'm mentioning these two things together is that it's very high yield to know for bored exams that you can never get tolerant to the meiosis and constipation side effects of opioids. You can never get tolerance to any of those things, okay? And it so happens that there's actually one opioid that does not cause meiosis, it actually causes mydriasis. And that opioid is known as myperidine. Myperidine, in addition to being an opioid, you may be able to see like, okay, do I wait? Why does it cause mydriasis? The thing is, in addition to being an opioid, it's actually a mascarinic receptor antagonist. So, if it has mascarinic receptor blockade activity, right?

You can see that, remember, if your parasympathetic system usually goes with meiosis, right? So, if you block your parasympathetic system, you get mydriasis. So, you do not get meiosis with myperidine because it's a mascarinic receptor antagonist. And it so happens that myperidine also does not cause spasm. Although this is like a weak effect, no one really thinks too hard about this in the hospital. But it causes sphinter of odyspasm, okay? I mean, sorry, it does not cause sphinter of odyspasm, okay? So, you can use it in people with like pancreatic and bilirid disease, right? So, if a person has like, like, really severe epigastric pain from pancreatitis, and you don't want to make their pancreatitis worse, you can give them myperidine. Myperidine does not cause spasm of the sphinter of odyspasm. So, the pancreas can keep draining right. Although, that's a weak effect, but it's just one of those weird things that they love to like pimple people on the world. So, just keep that in mind. Now, opioids, right? We all know that the cause respiratory depression, right? So, it suppresses like the medulla and the central nervous system. And you can actually reverse an opioid with naloxone, right? If you've worked in any eating, you've probably heard of NARCAN. NARCAN is naloxone. NA Loxone is a quick actin, opioid, new opioid receptor antagonist, okay? The thing is, there is another new opioid receptor antagonist as well that you read about in texts. Now, Trexone.

Now, here's one thing you want to be careful with. Now, Trexone is a long actin, new opioid receptor antagonist, okay? It's kind of like a maintenance treatment. If a person acutely has respiratory depression from taking, from overdosing on an opioid, you want to give naloxone, not naltrexone. Now, Trexone will not kick in fast enough, okay? To save the patient. You want to give naloxone not naltrexone. Now, Trexone for the most part is used for maintenance treatment. And it's also used for like, actually, I'll say for the most part, if you think about naltrexone, think about it as something that helps people stop drinking alcohol, okay? It's used to drink like a chronic alcoholism. Really, for the most part, people don't use naltrexone to reverse opioids. People use naloxone, because naloxone works fast. Now, so if a patient overdoses on opioids, obviously they'll have respiratory depression and they'll also have meiosis. But what if you get an exam question that talks about a patient that has respiratory depression and they have like a normal pulpit, right? They have like normal, pulpularity findings. What are you thinking about? Well, I hope you're thinking about a benzene or a bit worth overdose, okay? Remember, we've talked about benzene already. We said that you can reverse benzene with flomazineol. Flomazine is a GABA receptor antagonist. You can actually also reverse Z drugs, right?

So, like your Zopidem, your Zaloplone, your Zopiclon, you can actually reverse those with flomazineol, as well. However, you cannot reverse a bit of it with flomazineol. And then while we're on the topic of opioids, right? Don't forget your pre-norphine. It's actually a partial mu opioid receptor agonist. You can actually use it to treat like opioid dependence. I believe this is one of the components of suboxone. You can use it to treat opioid dependence because it gives you like partial opioid effect, or doesn't give you the full effect, okay? But one thing I want to mention here though is that if a patient, for example, has overdose on an opioid, you actually don't want to give pre-norphine because pre-norphine by giving something that is a partial agonist at new opioid receptors, you are actually making it sort of an antagonist, right? So, if you remember from previous podcasts, we've talked about acybutolol and pindolol in the context of bitter receptors, right? We said that they are partial bitter receptor agonists, okay? But in the presence of a full bitter receptor agonist, they're giving you like less than full effect. So, they're actually acting as antagonists. That's the same thing with pre-norphine. If a patient is in like an opioid overdose, I mean, sorry, if a patient is like very dependent on opioids, right? So, like an opioid dependence kind of scenario. Initially, you may want to like lay off the pre-norphine, okay?

Because by giving them that pre-norphine acutely, you're actually sort of causing like an opioid antagonism effect because it's a partial mirror receptor agonist and that can actually trigger withdrawal, okay? So, you want to be careful with that. Now, morphine is another high-yield opioid, right? So, it's actually metabolized by gluconeidation. So, you basically convert it from morphine to morphine 6 glucoronide, okay? morphine 6 glucoronide is actually a lot more potent than morphine itself, okay? And now, if a patient has an activating mutation in the enzyme that makes that glucoronidation happen, those patients will generally need a smaller dose of morphine, okay? So, they could give you an exam question and sort of mask it as a genetics question where a patient gets like too much more, like they get like a mummob dose of morphine and then they have like profound respiratory depression, right? You want to go ahead and obviously give them an oxon first, but then you say, oh, like what's the mechanism behind this? The mechanism behind this may just be that they have an activating mutation in the enzyme that makes that glucoronidation happen. And then coding, right? So, coding is a drug that's found out, it's found in many like cough mixtures, it's also actually metabolized to morphine, okay? And then you give an exam question, where a person gets like cough syrup and then they die or something from taking that cough syrup.

The thing you want to think about is that again, they have an activating mutation in the enzyme that converts the coding to morphine, okay? So, coding actually is metabolized to morphine. So, just one of those weird things you want to keep in mind as well. And then the final drug I'll mention today, because this podcast has gone along the office, Dextramethorphan. Dextramethorphan is an opioid that is also an NMD receptor antagonist, okay? It's actually used as a cough suppressant, okay? And you can reverse Dextramethorphan because it's an opioid with the loxone. So, that's all I'm going to see here. The next podcast I will talk about I-pharmacology and then we will essentially be done with neuropharm, okay? It's very high up to know for exams and it's kind of a lot of information, but just learn a bit by bit and you should be good to go for your tests. So, I'll have a podcast on I-pharmacology and that will be the end of the neuropharmacology series of podcasts. So, I'll see you at a different time, most likely tomorrow. Thank you.

Size matters more than myelination; the smallest fibers are most susceptible to blockade.

Propofol (Milk of Amnesia).

They activate mu-opioid receptors, causing a decrease in the release of norepinephrine.

Naloxone (a rapid-acting full agonist).

Unilateral, severe pain often accompanied by lacrimation/rhinorrhea; treated acutely with 100% oxygen.

Codeine (because it is metabolized to morphine).

Anaphylaxis; Epinephrine.

Etomidate.

Myperidine (because it is also a mA ChR antagonist).

Tension headaches, Migraine headaches, and Cluster headaches.

Triptans (e.g., Sumatriptan).

Malignant Hyperthermia; Dantrolene.

Anaphylaxis; Epinephrine.

Etomidate.

Myperidine (because it is also a mA ChR antagonist).

Tension headaches, Migraine headaches, and Cluster headaches.

Triptans (e.g., Sumatriptan).

Malignant Hyperthermia; Dantrolene.