Antiarrhythmic Drugs

foreign what's up Ninja nerds in this video today we're going to be talking about antiarrhythmic drugs there are so many of these so much to talk about I want you guys to stick in there with me hang in there with me I hope that at the end of this video you'll truly be able to understand this and Ace any questions that you get on your exam if you guys do benefit from this video it helps you it makes sense please support us and one of the best ways that you can do that is by hitting that like button commenting down in the comment section and please subscribe also I really urge you guys our engineering team works really hard to make some awesome illustrations and notes that are kind of built on this whiteboard lecture so get those follow along with me and I think that it'll really enhance your learning experience so check that out we'll have a link in the description box below which will take you to our website all right without further Ado let's get into antiarhythmic medications though but I'm going to kind of get there in a second all right so anti rhythmic medications are pretty challenging when you look at them in the entire Gambit of everything that we have to cover what I think will really help us first is to cover a little bit of physiology so we have to go back into that kind of anatomy and physiology part into the cardiac physiology section and really remind ourselves of the action potential all the phases all the channels all the ions that are kind of involved in that phase is so that whenever we start talking about these drugs and their mechanism of action you'll know which channel which part of the curve which tissue of the heart it's actually going to be affecting and that's really really important so let's take a quick second to go through that so in the heart tissue what I want you to know is that we have two types of like myocardial tissue one of those myocardial tissues is the ones that conduct like action potentials either generate it or they conduct Action potentials in other words you have these cells have the ability to intrinsically depolarize themselves they don't depend upon the nervous system because you know how when tissues in order for them to kind of depolarize the nervous system has to release neurotransmitters on them and then cause them to depolarize these guys have the ability to do it on their own and so they can intrinsically depolarize and generate Action potentials throughout the heart so those are called like your pacemaker cells or your nodal cells if you will there's a lot of them so they kind of start here at your essay note at the top of the right atrium near the superior vena cava right atrial Junction so you have your essay node what it does is it generates Action potentials and these this is the primary kind of like pacemaker of the heart so it'll send action potentials throughout the Atria and eventually throughout all these atrial cells it'll eventually converge onto the AV node which is the nodal cell right there at the kind of like the Gateway between the Atria and the ventricles so you have your essay node then you have your AV node from The Av node let's say that the SA node failed it did no longer you know generate the action potentials the AV node has the ability to generate Action potentials but if it doesn't it receives the action potentials and then conducts it through him down into the bundle of hiss or the AV bundle then from The Av bundle it goes into the right and left bundle branch from there it'll go into your purkinje fibers and so they have the ability to generate action potential so if one fails the other one can take over so your essay node is the primary pacemaker but it'll send the action potentials through the AV node through the bundle of His the bundle branches in the purkinje system so it's important to be able to remember that that our pacemaker cells are primarily going to be in kind of a sequential favor here your SA node and then it'll conduct action potentials that'll move down to the AV node and then from The Av node that'll go into what's called your bundle of his and then from there it'll go into your bundle branches and then from here it'll go into your purkinje fibers so that's kind of the order of how this kind of information is sent and for this this is significance of this this will be the generator so it'll send these Action potentials from the SE node he is the pacemaker of the heart so he's truly the one that has the intrinsic automaticity that term that we talked about if he fails the AV node will take over and it'll gain the ability to do that if the AV node failed and the bundle of hiss would gain the ability to do that if the bundle of hiss lost it then the bundle branches would be able to do that in the purkinje system I think though one of the most important things to remember is out of all of these pacemaker cells the two most important ones that you really need to actually have some degree of survival and adequacy in life is you really need to remember your essay node and your AV node these are the primary pacemaker cells if you did lose your acetone your AV node took over you'd still be able to have enough to to have a heartbeat adequately but if you lost the AV known you're depending upon your purkinje system that's not enough adequacy to be able to properly live so it's important to remember that these are the two pacemaker cells what we'll do is is I'm going to take a pacemaker cell over here so I'm going to look at AV nodal and Essay nodal cells here and I'm going to take a piece of these tissues here so I'm going to take a piece of this essay nodal tissue a piece of these AV nodal tissues and I'm going to zoom in on one of these cells and look exactly at how the action potentials are occurring in these cells so how does that work it's really cool actually let's say here and this essay nodal cell or AV nodal cell I have this really interesting channel here in Orange so this interesting channel is called a funny sodium channel it's called a funny sodium channel so sometimes we denote this as like I F it's a funny sodium inward Channel what happens is this channel is usually always kind of like open and what it does is it allows for sodium to trickle in to these actual essay nodal cells and AV nodal cells so the sodium will trickle in to this actual pacemaker cells and if it does it'll bring some degree of positive ions into the cell now why is that important well if we look here at a graph this is going to be a graph representing the pacemaker cells the essay nodal and AV nodal cells these cells have something called a resting membrane potential this is the potential at which the cell is at rest it has not been stimulated it's ready to be stimulated at any moment but whenever we take the cell in order to be able to get it to be stimulated to open up specific channels which is going to be represented here in this actual pink one this is called a voltage-gated sodium Channel and really in order for me to activate that voltage-gated sodium Channel I have to bring the resting membrane potential to threshold how do I do that well usually that's where nerves will stimulate something and bring it up to that point well this channel is kind of always open this inward sodium Channel a funding sodium Channel and what it does is it'll bring the resting membrane potential close and closer and closer to the threshold potential so who is responsible for this one this right here is the job of the funny I'm going to put like the little Channel there this is the job of the funny sodium Channel that'll bring the cell closer towards the actual threshold potential so what is this potential at negative 40 this is the threshold potential the funny sodium channel will help with that so it'll offer a little bit of sodium to trickle in on top of that once this funding sodium channel is open these positive ions here they can activate another Channel nearby and this channel is called T-Type calcium channels either called T type T type calcium channels now when these open they allow for a little bit of calcium to be able to trickle in to the cell so now it's going to allow for a little bit more positive ions to trickle into the cell and make the cell again more increasingly positive so now if we make this cell more increasingly positive with the funny sodium channels and then on top of that we make it even more positive with the T-Type calcium channels that should bring it to threshold potential so who is really allowing for this process to occur for me to bring the resting membrane potential to threshold potential slowly it's the job of two particular channels one is the job of the funny sodium Channel and then later it's the job of the T-Type calcium channels now once it brings it to threshold potential now we're at an actual potential negative 40 millivolts where the voltage-gated sodium channels which are currently closed at rest open once they open these are called your L Type calcium channels these are called your l-type calcium channels they really allow for a ton of calcium to flood into this actual pacemaker cells and make the cell extremely positive to the point where now this thing is going to shoot upwards and usually above one of the peak potentials which is zero millivolts it'll pop up all the way up here so who is responsible for this this upward phase here is due to the l-type calcium channels being opened and calcium flooding into the cell making the cell super super positive now the cell is depolarized and once it's depolarized it can then have another way of being able to spread these Action potentials this positive charge onto another cell do you know how it does that it's really cool there's another cell maybe right next door to this one and the way that it may communicate with a nearby atrial cell so let's say that the SEO it's the one that generates the action potentials it'll send the action potentials and it'll send it to other atrial cells via what these little things here called Gap Junctions and then some of these positive ions will leak over into the nearby cell and generate an action potential in that next cell so that's really really a cool concept here but nonetheless let's keep going through the channel processes here once we get to the positive charge here we get above zero millivolts what happens is the voltage you get a calcium channels close so once you get them to the peak point of good the actual depolarization they start to close as they start are to close what happens is now no calcium will be flooding in usually the funny sodium channels and the T-Type calcium channels they should be closed at the point whenever they hit threshold potential so once the thresh once the threshold potential is hit these generally close and the voltage-gated calcium channels open calcium rushes in once it gets really really positive above zero millivolts the calcium channels will close once they close another channel will start to open and this channel nearby here is actually really kind of cool and this is called a voltage-gated potassium channel so what is this channel here called on the side here this is called a voltage gated potassium Channel this will open once the actual cell is super super positive it'll activate this Channel and this channel which was once closed is now going to open and it's going to allow for a ton of potassium ions to leave the cell if positive ions are leaving the cell what's going to happen to the charge inside of itself you're losing positive ions you're going to now make the cell super super negative and what that's going to do is it's going to cause this actual voltage to start moving downwards until you head to resting membrane potential so who's going to be responsible for the downward phase of the action potential this is due to the voltage-gated potassium channels so the voltage-gated potassium channels are going to be the ones responsible for this downward phase okay and then what happens is you'll get to the resting membrane potential and it'll be maintained for a while and the way that we maintain the resting membrane potential is through these other pumps called sodium potassium ATP Aces and all these are going to do is they're going to pump sodium out of the cell and they're going to pump potassium into the cell because they're trying to regenerate the concentration gradients so you've been pushing potassium out of the cell you've got to replenish it and push it back into the cell and then on top of that you were pushing sodium into the cell you got to push it back outward so you have it available you want to regenerate those concentration gradients but whenever you do this you actually have more positive ions that are actually going to be again leaving the cell than positive ions are coming into the cell and that kind of just allows for this cell to be in a resting state so resting membrane potential may be maintained for a little bit via these sodium potassium pumps but then once it's at rest for a while guess what happens the funny sodium channels open once they do that they cause the T-Type calcium channels to open once the T-Type calcium channels open they cause the cell to go to threshold potential voltage-gated calcium channels open they go upwards above zero millivolts they close voltage-gated potassium channels then start to open and eventually they go to Resting membrane potential which is maintained via the sodium potassium ATP Aces that is how this all works within the sa nodal and AV nodal cells my friends this is how that processor generally occurs so that is what I really want you to understand but there's actually one other thing that we have to add on here we utilize terminology of phases which are going to come up a lot whenever we talk about the mechanism of action of these drugs which is really important there's phases to this upwards of this pacemaker potential due to the funny sodium channels and the T-Type calcium channels and this phase is called phase four okay it's called phase four so it's whenever you're going from resting membrane potential up to threshold potential then whenever the usually at the end of phase four going into this next phase where we really have the rising phase where the l-type calcium channels open this is called phase zero then afterwards we go into this next one which is a little odd it looks you'll understand later when we get into the non-pacemaker cells but once the voltage-gated calcium channels close and the voltage-gated potassium channels open and you have this downward phase going towards resting membrane potential this is called phase three so again recap phase four is the resting to threshold due to the funny sodium channels and T-Type calcium at the end of phase four going upwards phase zero is the voltage-gated calcium channels are the l-type calcium channels and then going downward the downward phase of the action potential is due to voltage you get a potassium channels this is phase three very very important to remember that this is the way the action potentials occur and are conducted within the pacemaker cells most primarily the assay node and the AV node okay that's super important what we now need to talk about and then one more thing here is that the way that this types of action potentials are are generated are not as fast they're kind of a slow kind of action potential type of tissue so that's a really important to remember is that this is kind of what's called a slow action potential tissue now let's talk about the other scenario okay now we have the other parts of the cardiac tissue that is not a part of this black system here the SC node the AV node the bundle of hiss the bundle branches and the purkinje fibers we're talking about any other atrial or ventricular tissue that's not a part of that nodal system most significantly the essene or the AV node so now I'm talking about maybe this tissue here in The ventricle or this tissue here in the Atria that is not a part of the nodal system so all we need to write down here is that this is any type of atrial or ventricular myocyte that does not have any intrinsic automaticity in other words it doesn't have the ability to generate these what's called pacemaker potentials this phase four that's only the capability that can be gained in pacemaker cells so they don't have that intrinsic automaticity to generate their own Action potentials and cause them to produce them and then generate and pass it on to other cells these cells don't have that so they're non-pacemaker producing cells so how do these ones actually allow for the conduction of action potential and then generate Action potentials well the way they do it is imagine here is a pacemaker cell so here's like a nodal cell of some type right or maybe it's another you know myocyte atrial ventricular myocyte but it received Action potentials from this pacemaker cell what did I tell you is here that is allowing for communication between these cells Gap Junctions and GAP Junctions can allow for some degree of positive ions to enter into the cell and once they allow for these positive ions to enter into the cell from a nearby pacemaker or nearby ventricular atrial myocyte once they get in they can actually kind of cause this action potential process to occur which is really interesting so how does it actually occur well again going back here here's going to be a graphical representation of the atrial or ventricular myocytes and how they generate Action potentials or allow for the conduction of action potentials well here on this graph here we're going to have negative 90 millivolts in this Atrium ventricular monocytes this is referred to as their resting membrane potential now these actual atrial ventricular monocytes can have threshold potentials but they're kind of variable and they're not super significant in the discussion of this actual lecture what's really important is what happens in this process here is that let's say here we have an atrial ventricular myocyte some positive ions leak into it it's in resting state right it's an arresting State what happens is these Gap Junctions so this is your Gap Junctions allow for ions to pass from this cell to this cell it makes the cell just a Teensy bit positive enough positivity that what it can do is it can activate these channels here what are these channels here in blue these channels are called voltage-gated sodium channels what are these ones here called these ones here in blue are called your voltage gated sodium channels super important here guys I really want you guys to pay attention at this point here because what happens is once these are open they're going to allow for sodium to flush into the cell extremely quickly this flies in like a son of a gun and it makes the cell extremely positive very very quickly so we can go from zero to 100 real quick all right so what happens is that negative 90 millivolts Gap Junction is allow for a little bit of ions to trickle in to activate these voltage-gated sodium channels when they open up it'll go and have this acute rise so it's going to go here from here and it's going to fly straight up okay so it's going to fly straight up and this is usually Going To Fly Above kind of zero millivolts which is part of the peak potentials generally and this is actually going to come up really really high due to what what channel is responsible for this it's that blue Channel there this is due to the voltage-gated sodium channels all right so voltage-gated sodium channels open and they allow for this cell to go from resting membrane potential all the way up and generate this positive phase or Rising phase of the action potential once it does that and the cell becomes super positive what happens is we'll talk about this a little bit later but sodium channels have different types of gates if you will they have what's called a activation gate an inactivation gate when they're at the resting state what happens is they're inactivation gait in this situation is actually going to be what it's going to be open and then their activation gate is closed once you kind of get them out of that resting state and stimulate them their activation gate opens and sodium floods in then once you hit this positive point of the action potential they're inactivation gate closes okay and so now sodium can't come into the cell anymore now once that happens and it starts kind of like closing off what it does is it activates two channels so once this cell gets to this very very positive type of charge inside of the cell it's going to activate two particular channels that can activate this channel and it's also going to activate this channel here it's going to activate these two particular channels this pink channel here is called your l type calcium channels and once they're activated they're going to allow for calcium to rush into the cell and then this is going to be a voltage gated sodium I'm sorry potassium Channel potassium Channel and they're going to allow for potassium to leak out of the cell and positive ions are going to leak out of the cell what happens first is what happens first is once we get upwards so once sodium rushes in and it makes the cell super positive it activates the voltage gate of potassium channels just a little bit earlier than the voltage-gated I'm sorry the l-type calcium channels so then what happens is you get this kind of like small dip if you will you see the small little dip and that small little dip right there where the cell becomes a little bit more negative why because positive ions are leaving the cell if positive ions are leaving the cell then you're going to have the cell become slightly negative and what that does that cause this little dip here on this actual kind of like phase of the actual potential this little dip where the cell becomes just slightly negative is due to voltage-gated potassium channels just opening up just a little bit earlier than the l-type calcium channels then the l-type calcium channels finally are super open and they start flooding in at the same time the potassium is still leaving the cell so we have positive ions coming into the cell and positive ions leaving the cell so if I have positive ions leaving the cell it's making the cell negative but I have positive ions coming into the cell that's making the cell positive they cancel each other out and when they cancel each other out you kind of get this Plateau phase if you will where it kind of stays at the same voltage and then eventually what happens is the voltage-gated calcium channels eventually shut down they actually close but during this phase right here where it's this Plateau phase where it kind of stays the same what is this this is actually due to two particular channels this is due to the l-type calcium channels being open in addition to the voltage-gated potassium channels being open so you have two channels that are open during this particular Plateau phase now eventually what happens is as you in this Plateau phase as calcium is coming in and potassium is going out eventually gets to the point where what happens is just really quickly once positive ions like calcium comes into the cell what it does is it activates this channels here on what's called your sarcoplasmic reticulum and it stimulates these calcium ions will stimulate the sarcoplasmic reticulum and cause it to release calcium ions out of it to trigger kind of a muscle contraction process once that happens during the plateau phase and you already have the calcium being released then we don't need this calcium to continuously keep coming in so we shut that calcium channel off once we shut the calcium channel off what we want to do is we're done with contraction the calcium's already started the contraction process we want the cell to start beginning to relax so what happens is what we do is we actually start pumping calcium out of the cell and back into the sarcoplasmic reticulum so all the calcium that was actually present in the cell during this Plateau phase we're going to pump it back in here or we're going to take the calcium and we're going to pump it out of the cell we're going to try to get the calcium out of the cell and then we're going to keep these voltage-gated potassium channels continuously open super super important I can't stress this enough once we get to the end of the plateau phase the calcium stimulated the sarcoplasm curriculum to release calcium trigger the contraction process after the contraction process is done we want the cell to rest so we want to shut these voltage-gated calcium channels off we want to push the calcium that was present in the cytoplasm back into the sarcoplasmic reticulum or push the calcium ions out of the cell we don't want the calcium in here anymore causing contraction so what we do is we push the calcium ions out or we push the calcium lines back into the sarcoplasmic reticulum but we keep this poppy open and then what happens if it stays open the potassium ions are going to keep leaving and leaving and leaving and causing the cell to become increasingly more negative to the point where now look what's going to happen we're going to cause this cell to become negative negative negative and it's going to go back to the resting membrane potential and we're going to maintain the resting membrane potential via what type of channels here the sodium potassium epases we're going to pump the potassium back into the cell to regenerate the gradient and pump the sodium out of the cell to regenerate the gradient but since we pump more positive ions out of the cell and less positive ions into the cell we make the cell more slightly negative and that maintains the resting membrane potential okay but who is going to be responsible for this downward phase here that's just going to be the voltage-gated potassium Channel Okay so to recap this sells at rest Gap Junctions allow for ions to from a pacemaker cell or nearby atrial ventricular myocyte to pass those positive ions into him when he gets these positive ions activates the upward phase where the voltage-gated sodium channels open and sodium rushes and making the cell super positive this right here my friends is called phase zero okay sodium rushes in then once sodium rushes in it makes the inside of the cell super positive and it shuts off the voltage sodium channels they're they're closed now they're not going to allow for sodium to enter in anymore once we're at this peak point then what it does is when it's at this peak point it opens up two channels the voltage you get a potassium channels and the voltage-gated or l-type calcium channels when they open up potassium is going to open up a little bit quicker and start exiting out of the cell when it exits out of the cell it makes this actual charge inside of the cell drop down become more negative this right here with just this downward phase here is called phase one so the downward phase here is phase one then as the voltage of the calcium channel is a voltage of potassium channels maintain their patency they keep open they keep allowing for potassium to leave but then these l-type calcium channels finally open enough to allow calcium to rush in so then you have positive ions like calcium coming in and positive ions like potassium going out but it makes this inside of the cell the same electronutrality because you have positive ions coming in making the cell positive positive ions leaving which are causing the cell to become negative those cancel each other out and maintain this Plateau phase this is called phase two then once the voltage-gated calcium channels close because what you want to do is you want the calcium to come in Via these l-type calcium channels stimulate the sarcoplasmic reticulum to pump calcium out cause the muscle cell to contract once it's done Contracting you want it to relax so that it can be stimulated again so then what you do is you take the calcium pump it into the sarcoplasm curriculum you shut these calcium channels off and you pump the calcium out of the cell so that you can regenerate that gradient because you want calcium in the sarcoplasmic reticulum to be available again and you want to push calcium out of the cell so that you can use it again to come back in so by doing that you shut the calcium channels off pump the calcium back in here and pump the calcium out now no more calcium should be coming in only voltage-gated potassium channel should be open at this point and when they're open they allow for positive Minds to leak out making the cell negative and this is going to be phase three then as you go downwards here into this flat phase this flat phase right here until you get ready to generate another action potential it's called phase four that's when you're at the resting state the cell is in the resting state generated by the sodium potassium ATP Aces okay now that we've talked about that this is important to remember that this is what occurs in the non-pacemaker cells and because of this look how fast this kind of action potentials occur these are kind of your fast action potential inducing tissue all right so now that we understand the cardiac action potentials in both the pacemaker cells how they look like with all the channels all the flowing of ions and then how they look in the graph and we can compare that to the non-pacemaker cells the atrial and matricular myocytes how their channels are all working how they're flowing and what it looks like on the graphical representation now what I think we can start to begin to do is is generate a concept of how arrhythmias are generated and then how we can really approach to actually treat arrhythmias because if I can find drugs that really block the slow AP producing tissue the nodal tissue so the SA node AV node primarily I should have some drugs that can really block the AV node and that may be useful in certain arrhythmias in other situations I want to give drugs that could actually block the action potentials that are present in the fast action potential tissue so the atrial and ventricular tissue that's not a pacemaker tissue if I can suppress those tissues from generating arrhythmias that might be helpful and so what you'll see is that in this tissue we're primarily going to be focusing on drugs that can block the pacemaker cells particularly the AV node and how they're actually going to block the AV node we'll talk about in detail but if we can block the action potentials being produced or the conducting of action potentials through the AV node we can slow the heart rate down which is important in what type of arrhythmias tachyarrhythmias so whenever the patient's heart rate is greater than 100 beats per minute that's what we're really going to be utilizing antiarrhythmic medications is tachy arrhythmias so I'm going to talk about drugs that will really help to suppress the conduction of action potentials through the AV node and SA node via the pacemaker cell blockade and then what I'll do is I'll talk about some drugs that we can utilize to suppress the action potentials and electrical activity within the non-pacemaker cells the atrial and ventricular myocytes that gained some ability to generate Action potentials undesirably and we'll talk about how they can actually do that a little bit later but that's what I want you guys to understand so now let's come down for a second let's talk about how do arrhythmias actually develop we're going to do this very basically if you guys want to know more about arrhythmias and the pathophysiology go watch our video on arrhythmias and they'll tell you a little bit more about that but I'm going to basically kind of introduce it and then we're going to talk about a strategy and then we'll go into each drug category their mechanism of action how they're actually going to treat these arrhythmias and then we'll go into a little bit more a little bit later about what's the approach to every single type of arrhythmia how do I actually kind of like get this fit into my brain we'll get into that so let's now come down and talk about that whenever patients actually develop arrhythmias we're not going to go through the crazy pathophys I don't think it'll actually give us much in the understanding of anti-rhythmic so to really go down that depth I I don't know if it'll give you much benefit so what I really want you to understand is when patients actually develop a rhythmia as they can develop in three particular pathophysiology like pathophysiological reasons one is that their SA node may be firing maybe a little bit too fast and sending Action potentials down really really quickly to the AV node and then down into the ventricles and so if that's happening you're having a very fast type of rate that's being generated from the SA node or maybe being quickly conducted through the AV node and in those situations that's due to an intrinsic problem within the SA node in the AV node where they're either conducting Action potentials through fat too fast they are generating Action potentials too fastly and that's usually due to what's called increased or enhanced automaticity and you can see this really in any type of like increased sympathetic State really is what you what you'll have but we don't usually use anti-rhythmic drugs in these particular scenarios so again that's usually just due to an increased conduction like an increased essay node or an increased activity of the AV node where they're just conducting Action potentials or generating Action potentials super fast but this is what you see in like sinus tachycardia so it's not going to be super beneficial because we don't really give medications to treat a sinus tachycardia you treat the underlying cause of their increased sympathetic outflow another mechanism is that sometimes what happens is we take an atrial cell or we take a ventricular cell that's not a part of this pacemaker system and we cause it to become agitated we trigger it in a particular way we load them with calcium ions and we cause or we prolong their uh kind of like their what's called their their QT interval and when we do that what we do is we create an opportunity for these cells to become agitated and regenerate they somehow generate an abnormal automaticity so they start kind of generating Action potentials and they generate Action potentials faster than the SA node and AV node can and because of that they start generating super fast Action potentials that go to the AV node or that spread throughout the ventricles and so in these situations we can see very dangerous arrhythmias due to what's called triggered activity triggered activity and these are usually what we refer to as something called you'll you may have heard these terms in our arrhythmia lecture Eads so early after depolarizations or what's called dads delayed after depolarizations so Eads are something that you usually see with patients who are having what's called prolonged QT intervals so they're utilizing drugs and we'll talk about some of these here that actually prolong the QT interval and so that creates an opportunity for these Eads to form or certainly like electrolyte abnormalities like low potassium low magnesium May create opportunities for this whereas dads are usually due to lots of calcium loading in the cells which so lots of sympathetic overdrive particularly like ischemia to the actual myocardium or hypoxia digoxin toxicity you can see a lot of these things with this but these tissues the atrial and ventricular tissue not the pacemaker tissue generate the ability to intrinsically depolarize and generate Action potentials faster than the essay in an AV node so that's an interesting concept and you know what actually may be good for that there may be good particular drugs that may be helpful to either block the AV node or maybe give drugs that actually block the triggered activity at the atrial and ventricular myocytes that are generating these triggered active activity so we'll talk about that a little bit later the third mechanism is that there may be something called a re-entrant circuit so sometimes this can be anatomical so you can sometimes have this like weird kind of like anatomical structure here called like the bundle of Kent and it allows for this kind of re-entrant kind of cycle to occur where electrical activity May flow down the AV node through the ventricles and then back up through this accessory pathway and it can go really really fast and so sometimes you can see that with these very anatomical things called uh like the bundle of kitten wpw you can also see that sometimes you can develop re-entrant circuits like in particular nodal tissue so sometimes you can generate these re-entrant Cycles within the AV node or you can generate re-entrant Cycles within the Atria or you can generate re-entrant Cycles within the ventricles we're not going to go through all the mechanisms here but you can have atrial tissue ventricular tissue AV nodal tissue or these large kind of like anatomical accessory Pathways that allow for these re-entrant circuits and the problem with these reentrant circuits is they generate really really fast Action potentials and so that's another particular mechanism that I want you guys to be aware of which are called re-entrant circuits and we can see these as anatomical so they can be kind of like anatomical types of abnormalities and we see this a lot with what's called wpw or sometimes they can be functional and you see these functional abnormalities you see this in things like AV nrt which is a type of SVT you can see this in things like vtac you can see this in things like atrial fibrillation atrial flutter a lot of like weird kind of re-entrant circuits that can develop due to fibrosis or scarring or particular types of structural abnormalities within the myocardial tissue but either way the whole concept here is that when you look at this the problem is becoming of what with with arrhythmias that you're not following the normal cardiac conduction pathway if you are it's usually increased automaticity right so this SC note is just super hyperactive or the AV node is conducting potentials super fast that's not the arrhythmias that we're going to utilize antiarrhythmics for it's really these it's when you have an atrial tissue or ventricular tissue that's not a pacemaker tissue generating Action potentials because you trigger it or atrial tissue ventricular sorry atrial tissue or ventricular tissue is generating re-entrant circuits and generating these super fast rates and abnormal rhythms that are going to be causing very abnormal types of tachyarthemias and so really what I want us to really talk about here is how do we actually kind of utilize these medications because this is the way that I like to remember them I really think helps you when you think about arrhythmias is and what we're talking about for utilizing anti rhythmics is that when patients develop a tacky cardia they're beating at very fast rates so greater than 100 beats per minute and the reasons why they can develop that is because of increased automaticity increased conduction this is the one that we don't really care about though it's these two that we care about they can develop very fast heart rates due to triggered activity or re-entrant circuits I think one of the best ways to understand how these anti-rhythmics can be utilized approach wise is to look at it in two particular fashions one is let's say that we have this tissue here let's actually use the colors that we've been using whether it be due to the atrial tissue whether it be due to the atrial tissue generating these triggered activities so you have an ectopic Foci here that's triggering and firing super fast or whether it be due to a re-entrant circuit here that's developing within the Atria and it's generating these very fast Action potentials and atrial types of arrhythmias are superventricular tachyrhythmias what are the different types of supraventricular tachy rhythms do you guys know here let's say we got a couple of them the primary ones that you want to know one is atrial fibrillation right one is called atrial flutter the other one is called SVT these are the primary types of atrial or supraventricular tachy arrhythmias what happens with these is whether you have a re-entrant circuit or a triggered activity all of this electrical activity is going to one particular point the electrical Gateway or window between the Atria and the ventricles so the electrical activity from this reentrant circuit will go here to the AV node this ectopic focus in the Atria is going to be going towards the AV node so all the electrical activity from this kind of like tissue here tissue here they're generating super fast rates it has to go to the AV node who will then conduct the action potentials into the ventricles that's the issue right and if I get these rates to go fast onto the ventricles and the ventricles are going to be beating at super fast rates so what if I could come up with drugs that specifically inhibit or suppress the conduction of action potentials from these fast tissues here I suppress the AV node and I block it and if I block it I block all these fast actual Action potentials that are occurring in Atria from going on to the ventricles because you know why that's dangerous if the atrial is beating at let's say 300 beats per minute that's pretty fast right but the Atria isn't the one that's responsible for squeezing blood out of the heart it's the ventricles so if my ventricles are beating at 300 beats per minute there's like literally no chance it's going to be able to fill or really generate adequate contractility and that is not compatible with Life so what we don't want is a patient's Action potentials that are coming from the Atria maybe at 100 or 200 beats per minute to be generated into the ventricles at that fast of a rate so what we want to do is we want to give drugs that can rate control and block the AV node so this is where drugs where we utilize here in this particular scenario what we're going to do with them is we're going to rate control and we're going to do that by suppressing or blocking the electrical activity from the Atria Into The ventricle at the AV node what drugs that we're going to talk about later are going to be good at suppressing and blocking the AV node and we'll talk about how they actually do it a little bit later but this is the ones that I want you to remember first ones are going to be what's called your beta blockers so your beta blockers are very good at blocking the AV node and suppressing a lot of the electrical activity from the atrial tissue going through the AV node and into the ventricles we also give another name for this there's what's called like this Vincent kind of classification system we use like class or types so this is a class or type two antiarrhythmic drug and we'll talk about these a little bit later the next one we can do to suppress the actual AV node is we can give drugs called calcium channel blockers so calcium channel blockers are also decently utilized drugs in these particular kind of diseases here and these are what's called a class or type 4 anti-arhythmic drug okay the next ones that we can use here are technically not a part of that like Vince kind of classification system the typical classification system we put them in miscellaneous which is like a class 5 drug and there's two types here one is called adenosine so adenosine is another particular drug that we can utilize here and this is kind of like a miscellaneous but we sometimes we just put this in What's called the type 5 or class five anti-arrhythmic drug class so here we'll put these in like the the type or class five anti-rhythmic drug category and there's one more and this one is called digoxin this one is called digoxin again it's a part of that miscellaneous or class 5 anti-arythmic drug category but what I want you to remember is all of these drugs are working in some way shape or form to suppress the AV node which is going to work on this type of tissue the slow action potential producing tissue it's going to alter the channels in this particular tissue that's why I focused on that so much so we're going to utilize these drugs to suppress particular channels or at like action potential processes in the AV nodal cell primarily that's why I focused on the pacemaker cell activity there and the other situation that's going to be for these types of arrhythmias things like afib a flutter SVT and with SVT there's two types there's AV nrt as well as what's called um avrt so avnrt is like the nodal reentrant tachycardia and then avrt is like your wolf Parkinson's white syndrome but we can utilize it in these particular scenarios okay the non-pacemaker blockade is a little bit different so now what we're trying to do is we're saying okay here's that tissue here here's the atrial tissue and it's generating these ectopic Foci it's becoming a triggered activity there or we have a re-entrant circuit here maybe we have a re-entrant circuit generating within the Atria okay or same kind of concept here we have a re-entry tissue here within the ventricle kind of re-entrant circuit that's developing within the ventricle or an ectopic Focus that's developing within the ventricle so now we already talked about ways that we can block the atrial signals from getting down into the AV node and then into the ventricles we've already talked about that that's going to be these drugs that block the AV node what if there was a way that I could shut down the re-entrant circuit or shut down the triggered activity in both the atrial cells and the ventricular cells what if I could do that what if I could somehow a patient who has superventricular tachyarthy so let's say for the atrial ones we're talking about patients who have atrial fibrillation we're talking about atrial flutter we're talking about maybe even SVT but this is going to be a plus or minus and we talk about the ventricular arrhythmias so we're talking about things like vtac we're talking about things like torsods to points and these particular situations what if I could suppress or reduce the action potentials that are being generated by the atrial and ventricular myocytes that are non-pacemaker tissues that are responsible for causing these rhythmias what if I could stop them from producing these types of arrhythmias wouldn't that be beneficial I'm not going to block the AV node I'm just going to suppress them and try to get them back into a normal sinus rhythm so we call this type of process here where we're trying to take and switch these over and suppress them we call this kind of a rhythm control we call this more of a rhythm control or a cardioversion type of process now what drugs are going to be good at actually suppressing the actual potentials and particularly these atrial and ventricular monocytes that's the good question right the tissues that the drugs that are really good in this particular activity is going to be drugs that block the sodium channels the voltage-gated sodium channels and drugs that block the voltage you get to potassium channels so we call these drugs your sodium channel blockers okay and these are sometimes referred to or commonly referred to that car that classic system there class one uh anti-arhmic drugs okay the other one is the potassium channel blockers so the potassium Channel blocks we have sodium channel blockers and then we have what's called potassium channel blockers and this is going to be What's called the class three anti-arrhythmic drugs okay so these are really really really important that I need you to understand that the class 2 class 4 and some of the miscellaneous class five they suppress the atrial rhythmias by blocking the AV node to rate control these patients prevent their atrial rate from causing very fast ventricular rates they don't convert them back into a normal rhythm and patients who have atrial or ventricular arrhythmias where we're not going to suppress the AV node but we want to try to take and convert these kind of abnormal triggered atrial cells or reentrant atrial cells or triggered ventricular cells or re-entrant ventricular cells we want to suppress them shut them down and allow for the normal sinus rhythm to go back into a place here that's called rhythm control of a cardioversion kind of technique in those situations we use sodium channel blockers potassium channel blockers class 1 class 3 and in some ways we can even potentially use a plus or minus here for the third situation you also may be able to use beta blockers and I'll talk about this a little bit more later but beta blockers which are your class Two anti-rhythmic drugs they're really good at suppressing the sympathetic nervous system because if you suppress the sympathetic nervous system you can actually potentially inhibit the triggered activity and you may be able to be able to suppress some of the re-entrant cycles because sometimes the sympathetic nervous system can just really exacerbate triggered activity especially and re-entrine circuits and so if you give a beta blocker you may be able to suppress the sympathetic drive on these types of cells but again these are going to be the two primary ones for rhythm controller conversion and this is going to be primarily the ones for raid control so I want you guys to understand that so now that we've done that we've built a very strong Foundation knowing that these drugs are going to work potentially on the atrium ventricular myocytes they're going to be altering those channels so the sodium channels the potassium channels that are involved in the fast action potential producing tissue now that I know that and I understand this mechanism let's now go into the drugs that are actually going to cause blockade of the AV node and how they're actually going to to helply specifically suppress the AV node reduce the action potentials how they alter the graph here and then what we'll do is we'll then go later after we go through all of these drugs we'll then go into how do the sodium channel blockers and potassium channel blockers really work to alter the electrical activity inside of these atrial and ventricular cells by how do they specifically do that in the sodium channels the potassium channels and how does that alter the graphical representation here so let's do that now we have a lot to talk about let's get into it all right my friends so now we're going to talk about beta blockers first okay so this is going to be kind of our type or Class 2 anti-rhythmic drug now when we talk about beta blockers let's talk about some of the beta blockers the actual names of those drugs so a lot of them you can just remember the olalls right so there's the metoprolol which is a very commonly utilized one you can also remember like a tenolol propanolol anything really with a law so there's a lot of these drugs out there okay now what I really want you to understand with these drugs is how exactly do they block the AV node which will suppress the actual super fast rates from going from The Atrium to The ventricle and diseases such as afib a flutter SVT things to that effect how are they really working here and then we talk about them a little bit later that they also can be used to suppress the sympathetic effect in situations like vtac they can actually are very helpful in vtac but nonetheless we have a patient here who has some disease okay whether that disease is again very commonly utilized here in situations such as atrial fibrillation it can be utilized in atrial flutter and it can even be utilized in things called SVT as a prophylaxis but what happens with these diseases that you have this irritated area of an atrial Focus which is sending super fast Action potentials way faster than the SA node that's getting to the AV node and if we have these Action potentials go through the AV nude super quick they can cause very fast ventricular rates so then we can end up with what's called afib with a rapid ventricular rate or a flutter with a rapid ventricular rate or SBT that can can sometimes go super super fast but how can we suppress basically block the action potentials from going through the AV node and suppress this actual super fast rate well let's say that I take this AV nodal cell right here I'm going to zoom in on one of the cells in the Avio and look at how beta blockers actually do this so on these uh AV noodle cells here we're going to have something called a beta receptor so what is this receptor here this is called a beta one receptor now what happens is epinephrine norepinephrine usually what they do is they bind onto so let's say that here we have something called epinephrine and norepinephrine when they bind onto this actual receptor here what they do is they activate a protein called a g stimulatory protein the G stimulatory protein will then activate an enzyme here called adenylate cyclase and what a dental cyclase will do is it'll take a molecule called ATP and convert it into cyclic amp and that'll activate something called protein kinase a and protein kinase a will go in phosphorylate what it'll do is it'll put phosphate groups on these channels don't these look familiar on the pacemaker cells so if you look at the pacemaker cells remember the pacemaker cells had the funny sodium channels they had the T-Type calcium channels they add the l-type calcium channels these are l-type calcium channels what are these channels called l-type calcium channels what I'm going to do is is when epinephrine and norepinephrine bind on here so here's epinephrine norepinephrine they bind on here they stimulate this pathway they cause the phosphorylation of these channels and cause calcium to flood in and if calcium floods into the cell it makes the cell super positive which increases the speed of the action potentials now what I'm going to do is I'm going to give a drug called metoprolol Atenolol perpendolol any of these drugs and what I'm going to do is I'm going to suppress or block the effect here of norepinephrine epinephrine at the beta 1 receptor what I'm going to do is I'm no longer going to stimulate the G stimulatory protein I'm going to inhibit the G stimulatory protein I'm going to inhibit the activation of adenyally cyclase I'm going to decrease the conversion of ATP into cyclic amp I'm going to decrease the activation of protein kinase a I'm going to not phosphorylate the l-type calcium channels therefore I won't open them as nicely and therefore calcium will not enter into the pacemaker cells go back now to the phases here is what phase phase four this is Phase zero this is phase three phase four is funny sodium channels T type calcium channels phase zero is l-type calcium channel space three is voltage-gated potassium channels if I block the l-type calcium channels from opening these generally open right at the end of phase four going into phase zero so now I'm going to block them what is the overall effect going to be now so now instead of me allowing for so let's say that we started off here right I'm going to block right here at the end of phase four going into phase zero so now instead of me allowing for this phase four to go here and then up I'm going to delay it it's going to take a longer time for me to be able to get this phase four up here to phase zero and then this is going to cause look at this less frequency of action potentials so now there's going to be a decreased frequency of action potentials moving through the AV node so what is it going to do beta blockers on this effect here are going to inhibit the l-type calcium channels from opening and that is going to decrease the slope of phase four and even if you think about it here because it also will block the calcium channels from entering you may even get a little bit of a decrease in slope of phase four but also in Phase zero so your phase zero may also be a little bit slower as well so if you look here you may also have a slower phase zero okay so phase four and phase zero in what in the AV node so what that's going to do is you're going to decrease the conduction of action potential throughout this AV node which is going to help to rate control it'll help with the rate control of afib a flutter and SVT so that's what I want you to understand about this drugs now when we talk about these drugs they have many different types of adverse drug reactions we'll talk about them a little bit more later but obviously with any type of beta blocker you suppress the AV node if you do suppress the AV node what are some of the things that you have to watch out for my friends watch out for bradycardia also it can actually block the beta receptors on the contractile portion of The myocardium which can cause decreased contractility so make us hypotension especially in decompensated heart failure it also can cause activation or inhibition of the beta 2 receptors and the bronchials which will cause bronchoconstriction and it may even cause hypoglycemia unawareness we'll talk about that later but things to watch out for with this drug so now we know the mechanism of action we know the diseases and it's actually used to treat and how it treats those diseases and we know what it would look like specifically on the actual graphical representation so if they were to ask you what does this one look like well it slows phase four a little bit of phase zero should not affect phase three slows or delays the the slope of phase four and zero should not affect phase three but the primary one that you're going to see most likely in the test here is phase four it has a little bit of effect on phase zero so does the next one that we're going to talk about called calcium channel blockers let's talk about those all right so now calcium channel blockers these are your class 4 Type 4 anti-rhythmic drugs so there's a couple of these so ones that I want you to remember primarily is Verapamil so varapamil is going to be one and then the other one is called diltiazam so the thiazine might be the more commonly one utilized one that you may see in clinical practice but with these drugs okay what are they potentially being utilized for again they're blocking and suppressing the AV node so remember I told you that they're utilized in particular like you know triggered activity or re-entrant circuits of some type that are causing very fast rates from The Atrium to try to move down through the Avi node into the ventricles so situations such as AFib a flutter right and SVT prophylaxis we're utilizing these drugs how are we actually going to do that well let's take this AV nodal cell and kind of blow it up and take a look at how it's actually going to be blocked well here on this AV nodal cell you'll notice something very interesting these pink channels here what are these pink channels here called these channels are called your L Type calcium channels so we blocked the l-type calcium Channels with beta blockers right because they help to be able to decrease the phosphorylation of these channels especially at the end of phase four that's one of the most interesting things that you block them at the end of phase four which really delays and decrease the slope of phase four but they may also have less calcimentary during phase zero so it also should kind of decrease the slope there with this one it's the same concept you're blocking the actual l-type calcium channels if calcium is supposed to Rush In during the beginning of phase four and during phase zero you're supposed to have these positive lines coming into the cell and cause this Rising phase of the action potential so generally if you go back to the phases here you should have phase four at the end of phase four l-type calcium channel should open during phase zero L Type calcium channel should be open and flooding through and during during phase three there should be potassium exiting causing repolarization what I'm going to do is I'm going to give these drugs and they're going to block calcium entry and so what I'm going to effectively see here is I'm going to see a d a decrease and the slope of phase 4 and a decrease in the slope of phase zero and because of that I should effectively see less conduction of action potentials through the AV node if I see less conducting of action potentials through the AV node that means all of these atrial signals that are trying to go through the Avion into the ventricles I'm going to suppress them and lead to rate control so what is the overall effect that I will see as I will block the calcium entry I'll block the positive ions entering into the cell and I'll decrease the slope if I block these I'll decrease the slope of phase four and phase zero in the AV node and this is going to be both of them you're going to really really strongly more than beta blockers block the phase four and phase zero so that's one of the cool things about these calcium channel blockers but the same kind of effect is seen here is that you are really suppressing and blocking the AV node for blocking the entry oh it's the Gateway between the atrium to The ventricle so all these increased atrial signals that are trying to get to the AV node and then down to the ventricles you're blocking it right there to suppress all those electrical activity from getting down into the ventricles really really cool concept so with calcium channel blockers adverse drug reactions to watch out for same with beta blockers they block the AV nodes so watch out for any bradycardia AV blocks they also really suppress the actual um calcium channels and the contractile myocardial cells and that can actually really cause hypotension and worsening uh decompensated heart failure so be careful for that and it also may cause some constipation but that's the effect of the calcium channel blockers and how they actually do this now we understand these let's talk about the next two drugs that are utilized as AV noodle blockers adenosine and digoxin all right my friends so now let's move on to adenosine and digoxin this is kind of that later kind of like miscellaneous class 5 antiarrhythmic drugs so with these we did say that they're all kind of utilized to suppress or the AV node and afib a flood or SVT that's true however adenosine is very short acting so it's not a great drug for more of kind of rate controlling patients with afib and a flutter it's more of a drug that will really shut down SVT acutely so when patient goes into a really rapid super ventricular the tachycardia the rates are 170s 200s what we can do is we can give a drug that's very short acting very powerful and it'll really suppress the AV node and that's that's going to be adenosine so with that being said I'm patients of what's called SVT this is more of an indication particularly for adenosine and we'll talk about all these like arrhythmias a little bit later but adenosine is not very good in afib and a flutter because it's not a longer acting drugs it's a very short acting so it's not good in patients who are going to have afib and a flutter so remember that it's going to be not very helpful for afib and not very helpful for atrial flutter with that being said we also have digoxin digoxin is actually going to be utilized primarily for atrial fibrillation we don't really utilize this very much for a flutter it's not really utilized very much for SVT as well primarily atrial fibrillation and that's going to be digoxin and what we'll talk about later is it's not going to be your first line Choice it's really only going to be a drug that we give to patients if they have heart failure with a reduced ejection fraction so if a patient has a heart failure with a reduced ejection fraction and atrial fibrillation digoxin seems to be a drug that may be potentially beneficial but again not super helpful for patients who are going to be utilizing it for atrial flutter and it's not really a drug that we get for SVT okay so just when I talked about that in the beginning with the AV node blockade that is their mechanism of action it's just when we talk about their utilization of particular diseases it may be a little bit different that beta blockers calcium channel blockers can treat all three of those atrhythmias adenosine it could theoretically do that but it's more specifically very short acting so it's really only given an SVT and digoxin it could treat atrial flutter it could treat SVT but it's only been shown to be really beneficial and somewhat beneficial in atrial fibrillation and patients who have heart failure with a reduced ejection fraction not super helpful in a flutter or an SVT okay with that being said how exactly do these drugs block the AV node because it's the same mechanism regardless they're all going to have these triggered activity or you're going to have those re-entrant circuit the sending Action potentials quickly to the AV node and you want to block that AV node and prevent the fast atrial circuit electrical activity from going down to the ventricular circuit so you're trying to rate control these patients it's the same concept it's all rate control how do we block Davey notes let's take a piece of this AV nodal cells and zoom in on it here okay here we're going to have a receptor and this receptor is for adenosine and what happens is when adenosine binds on to so this is going to be adenosine when you give adenosine that binds onto adenosine receptor here when it binds onto the adenosine receptor it's actually coupled with a G inhibitory protein so it binds on and activates a g inhibitory protein the G inhibitory protein will then work to inhibit um because you know when a g inhibitory proteins they specifically inhibit it Inlet cyclase so they don't take ATP and convert it into cyclic amp so that's one thing it will inhibit your you know activation of adenylate cyclase and so yes you will have less ATP converted into less cyclic amp and that will lead to less protein kinase a and so yes to a mild degree you'll have less phosphorylation of the l-type calcium channels but that's not the primary mechanism by which adenosine works the primary mechanism is yes you made some mild degree this is I'm going to put here a very mild degree block the calcium channels right and have less calcium enter into the cell right so that may be a possibility but it's very very mild effect the more powerful effect from adenosine is that when you stimulate G inhibitory there's two different types of well there's three subiness there's an alpha beta and gamma subunit the alpha and beta subunit really what inhibits the identity cyclase the gamma subunit is the one that actually goes and acts on another channel so there's really when we talk about this G inhibitory unit what it does is it actually activates what's called Alpha and beta subbing and that really goes and inhibits the identity cyclase but it also so it'll stimulate this pathway here but it'll also stimulate another pathway called the gamma subunit and the gamma subunit and this is all the inhibitory component of the G inhibitory protein so the G inhibitory protein is actually made up of a gamma Alpha and beta subunit Alpha Beta will go and work and to inhibit the adenylate cyclase the gamma one will go and act on these potassium channels and open up these potassium channels when they stimulate or open up these potassium channels potassium will vary powerfully leak out of the cell and when potassium exits the cell the cell becomes super electronegative when it becomes electronegative it makes the inside of the cell very negative to the point where if you had this cell that's at rest if this cell was at rest this abnormal cell was at rest and you bring the inside of the cell even more negative than resting membrane potential it's called hyper polarization so what does it do it causes hyper polarization the cool concept about this okay we're going to put calcium right over here to make room the cool concept about this if you think about this this is our resting membrane potential this is where the cell is at rest right here's the threshold potential now what I'm going to do is I'm going to make the inside of the cell even more negative than resting membrane potential so now let's actually represent this in this uh kind of like maroonish color here this is the new Point here I'm making the cell even more negative I'm bringing it below the resting membrane potential so I'm going to call this the hyper polarized state hyper polarized state so I'm making the cell even more negative than the resting membrane potential the problem with that is is if I cause this hyperpolarization now this cell will have to go from this state the hyperpolarized state all the way up here maybe it won't change the slope so the slope may still kind of be the same but now it's going to take a longer time for it to be able to get to the threshold potential because it has to go from maybe negative 90 maybe negative 95 all the way up to negative 40. so because of that I'm really hyper polarizing this thing so you see what I'm doing here is I'm taking and moving the cell to become more negative I'm just going to put a random number here negative 95 millivolts so now instead of going from a negative 70 to negative 40 I'm going from negative 95 to negative 40. so this is called hyperpolarization I'm going to cause the cell to have to go from a lower like charge to bring this up to a threshold potential that's more movement that's going to be more difficult to be able to get the cell to that point and that can really shut the AV node down pretty powerfully so one of the things about adenosine here that I want you to remember is adenosine and we're going to talk about how digoxin will do the same type of effect here adenosine and digoxin are going to cause hyper polarization they're going to make the cell very very negative and that's going to make it more difficult and take a longer time to go from this hyperpolarized state to threshold potential so it's going to increase the time to the threshold potential and that will decrease the amount of action potentials that you're going to be able to generate because it's going to take you a longer time to get to threshold potential to generate an action potential pretty cool concept okay that's for adenosine how does the Jackson do this and digoxin is also pretty cool so what happens is you know your vagus nerve your vagus nerve releases something called acetylcholine right so here's your vagus nerve now the vagus nerve will act will release acetylcholine which will act on what's called muscarinic two receptors right this is an adenosine receptor this is a muscarinic 2 receptor when acetylcholine binds onto this muscarinic II receptor what it does is it does the same exact process it activates a genehibitory protein and there's two components of that one is the alpha and beta inhibitory subunit and that'll go and inhibit adenine cyclase decrease ATP decrease cyclic amp decrease protein kinase a less phosphorylation less calcium comes in but that's very very mild it's more this effect that's the more potent effect where it inhibits the I mean sorry it actually causes the stimulation of the gamma subunit and the gam subunit will come and bind onto these potassium channels and they will cause the potassium channels to open and potassium will leak out of the cell very powerfully and that'll cause the inside of the cell to become very electronegative and this will cause again what type of effect here hyperpolarization making the cell very negative which will cause it to go to this hyperpolarized state making it now have to work harder to be able to go from a negative potential all the way up to negative 40. it's a longer time to get to threshold potential and that's going to slow down the action potentials moving through the AV node but all right we just talked about the vagus nerve here and how acetylcholine Works how does the Jackson actually come into play here digoxin has been shown through not a completely known mechanism here but to stimulate the increase of acetylcholine release from the vagus nerve and that will increase the activation of the alpha beta and gamma subunits that'll increase the activation of these potassium channels and that'll increase potassium exiting and that will increase hyperpolarization make the cell super negative and now it's going to have to go from like a negative 95 millivolts I'm just using a random number here it's just more negative potential it's going to have to go from that potential all the way to threshold which is more than it would have been from the normal resting membrane potential okay so that's one of the interesting concepts of this drug category so again to recap this adenosine digoxin still block the AV node and atrial arrhythmias but to be more specific they really only treat SVT such as adenosine and afib such as digoxin in patients with heph-ref heart failure where they reduce the ejection fraction how do they do it they hyperpolarize the AV nodal cell they make the inside of the cell negative now it has to go from a very negative charge to rest I'm sorry to the threshold potential so giving an example if the resting member potential is negative 70 I made the cell even more negative than that negative 95. now it has to go from negative 95 to negative 40. in comparison to negative 70 to negative 40. that's going to take a longer time to get the threshold potential a longer time to generate Action potentials and that decreases the conduction of action potentials through the AV node into the ventricles again adenosine will do that via the G inhibitory process by causing potassium efflux the joxin will increase vagal nerve stimulation causing increased acetylcholine release which will also cause potassium reflux these can to a very mild degree it's not even relevant though to put that on the graph can mildly block the voltage-gated potassium channels and so if you really wanted to they theoretically could even decrease the slope of phase four okay and very mildly phase zero but they're primarily hyperpolarizing the cell all right now that we've talked about these drugs let's now come into the next category we've talked about all the drugs that are utilized to suppress or block the conduction through the AV node the beta blockers the calcium channel blockers adenosine and digoxin used in atrial arrhythmias to really rate control those patients what about the diseases of the atrial and ventricular myocytes where instead of actually rate controlling blocking the AV node I try to block those those cells those triggered cells re-entrant cells abnormal cells from firing and preventing them from having AFib or preventing them from going into a flood or preventing them from going to v-tac or preventing them from going into torsos to points taking converting them out of that abnormal Rhythm into a normal Rhythm how do I utilize those drugs in this particular scenario and how is their mechanism of action going to be working let's talk about that now all right so now let's talk about the sodium channel blockers your class one type one anti-rhythmic drug category now what do these utilize for they're not going to block the AV node they're going to try to block those non-pacemaker tissues those atrial and ventricular tissues that are generating abnormal rhythms so remember I told you that maybe you have some type of abnormal triggered activity occurring within the Atria and it's causing this Atria to generate these really fast rates right or maybe you have a re-entrant circuit within the Atria and it's causing to generate these very fast rates or maybe you have a ventricular Focus here that's causing a lot of triggered activity or you have a ventricular Focus that's creating a lot of re-entrant circuits either way you're not going to be able to blocking the AV node in these ventricular circuits is not going to be helpful right it's more blocking the AV node for the atrial arrhythmias was that I'm even blocking the AV node for these atrial rhythmias what if I just tried to get these atrial cells to stop firing okay so particularly in diseases such as atrial fibrillation atrial flutter what if I just go ahead and I kind of cardiovert them in other words I try to take and convert them from this abnormal Rhythm that they're generating due to triggered activity or re-entrant circuits and I try to suppress those reentration circuits or suppress the actual triggered activity and cause them to go back into normal sinus rhythm or what if I have a patient who's in vtac or V uh what's called um torsad's the points of something of like that nature or torsad's the points and I try to again cardiovert them this may be where these drugs could potentially be useful and we'll talk about that actually now when we talk about these drugs these uh sodium channel blockers what are some of them there's a lot of them and we actually are going to talk about these in a subtype so when we talk about sodium channel blockers they're all going to block the voltage-gated sodium channels in those non-pacemaker atrial and ventricular myocardial cardiomyocytes right but they're going to block a little bit differently and they have different names for the different subtypes so there's class 1A class 1B and class one C or type 1A type 1B type 1C with these there's a lot of them names so here's the way that I usually remember them I remember for type 1A it's Double Quarter Pounder so Daiso pyramide I sound so fat saying that but that's the way I remember it so dysopiramide so Double Quarter quinitine quinitine and then pounder the most commonly utilized one here is procainamide so Double Quarter Pounder with lettuce so lidocaine is going to be for the type B so lidocaine Lido cane and the last one is and fries please I'll take a Double Quarter Pounder with lettuce and fries please so flecanide and propofinone so this is just the way that I remember these particular drug names is again type 1A type 1B type 1C or class 1A class 1B class 1C I remember Double Quarter Pounder disoperamicquinone brucainamide with lettuce lidocaine and fries please flucanamide and propofenone with these drugs they're all going to block the sodium channels but the reason why we subclassify them is they block the sodium channels to some degree a little bit different in response to the powerful kind of like uh the the sense of how strongly they block the sodium channels so in other words type 1A type 1B type 1C they can differ in the degree of blockage the strength of blockage of the sodium channels and we'll talk about that I'll teach you a little trick to remembering that but either way here's this atrial or ventricular myocyte and this is the cell who has who's generating this triggered activity he's the he's the problem child right so he's in the atrials in The ventricle and he's causing triggered activity or he's in The ventricle cells and he's causing like these re-entrant circuits what I want to do is I want to suppress I want to inhibit this cell from generating triggered activity or generating these re-entrant circuits how do I do that how do I actually do that process well I'm going to give these drugs to block particularly the sodium channel so here's my voltage-gated sodium channels these are going to allow for sodium to rush in to the cell now whenever sodium is these voltage-gated sodium channels are open they allow sodium to Rush In and that causes the upstroke of the action potential which is what phase phase zero so all this is Phase zero on the fast action potential to producing tissue again this is the non-pacemaker tissue so these will not work very well or won't work really at all and the pacemaker tissues because there is no specific voltage-gated sodium channels on those tissues that's important to remember that's why they're going to be more specific to the fast action potential producing tissue such as the atrial and ventricular monocytes that are non-pacemaker tissue but anyway I'm going to give these drugs and what they're going to do is they're going to block this sodium Channel if they block the sodium Channel they block the entry of sodium into the cell and so they decrease the positive charges rushing into the cell and they decrease the upstroke of phase zero so again here is my phase zero if we were to kind of go through this whole process here's phase zero here's phase one here's phase two here's phase three and then here's phase four and then phase four here as well same concept with this one phase four phase zero is this upstroke with the Sodium influx phase one is the potassium reflux phase two is the calcium influx and potassium efflux phase three is the primarily potassium efflux resting memory potential via the sodium potassium channels zero is going to be sodium influx one is the potassium efflux two is the plateau with the calcium influx and potassium reflex three is primarily potassium efflux and four is the resting membrane potential okay if I block the sodium entry into this cell I'm going to reduce the upstroke the rapid phase of the action potential in these triggered or re-entrant atrial and ventricular cells so now what's going to happen is I'm going to notice a difference in the slope I'm going to decrease the upstroke so instead of me having a very crisp rise in Phase zero it's going to be very delayed and it's going to have a slope that moves this way now which is going to take a longer time for it to be able to generate these Action potentials and that's a really helpful concept but the port important thing in here is knowing how strongly they do it because this is what you'll be tested on on the exam so here's the way I remember which one strongly blocks it to which one least strongly blocks it so the most powerful sodium blocker out of these class 1A class 1B class 1C I easily remember it by cap so type 1C type 1A type 1B or class 1A class 1 class 1C class 1A class 1B so cap so what I'm going to do is I'm going to show you what it will now look like this is going to be the strongest so this is going to have the most sodium blockade so when I look at this I'm not going to have this very fast upstroke I'm going to have a very slow type of upstroke here and here's the other thing that's interesting about this one because there's this very very kind of very powerful kind of upstroke here what happens is now I'm going to have my Plateau phase but I'm going to try to end this at the same time it shouldn't really have any effect on the action potential duration so the action potential duration is from the beginning the end of phase four beginning of phase zero all the way till we go back to phase four so this is my action potential duration from here to here I shouldn't have any effect on my action potential duration but what I will see is a very kind of decreased slope a rise or upstroke in Phase zero but by again my refractory period and my action potential duration should be the same almost no effect little to no effect so what I'm going to see is look at my phase zero it's shifted phase one kind of the same phase two kind of the same phase three kind of the same and then phase four again kind of the same here but what I'm going to notice is a decreased slope of phase zero so what I'll notice here as the effect of the sodium Channel blockade is I'm going to notice a a decrease in the slope of phase zero and that is the cool concept here of how this drug actually works so this would be which drugs this would be fluconide and propofenone so these are actually utilized and we'll talk about this later in patients with atrial fibrillation atrial flutter sometimes even you can consider SVT to be able to maintain normal sinus rhythm to maintain normal sinus rhythm in patients who have atrial fibrillation or atrial flutter because they are the most powerful sodium channel blockers okay but I have no they should have no effect no change this is like I can't stress this enough the action potential duration should be the same I shouldn't have any change in my action potential duration so that should be the same as compared to this black side with the blue ones no change there we come to the 1A a little bit different for these these have let's say this one is the strongest so we'll put three arrows this one is going to have like middle or moderate sodium Channel blockade so middle or moderate sodium Channel blockade so you're going to see the same effect here with this type of drug so this is going to be which ones you're going to see procainamide disoperamide and quinitine for the type 1as okay Double Quarter Pounder with this what you'll see is they're going to have a powerful sodium Channel blockade but just not as powerful so it won't be shifted the the slope won't be as intensely shifted to the right so we'll kind of go like right here so you see how this one was more powerful this one again it's not going to be as intense now what's going to be different here is this watch this this is what's interesting you're going to be like wait what what happened to my action potential duration the refractory period's longer now so it's got a more drawn out refractory period but what you'll notice here is that my action potential duration is increased whoa I have an increased action potential duration I had no effect on the type 1C but in the type 1A there is this shifting of the phase zero but then I have a prolonged kind of refractory period we call this the refractory period when potassium is kind of like leaving the cell in the phases once you kind of go into this downward phase here we call that the refractory period you have two parts of your factory period you're the effective refractory period is kind of the big way to think about it but once the cell kind of ends it's kind of depolarization starts repolarizing we're going into what's called a refractory period look what happens it's shifted to the right a little bit that's weird that means the type 1A drugs also have potassium Channel blockade that's one of the interesting things here so this also has a little bit of potassium blockade so because it blocks the potassium channels a little bit you get a longer it takes a longer time for this cell to repolarize so the action potential duration is increased so what I'll notice with this drug is that it will decrease the slope the upstroke of phase zero and I noticed that it'll actually cause a longer it'll actually cause a longer repolarization period so it'll increase what's called your effective refractory period and that will increase your action potential duration so again what is the overall effect with this drug it will decrease the slope of phase zero but also increase the reflective refractory period so that will increase the action potential duration this is primarily which drugs again procainamide disoperamide quinitine I can't stress this enough this is the only one out of the sodium channel blockers that increases the effect of refractor bear to increase the action potential duration okay so so far we have the most sodium Channel blockade the middle sodium Channel blockade with a little bit of potassium blockade that's what's really interesting about this drug because this will decrease the upstroke of phase zero the most this will decrease the upstroke of phase zero like in the moderate middle amount but it also prolong the effect of refractory period increase action potential duration type 1B so this is going to be lidocaine this one's weird it'll have the least amount of the least amount of so here we'll just put one Arrow so this had three arrows for type one C two errors for type one um a this will only have one Arrow so it has a little bit of sodium blockade the least amount out of all three of these subclasses so because of that if we were to look here it's really not going to have a very profound effect here on the of the upstroke so this one had a very powerful this one at a very powerful kind of delay and this one's going to have a little bit of a delay here all right but here's what's also really interesting look what happens to the action potential duration oh you're like man I can't remember all this stuff I'm supposed to remember all this stuff what I noticed here is that my phase zero is decreased slope not as powerful but there is a decrease upstroke of phase zero but what I noticed is that my refractory period kind of like decreases a little bit so now I notice that I shift this thing a little bit towards the left this has nothing to do with the potassium channels it's that you know usually with sodium channel blockers there's different phases when you can block them so you have different faces you have What's called the resting state so when you go through these channels here let's say that this is a it's in the resting membrane potential there's two gates usually and whenever these patients are in What's called the resting state their their voltage-gated sodium channels let's say resting membrane potential this is when it's active and this is when it's inactive and then usually it kind of Cycles back up to this point so it's kind of like a circle here it's a cycle right and the resting membrane potential you have what's called your inactivation Gates these are usually open but your activation gate is closed what happens is once this cell becomes stimulated it goes into this active configuration which is where the activation gate is open and the inactivation gate is open and this is really the phase where lots of sodium ions are flooding in and then you have the inactive state which is basically where the again the inactivation gate closes here but you still have the activation gate open so this is the three configurations what we see with the type 1B is that it might be able to kind of block this state the type 1B so the one B's can block here and they've also been shown to block here which really none of the other ones can do and so this may alter to some degree the plateau phase so it may alter the plateau phase and the repolarization period a little bit and shorten the action potential duration which is really interesting so that's one of the big things to remember here is that with this drug type 1B or the class would be the lidocaine it will block the sodium channels and if you do block the sodium channels very moderately you will decrease the slope of phase zero but it also will decrease the action potential duration and the way it may do that is by kind of keeping the sodium channels inhibited in both the active and inactive state and so look at the action potential duration here now the action potential duration is decreased and that's what's really interesting about this drug category so to quickly recap sodium channel blockers we're utilizing these this is a Class one you got the drugs class 1A class 1B class 1C Double Quarter Pounder again with lettuce and fries please disappear myquinidine procainamide lidocaine flecanide propofenone that's how you remember those what do they utilize for they're utilized to cardiovert or to kind of shift people from these abnormal rhythms that are generated by these abnormal atrial or ventricular cells into a normal sinus rhythm so we use this in afib a flutter v-tac maybe even torsos to points okay when we talk about these how do they work they block these so a voltage-gated sodium channels and decrease the slope of phase zero but on top of them all decreasing the slope of phase zero some of them do it a little bit more powerfully than others you can remember the strength of it by cab so when c one a one B strongest with one C Middle with one a the weakest with one b but then don't forget that with one C it has no effect on the actual potential duration it doesn't affect the plateau phase it doesn't affect the actual effect of refractory period And so because of that it only just strongly decrease the slope of phase zero with one a it has sodium Channel blockade so it decreased the slope of phase zero but it also has a little bit of potassium Channel blockade so it prolongs the refractory period of the repolarization period And so you may get an increase in action potential duration whereas lidocaine weakest sodium channel blocker but because it may inhibit the sodium channels in both the active and inactive state it may be able to not only decrease the upstroke of phase zero but shorten the action potential duration so it may affect the plateau phase and it may also to some degree affect the effect of refractory period and so because you shorten that kind of plateau phase a little bit you shorten the action potential duration and so that is another cool concept of these structs now that we've talked about the sodium channel blockers let's finish up with the last type of drug category here which is your potassium channel blockers your class III drugs all right my friends class three antarrhythmic drugs okay so these ones are really cool the potassium channel blockers one of these I really really like but when we talk about the names of these like because there's a lot of names right so I think it helped you guys remember maybe the sodium channel blockers with the Double Quarter Pounder with lettuce you know fries please with these ones is not the best mnemonic but it works it comes out from the first aid USMLE one but usually you can remember AIDS so it's terrible but this is amiodarone amiod around for the a a butylied for the I and then do fetalide and there's even another one called draneterone do fetalide and then s for so to law so this is you can remember these again with the mnemonic AIDS terrible one but it works so when we talk about these particular drugs what are they actually going to be utilized for it's the same concept we talked about with the Sodium channel blockers we're utilizing this in particular diseases where you have an atrial Focus or a ventricular Focus that are not a pacemaker tissue that are generating these triggered activity or re-entrant circuits and what you're trying to do is to shut down the ventricular atrial tissue from generating these abnormal rhythms so when diseases such as atrial fibrillation atrial flutter you're utilizing these two Rhythm control these patients are to cardiovert them in some particular way to either maintain normal sinus rhythm or switch them back to normal sinus rhythm that's what you're trying to utilize it for and the other one is vtac and again you're trying to cardiovert these patients you're trying to stop that ventricular Focus from generating these very abnormal triggered activity or re-entrant circuits and shut that down so they can regenerate a normal sinus rhythm so again when we talk about cardioversion there's obviously one thing that I didn't mention here is we can chemically cardiovert patients that's what we're using with these type 1 and type 3 antiarhythmic drugs but you can also use electricity to cardiovert a patient out of atrial fibrillation atrial flutter or v-tac into a normal sinus rhythm but we'll talk about some of the downsides to utilizing chemical cardioversion and why electricity actually may be potentially superior but we'll talk about some of the downsides as well that you have to be careful with when you're cardioverting a patient one of those if I mention it right here if a patient's atrial fibrillation ratio flutter with a high risk of what's called atrial thrombi so they can form clots within their left atrium if you cardiovert them they now gain that actual atrial Kickback and they can break off a clot and then embolize that and cause a stroke so it's important to remember that whenever we cardiovert a patient who has afib despite if we're doing it with electricity or with these drugs like amiodarone abutilide to fetal isotolol the type 1 sodium channel blockers whatever we're doing if we're converting the patient we better make sure that we either wash it they don't have a clot within their left atrium because if that's the case we should anticoagulate those patients for a little bit before we actually do it or continue anticoagulation afterwards so very important to be able to remember that but either way when we utilize these drugs how are they particularly working they're blocking the voltage-gated potassium channels so with the voltage-gated Sodium channels that was here right so we have the phases here that are respective here we have phase four which is the resting membrane potential that's due to the sodium potassium pumps then you have phase zero phase zero was the sodium influx via the voltageated sodium channels then you have phase one phase one is what what channel opens up do you guys remember these two channels so potassium channels should open up and calcium channels should open up but potassium channels will open up quicker and potassium will exit a little bit early and so this is going to be phase one that's the potassium channels leaving then phase two is when calcium is entering in and potassium is exiting out so that's the plateau phase and then calcium channels close and the only one that's open here is going to be potassium and that's phase three so potassium channels are open at what phases three phases phase one phase two and phase three so if what we do is we give a drug like amiodarone a butylite to fetalid or sotolol what they are doing is is they are blocking the potassium channels from opening at all three of these phases phase one phase two and phase three so what you'll see is that with this dragon with blue you'll see the same phase zero but what you'll notice is that phase one less potassium is going to be leaking out so what it's going to do is it's going to decrease potassium eflux if you decrease potassium efflux if the potassium won't leave as easily so now you're going to decrease the rate at which potassium starts to cause that drop and you're also going to decrease the potassium leaving during the plateau phase and then on top of that you're going to decrease the amount of potassium that's leaving During the repolarization period and it's going to take a longer time for it to get back to resting membrane potential so what you'll see here is this very prolonged action potential duration look what happens to the actual potential duration from the beginning here it's all the way here in comparison to what it was here to here the action potential duration is increased the refractory period is increased so you have an increase in your refractive refractory period and you have an increase in the action potential duration so now it's going to be in this repolarization period a lot longer and it's going to be harder to re-stimulate this agitated tissue which is great in situations of atrial and ventricular tachyurythmias just like in the sodium channel blockers you're decreasing the upstroke you're decreasing its ability to generate these fast Action potentials inside of those tissues which is going to slow the upstroke of phase zero here you're causing a prolonged repolarization period decreasing its ability to be stimulated again so the same thing here now look at this one it's going to have this next Point here where it's in the repolarization period it should still have a normal phase zero but what you're going to see here is you're going to see a very prolonged kind of phase one two and three and so because of that the effect of refractory period will be significantly increased so to summate here what do we see with the potassium channel blockers what we're seeing with potassium Channel blockade is we're causing a decrease in potassium reflux so a decrease in potassium efflux less potassium is leaving and that's going to be occurring in what phases phase one phase two but most important phase three and what that's going to do is all three of these phases if that's slowed down it's going to prolong the effective refractory period and increase the action potential duration and both atrial and ventricular cells and that's going to help to be able to suppress these atrial cells and ventricular cells from generating these fast triggered activity or reentrant circuits causing these tachyurythmias Isn't that cool now we've talked about these drugs pretty effectively right amiodarone we've talked about a butylite to fetalisodil there's even another one called dranetarum one of the big things to remember we're going to talk about this a little bit more to really kind of nail down on this concept is some of these drugs work more to suppress the ventricular tissue and less of them um can actually some of them will be able to only suppress ventricular tissue and pretty much all of them can suppress atrial tissue but it's important to remember that primarily what we'll talk about a little bit later is really only amiodarone and soda law are utilized here in the ventricular tissue suppression but they will not the the abutilide to fetal hydronetron those won't be as effective or really effective at all in the ventricular tissue suppression they all are good for atrial atrial tissue so atrial fibrillation atrial flutter cardioverting that tissue all of them are effective but for them should attack a cardia only amiodar and soda law will be effective and again we'll talk about a little bit later so up to this point we've discussed action potentials in both pacemaker tissues and non-pacemaker tissues we talked about all the channels that are involved we talked about all the phases and what they look like graphically we talked about the approach to how we're going to Target arrhythmias some will suppress the AV node for a lot of the atrial arrhythmias to rate control those patients especially in afib a flutter SVT we talked about how beta blockers do that calcium channel blockers do that adenosine digoxin do that then what we did is we took and we said okay we know how those drugs block the pacemaker tissues how they decrease the slope of phase four phase zero how they hyperpolarize the cell make it harder to get to threshold potential what about the atrial and ventricular tissue that's not pacemaker tissue they're generating triggered activity they're generating some type of reentrant circuit and they're not caring about suppressing the AV node to suppress the atrial input you're trying to stop those tissues from generating those arrhythmias and convert them and Rhythm control them and switch them back into normal sinus that's where we use class 1 and class 3 drugs sodium channel blockers to decrease the upstroke of phase zero some of them can even increase the action potential duration increasing the effect of refractory period one of them can even decrease the action potential duration right then we talked about the potassium channel blockers how they also prolong or increase the effect of a fractal period and increase the action potential duration either way if we're decreasing the upstroke or prolonging the refractory period it makes it harder for those atrial and ventricular tissues to generate triggered activity to generate re-entrant circuits and cause those tachy arrhythmias but what I want to do now is because you hit with so much information let's summate if a patient comes in and you're the one responsible for taking care of them hey Doc you got a patient in atrial fibrillation right now what do you want to do you need to know are you going to rate control Rhythm control what's the drug of choice in this particular situation and what may be some potential like conditions that you have to be aware of that they may not respond better to this one in comparison to this one so if a patient comes up and they have one of these arrhythmias how do we go about treating it with all the agents that we talked about putting the depths of the mechanism of action and all the stuff aside now saying okay quick quick you know clinical approach here patient has this disease what do you give them and why let's talk about that you have a patient who's an atrial fibrillation or they're an atrial flutter the nice thing about kind of combining those is that regardless of their kind of pathogenesis or the actual disease itself you kind of treat atrial fibrillation atrial flutter relatively the same so if I have a patient who's having a re-entrant circuit because of afib or they have a re-entrant circuit because of atrial flutter they have a triggered activity because of afib whatever they're generating these very fast electrical activities that are trying sometimes up to 300 beats per minute and they're trying to generate these fast Electro activities to move through the AV node into the ventricles and make the ventricles beat at a similar very fast rate that the Atria are beating at and so it's a very dangerous concept so what I want to do is I want to shut down the AV node so all the electrical activity that's moving through the Atria towards the AV node and then from AV node down to the ventricles I'm going to shut the AV node down and say hey don't allow for a lot of that electrical activity that's coming from the atrial cells that are agitated or re-entrant circuits that they're generating to go down to the ventricles shut it down and only allow for some of the electrical activity to go down and so that's what it's really doing and so when we do that when we rate control them we try to block the so what you're doing with this one is you're inhibiting the AV node this is your beta blockers your calcium channel blockers that's going to be the drugs and then one more for afib flutter particularly afib digoxin so this would be what drugs your beta blockers this will be your calcium channel blockers and this will be digoxin but again when we talk about Digoxin they have to have heart failure with a reduced ejection fraction that's really the primary indication of this drug because it's a positive inotropic agent so it'll help to increase the contractility of the heart and if you give it to a patient who has afib and congestive heart failure with a reduced DF you may get a double kind of benefit from those two particular drugs all right so that's going to be rig controlling the patient suppressing the AV node beta blockers calcium channel blockers digoxin you're probably like what about adenosine Zach doesn't it block the even node remember I told you it's so short acting that it will have no long lasting benefit and patients who have atrial fibrillation or atrial flutter what about a patient who has atrial fibrillation or atrial flutter and you're trying to now suppress those triggered atrial cells right or the reentrant circuits from those atrial cells that are being developed and causing these fast rates to run down into the ventricles right so in other words patient has afib a flutter you can rate control them by blocking the pacemaker cells particularly the AV node and to reduce the amount of electrical potentials that's going from The Atrium to the ventricles what if we just shut off those triggered activity triggered atrial cells are re-entrant circuits in those atrial cells we shut those off and we just maintain or convert a patient into a normal sinus rhythm wouldn't that be beneficial so that's called your cardioversion so what we're trying to do is not inhibit the AV nodal cells we're trying to inhibit the non pacemaker cells so remember I told you if you're suppressing AV node that's your beta blocker so that's class two if you're trying to do the you know this one for calcium channel blockers that's class four and the joxen's kind of one of those miscellaneous class fives we don't use adenosine because it's too short acting but in this particular population for cardioversion and of the non-pacemaker cells that's the sodium channel blockers and potassium channel blockers that are really good so I can use type 1 agents and I can use out of those type 1 agents I can use one a or I could use one C so with type 1A right this is the Double Quarter Pounder so disoperamicquinone procainamide the most commonly utilized one here is going to be procainamide procainamide and really what we're utilizing this drug for is in what's called wpw plus they have atrial fibrillation or atrial flutter so if they have atrial fibrillation and atrial fluid are a pre-excitation syndrome and an accessory pathway this is a super scary poop in your Huggies kind of like drug disease process because what can happen is when a patient has this accessory pathway and they have a very pre-excited heart the electrical activity could run right through that accessory pathway into the ventricles so if the Atria is generating beats of 300 to 350 beats per minute and it has this little electrical window besides the AV node that it can go through into the ventricles your Atria can cause your ventricles to beat at the same rate that could cause v-fib instantly and cause the patient to die so in this particular situation it's important to remember that we can give type 1 your sodium channel blockers sodium channel blockers like procainamide primarily in wpw and afib or a flutter just avoid anything that suppresses the AV node if they have this don't give them adenosine don't give them beta blockers don't give them calcium channel blockers don't give them digoxin because you can create this really nasty circuit for these patients and kill them for type 1C this is either one of them so if this is both this is going to be the fries please so flecanide and propofenone for these ones you can actually use this an A-fib or a flutter but one of the big things that I think is important to remember with this drug is they can have no like coronary artery disease no heart failure no LVH if they have any of these things it can kill the patient if you give them this drug because these drugs type 1C which we'll talk about later is pro arrhythmic especially if a patient just had an MI they're post Mi so that's another thing if they if they have no coronary artery disease heart failure LVH and for the love of goodness no am I do not you can give them this drug category flight or propofolone but if they have these you could kill them because you could actually put them into a pro rhythmic State cause them to go into ventricular fibrillation so the only indication for this drug is atrial fibrillation atrial flutter it's more of an outpatient type of drug so we utilize this more kind of treatment as outpatient it's kind of a pill in a pocket approach to be able to maintain normal sinus rhythm in patients who have atrial fibrillation at your flutter but do not have any of these diseases do not give them that drug if they have these diseases you'll kill them all right so we got the sodium channel blockers type 1 a and type one C that we can utilize as cardioversion therapy the other one is your type or class three drugs this is your potassium channel blockers for these ones we can use any of them amiodarone abutilide di fetalide sotolol any of those drugs these are also going to be beneficial again to be able to convert a patient who is an acute afib or a flutter you can switch them over into normal sinus rhythm and even maintain them in normal sinus rhythm one of the best ones for converting them immediately is amiodarone or a butylite but again any of these agents could be potentially utilized for the class 3 or type 3 types of antiarhomic drugs the potassium channel blockers so again patient has afib a flutter your decision comes down to am I array controlling them or Rhythm controlling them cardioverting them well if I'm going to rate control I'm suppressing the pacemaker cells particularly AV node beta blockers calcium channel blockers don't do adenosine because it's too short acting or digoxin if they have half ref if I'm not going to rate control them I'm going to try to suppress those agitated or re-entrant circuits in the atrial and ventricular cells that are not pacemaker tissues so I'm going to give sodium channel blockers or potassium channel blockers if I give sodium channel blockers it's only type 1 a and type 1C type 1A is only really good in patients who have wpw and afib type 1 C is in patients who have no CAD no heart failure no LVH and no post Mi if you give them that drug you will kill them it's primarily outpatient medication pill in a pocket approach to maintain normal sinus or to convert them in an outpatient setting type 1C I'm sorry type 3 you can use any of them amiodarone defetilide abutilized sodalol any of them are going to be beneficial in converting the patient to normal sinus rhythm amiodarone will probably be the best one the way that we pick which one sometimes depends upon the adverse drug reactions of those drugs okay but that's the concept there okay now that we got afib a flutter down what about SVT so patient develops an SVT you can Rhythm control these patients however it's not usually the preferred approach usually the most preferred approach with SVT is going to be more of the AV nodal blockade so with SVT you're going to try to suppress the AV node you're going to try to suppress a lot of the electrical activity that's going from the Atria into the ventricles via the AV node so if I'm going to do this acutely so acutely the drug of choice is adenosine so a patient comes in they're in scdt they're hypotensive they're symptomatic and we want to abort the SVT adenosine is going to be the best drug because it'll acutely suppress their AV node and get them back into a normal sinus rhythm you can give it as a six milligram bolus and then if that doesn't work at 12 milligram bolus but after that after they have converted and they've actually suppressed the AV node enough that it actually put them back into normal sinus then what you can do is a prophylactic therapy to prevent them from going back into SVT as you can again give them drugs that'll always keep kind of suppressing the AV node and given lower doses such as a beta blocker or a calcium channel blockers okay so that is the concept that I want you guys to remember so again SVT you're going to block Dave you know a lot of the electrical activity from these atrial cells moving into the AV node into the ventricles you're going to suppress the AV node you can do that with acutely adenosine or prophylactically to maintain their normal sinus beta blockers calcium channel blockers digoxin is not helpful in SVT okay what else okay now here's the other thing I want you to think about with the atrial cells we've talked a lot about the atrial tissue there's another particular situation here so you know atrial cells sometimes they can develop triggered activity but it's not sustained so in other words they generate this electrical activity that's faster than the SA node or it suppresses the SA node but it's not a continuous sustained activity and these sometimes can occur within the Atria called Pacs premature atrial complexes this is usually due to increased sympathetic nervous system activity so what if I give a drug that inhibits the epinephrine and norepinephrine from increased sympathetic activity on beta receptors what drug category would be best to suppress Pacs beta blockers so I would inhibit this by giving beta blockers okay all right the next concept here if I have a patient who has what's called torsads deploy so torsos to points is basically what's called a polymorphic v-tac with a prolonged QT interval so in other words a patient is taking multiple drugs there's so many drugs that can cause a prolonged QT interval it could be antiarrhythmics and so this is what we'll talk about a little bit which antiarrhythmics did you notice increase the action potential duration so if you increase the action potential duration you increase the QT interval do you guys remember for the sodium channel blockers it was the type 1A and then all the potassium channel blockers increase the effect of refractor period in the action potential duration so they also increase QT interval so antiarhmic such as type 1A and type 3 are class 3 and antiarismic drugs could prolong the QT interval increase the risk of torsods antibiotics like macrolides tetracyclines fluoroquinolones things like that they can also increase the QT interval antipsychotics so any kind of antipsychotic agent can actually increase the QT interval so things like haloperidol things like um what's called Seroquel or also known as Quetiapine so there's there's all these different drugs that have the ability to increase the QD interval antipsychotics antidepressants so tricyclic antidepressants anti Medics like ondansetron or metaclopramide all those things can increase the QT interval which can increase the risk of torsods to points so you want to give things that can reduce the QT interval and so if you can reduce the QT interval you can reduce the risk of torsoes to points what things reduce the QT interval do you remember the one antiarrhythmic I told you because again it was one of the class ones that actually shortened the action potential duration it was only one of them it was the class one B lidocaine so I could actually give what's called a type or class 1B drug such as lidocaine why because it yes not only did it actually reduce the sodium Channel entry so it decreased the slope of phase Zero by sodium Channel blockade but it also caused a little decrease in the action potential duration if I decrease action potential duration I'll decrease QT interval all right what else another one is magnesium we don't really know exactly how but it actually magnesium has been shown to be one of the most effective things at reducing the QT interval and then one more anything that increases the heart rate will actually decrease the action potential duration and decrease the QT interval so I want to give things to increase the patient's heart rate so I can give things like isoproterenol or I can actually Pace the patient and that will increase the heart rate but one of the biggest things I think that's important to remember here is torso deployments is due to drugs or things that increase QT interval discontinue the drugs that increase QT interval so discontinue those drugs give them magnesium that's the most important one consider lidocaine because that will also reduce the QT interval and then you can try to increase the patient sorry this is not really relevant to anti-runic drugs but it just tells you how you treat this you can increase the heart rate because if you increase the heart rate you shorten their action potential duration because their heart's beating faster they have less of a diastolic heart rate a period And so their QT interval will decrease and that reduces the torsos to points but either way that's the one the things I want you to think about but the most important ones being magnesium and Lidocaine because these are antiarrhythmics okay what about the other Concepts here what about patients who develop PVCs so again usually PVCs and v-tac there's some type of increased sympathetic nervous system activity so what if I could give drugs that inhibits the sympathetic effect here which would reduce a lot of the PVCs from generating triggered activity or ventricular cells from causing a lot of ventricular tachycardia this would be beta blockers so beta blockers tend to be very beneficial at suppressing the PVCs as well as suppressing ventricular tachycardia due to increased sympathetic nervous system activity okay if I'm trying to also take these ventricular cells that are triggered all right so they're generating Trigon activity whether it be Eads usually Eads is torsos to points but dads so delayed after depolarizations causing ventricular tachycardia or re-entrant circuits causing ventricular tachycardia or a lot of sympathetic Drive causing this ventricular tachycardia what I want to do is I want to suppress and take those ventricular cells that are kind of beating at very fast rates and just suppress them and stop them from generating vtac so what drugs would do that sodium channel blockers which are your class one and potassium channel blockers class three because those are the ones that are targeting what type of cells non-pacemaker cells I need to inhibit the non pacemaker cells those ventricular monocytes so I'm going to use which ones I'm going to use class 1. okay or class three now with the class one there's really only two drug categories type 1C no you do not give type 1C or class 1C and v-tac but you can consider 1A and you can consider one b one a you can give quintidine maybe even potentially a procainamide but generally these are usually last line we do not go to these right away these are usually last line okay so if a patient is an nvtac you're not going to be reaching for procainamide you're not going to be reaching for quinitine as a first line agent it's something that you could consider but it's not first line sometimes in textbooks they'll actually put down impatience of what's called brugada syndrome brugada syndrome is usually when the patients have usually some type of like right bundle branch block some SD segment elevations in like either kind of beginning parts of their precordial leads usually in those particular scenarios and they have increased risk of v-tac you can give them things like quinitine but again I wouldn't be too crazy about remembering that fact procainamide is another one that you can actually utilize to suppress the ventricular cells but again it's not going to be your first line agents and dysopiramide don't worry about that one the 1B is the one I would actually remember for the for the sodium channel blockers for one B this is going to be again your lidocaine this is actually an important fact to remember that these are these sodium channel blockers are the best and patients who just had a myocardial infarction post Mi if a patient just had a myocardial infarction they infarcted their myocardial tissue they've increased risk of triggered activity they have increased risk of retention tachycardias and they can go into vtac one of the sodium channel blockers that is the best after a patient had an MI is going to be lidocaine so remember that fact class 1a not as great not your first line agent the next one is going to be the class 3 or your type 3 antiarrhythmics so this is going to be your potassium channel blocker so type 1 is the sodium channel blockers and then type 3 is going to be the potassium channel blockers what did I tell you out of all these which ones out of the AIDS that's a terrible thing amiodarone abutilide to fetalide dronetron and Soto law which ones were primarily only effective in ventricular tissue that's caused the trigger activity or lots of reentrant circuits amniodarone and sotomol so out of those and if a patient goes into vtac amiodarone is usually the most commonly utilized one out of all these really and then sotolol is another one that you can potentially consider but when a patient is posed to my lidocaine should be first if a patient did not have an MI and the Mi is not the responsible cause of their v-tac amiodarine is a very very good drug that people will reach for Soto law is another one to consider beta blocker is another one to add on just again usually for you know patients who have vtac we don't automatically go to procainamide orquinidine again remember the quinitine factor the brugada syndrome but if a patient goes into vtac it's post to my lidocaine if it's not posed to my amiodar and soda law tend to be one of the more beneficial agents and then to suppress the sympathetic nervous system effect that could be worsening their v-tac give beta blockers okay I hope that makes sense all right we had a patient now that we've gone through and we've talked about if they have this arrhythmia how do you treat it the next thing that I need you guys to realize whenever you will give an antiarhythmic agent to these patients all right from one of these particular scenarios is what are the adverse effects that maybe deter you from using this agent over another agent or you put this medication on and the patient develops this adverse drug reaction you need to know is that expected or not expected is that a little bit different okay so I need to be able to recognize things I have watched out for when I give these medications to patients so how do I talk about adverse drug reactions let's get into that now all right my friends we're going to move on to adverse drug reactions so you have a patient comes in they have a particular arrhythmia you start treating them with this drug so let's say you have a patient who's an afib a flutter SVT you give them a beta blocker one of the things that you should be careful of and be cautious of and realize a potential adverse drug reactions when you get the beta blocker they're suppressing the AV node my friends so if you suppress the AV node you're suppressing a lot of electrol activity from going into the heart so I bet you give a pretty good Hefty dose of a beta blocker you could actually suppress the AV node so significantly that almost no electrical activity goes from The Atrium to The ventricle so you can develop like an AV block so watch out for that it may cause bradycardia that may be one potential thing to watch out for is a low heart rate because it's really suppressing the electrical activity via the AV node from the atrial to the ventricles it may potentially cause an AV block so you want to watch out for those potential effects the other thing is that not only do you inhibit the AV node you inhibit the contractility so you inhibit the contractility of your myocardial cells because if you inhibit those cells you can actually reduce contractility the squeeze of the heart and so if I reduce contractility the downside to that is that that can reduce cardiac output so if I reduce cardiac output that could cause the patient's blood pressure to tank and the indication of these particular situations of where it could cause the blood pressure to tank is impatient to have what's called decompensated heart failure so watch out for that if a patient has decompensated heart failure so they're in very like significant heart failure with cardiogenic shock don't give them a beta blocker you could really kill them so be careful and cognizant of that so again watch out for bradycardia particularly sinus bradycardia watch out for AV blocks with very high doses and watch out for reduced contractility that can drop cardiac output and blood pressure and decompensated heart failure patients next thing there's beta 2 receptors so this is all via the blockade of beta 1 receptors in the heart but what about the beta 2 receptors that are present on the bronchial smooth muscle so naturally when you hit those beta 2 receptors in the bronchial smooth muscle it causes bronchodilation if you block them if you inhibit The beta-2 receptors especially with like propanolol you can actually cause bronchospasm and if you cause bronchospasm that can definitely cause a lot significant worsening in patients with like COPD or patients with asthma that will really worsen them so be cognizant of that if a patient has these two particular diseases the other thing is that when you know when patients have low blood glucose levels so whenever they have what's called hypoglycemia so if a patient has hypoglycemia maybe it's because their blood glucose is low they took too much insulin whatever it may be and in these situations what you're supposed to do is this hypoglycemia will kind of increase the sympathetic outflow so it'll increase the sympathetic outflow and increase the sympathetic effects to make you aware that your blood glucose is low so making kind of your heart rate beat a little bit faster give you palpitations it may cause you to become like tremors so you may develop Tremors you may develop a lot of diaphoresis and so these are some of the potential signs of hypoglycemia if you give a beta blocker what you're doing is you're suppressing the sympathetic nervous system effect so if I give a beta blocker I'm hitting the sympathetic nervous system effect so I'm inhibiting both the maybe the beta 1 so that's causing my tachycardia and I'm hitting some of the beta 2 receptors that may be causing some of the Tremors I'm inhibiting kind of the diaphoretical process and so because of that I lose my ability to be aware of my hypoglycemia so this can cause what's called hypoglycemia unawareness because you're blunting the sympathetic nervous system response so a very very important thing to watch out for in these patients who have what's called diabetes so hypoglycemia unawareness and patients who have diabetes be very cautious of another kind of thing that you really want to watch out for is if a patient is taking booger sugar so they're taking something called cocaine now what cocaine can do is it really powerfully binds on to The alpha-1 receptors when you bind onto alpha-1 receptors that causes intense vasoconstriction and when you cause vasoconstriction what you do is you increase systemic vascular resistance and increase the patient's blood pressure okay now cocaine can bind onto Alpha One receptors and beta 2 receptors and if it binds into beta 2 receptors what that's going to do is when these are stimulated they cause vasodilation and if you vasodilate you reduce systemic vascular resistance and that will actually work too reduce your blood pressure okay so you see how it's kind of like there's a balance between these two now if I give a beta blocker a beta blocker is going to block cocaine from being able to bind onto the beta2 receptors so here I'm going to give a beta blocker and the beta blocker so this is a beta2 receptor blocker such as like propranolol what it'll do is it'll block the cocaine from binding onto the beta 2 receptors so that'll decrease the vasodilation it'll decrease the kind of systemic vascular resistance effect and only allow for cocaine to bind onto the alpha-1 receptors which will increase the vasoconstriction effect increase systemic vascular resistance and shoot the BP up even more so really one of the things that you want to be very very cautious of is not giving beta blockers in patients who have cocaine-induced hypertension because when you give them that drug you're blocking cocaine from binding to the beta 2 receptors which is causing vasodilation so now you have less vasodilatory effect and you're allowing for it to have unopposed action on the Alpha One receptors which is going to cause an intense vasoconstrictive response and increase your blood pressure so just be cognizant of that if a patient has cocaine in their system they're hypertensive maybe they're tachycardic related to that and you give them a beta blocker they will now have unopposed alpha-1 vasoconstriction and shoot their blood pressure up even more so be careful of that all right calcium channel blockers what are things to watch out for well again my friends you're blocking and inhibiting the AV node because of that if you block the AV node watch out for bradycardia all right watch out for potentially an AV blockade these are things to be cognizant of and think about the other things that you're inhibiting the contractility because calcium L Type calcium channels are also present on the contractile portion of the heart so you're inhibiting that which can reduce contractility if you reduce contraction of The myocardium you're going to reduce the what cardiac output and reduce the blood pressure this could be catastrophic in patients who have decompensated heart failure so in this one with beta blockers they say you really be cautious about giving beta blockers and decomposite arm failure do not give calcium channel blockers in decompensated heart failure you will put them in a cardiogenic shock okay the other thing is that calcium channel blockers will also block the calcium that are present on the smooth muscles of the GI tract and so you know smooth muscles are supposed to contract the git muscles and cause you know you to poop but now if I block that effect I'm actually going to decrease my geometility if I decrease GI motility I am going to pull and so this is going to lead to constipation so other things to be cognizant of as well with these drugs the other thing is that they can also relax your blood vessels so they can actually cause vasodilatory effect and so they may actually cause a little bit of hypotension but also they can cause uh sometimes uh when they cause a vasodilation a fact you can't even see some kind of like a edema effect with these drugs but again calcium channel blockers are class four and then beta blockers are class two we now know their adverse drug reactions to watch out for big thing suppressing the AV node causing bradycardia AV block decomposite heart failure do not give these drugs they can suppress your cardiac output bronchospasm hypoglycemia unawareness and then cocaine-induced hypertension it can actually cause a worsening vasoconstriction with this calcium channel blocker they can also cause constipation okay let's come down and talk about the next one which is adenosine all right my friends adenosine if we give this drug to a patient who is SVT so we talked about beta blockers calcium channel blockers those are good in afib a flutter SVT really is a RAID control agent adenosine can give an SVT acutely to abort the amount of SVT what are things that you want to watch out for when you give this drug it's it's super short acting but the side effects that you can get from that kind of like short acting effect is very intense so sometimes it can cause a very interesting type of like since I've been pending Doom that's one of the weird things that happens with this drug how that actual like you know pathophysiology occurs I'm not completely understanding of but one of the things that's really interesting is that adenosine can cause a Visa dilation of the coronary vessels but when it causes vasodilation of the coronary vessels it can't do it of the plaque vessels so when you give adenosine what it'll do is adenosine will work and actually cause coronary artery vasodilation so it'll vasodilate the healthy coronary vessels but won't be able to vasodilate the plaque vessels so now imagine here you have kind of like this vessel that you're trying to feed into these two bifurcating coronary vessels this one is not going to dilate this puppy is going to get big as ever and now what's going to happen you're going to be able to have blood flow just rushing through this one and the blood flow That was supposed to be going to this coronary vessel you're going to steal it and then rush it down through this vessel because blood likes to flow from you know in areas of you know high resistance to low resistance well if I have a lot of resistance because of this big plaque I'm not going to allow blood to flow there so I'm going to steal it and it's going to go to this coronary vessel and so now the blood flow through here is going to be very diminished none of myocardium will suffer and undergo hypoxia and ischemia and this will lead to a chest pain and this is called coronary steel syndrome so this can cause coronary steel syndrome which can lead to a chest pain the other thing is it actually can act on some smooth muscle cells here present in the bronchial smooth muscle and cause bronchospasm so just be careful of it actually can cause some degree of bronchospasm very short-lived but it can cause that so it can cause chest pain a sense of impending doom bronchospasm and also conveysodilate these the actual smooth muscle of our blood vessels and the blood vessels near the skin very intensely so you have a lot of blood flow through the actual skin capillaries and so if I have an increased blood flow through the actual skin capillaries what this will do is this will give kind of a flushing appearance so the patient may look flushed the other thing is it can actually bind onto some of the adenosine receptors on the arterials and cause them to vasodilate and if they vasodilate then what you do is you decrease systemic vascular resistance and decrease the blood pressure so it may even cause a little bit of hypotension so things to watch out for with adenosine is it can cause coronary steel syndrome which can cause chest pain a sense of impending doom which we don't know how it can cause bronchospasm it can cause flushing of the cutaneous it can cause flushing via the vasodilation of cutaneous vessels and it can cause a temporary or transient hypotension due to arterial vasodilation this is the adverse effects to watch out for with adenosine okay now let's move on to the next one which is digoxin all right the Jackson what about this son of a gun all right so this type 5 antiarrhythmic drugs when we talk about Digoxin we know that we can use in a patients with afib with a reduced ejection fraction right specifically afib and heart failure patients with a reduced DF we kind of have a double whammy with that drug you can increase the contractility of their heart and you can also block their AV node what are some downsides to this drug one of the big things to remember is that it's a sodium potassium channel blocker on the actual contractile portion of the myocardial cells so we talked about its effect on the AV nodal cells which was to increase vagal nerve outflow so one of the big things to think about here is that since digoxin did have this ability to increase this is your vagus nerve right so this is the tenth nerve so your cranial nerve number 10 so you're going to increase the outflow of acetylcholine so you're going to increase the acetylcholine release from the vagus nerve so it has the ability to do that because of that you may see a lot of cholinergic types of side effects and so watch out particularly for like nausea vomiting diarrhea some like Blurry or like vision changes and things of that effect but these are some of the things to watch out for when it comes to the other activity so we talked about how it would actually be able to again increase acetylcholine release which would give you cholinergic side effects plus again it'll inhibit the AV node which was what's beneficial in patients who have afib why is it beneficial in those patients who have heart failure with a reduced TF because if we block the AV node that's good in patients who have atrial fibrillation here's the other concept here on these contractile cells so this is going to be non pacemaker cells is the non-pacemaker cells these are the ones that are actually going to contract you have these channels here these pumps and what they do is they pump sodium out of the cell and they pump potassium into the cell so they're going to pump sodium out and they're going to pump potassium into the cell okay that's the whole job they're designed to be able to kind of maintain the nice gradient of keeping sodium high outside the cell potassium in the cell and they also maintain resting memory potential we know that but what's interesting is that if we give digoxin what the Jackson is going to do is is it inhibits the sodium potassium ATP Aces so then the basic concept is that you're not going to allow for sodium to move out of the cell and you're not going to allow for potassium to move into the cell so I can't get sodium out of the cell okay so if I can't get sodium out of the cell there's a problem with that so now I'm not going to be able to get sodium out of the cell but on the other end out of this situation here is I'm not going to be able to get sodium out here into the extracellular space all right why is that important well now if I inhibit these pumps what's going to happen is my sodium inside of the cell is going to increase and then I'm not going to have as much sodium out here okay in the extracellular space well you have these particular channels here and they're very important in contractility sodium naturally if it's in higher concentration outside of the cell should flow into the cell and then allow for calcium to flow out of the cell okay but if I inhibit the sodium potassium ATP Aces I inhibit the gradient from being formed because naturally I want sodium to be higher outside the cell and lower inside the cell so because of that as a result I'm going to cause this abnormality high sodium in the cell low sodium out of the cell so now sodium won't enter into the cell down its concentration gradient so this process is inhibited and if sodium can't come into the cell calcium can't go out of the cell so that leads to calcium staying inside of the cell if calcium stays inside of the cell it activates particular types of myofilaments it'll activate different like things like calcium calmodulin complexes and cause the stimulation of the myofilaments and cause contraction so the overarching effect here is that it will increase contractility and that's why it's beneficial in those patients who have heart failure with a reduced ejection fraction that's why we would give this what's the downside though if you give digoxin it inhibits the sodium potassium pumps so one of the downsides here a couple of them is that if I inhibit the sodium potassium pump I don't pump potassium into the cell so what happens to the potassium level outside of the cell if I can't pump the potassium back in it builds up outside of the cell in the extracellular fluid and I end up with hyperkalemia so because I inhibit the sodium potassium atpase I can increase my potassium levels in the blood hyperkalemia is one effect the second thing is that I increase calcium inside of these particular cells when you increase calcium too much way too much you know what's the downside of that if you increase intracellular fluid calcium levels it can increase the risk of delayed after depolarizations if you increase the risk of delayed after depolarization's triggered activity this can cause v-tac oh my gosh that's so terrible so one of these drugs that's actually utilized to inhibit the AV node from kind of quickly depolarizing and also used to increase contractility if it's in higher doses it can cause too much calcium to be in those cells that they become triggered and now they start firing and cause the patient to go into vtac one of the big things to remember here with digoxin is that the toxicity effect the worsening hyperkalemia and worsening ventricular tachycardia that they can develop happens whenever the potassium levels are low or they have super therapeutic digoxin levels if you've given too much digoxin it can cause hyperklemia and it can cause v-tac but you can actually increase the toxicity of digoxin whenever a patient has hypokalemia so this digoxin toxicity is just important to remember that low potassium can increase digoxin toxicity and the reason why is potassium normally competes with digoxin at the sodium potassium pumps but if you don't have as much potassium you don't have digoxin competing with it anymore and digoxin has no competition and it's just going to inhibit inhibit inhibit inhibit those sodium potassium into pieces and so that will worsen this inhibition of the sodium potassium pumps so yes remember this is one of those confusing things digoxin can directly cause hyperkalemia by inhibiting the sodium potassium pumps it can also cause intracellular calcium levels to be super high which can increase the risk of delayed after depolarizations in the ventricular myocytes causing v-tac but you can worsen digoxin toxicity and patients who are having hypokalemia and then watch out that it can increase cholinergic side effects such as nausea vomiting diarrhea and blurry vision okay now that we've talked about the joxen one of the last things I want you to remember is how do we actually treat a patient so we talked about these before with beta blockers if a patient has a beta blocker overdose we actually give something called glucagon and calcium channel blocker overdoses we give them calcium and digoxin overdoses we actually give them something called digibind and it's one of these kind of monoclonal antibodies that actually bind onto digoxin and prevent it from causing its toxic effects all right now that we've talked about this drug category let's move on to the next one which is your sodium channel blockers all right so next one sodium channel blockers this is again your class one or type one anti-ring link drugs so these are going to be utilized in patients who you want to cardiovert who have atrial fibrillation atrial flutter right or have some type of ventricular tachycardia or they have torsos to points and you want to shorten their action potential duration so when we talk about these drugs what are some of the adverse effects that you want to be careful of and cognizant of well one of the big things is particularly the class 1a or type 1A anti-rhythmic drugs so this is again your Double Quarter Pounder so dysoperamide isquenidine burkinaide what are the downsides to this drug class remember I told you that with all of these they're going to block the sodium channels okay with type 1A or class 1a they'll have moderate so they'll be in the middle so they'll have a decent sodium Channel blockade but what else did I tell you that they have they also have a very weak potassium Channel blockade so because they block the potassium channels they're going to prolong the refractory period so you get two effects here one is you decrease the slope of phase zero but you also prolong the effect of refractor period and increase the action potential duration so my action potential duration is going to be increased in comparison so here's the beginning and here's the end for the first for the normal situation now here to the end of that blue line that's the new action potential duration it's increased the problem with increasing action potential duration is it prolongs something on your EKG so you're on your EKG when you look at the EKG you have your P wave then you have what's called your q r s then you have your ST segment and then you have what's called your T wave okay from this point here it's actually doing a red from this point here from the Q wave all the way here this is called your QT interval when the action potential duration is longer your QT interval is longer so this drug category if they increase the action potential duration they're going to increase the QT interval what's the problem with increasing the QT interval what did I tell you this increases the risk of this increases the risk of something called early after depolarizations which increase the risk of something called torsods to points and with torsaza points what you'll see is you'll see this like very freaky looking EKG where you'll see the QT interval getting longer longer longer and then eventually you'll start looking something like this where they have this very very odd kind of like twisting of the points on their EKG a very scary one don't want to see this this will make you poop your Huggies so because of that it's important to be able to realize that the Double Quarter Pounder drugs so dysopira myquinone procainamide have the ability to increase the action potential duration prolong the QT interval and put these patients into torsoes to points that's one of the downsides of that now again they work by doing what well they work by blocking sodium influx moderately and then they also work by blocking potassium efflux very mildly and so because you have this kind of double action of the type 1A drugs that is how you get this type of effect here okay so that's an important thing to remember so the type 1A drugs they're the only ones out of this drug category that increase the action potential duration increase the risk of tors odds to points okay what about some other additional types of problematic issues here because all we did was we took a piece of a of atrial ventricular tissue zoomed in on it and looked at how exactly we're inhibiting these we're inhibiting sodium channels and potassium channels mildly with type 1A and we see how we get that increased action potential duration let's see that we take all the other drugs in this category again type 1A or class 1A what are some additional adverse drug reactions besides them increasing the QT interval and increasing the risk of tors odds the other thing to remember is that disoperamide has what's called anticholinergic side effects anti-cholinergic side effects so watch out for that dry eyes dry mouth urinary retention constipation fevers and potentially again with other anticholinergic effects you may see like things like um tachycardia and hypertension things to that effect watch out for those anticholinergic side effects okay with quinitine one of the son of a gun one of the big things that you want to watch out for liquidity is this can cause something that's I hate the name of it because I never know if I'm saying it right synchronism so synchronism you want to watch out for with this one and this is usually when you have patients who have what's called like you know you usually have headaches they have vertigo they have some degree of tinnitus they may have kind of like visual changes so this is something that you want to watch out for with this particular drug category okay so that's up here might watch out for anticholinergic side effects with quinitine you want to watch out for synchronism with procainamide which you want to watch out for with this one is what's called drug induced lupus so drug induced systemic lupus erythromatosis okay so class 1a type 1A they all increase your QT interval and increase the risk of torsos to points individually disappearamide can cause anticholinergic side effects so again this can cause things like delirium it can cause them to have dry eyes dry mouth and cause tachycardia hypertension it can cause fevers it can cause urinary retention constipationism so headache vertigo tinnitus visual changes procaine and Mig and cause drug-induced lupus okay with the type 1B so this is lidocaine lidocaine is weird to be honest with you there's not much evidence of how exactly they do this but remember that lidocaine can cause AV nodal blockade um because it does have some sodium Channel kind of blockade but the other thing it can actually do is can cause CNS depression or CNS stimulation so what you're like well which one is it so watching Garcinia stimulation which can increase the risk of seizures but it can also cause CNS depression and so watch out for things such as like somnolence and altered mental status and maybe even depression okay the next one here is your type 1C or your class 1C this is the fries please so flecanide and also propofinone with these ones one of the big things and I already told you about this if a patient has underlying coronary artery disease they have underlying LVH they have underlying post Mi or they have some type of um another situation here such as heart failure so they have CAD LVH Mi are they a heart failure and you give them this drug it can increase the risk of these patients developing very nasty arrhythmias it's super super pro rhythmic and it can increase the risk of going into v-fib and sudden cardiac death so I think that's a pretty important one to remember so in patients who have coronary artery disease left ventricular hypertrophy Mi heart failure and you give them fluconide and propofenone it is extremely Pro rhythmic and can increase the risk of again sudden cardiac death patients going into ventricular fibrillation so please be careful with that drug category all right we talked about sodium channel blockers the last one that we got to discuss when we're done guys is the potassium channel blockers all right my friends let's talk about the last one potassium channel blockers this is your amnio right this is the abutily this is the fetalide this is going to be sodalol and we've talked about dronetta on as Anita lunch you can add in there but when we talk about these drugs we talked about how they're used to be able to treat things like atrial fibrillation atrial flutter particularly more in cardioverting these patients so getting them out of that abnormal Rhythm and those reentrant Cycles or in those patients who have kind of like the triggered activity in their Atria because again what you're trying to do is suppress that we can also use things like amiodar and a soda law on patients who have ventricular tachycardias so again triggered activity or reinsurance organs within the ventricular tissue when we give these drugs what are the things that you have to watch out for so if I gave someone amiodarone or if I give someone any of these drugs all of these drugs have the ability to prolong the QT interval like the type 1A or class 1a drugs how do they do that well remember with these drugs they're particularly blocking if we take a piece of this kind of like ventricular tissue here and we zoom in on it here we're going to have these potassium channels and these potassium channels are going to be allowing for potassium to exit during what phases again phase one phase two phase three basically again you have phase zero phase one phase two phase three and then we go to phase four right well what happens here is when you block or you inhibit when you give potassium channel blockers you inhibit the potassium channels you don't allow for the potassium to exit the cell easily and so because of that what you start to notice is you have a normal slope but you have a very prolonged effective refractory period And so you're increasing the distance of your effective refractory period super long right and so because of that your effective refractory period increases but then on top of that the action potential duration from this point here to this point here is significantly increased so you have an increase in your action potential duration and what do we say happens if you increase action potential duration you increase the QT interval if you increase the QT interval you increase the risk of early after depolarizations which increase the risk of torsods to points which is an arrhythmia that will cause you to poop your Huggies we said so that's an important concept because again we're prolonging the amount of potassium that's leaving during phase one phase two phase three so we're prolonging that entire refractory period more profound effect on phase two and phase three though is what you're going to see so because of that all of these drugs all the age drugs amiodarone abutili to fetal hydronetron and sotalol have the ability to increase the QT interval and increase the risk of tors odds to points so remember that all right so it would be important if these patients developed torsos to point so they developed a very prolonged QT interval think about discontinuing those drugs to prevent them from going into dorsods but if they went into our side we treat it again we discontinued those medications we give them magnesium we give them one of the anti rhythmics that shortens the action potential duration such as lidocaine and we can also consider things like pacing or isoproterenol to increase their heart rate either way what are some other things to think about so all these drugs they increase the QT interval but it's really amiodarone if it's utilized long term that is the one that you'll likely be tested on for the boards amioda is a great drug acute Leaf but using it long term there is some downsides to this drug one of the things here is it can cause interstitial lung disease so it has the ability to cause interstitial lung disease so because of that because it can cause all this fibrosis it's important to be able to monitor the patient's pfts and watch out for any increased risk of interstitial lung disease amiodarone can also cause destruction of the thyroid tissue but it's also amiodarone has a lot of iodine in it like 40 percent of the structure of amiodar and is iodine so it can also be taken up into these actual thyroid tissues and be utilized to make thyroid hormone so you can see two effects here one as you can see low T3 and low T4 but you can also see high T3 and T4 so it's important to be able to monitor the patient's thyroid function tests as well let's actually do these in red here so again it can cause interstitial lung disease so monitor PFT so check their pfts to watch out for increased risk of that it can also cause hypo or hyperthyroidism so monitor their thyroid function tests to check for that it also can cause fibrosis of the liver so it can cause some hepatotoxicity causing there to leak out a lot of alt AST molecules so you want to be able to check there lfts for any types of hepatotoxicity that they can cause you know what else this drug can do it can actually prolong the QT interval just like all the other ones so it's important to be able to get EKGs on patients who are taking any of the Class III drugs and get EKGs on the type 1A drugs but the other thing is this is another one this is a son of a gun here it can actually cause bluish discoloration and deposition in the skin and around the actual cornea so watch for any bluish discoloration so watch for any bluish discoloration or patchiness of the skin of the skin and eyes these are some of the things that you have to watch out for with ambigorno great drug short term not a great one long term okay so with that being said potassium channel blockers they all can prolong your QT intervals so make sure that you check a EKG on these patients to monitor that QT interval and prevent them from going into torso's the points long term amiodarone big thing to watch out for here with this one interstitial lung disease watch over pfts hypo hyperthyroidism so check their tfts hepatotoxicity and hepatitis so lft checks and then bluish skin disc bluish discoloration of the skin and eyes watch out for that as well again if you want to think about the other ones dronaterone very very also um you can see some of how to toxicity with that one the other thing is um with Soto law so it all has a little bit of a beta blocker activity so you may see some beta blocker kind of effects with that one as well but nonetheless that covers the potassium channel blocker adverse drug reactions and that covers our antiarhythmic drug classes all their mechanisms how we use them everything so now let's do a couple cases and really reinforce everything that we learned iron Engineers let's go ahead and do some actual questions here so we have a patient a 60 year old woman had a myocardial infarction so she's posting my which agent should be used to prevent life-threatening arrhythmias that can occur post mi in this patient so digoxin no digoxin is not going to be utilized there's no indication for digoxin post-dimline for reducing arrhythmias if a patient had a heart failure where the reduced ejection fraction and afib it actually may be beneficial but no not for postmi um that's not really an indication for it flecanide no absolutely not it's actually Pro rhythmic especially in patients who are postomy so to that um It's Over Law absolutely it's a beta blocker any kind of beta blocker is really good post in my because again it reduces a lot of the excessive ectopy that you can see with patients who have some type of underlying heart disease and increase kind of like PVCs from a lot of the re-entrant circuits from that post to my scar tissue it also helps to be able to prevent any kind of excessive like delayed after depolarization so in general beta blockers are really good at suppressing any kind of like vtac or PVCs that could be non-sustained in patients who are post Mi plus it reduces a lot of like abnormal cardiac remodeling in patients who are posed to my reducing the risk of you know problematic issues Downstream from that like mortality and morbidity so definitely going to be metoprolol but canamide again has no indication for really posting my patients with increased risk of arrhythmias so if they put like lidocaine or something like that then that'd be a different story but again it's got to be metoprolol here all right so that should be the answer for this puppy all right good next one 57 year old man is being treated um for an atrial rhythmia he complains of dry mouth blurred vision urinary hesitancy which antiarrhythmic drug is most likely taking um so sounds like kind of like cholinergic side effects in this situation here right so patients who have lots of acetylcholine release what happens when you have lots of acetylcholine release generally that causes kind of like a lot of changes like in this case it would actually cause increased level the secretions it would actually cause these patients to have lots of urinary frequency in situations like that but in this patient they're dry so we're probably blocking the acetylcholine effect here so you're seeing like an anticholinergic property of a drug because it's preventing secretions from the mouth so that's why they're having dry mouth and it's causing urinary hesitancy so that could be due to like a retention effect so that's definitely an anticholinergic effect metoprolol is a beta blocker it doesn't really have any kind of anticholinergic effect here dysopiramide is a type 1 a sodium channel blocker and isoperamide does actually have anticholinergic properties we mentioned that on the Whiteboard so dysoperamide is likely the right answer dronetarone no it doesn't have any it can have some padotoxic effects and increase risk of mortality especially if the patient has like heart failure and things of that nature but no dranedarone doesn't really have any kind of anticholinergic and neither does so to law so with that being said I'm definitely going to say disoperamide for the correct answer here all right 70 year old woman has newly been diagnosed with atrial fibrillation she's not currently having any symptoms of palpitations or fatigue which is appropriate to initiate for rate control as an outpatient so rate control is primarily beta blockers calcium channel blockers are digoxin if they have heart failure where they reduce DF so they don't have digoxin there's no calcium channel blocker that's mentioned here so it's got to be a beta blocker so dronetron is not gonna be the right answer because that's a type three it's a potassium channel blocker as well as a beta blocker but and you would think that'd be the right answer but we also have metoprolol what's the difference metoprolol is primarily it can be given IV but it can also be given po so you can give this as an outpatient as well as primarily IV so because I can't put this patient on an IV infusion of asmallow I'd have to do an oral agent outpatient especially for Ray control so metoprolol would be the correct answer and again fleconide is not going to be the right answer because it's more for rhythm control so it's designed to be able to allow for maintaining a patient in normal sinus rhythm and preventing them from converting back into paroxysmal afib so it maintains normal sinus rhythm in patients who have proximal atrial fibrillation without any underlying coronary artery disease or LVH or heart failure so it's definitely not going to be flecanide it's not dronetron it's not as small because it's IV it's definitely got to be metoprolol which of the following is correct regarding digoxin one used for atrial fibrillation it works by blocking voltage-gated sensitive calcium channels no it increases acetylcholine release from the vagus nerve which actually helps to allow for potassium efflux so that's not the correct answer B is used for rhythm control it's actually only used for rate control so because the presses and blocks the AV node and reduces the amount of electrical activity from the Atria into the ventricles reduces the rapid matricular rates actually so that's not the right answer digoxin increases conduction now it actually decreased conductor velocity through the AV node so I'll use the last answer which is D which is the correct answer obviously because it's the last one that's available but it's the right answer because if we approach this particular serum level this is the appropriate level which allows for us to suppress the AV node as well as give a positive inotropic effect without causing any digoxin toxicity or allowing for it to be at subtherapeutic levels so this is a proper kind of like therapeutic index of this drug of one to two as you get lower sub therapeutic as you go above you increase your risk of toxicity all of the following are adverse effects of amiodarone except synchronism is actually same with um quintine so that can't be the right answer because that's the headaches the tinnitus and those types of problems hypothyroidism is definitely seen with amiodarone remember we've got to watch out for that and hyperthyroidism pulmonary fibrosis absolutely and blue skin discoloration as well as even of the eyes so yeah so the only one that actually is not the correct answer is synchronism which is actually seen in particularly quinitine so it's going to be a which arithmic can be treated with lidocaine so it's going to be patients who are post Mi who have an increased risk of ventricular tachycardia or they have vtac so they go into vtac and they just were post Mi that would be the particular indication for this so peroxismal superventricular tachycardia nope that's not a v-tac atrial fibrillation atrial flutter those are all superventricular they're all atrial stuff so it's got to be vtac D a clinician would like to initiate a drug for rhythm control of atrial fibrillation which of the following coexisting conditions would allow for initiation of laconite hypertension that's absolutely a you know appropriate so the patient is going to be put on flecanide which is a type 1C that's that pill in the pocket approach to atrial fibrillation in other words you're trying to keep a patient in normal sinus rather than maintaining their normal sinus rhythm and a patient who has paroxysmal afib no permanent afib it's proximal afib and they're trying to maintain them in normal sinus rhythm and the outpatient population they don't have any coronary artery disease ischemic heart disease they don't have any left ventricular persevere they don't have any heart failure if they have none of those things then you can utilize this drug if they have those things you increase the risk of arrhythmias and putting them into sudden cardiac death so hypertension is the only appropriate answer here all right that would conclude all of these questions here on the anti rhythmics I hope it made sense I hope that you guys liked it and as always love you thank you until next time engineers [Music]

Channel: Ninja Nerd

Views: 265,722

Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science

Id: VgqbICq8ZZk

Length: 160min 46sec (9646 seconds)

Published: Fri Nov 11 2022