[Music] what's up guys this is muscle relaxants for the USMLE step one by step one domination so the mecca notice of action is pretty simple the action potentials propagated down the axon it reaches the presynaptic membrane where the action potential causes the voltage-gated calcium channels to open up and cause an influx of calcium that influx of calcium is going to cause the vesicles with the neurotransmitters to exocytosis and fuse at that presynaptic membrane and release the neurotransmitters these excitatory neurotransmitters are going to travel across the cleft and they're going to act as ligands at these nicotinic receptors and when they bind these nicotinic receptors you're gonna have a depolarization or you could have a non depolarization depending on the class of muscle relaxant and it's gonna cause if it's a issue of a depolarization like succinylcholine it's gonna cause sodium influx and thus also cause potassium efflux to sneak out and that will show one of its effects for later if it's a non depolarization let's draw another one say there's a non depolarization one binding here the non depolarization the nondepolarizing ligand will bind and it will basically just antagonize so it's just gonna antagonize the nicotinic receptor here whereas succinylcholine or the depolarizing agent is gonna act as a partial nicotinic receptor agonist and that's as simple as that that's the two classes that we're going to talk about so moving forward looking at the classes the first class that I mentioned was the deep polarizing agents then the main one to know succinylcholine succinylcholine and in this this drug acts you may be wondering if it's a depolarizing agent how do you have the effects of muscle relaxation wouldn't you have muscle contraction well year you would be right and what there's two phases of this the first phase is when you is when so if we're back at the synaptic cleft here's the presynaptic membrane here's the postsynaptic membrane and here's the cleft we have all of these neurotransmitters and let's say in this case this is succinylcholine here's the nicotinic receptor where succinylcholine will bind and this will cause a depolarization but you have to remember something from pharmacology this is not a cetyl choline this is succinylcholine if it would have been acetylcholine acetylcholine is broken down by acetylcholinesterase which is at a very high level in the synaptic cleft because this is succinylcholine because this is succinylcholine succinylcholine is broken down by pseudo cholinesterase and pseudo cholinesterase is at a very low level in the synaptic cleft because of this it's it's very difficult to clear the succinylcholine and get it off of these nicotinic receptors and because it acts as a depolarizing agent as an agonist in this site you're gonna have sodium influx and you're gonna have potassium efflux at a very high level thus one of the side effects that we're going to talk about you're gonna see here hyperkalemia that's why that happens you're also going to have a massive level of sodium influx and depolarization this action potential signal is going to be propagated down these T tubules that will then enter into the muscle cells and remember in the muscle cells the sarcoplasmic reticulum releases calcium whenever the action potential reaches it this release of calcium is caused controlled by the ryanodine receptor and that will explain this side effect vo sorry the malignant hyperthermia right here malignant hyperthermia so those two effects are explained just from the mechanism of action you also have but as far as back to the phase one and Phase two in phase one this is just simply when the drug first binds you're going to have that massive depolarization and fasciculation is just a fancy word for saying like at which a muscular twitch so you could have a lot of muscular twitching that can be evident when you look at the patient they could see it and you know anywhere in the body where there's muscle you could see this and that's gonna be the first faith and that's just because this massive sodium influx this is an action potential this massive sodium influx is causing actually high depolarization which is causing a really high action potential propagation to come down here so tons of action potentials are being sent with little inhibition because of the low suit of cholinesterase and this is going to cause a ton of muscular contraction dusta fasciculations but after this when the succinylcholine unbinds here and when you know acetylcholine is now free to bind again the problem is that acetylcholine or succinylcholine can't by now because the receptors will desensitize there's such a massive input of propagation to have muscle contraction that your body will basically adapt and it will lower the number of receptors that are on the postsynaptic membrane so when this succinylcholine now is unbounded it's done doing its job all of a sudden you can't even get acetylcholine to forget the succinylcholine bond you can get you can't even get a single coin to mine and this is gonna cause now the effect that we want in the muscle relaxant class that is the muscle paralysis and that's in Phase two another important point to note phase one the fasciculation part of succinylcholine has no antidote well that's not too much of an issue because if you're just dealing with muscle twitching as long it's not completely out of control that's not a real serious issue the serious issue comes in with muscle paralysis especially with respiratory muscle paralysis if you paralyze the diaphragm from getting too much succinylcholine you have a problem but luckily there is an antidote the antidote for here is acetylcholinesterase inhibitors acetylcholinesterase inhibitors some drugs that are that fall under that purest IgG main neostigmine those are the two main ones you could put Edra phone IAM in here too but that's an aura I apologize for that you could put edger or phone IAM in here too but Andhra phone eum's more use as a diagnostic tool for some diseases that we'll talk about in other videos you cannot put physostigmine in here do not use physostigmine in treating this phase to muscle paralysis because physostigmine remember is lipid soluble and lipid soluble drugs can cross the blood-brain barrier so you're gonna have CNS effects if you give that you do not want CNS effects when treating this so you want to give one of these three probably preferably one of these two alright so that covers a lot of the main points of the deep polarizing agent succinylcholine you have the ADR fasciculations muscle paralysis phase one and phase two respectively you have malignant hyperthermia I've explained because of the the Ryan and Dean too much right at E and receptor activation from the action potential being propagated down the T to be over here in the picture I drew and releasing tons of calcium out of the circle plasmic reticulum of the muscle cell and then you have hyperkalemia remember I said that this depolarization this succinylcholine binding to this receptor will cause a sodium influx but you also have potassium level a potassium ion sneaking out of that same opening because remember there's higher levels of potassium in a cell than outside the cell so I hope that explains it all well for that next clot that you get a ton of questions from succinylcholine alone so it's very important to know those main points next section is going to be the nondepolarizing agents you have kirari like and amino steroids those are the two subclasses within these nondepolarizing agents the core Ori like you need to look at the suffix for curium anything that has the suffix curium you see curium you see here Miha curium atracurium you see the ending and all of these right that's gonna give it away that this is under the quarry like a subclass of nondepolarizing agents so it's a satiric uranium i know it may not be pronounced this way but i pronounce it this way when i see sis atracurium i see curium and sister if you think of like sisters in a Catholic Church they're they're very like you know they're very like holy people and safe people to be around so this is the safe drug in the karora like category look at it has everything good it has long duration so that's good it has a long effect Klee it's cleared in the plasma and so since it's clear in the plasma you don't have any sort of um issue with renal like say somebody is in renal failure or liver failure that's not an issue if you're taking sassette your curium because it's clear spontaneously in plasma so it's safety you don't have to adjust the dose in those patients and also you don't have any histamine release you will see a trend of a history meaning release especially with a medic urine that we're about to talk about there's there's no histamine release in this drug so a patient who is asthmatic or who has a let's say you had a lung pathology where you were at you had emphysema or you had a restrictive lung disease you would not want to bronchospasm from the histamine release this is the drug to give this is the safe one to give and that's kind of how a question could be set up on this step movor curium this is the bad one this is a short-duration you need to drop you need a taper or lower the dose if a patient is in renal or if they have kidney or liver failure or any sort of renal or hepatic problems you need to lower the dose because it's cleared by not just by plasma button but by these some of these mechanisms as well and also um oh this is a kind of in a weird spot this has histamine release you have to remember that this mythic curium is known for having histamine release this is going to lead to bronchospasm and everything else you're gonna think an allergic reaction so you need to really be mindful that a patient who has bad allergies in a patient who is asthmatic all of these things can be a really detrimental and a patient who has taken me curium with atracurium it's it's a lot of it's just the same as Justice atracurium so just think of all it's relatively safe kind of the prototype time drunk for the next one of the amino steroids this is the second subclass this is going to be the caronian drugs now up here we saw curium Suffolk's this is caronian Suffolk's so here are the drugs pancuronium look at the ending 'i'm like i said this has a side effect of a muscarinic blockade urns it's called Vega lytic and it's also clear renal e so this is important because remember muscarinic s-- when you hear muscarinic you need to think parasympathetic effects I know I know that's kind of oversimplified but that's the way you can really understand what its gonna do somebody who has parasympathetic effects you're having the opposite of sympathetic effects and you know that with sympathetic effects it's a fight-or-flight response everything that would need to happen when you're running from some some danger so in a sympathetic your response you're gonna have increased heart rate increased blood pressure pupil dilation to bring in more light so you can be more aware of what's going on with parasympathetic it's all the opposite you're gonna have smaller pupils you're gonna have a decreased heart rate decrease blood pressure and you're also gonna have increased digestion so anything that would help with digestion you're gonna have increased salivation increase GI motility you would want to go to the bathroom or with a parasympathetic response but in this case we have a muscarinic blockade so it's in essence they're telling you that you're gonna see sympathetic effects you're blocking the effects of parasympathetics so in this case a common way they'll present this is increase heart rate or increase blood pressure keep those in mind okay Vega lytic and this is cleared renal e this is important because if a patient is in renal failure this could make the situation worse you would have to adjust the dose or maybe not give it at all another one here in this category is rocuronium as we move on rocuronium RR rocuronium rapid onset so this is one of the most rapid onset within this amino steroid class the last one to vecuronium there's really nothing to say about that so that is a quick rundown of muscle relaxants let's get into some questions okay here's the first question and I'll read this and then if you need to pause the video you can pause the video but I'll go ahead and start explaining after the reading and the explanation a patient who is in need of mechanical ventilation is administered a Meccan as part of the protocol prior to the procedure a minute after the medicine is administered the patient experiences multiple muscle twitches that's important multiple multiple muscle twitches in her operation which of the following mechanisms of action describe the drug most likely given before the vent mechanical ventilation that caused this side effect so you can see a minute after the medicine is administered this this is a very rapid acting and it also is causing multiple muscle twitches in the upper chest so we're seeing fasciculations as the first presenting side-effect a minute after it's a given so you need to I'm hopeful iing that you can be thinking that this is going towards the VD polarizing agent succinylcholine that's the that is the one drug that calls us in phase one effect you will see it will cause muscle twitching which will then lead to a muscle paralysis so the answer is see here this is a depolarizing agent okay the next question a patient is in need of a muscle relaxant that does not carry the risk of malignant hypertension with it okay so the patient needs a drug with no risk of malignant hypertension the patient has a serious seasonal allergy issue and it's closely monitored as it relates to the patient's asthma so this is showing the patient has asthma and allergies okay so I hope I hope you're beginning to think of what drugs you can give him which ones you can't the patient was born with a congenital ectopic foci that causes chronic tachycardia okay so we this is telling you half the patient has chronic high heart rate which of the following medications would be best for the patient let's go through and say what we shouldn't give we're looking for a muscle relaxant that does not carry the risk of malignant hypertension so we need know so first let's do it like this which drugs cause malignant hypertension this is incorrect hyperthermia hyperthermia that's a Mis type so which of the ones causes malignant hyperthermia remember that's with your Anna Dean receptor and the one that causes that is succinylcholine the reason that's the only one that causes that is because that's the only depolarizing agent that we've talked about so you can't give succinylcholine egg so this is saying which of the following medications would be best for the patient well you don't give that the patient would good could have a risk of going too malignant hyperthermia alright next the patient is a serious seasonal allergy issue and it's closely monitored as it relates to the patient's asthma so we can't give a drug that's gonna cause histamine release because remember histamine release can cause bronchospasm an anaphylactic type situation especially in someone with asthma so what are the drugs that would cause a histamine release well mother curiam remember medve curiam is the one that can cause that so you can't give him a vacuum the safe one would be a sis atracurium right or as I pronounced it sister curiam because sisters in the Catholic the Catholic nuns are very safe to be around that's the safe drug in that category okay and let's read again the patient is born with a congenital ectopic foci that causes chronic tachycardia as well so the patient has a really high heart rate so you can't give a drug that is going to cause anything that would increase your blood pressure so which of these drugs may increase your blood pressure give you a second to think about that so remember it's not just it may just not be that clear me see you can see that we know that there's a drug that causes a muscarinic block we know there's a drug that does that so the drug that causes the muscarinic block is gonna be pancuronium remember pancuronium there's the endings to help you caronian curium curium so that'll help you distinguish member curium it's a kirari like caronian it's gonna be the amino steroid class succinylcholine you just have to know that's the depolarizing agent so you can't give pancuronium cuz that would be a put a muscarinic block and that would increase your heart rate this would increase heart rate so you can't give that so that's eliminated well fen a twin that's just you need just I made a previous video that is am anti epileptic as so is carbamazepine so they're not even you're trying to have a muscle relaxant that's not what those are so the answer is C okay so I hope this helped I will see you in the next video please like subscribe leave me any sort of comments or what I can do to make it better and I will see you soon you