Antiarrhythmic Drugs

0:02foreign

0:06what's up Ninja nerds in this video

0:08today we're going to be talking about

0:09antiarrhythmic drugs there are so many

0:12of these so much to talk about I want

0:14you guys to stick in there with me hang

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0:48without further Ado let's get into

0:49antiarhythmic medications though but I'm

0:52going to kind of get there in a second

0:54all right so anti rhythmic medications

0:56are pretty challenging when you look at

0:58them in the entire Gambit of everything

1:00that we have to cover what I think will

1:02really help us first is to cover a

1:04little bit of physiology so we have to

1:06go back into that kind of anatomy and

1:08physiology part into the cardiac

1:10physiology section and really remind

1:12ourselves of the action potential all

1:14the phases all the channels all the ions

1:17that are kind of involved in that phase

1:18is so that whenever we start talking

1:21about these drugs and their mechanism of

1:22action you'll know which channel which

1:25part of the curve which tissue of the

1:28heart it's actually going to be

1:29affecting and that's really really

1:31important so let's take a quick second

1:33to go through that

1:34so in the heart tissue what I want you

1:37to know is that we have two types of

1:38like myocardial tissue one of those

1:41myocardial tissues is the ones that

1:43conduct like action potentials either

1:45generate it or they conduct Action

1:47potentials in other words you have these

1:49cells have the ability to intrinsically

1:51depolarize themselves they don't depend

1:53upon the nervous system because you know

1:55how when tissues in order for them to

1:56kind of depolarize the nervous system

1:58has to release neurotransmitters on them

2:00and then cause them to depolarize these

2:02guys have the ability to do it on their

2:04own and so they can intrinsically

2:06depolarize and generate Action

2:07potentials throughout the heart so those

2:09are called like your pacemaker cells or

2:11your nodal cells if you will

2:13there's a lot of them so they kind of

2:15start here at your essay note at the top

2:17of the right atrium near the superior

2:18vena cava right atrial Junction so you

2:20have your essay node what it does is

2:22it generates Action potentials and these

2:25this is the primary kind of like

2:27pacemaker of the heart so it'll send

2:28action potentials throughout the Atria

2:30and eventually throughout all these

2:32atrial cells it'll eventually converge

2:34onto the AV node which is the nodal cell

2:36right there at the kind of like the

2:38Gateway between the Atria and the

2:39ventricles so you have your essay node

2:41then you have your AV node from The Av

2:44node let's say that the SA node failed

2:45it did no longer you know generate the

2:47action potentials the AV node has the

2:49ability to generate Action potentials

2:50but if it doesn't it receives the action

2:52potentials and then conducts it through

2:54him down into the bundle of hiss or the

2:57AV bundle then from The Av bundle it

2:59goes into the right and left bundle

3:01branch from there it'll go into your

3:02purkinje fibers and so they have the

3:05ability to generate action potential so

3:07if one fails the other one can take over

3:09so your essay node is the primary

3:11pacemaker but it'll send the action

3:13potentials through the AV node through

3:14the bundle of His the bundle branches in

3:16the purkinje system so it's important to

3:18be able to remember that that our

3:19pacemaker cells are primarily going to

3:21be in kind of a sequential favor here

3:23your SA node

3:25and then it'll conduct action potentials

3:27that'll move down to the AV node and

3:30then from The Av node that'll go into

3:31what's called your bundle

3:34of his

3:36and then from there it'll go into your

3:38bundle branches

3:40and then from here it'll go into your

3:42purkinje fibers

3:45so that's kind of the order of how this

3:48kind of information is sent and for this

3:51this is significance of this this will

3:54be the generator so it'll send these

3:55Action potentials from the SE node he is

3:57the pacemaker of the heart so he's truly

4:00the one that has the intrinsic

4:02automaticity that term that we talked

4:04about

4:05if he fails the AV node will take over

4:07and it'll gain the ability to do that if

4:09the AV node failed and the bundle of

4:10hiss would gain the ability to do that

4:12if the bundle of hiss lost it then the

4:13bundle branches would be able to do that

4:14in the purkinje system I think though

4:16one of the most important things to

4:18remember is out of all of these

4:20pacemaker cells the two most important

4:22ones that you really need to actually

4:24have some degree of survival and

4:26adequacy in life is you really need to

4:29remember your essay node and your AV

4:31node these are the primary pacemaker

4:33cells if you did lose your acetone your

4:35AV node took over you'd still be able to

4:37have enough to to have a heartbeat

4:39adequately but if you lost the AV known

4:41you're depending upon your purkinje

4:43system that's not enough adequacy to be

4:45able to properly live

4:46so it's important to remember that these

4:48are the two pacemaker cells what we'll

4:50do is is I'm going to take a pacemaker

4:52cell over here so I'm going to look at

4:54AV nodal and Essay nodal cells here and

4:57I'm going to take a piece of these

4:58tissues here so I'm going to take a

5:00piece of this essay nodal tissue a piece

5:02of these AV nodal tissues and I'm going

5:04to zoom in on one of these cells and

5:06look exactly at how the action

5:08potentials are occurring in these cells

5:10so how does that work it's really cool

5:13actually

5:14let's say here and this essay nodal cell

5:16or AV nodal cell I have this really

5:19interesting channel here in Orange so

5:21this interesting channel is called a

5:23funny sodium channel it's called a funny

5:26sodium channel so sometimes we denote

5:28this as like I F it's a funny sodium

5:32inward Channel what happens is this

5:34channel is usually always kind of like

5:36open

5:37and what it does is it allows for sodium

5:40to trickle in to these actual essay

5:43nodal cells and AV nodal cells so the

5:46sodium will trickle in to this actual

5:48pacemaker cells and if it does it'll

5:51bring some degree of positive ions into

5:53the cell

5:54now why is that important well

5:56if we look here at a graph this is going

5:58to be a graph representing the pacemaker

6:00cells the essay nodal and AV nodal cells

6:03these cells have something called a

6:05resting membrane potential this is the

6:07potential at which the cell is at rest

6:09it has not been stimulated it's ready to

6:12be stimulated at any moment

6:14but whenever we take the cell in order

6:16to be able to get it to be stimulated to

6:18open up specific channels which is going

6:20to be represented here in this actual

6:22pink one this is called a voltage-gated

6:24sodium Channel and really in order for

6:26me to activate that voltage-gated sodium

6:28Channel I have to bring the resting

6:30membrane potential to threshold how do I

6:33do that well usually that's where nerves

6:35will stimulate something and bring it up

6:37to that point

6:38well this channel is kind of always open

6:40this inward sodium Channel a funding

6:42sodium Channel and what it does is

6:44it'll bring the resting membrane

6:46potential close and closer and closer to

6:50the threshold potential so who is

6:52responsible for this one this right here

6:54is the job of the

6:57funny I'm going to put like the little

6:58Channel there this is the job of the

7:00funny sodium Channel that'll bring the

7:03cell closer towards the actual threshold

7:06potential so what is this potential at

7:07negative 40 this is the threshold

7:10potential

7:11the funny sodium channel will help with

7:13that so it'll offer a little bit of

7:13sodium to trickle in on top of that once

7:16this funding sodium channel is open

7:17these positive ions here they can

7:21activate another Channel nearby

7:24and this channel is called T-Type

7:26calcium channels either called T type T

7:29type

7:30calcium

7:32channels

7:33now when these open they allow for a

7:36little bit of calcium to be able to

7:38trickle in to the cell so now it's going

7:41to allow for a little bit more positive

7:43ions to trickle into the cell and make

7:45the cell again more increasingly

7:47positive so now if we make this cell

7:49more increasingly positive with the

7:51funny sodium channels and then on top of

7:52that we make it even more positive with

7:54the T-Type calcium channels that should

7:57bring it to

7:58threshold potential so who is really

8:00allowing for this process to occur for

8:02me to bring the resting membrane

8:04potential to threshold potential slowly

8:06it's the job of two particular channels

8:08one is the job of the funny sodium

8:11Channel and then later it's the job of

8:13the

8:14T-Type calcium channels

8:17now once it brings it to threshold

8:19potential now we're at an actual

8:20potential negative 40 millivolts where

8:23the voltage-gated sodium channels which

8:24are currently closed at rest open

8:27once they open

8:29these are called your L Type

8:33calcium channels these are called your

8:37l-type calcium channels they really

8:39allow for a ton of calcium to flood into

8:44this actual pacemaker cells and make the

8:47cell extremely positive to the point

8:51where now this thing is going to shoot

8:52upwards and usually above one of the

8:55peak potentials which is zero millivolts

8:57it'll pop up all the way up here so who

9:00is responsible for this

9:02this upward phase here is due to the

9:06l-type calcium channels being opened and

9:10calcium flooding into the cell making

9:13the cell super super positive now the

9:16cell is depolarized and once it's

9:18depolarized it can then have another way

9:21of being able to spread these Action

9:23potentials this positive charge onto

9:25another cell do you know how it does

9:27that it's really cool there's another

9:29cell maybe right next door to this one

9:33and the way that it may communicate with

9:35a nearby atrial cell so let's say that

9:37the SEO it's the one that generates the

9:38action potentials it'll send the action

9:40potentials and it'll send it to other

9:42atrial cells via what

9:45these little things here called Gap

9:47Junctions and then some of these

9:49positive ions will leak over into the

9:52nearby cell and generate an action

9:54potential in that next cell so that's

9:55really really a cool concept here but

9:58nonetheless let's keep going through the

10:00channel processes here

10:02once we get to the positive charge here

10:04we get above zero millivolts what

10:06happens is the voltage you get a calcium

10:08channels close so once you get them to

10:10the peak point of good the actual

10:12depolarization they start to close as

10:15they start are to close what happens is

10:18now no calcium will be flooding in

10:20usually the funny sodium channels and

10:23the T-Type calcium channels they should

10:24be closed at the point whenever they hit

10:26threshold potential so once the thresh

10:28once the threshold potential is hit

10:29these generally close and the

10:31voltage-gated calcium channels open

10:32calcium rushes in once it gets really

10:35really positive above zero millivolts

10:37the calcium channels will close once

10:40they close another channel will start to

10:42open

10:43and this channel nearby here is actually

10:46really kind of cool and this is called a

10:48voltage-gated potassium channel so what

10:51is this channel here called on the side

10:53here this is called a voltage

10:57gated

10:59potassium Channel

11:01this will open once the actual cell is

11:04super super positive it'll activate this

11:07Channel and this channel which was once

11:09closed is now going to open and it's

11:12going to allow for a ton of potassium

11:14ions to leave the cell if positive ions

11:19are leaving the cell what's going to

11:21happen to the charge inside of itself

11:23you're losing positive ions you're going

11:25to now make the cell super super

11:28negative and what that's going to do is

11:30it's going to cause this actual voltage

11:32to start moving downwards until you head

11:36to resting membrane potential

11:37so who's going to be responsible for the

11:39downward phase of the action potential

11:41this is due to the voltage-gated

11:44potassium channels so the voltage-gated

11:46potassium channels are going to be the

11:47ones responsible for this downward phase

11:51okay and then what happens is you'll get

11:53to the resting membrane potential and

11:55it'll be maintained for a while and the

11:57way that we maintain the resting

11:58membrane potential is through these

12:00other pumps called sodium

12:03potassium

12:05ATP Aces and all these are going to do

12:07is they're going to pump sodium out of

12:09the cell and they're going to pump

12:11potassium into the cell because they're

12:12trying to regenerate the concentration

12:14gradients so you've been pushing

12:16potassium out of the cell you've got to

12:18replenish it and push it back into the

12:20cell and then on top of that you were

12:21pushing sodium into the cell you got to

12:24push it back outward so you have it

12:25available you want to regenerate those

12:27concentration gradients but whenever you

12:29do this you actually have more positive

12:31ions that are actually going to be again

12:32leaving the cell than positive ions are

12:34coming into the cell and that kind of

12:36just allows for this cell to be in a

12:37resting state so resting membrane

12:39potential may be maintained for a little

12:40bit via these sodium potassium pumps but

12:44then once it's at rest for a while guess

12:46what happens

12:47the funny sodium channels open

12:50once they do that they cause the T-Type

12:52calcium channels to open once the T-Type

12:54calcium channels open they cause the

12:55cell to go to threshold potential

12:57voltage-gated calcium channels open they

12:59go upwards above zero millivolts they

13:02close voltage-gated potassium channels

13:04then start to open and eventually they

13:06go to Resting membrane potential which

13:08is maintained via the sodium potassium

13:10ATP Aces that is how this all works

13:13within the sa nodal and AV nodal cells

13:16my friends this is how that processor

13:18generally occurs

13:20so that is what I really want you to

13:22understand but there's actually one

13:24other thing that we have to add on here

13:26we utilize terminology of phases which

13:28are going to come up a lot whenever we

13:30talk about the mechanism of action of

13:31these drugs which is really important

13:33there's phases to this upwards of this

13:36pacemaker potential due to the funny

13:37sodium channels and the T-Type calcium

13:40channels and this phase is called phase

13:42four okay it's called phase four so it's

13:45whenever you're going from resting

13:46membrane potential up to threshold

13:48potential then whenever the usually at

13:51the end of phase four going into this

13:53next phase where we really have the

13:55rising phase where the l-type calcium

13:56channels open this is called phase zero

14:00then afterwards we go into this next one

14:03which is a little odd it looks you'll

14:05understand later when we get into the

14:06non-pacemaker cells but once the

14:08voltage-gated calcium channels close and

14:10the voltage-gated potassium channels

14:11open and you have this downward phase

14:13going towards resting membrane potential

14:15this is called phase three so again

14:18recap phase four is the resting to

14:20threshold due to the funny sodium

14:22channels and T-Type calcium at the end

14:25of phase four going upwards phase zero

14:27is the voltage-gated calcium channels

14:29are the l-type calcium channels and then

14:31going downward the downward phase of the

14:33action potential is due to voltage you

14:35get a potassium channels this is phase

14:37three very very important to remember

14:39that this is the way the action

14:41potentials occur and are conducted

14:44within the pacemaker cells most

14:46primarily the assay node and the AV node

14:49okay that's super important

14:52what we now need to talk about and then

14:54one more thing here is that the way that

14:56this types of action potentials are are

14:58generated are not as fast they're kind

15:00of a slow kind of action potential type

15:02of tissue so that's a really important

15:04to remember is that this is kind of

15:06what's called a slow action potential

15:08tissue

15:10now let's talk about the other scenario

15:13okay now we have the other parts of the

15:15cardiac tissue that is not a part of

15:17this black system here the SC node the

15:19AV node the bundle of hiss the bundle

15:20branches and the purkinje fibers we're

15:22talking about any other atrial or

15:25ventricular tissue that's not a part of

15:27that nodal system most significantly the

15:30essene or the AV node so now I'm talking

15:32about maybe this tissue here in The

15:33ventricle or this tissue here in the

15:35Atria that is not a part of the nodal

15:37system so all we need to write down here

15:39is that this is any type of atrial

15:43or ventricular

15:47myocyte

15:48that does not have any intrinsic

15:52automaticity in other words it doesn't

15:54have the ability to generate these

15:56what's called pacemaker potentials this

15:58phase four that's only the capability

16:01that can be gained in pacemaker cells so

16:04they don't have that intrinsic

16:05automaticity to generate their own

16:06Action potentials and cause them to

16:08produce them and then generate and pass

16:10it on to other cells

16:12these cells don't have that so they're

16:14non-pacemaker producing cells so how do

16:17these ones actually allow for the

16:20conduction of action potential and then

16:21generate Action potentials well the way

16:23they do it is

16:25imagine here is a pacemaker cell

16:29so here's like a nodal cell of some type

16:31right or maybe it's another you know

16:33myocyte atrial ventricular myocyte but

16:36it received Action potentials from this

16:38pacemaker cell what did I tell you is

16:40here that is allowing for communication

16:42between these cells Gap Junctions and

16:44GAP Junctions can allow for some degree

16:46of positive ions to enter into the cell

16:47and once they allow for these positive

16:49ions to enter into the cell from a

16:52nearby pacemaker or nearby ventricular

16:54atrial myocyte once they get in they can

16:57actually kind of cause this action

16:59potential process to occur which is

17:02really interesting so how does it

17:03actually occur well again going back

17:05here here's going to be a graphical

17:06representation of the atrial or

17:09ventricular myocytes and how they

17:10generate Action potentials or allow for

17:13the conduction of action potentials

17:15well here on this graph here we're going

17:18to have negative 90 millivolts in this

17:20Atrium ventricular monocytes this is

17:22referred to as their resting membrane

17:23potential now these actual atrial

17:26ventricular monocytes can have threshold

17:27potentials but they're kind of variable

17:29and they're not super significant in the

17:31discussion of this actual lecture

17:33what's really important is

17:35what happens in this process here is

17:38that let's say here

17:39we have an atrial ventricular myocyte

17:41some positive ions leak into it it's in

17:44resting state right it's an arresting

17:45State what happens is these Gap

17:47Junctions so this is your Gap Junctions

17:49allow for ions to pass from this cell to

17:52this cell it makes the cell just a

17:54Teensy bit positive enough positivity

17:57that what it can do is it can activate

17:59these channels here what are these

18:02channels here in blue these channels are

18:04called voltage-gated sodium channels

18:07what are these ones here called these

18:09ones here in blue are called your

18:10voltage

18:11gated

18:13sodium channels super important here

18:15guys I really want you guys to pay

18:17attention at this point here because

18:19what happens is once these are open

18:20they're going to allow for sodium to

18:23flush into the cell extremely quickly

18:26this flies in like a son of a gun and it

18:29makes the cell extremely positive very

18:32very quickly so we can go from zero to

18:34100 real quick all right so what happens

18:36is that negative 90 millivolts Gap

18:38Junction is allow for a little bit of

18:39ions to trickle in to activate these

18:41voltage-gated sodium channels when they

18:43open up it'll go

18:45and have this acute rise so it's going

18:47to go here from here

18:48and it's going to fly straight up okay

18:52so it's going to fly straight up and

18:54this is usually Going To Fly Above kind

18:55of zero millivolts which is part of the

18:57peak potentials generally and this is

19:00actually going to come up really really

19:01high due to what what channel is

19:03responsible for this it's that blue

19:04Channel there this is due to the

19:06voltage-gated sodium channels

19:09all right so voltage-gated sodium

19:10channels open and they allow for this

19:13cell to go from resting membrane

19:14potential all the way up and generate

19:17this positive phase or Rising phase of

19:19the action potential

19:21once it does that and the cell becomes

19:23super positive what happens is we'll

19:25talk about this a little bit later

19:27but sodium channels have different types

19:28of gates if you will they have what's

19:30called a activation gate an inactivation

19:33gate when they're at the resting state

19:35what happens is they're inactivation

19:38gait in this situation is actually going

19:40to be what it's going to be open and

19:42then their activation gate is closed

19:44once you kind of get them out of that

19:46resting state and stimulate them their

19:47activation gate opens and sodium floods

19:49in

19:50then once you hit this positive point of

19:53the action potential they're

19:54inactivation gate closes okay and so now

19:58sodium can't come into the cell anymore

20:00now once that happens and it starts kind

20:03of like closing off what it does is

20:06it activates two channels so once this

20:09cell gets to this very very positive

20:11type of charge inside of the cell it's

20:13going to activate two particular

20:14channels that can activate this channel

20:16and it's also going to activate this

20:19channel here it's going to activate

20:20these two particular channels this pink

20:22channel here is called your l

20:25type

20:27calcium

20:28channels

20:30and once they're activated they're going

20:32to allow for calcium to rush into the

20:35cell

20:36and then this is going to be a voltage

20:40gated

20:42sodium I'm sorry potassium Channel

20:44potassium Channel

20:46and they're going to allow for potassium

20:47to leak out of the cell and positive

20:50ions are going to leak out of the cell

20:52what happens first is what happens first

20:56is once we get upwards so once sodium

20:58rushes in and it makes the cell super

21:00positive it activates the voltage gate

21:02of potassium channels just a little bit

21:03earlier than the voltage-gated I'm sorry

21:06the l-type calcium channels so then what

21:09happens is you get this kind of like

21:11small dip if you will you see the small

21:14little dip and that small little dip

21:16right there where the cell becomes a

21:18little bit more negative why because

21:20positive ions are leaving the cell if

21:22positive ions are leaving the cell then

21:24you're going to have the cell become

21:25slightly negative

21:28and what that does that cause this

21:29little dip here

21:30on this actual kind of like phase of the

21:33actual potential this little dip where

21:34the cell becomes just slightly negative

21:36is due to voltage-gated potassium

21:38channels just opening up just a little

21:40bit earlier than the l-type calcium

21:42channels

21:43then the l-type calcium channels finally

21:45are super open and they start flooding

21:47in at the same time the potassium is

21:49still leaving the cell so we have

21:51positive ions coming into the cell and

21:53positive ions leaving the cell so if I

21:56have

21:57positive ions leaving the cell it's

21:59making the cell negative but I have

22:01positive ions coming into the cell

22:03that's making the cell positive they

22:05cancel each other out

22:07and when they cancel each other out you

22:08kind of get this Plateau phase if you

22:10will where it kind of stays at the same

22:12voltage and then eventually what happens

22:15is

22:16the voltage-gated calcium channels

22:18eventually shut down they actually close

22:21but during this phase right here where

22:23it's this Plateau phase where it kind of

22:25stays the same what is this this is

22:28actually due to two particular channels

22:30this is due to the l-type calcium

22:33channels being open

22:34in addition to

22:37the voltage-gated potassium channels

22:39being open

22:41so you have two channels that are open

22:43during this particular Plateau phase now

22:47eventually what happens is

22:49as you in this Plateau phase as calcium

22:52is coming in and potassium is going out

22:54eventually gets to the point where what

22:56happens is just really quickly once

22:58positive ions like calcium comes into

23:00the cell what it does is it activates

23:02this channels here on what's called your

23:05sarcoplasmic reticulum and it stimulates

23:08these calcium ions will stimulate the

23:10sarcoplasmic reticulum and cause it to

23:12release calcium ions out of it to

23:13trigger kind of a muscle contraction

23:16process

23:17once that happens during the plateau

23:19phase and you already have the calcium

23:20being released then we don't need this

23:22calcium to continuously keep coming in

23:23so we shut that calcium channel off

23:26once we shut the calcium channel off

23:28what we want to do is we're done with

23:30contraction the calcium's already

23:31started the contraction process we want

23:33the cell to start beginning to relax

23:35so what happens is

23:38what we do is we actually start pumping

23:40calcium out of the cell and back into

23:42the sarcoplasmic reticulum so all the

23:44calcium that was actually present in the

23:46cell during this Plateau phase we're

23:48going to pump it back in here or we're

23:51going to take the calcium

23:53and we're going to pump it out of the

23:54cell we're going to try to get the

23:56calcium out of the cell

23:57and then we're going to keep these

23:58voltage-gated potassium channels

24:00continuously open super super important

24:02I can't stress this enough once we get

24:04to the end of the plateau phase

24:06the calcium stimulated the sarcoplasm

24:07curriculum to release calcium trigger

24:09the contraction process after the

24:11contraction process is done we want the

24:12cell to rest so we want to shut these

24:16voltage-gated calcium channels off

24:18we want to push the calcium that was

24:20present in the cytoplasm back into the

24:22sarcoplasmic reticulum or push the

24:24calcium ions out of the cell we don't

24:26want the calcium in here anymore causing

24:28contraction

24:29so what we do is we push the calcium

24:31ions out or we push the calcium lines

24:34back into the sarcoplasmic reticulum but

24:36we keep this poppy open and then what

24:39happens if it stays open the potassium

24:41ions are going to keep leaving and

24:43leaving and leaving and causing the cell

24:45to become increasingly more negative to

24:47the point where now look what's going to

24:49happen we're going to cause this cell to

24:51become negative negative negative and

24:52it's going to go back

24:53to the resting membrane potential and

24:56we're going to maintain the resting

24:58membrane potential via what type of

24:59channels here the sodium

25:02potassium epases we're going to pump the

25:05potassium back into the cell to

25:06regenerate the gradient and pump the

25:08sodium out of the cell to regenerate the

25:10gradient but since we pump more positive

25:12ions out of the cell and less positive

25:15ions into the cell we make the cell more

25:17slightly negative and that maintains the

25:19resting membrane potential okay but who

25:23is going to be responsible for this

25:24downward phase here that's just going to

25:27be the voltage-gated potassium Channel

25:31Okay so

25:33to recap this

25:35sells at rest Gap Junctions allow for

25:38ions to from a pacemaker cell or nearby

25:39atrial ventricular myocyte to pass those

25:42positive ions into him when he gets

25:44these positive ions activates the upward

25:46phase where the voltage-gated sodium

25:48channels open and sodium rushes and

25:50making the cell super positive this

25:53right here my friends is called phase

25:54zero

25:56okay sodium rushes in then once sodium

25:59rushes in it makes the inside of the

26:01cell super positive and it shuts off the

26:04voltage sodium channels they're they're

26:06closed now they're not going to allow

26:07for sodium to enter in anymore once

26:09we're at this peak point

26:11then what it does is when it's at this

26:13peak point it opens up two channels the

26:15voltage you get a potassium channels and

26:18the voltage-gated or l-type calcium

26:20channels

26:21when they open up potassium is going to

26:23open up a little bit quicker and start

26:24exiting out of the cell when it exits

26:27out of the cell it makes this actual

26:29charge inside of the cell drop down

26:30become more negative this right here

26:32with just this downward phase here is

26:34called phase

26:35one

26:36so the downward phase here is phase one

26:39then as the voltage of the calcium

26:41channel is a voltage of potassium

26:43channels maintain their patency they

26:45keep open they keep allowing for

26:46potassium to leave but then these l-type

26:49calcium channels finally open enough to

26:51allow calcium to rush in so then you

26:54have positive ions like calcium coming

26:55in and positive ions like potassium

26:57going out but it makes this inside of

27:00the cell the same electronutrality

27:01because you have positive ions coming in

27:03making the cell positive positive ions

27:05leaving which are causing the cell to

27:06become negative those cancel each other

27:08out and maintain this Plateau phase this

27:11is called phase two

27:13then once the voltage-gated calcium

27:16channels close because what you want to

27:18do is you want the calcium to come in

27:20Via these l-type calcium channels

27:22stimulate the sarcoplasmic reticulum to

27:23pump calcium out cause the muscle cell

27:26to contract once it's done Contracting

27:28you want it to relax so that it can be

27:30stimulated again so then what you do is

27:32you take the calcium pump it into the

27:33sarcoplasm curriculum you shut these

27:35calcium channels off and you pump the

27:37calcium out of the cell so that you can

27:39regenerate that gradient because you

27:40want calcium in the sarcoplasmic

27:42reticulum to be available again and you

27:44want to push calcium out of the cell so

27:46that you can use it again to come back

27:47in

27:48so by doing that you shut the calcium

27:50channels off pump the calcium back in

27:52here and pump the calcium out now no

27:55more calcium should be coming in only

27:58voltage-gated potassium channel should

28:00be open at this point and when they're

28:01open they allow for positive Minds to

28:03leak out making the cell negative and

28:06this is going to be phase three

28:08then as you go downwards here into this

28:11flat phase this flat phase right here

28:15until you get ready to generate another

28:16action potential it's called phase four

28:19that's when you're at the resting state

28:20the cell is in the resting state

28:22generated by the sodium potassium ATP

28:25Aces okay now that we've talked about

28:28that this is important to remember that

28:30this is what occurs in the non-pacemaker

28:33cells and because of this look how fast

28:35this kind of action potentials occur

28:37these are kind of your fast

28:40action potential inducing tissue

28:44all right so now that we understand the

28:47cardiac action potentials in both the

28:50pacemaker cells how they look like with

28:52all the channels all the flowing of ions

28:54and then how they look in the graph

28:56and we can compare that to the

28:59non-pacemaker cells the atrial and

29:00matricular myocytes how their channels

29:03are all working how they're flowing and

29:05what it looks like on the graphical

29:06representation now what I think we can

29:09start to begin to do is is generate a

29:11concept of how arrhythmias are generated

29:14and then how we can really approach to

29:18actually treat arrhythmias because if I

29:20can find drugs that really block the

29:23slow AP producing tissue the nodal

29:26tissue so the SA node AV node primarily

29:28I should have some drugs that can really

29:30block the AV node and that may be useful

29:32in certain arrhythmias

29:33in other situations

29:35I want to give drugs that could actually

29:37block the action potentials that are

29:39present in the fast action potential

29:41tissue so the atrial and ventricular

29:43tissue that's not a pacemaker tissue if

29:45I can suppress those tissues from

29:47generating arrhythmias that might be

29:49helpful and so what you'll see is that

29:52in this tissue we're primarily going to

29:55be focusing on drugs that can block the

29:57pacemaker cells particularly the AV node

30:00and how they're actually going to block

30:02the AV node we'll talk about in detail

30:04but if we can block the action

30:06potentials being produced or the

30:08conducting of action potentials through

30:09the AV node we can slow the heart rate

30:12down which is important in what type of

30:14arrhythmias tachyarrhythmias so whenever

30:16the patient's heart rate is greater than

30:18100 beats per minute that's what we're

30:20really going to be utilizing

30:21antiarrhythmic medications is tachy

30:23arrhythmias so I'm going to talk about

30:25drugs that will really help to suppress

30:28the conduction of action potentials

30:29through the AV node and SA node via the

30:32pacemaker cell blockade and then what

30:35I'll do is

30:36I'll talk about some drugs that we can

30:38utilize to suppress the action

30:40potentials and electrical activity

30:41within the non-pacemaker cells the

30:43atrial and ventricular myocytes that

30:45gained some ability to generate Action

30:47potentials undesirably and we'll talk

30:49about how they can actually do that a

30:50little bit later

30:51but that's what I want you guys to

30:53understand so now let's come down for a

30:54second let's talk about how do

30:57arrhythmias actually develop we're going

30:58to do this very basically if you guys

31:00want to know more about arrhythmias and

31:01the pathophysiology go watch our video

31:03on arrhythmias and they'll tell you a

31:05little bit more about that but I'm going

31:07to basically kind of introduce it and

31:09then we're going to talk about a

31:09strategy and then we'll go into each

31:11drug category their mechanism of action

31:13how they're actually going to treat

31:15these arrhythmias and then we'll go into

31:17a little bit more a little bit later

31:18about what's the approach to every

31:20single type of arrhythmia how do I

31:22actually kind of like get this fit into

31:23my brain we'll get into that so let's

31:25now come down and talk about that

31:26whenever patients actually develop

31:28arrhythmias we're not going to go

31:29through the crazy pathophys I don't

31:31think it'll actually give us much in the

31:33understanding of anti-rhythmic so to

31:35really go down that depth I I don't know

31:37if it'll give you much benefit so what I

31:39really want you to understand is when

31:40patients actually develop a rhythmia as

31:42they can develop in three particular

31:43pathophysiology like pathophysiological

31:45reasons one is that their SA node may be

31:49firing maybe a little bit too fast and

31:52sending Action potentials down really

31:54really quickly to the AV node and then

31:56down into the ventricles and so if

31:58that's happening you're having a very

32:00fast type of rate that's being generated

32:02from the SA node or maybe being quickly

32:05conducted through the AV node and in

32:07those situations that's due to an

32:09intrinsic problem within the SA node in

32:11the AV node where they're either

32:12conducting Action potentials through fat

32:14too fast they are generating Action

32:15potentials too fastly and that's usually

32:17due to what's called increased or

32:19enhanced

32:20automaticity and you can see this really

32:23in any type of like increased

32:25sympathetic State really is what you

32:27what you'll have

32:28but we don't usually use anti-rhythmic

32:31drugs in these particular scenarios so

32:33again that's usually just due to an

32:35increased conduction like an increased

32:37essay node

32:38or an increased activity of the AV node

32:41where they're just conducting Action

32:43potentials or generating Action

32:44potentials super fast but this is what

32:47you see in like sinus tachycardia so

32:49it's not going to be super beneficial

32:50because we don't really give medications

32:52to treat a sinus tachycardia you treat

32:54the underlying cause of their increased

32:56sympathetic outflow

32:58another mechanism is that sometimes what

33:02happens is we take an atrial cell or we

33:05take a ventricular cell that's not a

33:06part of this pacemaker system and we

33:08cause it to become agitated we trigger

33:11it in a particular way we load them with

33:14calcium ions and we cause or we prolong

33:17their uh kind of like their what's

33:19called their their QT interval and when

33:22we do that what we do is we create an

33:24opportunity for these cells to become

33:26agitated and regenerate they somehow

33:30generate an abnormal automaticity so

33:33they start kind of generating Action

33:34potentials and they generate Action

33:36potentials faster than the SA node and

33:39AV node can and because of that they

33:41start generating super fast Action

33:43potentials that go to the AV node or

33:45that spread throughout the ventricles

33:47and so in these situations we can see

33:50very dangerous arrhythmias due to what's

33:52called triggered

33:54activity triggered activity

33:57and these are usually what we refer to

33:59as something called you'll you may have

34:01heard these terms in our arrhythmia

34:02lecture Eads so early after

34:04depolarizations or what's called dads

34:06delayed after depolarizations so Eads

34:09are something that you usually see with

34:10patients who are having what's called

34:11prolonged QT intervals so they're

34:14utilizing drugs and we'll talk about

34:15some of these here that actually prolong

34:17the QT interval and so that creates an

34:19opportunity for these Eads to form or

34:21certainly like electrolyte abnormalities

34:23like low potassium low magnesium May

34:25create opportunities for this whereas

34:27dads are usually due to lots of calcium

34:29loading in the cells which so lots of

34:31sympathetic overdrive particularly like

34:34ischemia to the actual myocardium or

34:37hypoxia digoxin toxicity you can see a

34:40lot of these things with this but these

34:42tissues the atrial and ventricular

34:43tissue not the pacemaker tissue generate

34:46the ability to intrinsically depolarize

34:48and generate Action potentials faster

34:50than the essay in an AV node

34:52so that's an interesting concept and you

34:55know what actually may be good for that

34:56there may be good particular drugs that

34:58may be helpful to either block the AV

35:00node or maybe give drugs that actually

35:02block the triggered activity at the

35:04atrial and ventricular myocytes that are

35:06generating these triggered active

35:07activity so we'll talk about that a

35:09little bit later

35:10the third mechanism is that there may be

35:13something called a re-entrant circuit so

35:15sometimes this can be

35:17anatomical so you can sometimes have

35:19this like weird kind of like anatomical

35:22structure here called like the bundle of

35:24Kent and it allows for this kind of

35:26re-entrant kind of cycle to occur where

35:28electrical activity May flow down the AV

35:30node through the ventricles and then

35:32back up through this accessory pathway

35:34and it can go really really fast and so

35:37sometimes you can see that with these

35:39very anatomical things called uh like

35:41the bundle of kitten wpw

35:43you can also see that sometimes you can

35:46develop re-entrant circuits like in

35:48particular nodal tissue so sometimes you

35:51can generate these re-entrant Cycles

35:52within the AV node or you can generate

35:55re-entrant Cycles within the Atria

35:58or you can generate re-entrant Cycles

36:00within the ventricles we're not going to

36:02go through all the mechanisms here but

36:04you can have atrial tissue ventricular

36:06tissue AV nodal tissue or these large

36:09kind of like anatomical accessory

36:11Pathways that allow for these re-entrant

36:13circuits and the problem with these

36:15reentrant circuits is they generate

36:17really really fast Action potentials and

36:20so that's another particular mechanism

36:21that I want you guys to be aware of

36:22which are called re-entrant

36:26circuits and we can see these as

36:29anatomical so they can be kind of like

36:31anatomical types of abnormalities and we

36:34see this a lot with what's called wpw

36:37or sometimes they can be functional

36:40and you see these functional

36:42abnormalities you see this in things

36:43like AV nrt which is a type of SVT you

36:48can see this in things like vtac you can

36:50see this in things like atrial

36:51fibrillation atrial flutter a lot of

36:53like weird kind of re-entrant circuits

36:55that can develop due to fibrosis or

36:58scarring or particular types of

37:00structural abnormalities within the

37:01myocardial tissue but either way the

37:04whole concept here is that when you look

37:06at this the problem is becoming of what

37:09with with arrhythmias that you're not

37:12following the normal cardiac conduction

37:14pathway if you are it's usually

37:16increased automaticity right so this SC

37:18note is just super hyperactive or the AV

37:19node is conducting potentials super fast

37:21that's not the arrhythmias that we're

37:23going to utilize antiarrhythmics for

37:25it's really these it's when you have an

37:28atrial tissue or ventricular tissue

37:30that's not a pacemaker tissue generating

37:32Action potentials because you trigger it

37:34or atrial tissue ventricular sorry

37:37atrial tissue or ventricular tissue is

37:39generating re-entrant circuits and

37:41generating these super fast rates and

37:43abnormal rhythms that are going to be

37:45causing very abnormal types of

37:47tachyarthemias and so really what I want

37:50us to really talk about here is how do

37:52we actually kind of utilize these

37:54medications because this is the way that

37:56I like to remember them I really think

37:58helps you when you think about

37:59arrhythmias is

38:01and what we're talking about for

38:02utilizing anti rhythmics is that when

38:04patients develop a tacky cardia

38:08they're beating at very fast rates so

38:10greater than 100 beats per minute and

38:13the reasons why they can develop that is

38:15because of increased automaticity

38:16increased conduction this is the one

38:18that we don't really care about though

38:19it's these two that we care about they

38:22can develop very fast heart rates due to

38:24triggered activity or re-entrant

38:27circuits I think one of the best ways to

38:29understand how these anti-rhythmics can

38:31be utilized approach wise is to look at

38:34it in two particular fashions

38:36one is let's say that we have this

38:40tissue here let's actually use the

38:41colors that we've been using whether it

38:42be due to the atrial tissue

38:45whether it be due to the atrial tissue

38:47generating these triggered activities so

38:49you have an ectopic Foci here that's

38:51triggering and firing super fast

38:54or whether it be due to a re-entrant

38:56circuit here that's developing within

38:59the Atria and it's generating these very

39:01fast Action potentials

39:03and atrial types of arrhythmias are

39:05superventricular tachyrhythmias what are

39:07the different types of supraventricular

39:08tachy rhythms do you guys know here

39:10let's say we got a couple of them the

39:12primary ones that you want to know one

39:14is atrial fibrillation right one is

39:17called atrial flutter the other one is

39:19called SVT these are the primary types

39:23of atrial or supraventricular tachy

39:25arrhythmias what happens with these is

39:27whether you have a re-entrant circuit or

39:30a triggered activity all of this

39:32electrical activity is going to one

39:34particular point the electrical Gateway

39:37or window between the Atria and the

39:39ventricles so the electrical activity

39:40from this reentrant circuit will go here

39:42to the AV node this ectopic focus in the

39:45Atria is going to be going towards the

39:47AV node so all the electrical activity

39:49from this kind of like tissue here

39:51tissue here they're generating super

39:52fast rates it has to go to the AV node

39:55who will then conduct the action

39:57potentials into the ventricles that's

39:59the issue right and if I get these rates

40:01to go fast onto the ventricles and the

40:03ventricles are going to be beating at

40:04super fast rates so what if I could come

40:07up with drugs that specifically inhibit

40:10or suppress the conduction of action

40:13potentials from these fast tissues here

40:16I suppress the AV node and I block it

40:19and if I block it I block all these fast

40:22actual Action potentials that are

40:24occurring in Atria from going on to the

40:26ventricles because you know why that's

40:28dangerous if the atrial is beating at

40:29let's say 300 beats per minute that's

40:31pretty fast right

40:33but the Atria isn't the one that's

40:34responsible for squeezing blood out of

40:36the heart it's the ventricles so if my

40:39ventricles are beating at 300 beats per

40:41minute there's like literally no chance

40:43it's going to be able to fill or really

40:45generate adequate contractility and that

40:48is not compatible with Life so what we

40:50don't want is a patient's Action

40:52potentials that are coming from the

40:53Atria maybe at 100 or 200 beats per

40:55minute to be generated into the

40:57ventricles at that fast of a rate so

40:59what we want to do is we want to give

41:01drugs that can rate control and block

41:04the AV node so this is where drugs where

41:07we utilize here in this particular

41:08scenario what we're going to do with

41:10them is we're going to rate control

41:14and we're going to do that by

41:16suppressing or blocking the electrical

41:18activity from the Atria Into The

41:19ventricle at the AV node what drugs that

41:23we're going to talk about later are

41:25going to be good at suppressing and

41:26blocking the AV node and we'll talk

41:28about how they actually do it a little

41:29bit later but this is the ones that I

41:30want you to remember

41:32first ones are going to be what's called

41:34your beta blockers

41:36so your beta blockers are very good at

41:39blocking the AV node and suppressing a

41:41lot of the electrical activity from the

41:42atrial tissue going through the AV node

41:44and into the ventricles we also give

41:46another name for this there's what's

41:47called like this Vincent kind of

41:49classification system we use like class

41:51or types so this is a class or type

41:55two antiarrhythmic drug

41:58and we'll talk about these a little bit

42:00later the next one we can do to suppress

42:02the actual AV node is we can give drugs

42:04called calcium channel blockers so

42:06calcium channel blockers are also

42:08decently utilized drugs in these

42:11particular kind of diseases here and

42:13these are what's called a class

42:16or type 4

42:19anti-arhythmic drug

42:21okay the next ones that we can use here

42:24are technically not a part of that like

42:26Vince kind of classification system the

42:28typical classification system we put

42:30them in miscellaneous which is like a

42:32class 5 drug and there's two types here

42:34one is called adenosine so adenosine is

42:38another particular drug that we can

42:39utilize here and this is kind of like a

42:41miscellaneous but we sometimes we just

42:43put this in What's called the type 5 or

42:44class five

42:46anti-arrhythmic drug class so here we'll

42:48put these in like the the type or class

42:50five

42:53anti-rhythmic drug category and there's

42:55one more and this one is called digoxin

42:58this one is called digoxin again it's a

43:00part of that miscellaneous or class 5

43:03anti-arythmic drug category but what I

43:06want you to remember is all of these

43:08drugs are working in some way shape or

43:10form to suppress the AV node which is

43:12going to work on this type of tissue the

43:15slow action potential producing tissue

43:17it's going to alter the channels in this

43:19particular tissue that's why I focused

43:21on that so much so we're going to

43:23utilize these drugs to suppress

43:24particular channels or at like action

43:27potential processes in the AV nodal cell

43:30primarily that's why I focused on the

43:31pacemaker cell activity there

43:33and the other situation that's going to

43:35be for these types of arrhythmias things

43:37like afib a flutter SVT

43:40and with SVT there's two types there's

43:42AV nrt as well as what's called

43:45um avrt so avnrt is like the nodal

43:47reentrant tachycardia and then avrt is

43:50like your wolf Parkinson's white

43:51syndrome but we can utilize it in these

43:53particular scenarios okay

43:56the non-pacemaker blockade is a little

43:59bit different so now what we're trying

44:01to do is we're saying okay here's that

44:02tissue here here's the atrial tissue and

44:05it's generating these ectopic Foci it's

44:07becoming a triggered activity there or

44:11we have a re-entrant circuit here maybe

44:13we have a re-entrant circuit generating

44:15within the Atria

44:17okay or same kind of concept here we

44:19have a re-entry tissue here within the

44:21ventricle

44:22kind of re-entrant circuit that's

44:24developing within the ventricle

44:26or

44:27an ectopic Focus that's developing

44:30within the ventricle so now

44:33we already talked about ways that we can

44:35block the atrial signals from getting

44:37down into the AV node and then into the

44:39ventricles we've already talked about

44:40that that's going to be these drugs that

44:41block the AV node what if there was a

44:44way

44:45that I could shut down the re-entrant

44:47circuit or shut down the triggered

44:49activity in both the atrial cells and

44:51the ventricular cells what if I could do

44:53that what if I could somehow a patient

44:56who has superventricular tachyarthy so

44:58let's say for the atrial ones we're

45:00talking about patients who have atrial

45:01fibrillation we're talking about atrial

45:03flutter we're talking about maybe even

45:05SVT but this is going to be a plus or

45:07minus

45:09and we talk about the ventricular

45:11arrhythmias so we're talking about

45:12things like vtac we're talking about

45:14things like torsods to points and these

45:17particular situations what if I could

45:19suppress or reduce the action potentials

45:22that are being generated by the atrial

45:25and ventricular myocytes that are

45:27non-pacemaker tissues that are

45:29responsible for causing these rhythmias

45:31what if I could stop them from producing

45:33these types of arrhythmias wouldn't that

45:35be beneficial I'm not going to block the

45:36AV node I'm just going to suppress them

45:39and try to get them back into a normal

45:41sinus rhythm so we call this type of

45:43process here where we're trying to take

45:45and switch these over and suppress them

45:47we call this kind of a rhythm control

45:51we call this more of a rhythm control or

45:53a cardioversion type of process now what

45:56drugs are going to be good

45:57at actually suppressing the actual

45:59potentials and particularly these atrial

46:02and ventricular monocytes that's the

46:04good question right the tissues that the

46:06drugs that are really good in this

46:07particular activity is going to be drugs

46:09that block the sodium channels the

46:10voltage-gated sodium channels and drugs

46:12that block the voltage you get to

46:14potassium channels so we call these

46:16drugs your sodium

46:18channel blockers

46:21okay and these are sometimes referred to

46:23or commonly referred to that car that

46:24classic system there class one uh

46:29anti-arhmic drugs

46:31okay the other one is the potassium

46:34channel blockers so the potassium

46:36Channel blocks we have sodium channel

46:37blockers and then we have what's called

46:38potassium channel blockers

46:41and this is going to be What's called

46:42the class

46:44three

46:46anti-arrhythmic drugs okay so these are

46:50really really really important that I

46:51need you to understand that the class 2

46:54class 4 and some of the miscellaneous

46:55class five they suppress the atrial

46:58rhythmias by blocking the AV node to

47:00rate control these patients prevent

47:02their atrial rate from causing very fast

47:04ventricular rates they don't convert

47:06them back into a normal rhythm and

47:08patients who have atrial or ventricular

47:11arrhythmias where we're not going to

47:13suppress the AV node but we want to try

47:15to take and convert these kind of

47:17abnormal triggered atrial cells or

47:19reentrant atrial cells or triggered

47:21ventricular cells or re-entrant

47:22ventricular cells we want to suppress

47:24them shut them down and allow for the

47:27normal sinus rhythm to go back into a

47:29place here that's called rhythm control

47:31of a cardioversion kind of technique in

47:34those situations we use sodium channel

47:35blockers potassium channel blockers

47:37class 1 class 3 and in some ways we can

47:40even potentially use a plus or minus

47:43here

47:44for the third situation you also may be

47:47able to use beta blockers and I'll talk

47:49about this a little bit more later but

47:51beta blockers which are your class

47:54Two anti-rhythmic drugs they're really

47:57good at suppressing

48:00the sympathetic nervous system because

48:02if you suppress the sympathetic nervous

48:04system you can actually potentially

48:05inhibit

48:07the triggered activity

48:11and you may be able to be able to

48:13suppress some of the re-entrant cycles

48:17because sometimes the sympathetic

48:19nervous system can just really

48:20exacerbate triggered activity especially

48:23and re-entrine circuits and so if you

48:25give a beta blocker you may be able to

48:27suppress the sympathetic drive on these

48:29types of cells but again these are going

48:31to be the two primary ones for rhythm

48:34controller conversion and this is going

48:36to be primarily the ones for raid

48:38control so I want you guys to understand

48:40that so now that we've done that

48:42we've built a very strong Foundation

48:44knowing that these drugs are going to

48:47work potentially on the atrium

48:49ventricular myocytes they're going to be

48:50altering those channels so the sodium

48:53channels the potassium channels that are

48:54involved in the fast action potential

48:56producing tissue now that I know that

48:58and I understand this mechanism let's

49:00now go into the drugs that are actually

49:02going to cause blockade of the AV node

49:05and how they're actually going to to

49:07helply specifically suppress the AV node

49:09reduce the action potentials how they

49:11alter the graph here

49:13and then what we'll do is we'll then go

49:15later after we go through all of these

49:17drugs we'll then go into how do the

49:19sodium channel blockers and potassium

49:20channel blockers really work to alter

49:24the electrical activity inside of these

49:26atrial and ventricular cells by how do

49:28they specifically do that in the sodium

49:30channels the potassium channels and how

49:31does that alter the graphical

49:32representation here so let's do that now

49:35we have a lot to talk about let's get

49:36into it all right my friends so now

49:38we're going to talk about beta blockers

49:40first okay so this is going to be kind

49:41of our type or Class 2 anti-rhythmic

49:43drug now when we talk about beta

49:45blockers let's talk about some of the

49:47beta blockers the actual names of those

49:48drugs so a lot of them you can just

49:50remember the olalls right so there's the

49:52metoprolol which is a very commonly

49:55utilized one you can also remember like

49:58a tenolol

50:00propanolol anything really with a law

50:03so there's a lot of these drugs out

50:05there okay now what I really want you to

50:08understand with these drugs is how

50:10exactly do they block the AV node which

50:13will suppress the actual super fast

50:15rates from going from The Atrium to The

50:18ventricle and diseases such as afib a

50:20flutter SVT things to that effect how

50:23are they really working here and then we

50:25talk about them a little bit later that

50:27they also can be used to suppress the

50:28sympathetic effect in situations like

50:31vtac they can actually are very helpful

50:32in vtac but

50:35nonetheless we have a patient here who

50:37has some disease okay whether that

50:39disease is again very commonly utilized

50:42here in situations such as atrial

50:43fibrillation it can be utilized in

50:45atrial flutter and it can even be

50:47utilized in things called SVT as a

50:49prophylaxis but what happens with these

50:52diseases that you have this irritated

50:54area of an atrial Focus which is sending

50:57super fast Action potentials way faster

51:00than the SA node that's getting to the

51:02AV node and if we have these Action

51:03potentials go through the AV nude super

51:05quick they can cause very fast

51:07ventricular rates so then we can end up

51:09with what's called afib with a rapid

51:10ventricular rate or a flutter with a

51:12rapid ventricular rate or SBT that can

51:14can sometimes go super super fast

51:17but how can we suppress basically block

51:20the action potentials from going through

51:21the AV node and suppress this actual

51:23super fast rate

51:25well let's say that I take this AV nodal

51:27cell right here I'm going to zoom in on

51:29one of the cells in the Avio and look at

51:31how beta blockers actually do this so on

51:34these uh AV noodle cells here we're

51:36going to have something called a beta

51:37receptor so what is this receptor here

51:39this is called a beta

51:41one receptor

51:42now what happens is epinephrine

51:44norepinephrine usually what they do is

51:46they bind onto so let's say that here we

51:48have something called epinephrine and

51:49norepinephrine when they bind onto this

51:52actual receptor here what they do is

51:54they activate a protein called a g

51:55stimulatory protein the G stimulatory

51:58protein will then activate an enzyme

52:00here called adenylate cyclase and what a

52:03dental cyclase will do is it'll take a

52:05molecule called ATP and convert it into

52:08cyclic amp and that'll activate

52:10something called protein kinase a and

52:13protein kinase a will go in

52:14phosphorylate what it'll do is it'll put

52:17phosphate groups on these channels don't

52:19these look familiar on the pacemaker

52:21cells so if you look at the pacemaker

52:23cells remember the pacemaker cells had

52:24the funny sodium channels they had the

52:26T-Type calcium channels they add the

52:28l-type calcium channels these are l-type

52:31calcium channels what are these channels

52:32called l-type

52:34calcium channels what I'm going to do is

52:38is when epinephrine and norepinephrine

52:40bind on here so here's epinephrine

52:41norepinephrine they bind on here they

52:43stimulate this pathway they cause the

52:46phosphorylation of these channels and

52:48cause calcium to flood in and if calcium

52:51floods into the cell it makes the cell

52:54super positive which increases the speed

52:56of the action potentials now what I'm

52:58going to do is I'm going to give a drug

53:00called

53:01metoprolol Atenolol perpendolol any of

53:05these drugs and what I'm going to do is

53:06I'm going to suppress or block the

53:09effect here of norepinephrine

53:11epinephrine at the beta 1 receptor what

53:13I'm going to do is I'm no longer going

53:16to stimulate the G stimulatory protein

53:18I'm going to inhibit the G stimulatory

53:19protein I'm going to inhibit the

53:22activation of adenyally cyclase I'm

53:25going to decrease the conversion of ATP

53:27into cyclic amp I'm going to decrease

53:29the activation of protein kinase a I'm

53:32going to not phosphorylate the l-type

53:35calcium channels therefore I won't open

53:37them as nicely and therefore calcium

53:40will not enter into the pacemaker cells

53:44go back now to the phases

53:46here is what phase phase four this is

53:50Phase zero this is phase three phase

53:53four is funny sodium channels T type

53:56calcium channels phase zero is l-type

53:58calcium channel space three is

54:00voltage-gated potassium channels

54:03if I block

54:04the l-type calcium channels from opening

54:07these generally open right at the end of

54:10phase four going into phase zero

54:13so now I'm going to block them what is

54:15the overall effect going to be now so

54:18now instead of me allowing for so let's

54:20say that we started off here right I'm

54:22going to block right here at the end of

54:25phase four going into phase zero so now

54:28instead of me allowing for this phase

54:30four to go here and then up I'm going to

54:32delay it it's going to take a longer

54:34time for me to be able to get this phase

54:36four up here to phase zero and then this

54:39is going to cause

54:40look at this

54:42less frequency of action potentials so

54:46now there's going to be a decreased

54:47frequency of action potentials moving

54:50through the AV node so what is it going

54:52to do

54:53beta blockers on this effect here are

54:56going to inhibit the l-type calcium

54:58channels from opening and that is going

55:00to decrease the slope

55:03of phase four

55:06and even if you think about it here

55:07because it also will block the calcium

55:10channels from entering you may even get

55:12a little bit of a decrease in slope of

55:14phase four but also in Phase zero so

55:17your phase zero may also be a little bit

55:19slower as well so if you look here you

55:21may also have a slower

55:22phase zero

55:26okay so phase four and

55:29phase zero in what in the AV node

55:34so what that's going to do is you're

55:36going to decrease the conduction of

55:38action potential throughout this AV node

55:41which is going to help to rate control

55:43it'll help with the rate control of afib

55:45a flutter and SVT

55:49so that's what I want you to understand

55:51about this drugs

55:52now when we talk about these drugs they

55:55have many different types of adverse

55:56drug reactions we'll talk about them a

55:58little bit more later but obviously with

56:00any type of beta blocker you suppress

56:02the AV node if you do suppress the AV

56:05node what are some of the things that

56:06you have to watch out for my friends

56:07watch out for bradycardia also it can

56:10actually block the beta receptors on the

56:12contractile portion of The myocardium

56:13which can cause decreased contractility

56:15so make us hypotension especially in

56:17decompensated heart failure it also can

56:20cause activation or inhibition of the

56:22beta 2 receptors and the bronchials

56:24which will cause bronchoconstriction and

56:26it may even cause hypoglycemia

56:27unawareness we'll talk about that later

56:28but things to watch out for with this

56:30drug so now we know the mechanism of

56:32action we know the diseases and it's

56:34actually used to treat and how it treats

56:35those diseases and we know what it would

56:37look like

56:38specifically on the actual graphical

56:41representation so if they were to ask

56:42you what does this one look like well it

56:44slows phase four a little bit of phase

56:46zero should not affect phase three slows

56:49or delays the the slope of phase four

56:52and zero should not affect phase three

56:55but the primary one that you're going to

56:57see most likely in the test here is

56:58phase four

57:00it has a little bit of effect on phase

57:01zero so does the next one that we're

57:02going to talk about called calcium

57:04channel blockers let's talk about those

57:05all right so now calcium channel

57:07blockers these are your class 4 Type 4

57:09anti-rhythmic drugs so there's a couple

57:10of these so ones that I want you to

57:12remember primarily is Verapamil so

57:14varapamil is going to be one and then

57:16the other one is called diltiazam so the

57:18thiazine might be the more commonly one

57:20utilized one that you may see in

57:22clinical practice but with these drugs

57:25okay what are they potentially being

57:26utilized for again they're blocking and

57:28suppressing the AV node so remember I

57:31told you that they're utilized in

57:32particular like you know triggered

57:33activity or re-entrant circuits of some

57:36type that are causing very fast rates

57:38from The Atrium to try to move down

57:40through the Avi node into the ventricles

57:41so situations such as AFib

57:44a flutter right

57:46and SVT prophylaxis we're utilizing

57:49these drugs how are we actually going to

57:51do that well let's take this AV nodal

57:53cell

57:54and kind of blow it up and take a look

57:55at how it's actually going to be blocked

57:57well

57:58here on this AV nodal cell you'll notice

58:01something very interesting these pink

58:02channels here what are these pink

58:03channels here called these channels are

58:05called your L Type

58:08calcium

58:10channels

58:11so we blocked the l-type calcium

58:13Channels with beta blockers right

58:15because they help to be able to decrease

58:17the phosphorylation of these channels

58:19especially at the end of phase four

58:20that's one of the most interesting

58:22things that you block them at the end of

58:23phase four which really delays and

58:24decrease the slope of phase four but

58:26they may also have less calcimentary

58:28during phase zero so it also should kind

58:30of decrease the slope there with this

58:32one it's the same concept you're

58:34blocking the actual l-type calcium

58:36channels if calcium is supposed to Rush

58:39In

58:40during the beginning of phase four and

58:42during phase zero you're supposed to

58:44have these positive lines coming into

58:46the cell and cause this Rising phase of

58:47the action potential so generally if you

58:49go back to the phases here you should

58:50have phase four at the end of phase four

58:52l-type calcium channel should open

58:54during phase zero L Type calcium channel

58:56should be open and flooding through and

58:58during during phase three there should

58:59be potassium exiting causing

59:00repolarization what I'm going to do is

59:02I'm going to give these drugs and

59:04they're going to block

59:06calcium entry and so what I'm going to

59:09effectively see here is I'm going to see

59:10a d a decrease and the slope of phase 4

59:13and a decrease in the slope of phase

59:16zero

59:19and because of that I should effectively

59:21see less conduction of action potentials

59:24through the AV node if I see less

59:26conducting of action potentials through

59:28the AV node that means all of these

59:30atrial signals that are trying to go

59:31through the Avion into the ventricles

59:33I'm going to suppress them and lead to

59:36rate

59:37control

59:39so what is the overall effect that I

59:42will see as I will block the calcium

59:43entry I'll block the positive ions

59:45entering into the cell and I'll decrease

59:47the slope

59:49if I block these I'll decrease the slope

59:51of phase

59:53four

59:55and phase

59:57zero in the AV node and this is going to

1:00:03be both of them you're going to really

1:00:04really strongly more than beta blockers

1:00:06block the phase four and phase zero so

1:00:10that's one of the cool things about

1:00:11these calcium channel blockers but the

1:00:13same kind of effect is seen here is that

1:00:15you are really suppressing and blocking

1:00:17the AV node for blocking the entry oh

1:00:20it's the Gateway between the atrium to

1:00:22The ventricle so all these increased

1:00:23atrial signals that are trying to get to

1:00:24the AV node and then down to the

1:00:25ventricles you're blocking it right

1:00:27there to suppress all those electrical

1:00:29activity from getting down into the

1:00:30ventricles really really cool concept

1:00:33so with calcium channel blockers adverse

1:00:35drug reactions to watch out for same

1:00:37with beta blockers they block the AV

1:00:38nodes so watch out for any bradycardia

1:00:40AV blocks they also really suppress the

1:00:42actual

1:00:43um calcium channels and the contractile

1:00:45myocardial cells and that can actually

1:00:47really cause hypotension and worsening

1:00:49uh decompensated heart failure so be

1:00:51careful for that and it also may cause

1:00:52some constipation but that's the effect

1:00:54of the calcium channel blockers and how

1:00:56they actually do this now we understand

1:00:58these let's talk about the next two

1:01:00drugs that are utilized as AV noodle

1:01:02blockers adenosine and digoxin all right

1:01:04my friends so now let's move on to

1:01:05adenosine and digoxin this is kind of

1:01:07that later kind of like miscellaneous

1:01:09class 5 antiarrhythmic drugs so with

1:01:11these we did say that they're all kind

1:01:13of utilized to suppress or the AV node

1:01:15and afib a flood or SVT that's true

1:01:18however adenosine is very short acting

1:01:22so it's not a great drug for more of

1:01:24kind of rate controlling patients with

1:01:26afib and a flutter it's more of a drug

1:01:28that will really shut down SVT acutely

1:01:31so when patient goes into a really rapid

1:01:33super ventricular the tachycardia the

1:01:35rates are 170s 200s what we can do is we

1:01:38can give a drug that's very short acting

1:01:39very powerful and it'll really suppress

1:01:41the AV node and that's that's going to

1:01:43be adenosine so with that being said

1:01:46I'm patients of what's called SVT this

1:01:49is more of an indication particularly

1:01:51for adenosine and we'll talk about all

1:01:53these like arrhythmias a little bit

1:01:54later but adenosine is not very good in

1:01:57afib and a flutter because it's not a

1:01:59longer acting drugs it's a very short

1:02:01acting so it's not good in patients who

1:02:04are going to have afib and a flutter so

1:02:06remember that it's going to be not very

1:02:08helpful for afib and not very helpful

1:02:11for atrial flutter

1:02:14with that being said we also have

1:02:15digoxin

1:02:17digoxin is actually going to be utilized

1:02:20primarily for atrial fibrillation we

1:02:22don't really utilize this very much for

1:02:24a flutter it's not really utilized very

1:02:25much for SVT as well primarily atrial

1:02:29fibrillation and that's going to be

1:02:31digoxin and what we'll talk about later

1:02:33is it's not going to be your first line

1:02:35Choice it's really only going to be a

1:02:37drug that we give to patients if they

1:02:39have heart failure with a reduced

1:02:41ejection fraction so if a patient has a

1:02:43heart failure with a reduced ejection

1:02:45fraction and atrial fibrillation digoxin

1:02:48seems to be a drug that may be

1:02:49potentially beneficial but again not

1:02:52super helpful for patients who are going

1:02:53to be utilizing it for atrial flutter

1:02:55and it's not really a drug that we get

1:02:57for SVT okay so just when I talked about

1:03:00that in the beginning with the AV node

1:03:02blockade that is their mechanism of

1:03:04action it's just when we talk about

1:03:06their utilization of particular diseases

1:03:08it may be a little bit different that

1:03:10beta blockers calcium channel blockers

1:03:12can treat all three of those atrhythmias

1:03:14adenosine it could theoretically do that

1:03:17but it's more specifically very short

1:03:19acting so it's really only given an SVT

1:03:22and digoxin it could treat atrial

1:03:24flutter it could treat SVT but it's only

1:03:26been shown to be really beneficial and

1:03:28somewhat beneficial in atrial

1:03:29fibrillation and patients who have heart

1:03:31failure with a reduced ejection fraction

1:03:33not super helpful in a flutter or an SVT

1:03:36okay with that being said how exactly do

1:03:39these drugs block the AV node because

1:03:42it's the same mechanism regardless

1:03:43they're all going to have these

1:03:45triggered activity or you're going to

1:03:46have those re-entrant circuit the

1:03:48sending Action potentials quickly to the

1:03:50AV node and you want to block that AV

1:03:51node and prevent the fast atrial circuit

1:03:54electrical activity from going down to

1:03:56the ventricular circuit so you're trying

1:03:58to rate control these patients it's the

1:04:00same concept it's all rate control

1:04:02how do we block Davey notes let's take a

1:04:04piece of this AV nodal cells and zoom in

1:04:06on it here

1:04:07okay here we're going to have a receptor

1:04:09and this receptor is for adenosine and

1:04:12what happens is when adenosine binds on

1:04:14to so this is going to be adenosine when

1:04:17you give adenosine that binds onto

1:04:19adenosine receptor here when it binds

1:04:21onto the adenosine receptor it's

1:04:22actually coupled with a G inhibitory

1:04:24protein so it binds on and activates a g

1:04:27inhibitory protein the G inhibitory

1:04:30protein will then work to inhibit

1:04:33um because you know when a g inhibitory

1:04:35proteins they specifically inhibit it

1:04:37Inlet cyclase so they don't take ATP and

1:04:39convert it into cyclic amp so that's one

1:04:41thing it will inhibit your you know

1:04:43activation of adenylate cyclase and so

1:04:46yes you will have less

1:04:48ATP converted into less

1:04:51cyclic amp and that will lead to less

1:04:54protein kinase a and so yes to a mild

1:04:56degree you'll have less phosphorylation

1:04:58of the l-type calcium channels but

1:05:00that's not the primary mechanism by

1:05:02which adenosine works

1:05:04the primary mechanism is yes you made

1:05:06some mild degree this is I'm going to

1:05:07put here a very mild

1:05:09degree

1:05:11block the calcium channels right and

1:05:14have less calcium enter into the cell

1:05:16right so that may be a possibility but

1:05:19it's very very mild effect the more

1:05:22powerful effect from adenosine

1:05:25is that when you stimulate G inhibitory

1:05:26there's two different types of well

1:05:28there's three subiness there's an alpha

1:05:29beta and gamma subunit the alpha and

1:05:32beta subunit really what inhibits the

1:05:34identity cyclase the gamma subunit is

1:05:36the one that actually goes and acts on

1:05:38another channel so there's really when

1:05:40we talk about this G inhibitory unit

1:05:42what it does is it actually activates

1:05:44what's called Alpha

1:05:46and beta subbing and that really goes

1:05:48and inhibits the identity cyclase but it

1:05:50also

1:05:52so it'll stimulate this pathway here but

1:05:54it'll also stimulate another pathway

1:05:57called the gamma subunit and the gamma

1:06:00subunit and this is all the inhibitory

1:06:02component of the G inhibitory protein so

1:06:04the G inhibitory protein is actually

1:06:05made up of a gamma Alpha and beta

1:06:07subunit Alpha Beta will go and work and

1:06:09to inhibit the adenylate cyclase the

1:06:11gamma one will go and act on these

1:06:13potassium channels and open up these

1:06:15potassium channels

1:06:17when they stimulate or open up these

1:06:19potassium channels potassium will vary

1:06:21powerfully leak out of the cell

1:06:24and when potassium exits the cell the

1:06:26cell becomes super electronegative

1:06:29when it becomes electronegative it makes

1:06:32the inside of the cell very negative to

1:06:34the point where if you had this cell

1:06:35that's at rest if this cell was at rest

1:06:38this abnormal cell was at rest

1:06:40and you bring the inside of the cell

1:06:41even more negative than resting membrane

1:06:43potential it's called hyper polarization

1:06:46so what does it do

1:06:48it causes hyper

1:06:51polarization

1:06:53the cool concept about this

1:06:56okay we're going to put calcium right

1:06:57over here to make room the cool concept

1:07:00about this if you think about this this

1:07:01is our resting membrane potential this

1:07:03is where the cell is at rest right

1:07:04here's the threshold potential

1:07:07now what I'm going to do is I'm going to

1:07:09make the inside of the cell even more

1:07:11negative than resting membrane potential

1:07:13so now let's actually represent this in

1:07:15this uh kind of like maroonish color

1:07:17here this is the new Point here I'm

1:07:20making the cell even more negative I'm

1:07:22bringing it below the resting membrane

1:07:24potential so I'm going to call this the

1:07:26hyper polarized state

1:07:30hyper polarized

1:07:32state so I'm making the cell even more

1:07:34negative than the resting membrane

1:07:35potential the problem with that is is if

1:07:39I cause this hyperpolarization now this

1:07:42cell will have to go from this state the

1:07:43hyperpolarized state all the way up here

1:07:46maybe it won't change the slope so the

1:07:48slope may still kind of be the same

1:07:50but now it's going to take a longer time

1:07:53for it to be able to get to the

1:07:54threshold potential because it has to go

1:07:57from maybe negative 90 maybe negative 95

1:07:59all the way up to negative 40. so

1:08:02because of that I'm really hyper

1:08:04polarizing this thing so you see what

1:08:06I'm doing here is I'm taking and moving

1:08:08the cell to become more negative I'm

1:08:10just going to put a random number here

1:08:11negative 95 millivolts so now instead of

1:08:14going from

1:08:15a negative 70 to negative 40 I'm going

1:08:18from negative 95 to negative 40. so this

1:08:21is called hyperpolarization I'm going to

1:08:23cause the cell to have to go from a

1:08:24lower like charge to bring this up to a

1:08:27threshold potential that's more movement

1:08:29that's going to be more difficult to be

1:08:31able to get the cell to that point and

1:08:33that can really shut the AV node down

1:08:35pretty powerfully so one of the things

1:08:37about adenosine here that I want you to

1:08:39remember is adenosine and we're going to

1:08:42talk about how digoxin will do the same

1:08:44type of effect here adenosine

1:08:46and digoxin

1:08:48are going to cause hyper polarization

1:08:51they're going to make the cell very very

1:08:54negative and that's going to make it

1:08:56more difficult and take a longer time to

1:08:59go from this hyperpolarized state to

1:09:01threshold potential so it's going to

1:09:03increase the time

1:09:06to the threshold potential and that will

1:09:09decrease the amount of action potentials

1:09:11that you're going to be able to generate

1:09:12because it's going to take you a longer

1:09:13time to get to threshold potential to

1:09:16generate an action potential pretty cool

1:09:18concept okay

1:09:19that's for adenosine how does the

1:09:20Jackson do this

1:09:22and digoxin is also pretty cool so what

1:09:24happens is you know your vagus nerve

1:09:26your vagus nerve releases something

1:09:28called acetylcholine right so here's

1:09:30your vagus

1:09:32nerve

1:09:34now the vagus nerve will act will

1:09:36release acetylcholine which will act on

1:09:37what's called muscarinic two receptors

1:09:39right this is an adenosine receptor this

1:09:41is a muscarinic 2 receptor when

1:09:44acetylcholine binds onto this muscarinic

1:09:46II receptor what it does is it does the

1:09:48same exact process it activates a

1:09:51genehibitory protein and there's two

1:09:53components of that one is the alpha and

1:09:55beta inhibitory subunit and that'll go

1:09:58and inhibit adenine cyclase decrease ATP

1:10:01decrease cyclic amp decrease protein

1:10:03kinase a less phosphorylation less

1:10:05calcium comes in but that's very very

1:10:07mild it's more this effect that's the

1:10:10more potent effect where it inhibits the

1:10:12I mean sorry it actually causes the

1:10:14stimulation of the gamma subunit

1:10:17and the gam subunit will come and bind

1:10:19onto these potassium channels and they

1:10:21will cause the potassium channels to

1:10:23open and potassium will leak

1:10:27out of the cell very powerfully and

1:10:29that'll cause the inside of the cell to

1:10:31become very

1:10:32electronegative and this will cause

1:10:34again what type of effect here

1:10:37hyperpolarization making the cell very

1:10:39negative which will cause it to go to

1:10:42this hyperpolarized state making it now

1:10:44have to work harder to be able to go

1:10:45from a negative potential all the way up

1:10:48to negative 40. it's a longer time to

1:10:50get to threshold potential and that's

1:10:51going to slow down the action potentials

1:10:53moving through the AV node

1:10:55but all right we just talked about the

1:10:57vagus nerve here and how acetylcholine

1:10:59Works how does the Jackson actually come

1:11:01into play here

1:11:02digoxin has been shown through not a

1:11:06completely known mechanism here but to

1:11:09stimulate

1:11:11the increase of acetylcholine release

1:11:13from the vagus nerve and that will

1:11:15increase the activation of the alpha

1:11:19beta and gamma subunits that'll increase

1:11:22the activation of these potassium

1:11:24channels and that'll increase potassium

1:11:25exiting and that will increase

1:11:27hyperpolarization make the cell super

1:11:29negative and now it's going to have to

1:11:31go from like a negative 95 millivolts

1:11:33I'm just using a random number here it's

1:11:35just more negative potential it's going

1:11:38to have to go from that potential all

1:11:39the way to threshold which is more than

1:11:40it would have been from the normal

1:11:42resting membrane potential

1:11:44okay so that's one of the interesting

1:11:46concepts of this drug category

1:11:48so again to recap this adenosine digoxin

1:11:52still block the AV node and atrial

1:11:54arrhythmias but to be more specific they

1:11:58really only treat SVT such as adenosine

1:12:00and afib such as digoxin in patients

1:12:03with heph-ref heart failure where they

1:12:05reduce the ejection fraction how do they

1:12:07do it they hyperpolarize the AV nodal

1:12:10cell they make the inside of the cell

1:12:12negative now it has to go from a very

1:12:15negative charge to rest I'm sorry to the

1:12:18threshold potential so giving an example

1:12:20if the resting member potential is

1:12:21negative 70 I made the cell even more

1:12:23negative than that negative 95. now it

1:12:26has to go from negative 95 to negative

1:12:2740. in comparison to negative 70 to

1:12:30negative 40. that's going to take a

1:12:31longer time to get the threshold

1:12:33potential a longer time to generate

1:12:34Action potentials and that decreases the

1:12:37conduction of action potentials through

1:12:38the AV node into the ventricles again

1:12:42adenosine will do that via the G

1:12:44inhibitory process by causing potassium

1:12:46efflux the joxin will increase vagal

1:12:49nerve stimulation causing increased

1:12:50acetylcholine release which will also

1:12:52cause potassium reflux these can to a

1:12:56very mild degree it's not even relevant

1:12:58though to put that on the graph can

1:13:00mildly block the voltage-gated potassium

1:13:02channels and so if you really wanted to

1:13:05they theoretically could even decrease

1:13:07the slope of phase four okay and very

1:13:11mildly phase zero but they're primarily

1:13:15hyperpolarizing the cell all right now

1:13:18that we've talked about these drugs

1:13:19let's now come into the next category

1:13:21we've talked about all the drugs that

1:13:23are utilized to suppress or block the

1:13:25conduction through the AV node the beta

1:13:27blockers the calcium channel blockers

1:13:29adenosine and digoxin used in atrial

1:13:30arrhythmias to really rate control those

1:13:33patients what about the diseases of the

1:13:36atrial and ventricular myocytes where

1:13:38instead of actually rate controlling

1:13:39blocking the AV node I try to block

1:13:41those those cells those triggered cells

1:13:44re-entrant cells abnormal cells from

1:13:46firing and preventing them from having

1:13:49AFib or preventing them from going into

1:13:51a flood or preventing them from going to

1:13:53v-tac or preventing them from going into

1:13:55torsos to points taking converting them

1:13:57out of that abnormal Rhythm into a

1:13:59normal Rhythm how do I utilize those

1:14:01drugs in this particular scenario and

1:14:03how is their mechanism of action going

1:14:04to be working let's talk about that now

1:14:06all right so now let's talk about the

1:14:07sodium channel blockers your class one

1:14:09type one anti-rhythmic drug category now

1:14:11what do these utilize for they're not

1:14:13going to block the AV node they're going

1:14:15to try to block those non-pacemaker

1:14:17tissues those atrial and ventricular

1:14:18tissues that are generating abnormal

1:14:21rhythms so remember I told you that

1:14:22maybe you have some type of abnormal

1:14:25triggered activity occurring within the

1:14:26Atria and it's causing this Atria to

1:14:28generate these really fast rates right

1:14:30or maybe you have a re-entrant circuit

1:14:32within the Atria and it's causing to

1:14:34generate these very fast rates or maybe

1:14:37you have a ventricular Focus here that's

1:14:38causing a lot of triggered activity or

1:14:41you have a ventricular Focus that's

1:14:42creating a lot of

1:14:44re-entrant circuits either way

1:14:47you're not going to be able to blocking

1:14:49the AV node in these ventricular

1:14:50circuits is not going to be helpful

1:14:51right it's more blocking the AV node for

1:14:54the atrial arrhythmias

1:14:55was that I'm even blocking the AV node

1:14:57for these atrial rhythmias

1:14:59what if I just

1:15:01tried to get these atrial cells to stop

1:15:04firing okay so particularly in diseases

1:15:07such as atrial fibrillation atrial

1:15:10flutter what if I just go ahead and I

1:15:12kind of cardiovert them in other words I

1:15:15try to take and convert them from this

1:15:18abnormal Rhythm that they're generating

1:15:20due to triggered activity or re-entrant

1:15:22circuits and I try to suppress those

1:15:24reentration circuits or suppress the

1:15:26actual triggered activity and cause them

1:15:28to go back into normal sinus rhythm

1:15:30or what if I have a patient who's in

1:15:32vtac or V uh what's called um

1:15:34torsad's the points of something of like

1:15:36that nature or torsad's the points and I

1:15:39try to again cardiovert them this may be

1:15:42where these drugs could potentially be

1:15:44useful and we'll talk about that

1:15:46actually now

1:15:49when we talk about these drugs these uh

1:15:51sodium channel blockers what are some of

1:15:53them there's a lot of them and we

1:15:55actually are going to talk about these

1:15:57in a subtype so when we talk about

1:15:58sodium channel blockers they're all

1:16:00going to block the voltage-gated sodium

1:16:01channels in those non-pacemaker atrial

1:16:03and ventricular myocardial

1:16:05cardiomyocytes right

1:16:07but they're going to block a little bit

1:16:08differently and they have different

1:16:09names for the different subtypes so

1:16:12there's class 1A class 1B and class one

1:16:14C or type 1A type 1B type 1C with these

1:16:17there's a lot of them names so here's

1:16:19the way that I usually remember them I

1:16:21remember for type 1A it's Double Quarter

1:16:23Pounder so Daiso pyramide

1:16:27I sound so fat saying that but that's

1:16:29the way I remember it so dysopiramide so

1:16:31Double Quarter quinitine

1:16:34quinitine and then pounder the most

1:16:37commonly utilized one here is

1:16:38procainamide

1:16:39so Double Quarter Pounder

1:16:42with lettuce so lidocaine is going to be

1:16:45for the type B

1:16:47so lidocaine

1:16:50Lido cane

1:16:52and the last one is and fries please

1:16:55I'll take a Double Quarter Pounder with

1:16:56lettuce and fries please so flecanide

1:17:01and propofinone

1:17:05so this is just the way that I remember

1:17:07these particular drug names is again

1:17:09type 1A type 1B type 1C or class 1A

1:17:12class 1B class 1C I remember Double

1:17:14Quarter Pounder disoperamicquinone

1:17:16brucainamide with lettuce lidocaine and

1:17:18fries please flucanamide and propofenone

1:17:21with these drugs they're all going to

1:17:24block the sodium channels but the reason

1:17:26why we subclassify them is they block

1:17:29the sodium channels to some degree a

1:17:32little bit different in response to the

1:17:34powerful kind of like uh the the sense

1:17:37of how strongly they block the sodium

1:17:39channels so in other words type 1A type

1:17:421B type 1C they can differ in the degree

1:17:45of blockage the strength of blockage of

1:17:47the sodium channels and we'll talk about

1:17:49that I'll teach you a little trick to

1:17:50remembering that

1:17:51but either way here's this atrial or

1:17:54ventricular myocyte and this is the cell

1:17:57who has who's generating this triggered

1:18:00activity he's the he's the problem child

1:18:03right so he's in the atrials in The

1:18:04ventricle and he's causing triggered

1:18:05activity or he's in The ventricle cells

1:18:08and he's causing like these re-entrant

1:18:09circuits what I want to do is I want to

1:18:12suppress I want to inhibit this cell

1:18:14from generating triggered activity or

1:18:16generating these re-entrant circuits how

1:18:17do I do that how do I actually do that

1:18:19process

1:18:20well I'm going to give these drugs to

1:18:21block particularly the sodium channel so

1:18:24here's my voltage-gated sodium channels

1:18:26these are going to allow for sodium to

1:18:28rush in to the cell now whenever sodium

1:18:30is these voltage-gated sodium channels

1:18:32are open

1:18:33they allow sodium to Rush In

1:18:36and that causes the upstroke of the

1:18:39action potential which is what phase

1:18:41phase zero so all this is Phase zero on

1:18:44the fast action potential to producing

1:18:46tissue again this is the non-pacemaker

1:18:49tissue

1:18:51so these will not work very well or

1:18:53won't work really at all and the

1:18:54pacemaker tissues because there is no

1:18:56specific voltage-gated sodium channels

1:18:58on those tissues that's important to

1:18:59remember that's why they're going to be

1:19:01more specific to the fast action

1:19:03potential producing tissue such as the

1:19:05atrial and ventricular monocytes that

1:19:06are non-pacemaker tissue but anyway I'm

1:19:09going to give these drugs and what

1:19:11they're going to do is

1:19:12they're going to block this sodium

1:19:14Channel if they block the sodium Channel

1:19:16they block the entry of sodium into the

1:19:19cell and so they decrease the positive

1:19:21charges rushing into the cell and they

1:19:23decrease the upstroke of phase zero so

1:19:26again here is my phase zero if we were

1:19:28to kind of go through this whole process

1:19:29here's phase zero here's phase one

1:19:32here's phase two here's phase three and

1:19:34then here's phase four and then phase

1:19:36four here as well

1:19:37same concept with this one phase four

1:19:39phase zero is this upstroke with the

1:19:41Sodium influx phase one is the potassium

1:19:43reflux phase two is the calcium influx

1:19:45and potassium efflux phase three is the

1:19:47primarily potassium efflux resting

1:19:50memory potential via the sodium

1:19:51potassium channels zero is going to be

1:19:53sodium influx one is the potassium

1:19:55efflux two is the plateau with the

1:19:58calcium influx and potassium reflex

1:19:59three is primarily potassium efflux and

1:20:01four is the resting membrane potential

1:20:03okay

1:20:05if I block the sodium entry into this

1:20:08cell I'm going to reduce the upstroke

1:20:10the rapid phase of the action potential

1:20:13in these triggered or re-entrant atrial

1:20:15and ventricular cells

1:20:17so now what's going to happen is I'm

1:20:19going to notice a difference in the

1:20:20slope I'm going to decrease the upstroke

1:20:22so instead of me having a very crisp

1:20:24rise in Phase zero it's going to be very

1:20:27delayed and it's going to have a slope

1:20:29that moves this way now which is going

1:20:31to take a longer time for it to be able

1:20:32to generate these Action potentials and

1:20:34that's a really helpful concept but the

1:20:37port important thing in here is knowing

1:20:39how strongly they do it because this is

1:20:41what you'll be tested on on the exam so

1:20:43here's the way I remember which one

1:20:45strongly blocks it to which one least

1:20:47strongly blocks it so the most powerful

1:20:49sodium blocker out of these class 1A

1:20:51class 1B class 1C I easily remember it

1:20:54by cap so type 1C type 1A

1:20:57type 1B or class 1A class 1 class 1C

1:21:01class 1A class 1B

1:21:03so cap so what I'm going to do is I'm

1:21:06going to show you what it will now look

1:21:07like

1:21:08this is going to be the strongest so

1:21:11this is going to have the most

1:21:14sodium blockade

1:21:17so when I look at this I'm not going to

1:21:20have this very fast upstroke I'm going

1:21:22to have a very slow

1:21:24type of upstroke here

1:21:26and here's the other thing that's

1:21:28interesting about this one

1:21:29because there's this very very kind of

1:21:31very powerful kind of upstroke here what

1:21:33happens is now I'm going to have my

1:21:35Plateau phase but I'm going to try to

1:21:36end this at the same time it shouldn't

1:21:39really have any effect on the action

1:21:41potential duration so the action

1:21:42potential duration is from the beginning

1:21:45the end of phase four beginning of phase

1:21:46zero all the way till we go back to

1:21:49phase four so this is my action

1:21:50potential duration from here

1:21:52to here I shouldn't have any effect on

1:21:55my action potential duration but what I

1:21:57will see is a very kind of decreased

1:21:59slope a rise or upstroke in Phase zero

1:22:04but by again my refractory period and my

1:22:07action potential duration should be the

1:22:09same almost no effect little to no

1:22:11effect so what I'm going to see is look

1:22:13at my phase zero it's shifted phase one

1:22:16kind of the same phase two kind of the

1:22:18same phase three kind of the same and

1:22:20then phase four again kind of the same

1:22:22here

1:22:23but what I'm going to notice is a

1:22:26decreased slope of phase zero so what

1:22:29I'll notice here as the effect of the

1:22:31sodium Channel blockade is I'm going to

1:22:33notice a

1:22:35a decrease in the slope

1:22:37of phase

1:22:40zero

1:22:41and that is the cool concept here of how

1:22:43this drug actually works so this would

1:22:45be which drugs this would be fluconide

1:22:48and propofenone so these are actually

1:22:50utilized and we'll talk about this later

1:22:51in patients with atrial fibrillation

1:22:52atrial flutter sometimes even you can

1:22:54consider SVT to be able to maintain

1:22:57normal sinus rhythm to maintain normal

1:22:59sinus rhythm in patients who have atrial

1:23:01fibrillation or atrial flutter because

1:23:03they are the most powerful sodium

1:23:04channel blockers okay

1:23:06but I have no they should have no effect

1:23:09no change this is like I can't stress

1:23:12this enough the action potential

1:23:14duration should be the same I shouldn't

1:23:17have any change in my action potential

1:23:19duration so that should be the same as

1:23:21compared to this black side with the

1:23:23blue ones no change there

1:23:25we come to the 1A a little bit different

1:23:28for these

1:23:30these have let's say this one is the

1:23:32strongest so we'll put three arrows this

1:23:35one is going to have like middle or

1:23:38moderate sodium Channel blockade so

1:23:40middle or moderate sodium Channel

1:23:43blockade so you're going to see the same

1:23:45effect here with this type of drug so

1:23:47this is going to be which ones you're

1:23:48going to see procainamide disoperamide

1:23:51and quinitine for the type 1as okay

1:23:53Double Quarter Pounder

1:23:55with this what you'll see is they're

1:23:57going to have a powerful sodium Channel

1:23:59blockade but just not as powerful so it

1:24:01won't be shifted the the

1:24:03slope won't be as intensely shifted to

1:24:06the right so we'll kind of go like right

1:24:07here so you see how this one was more

1:24:09powerful this one again it's not going

1:24:11to be as intense now what's going to be

1:24:13different here is this watch this this

1:24:15is what's interesting you're going to be

1:24:16like wait what

1:24:19what happened to my action potential

1:24:20duration

1:24:21the refractory period's longer now so

1:24:23it's got a more drawn out refractory

1:24:24period but what you'll notice here is

1:24:26that my action potential duration is

1:24:28increased

1:24:30whoa I have an increased action

1:24:33potential

1:24:34duration I had no effect on the type 1C

1:24:37but in the type 1A there is this

1:24:40shifting of the phase zero but then I

1:24:42have a prolonged kind of refractory

1:24:44period we call this the refractory

1:24:45period when potassium is kind of like

1:24:47leaving the cell in the phases once you

1:24:49kind of go into this downward phase here

1:24:51we call that the refractory period you

1:24:53have two parts of your factory period

1:24:54you're the effective refractory period

1:24:56is kind of the big way to think about it

1:24:58but once the cell kind of ends it's kind

1:25:00of depolarization starts repolarizing

1:25:02we're going into what's called a

1:25:04refractory period look what happens it's

1:25:06shifted to the right a little bit that's

1:25:08weird that means the type 1A drugs also

1:25:10have potassium Channel blockade that's

1:25:13one of the interesting things here so

1:25:15this also has a little bit of potassium

1:25:17blockade so because it blocks the

1:25:20potassium channels a little bit you get

1:25:22a longer it takes a longer time for this

1:25:25cell to repolarize

1:25:27so the action potential duration is

1:25:29increased so what I'll notice with this

1:25:31drug is that it will decrease the slope

1:25:33the upstroke of phase zero

1:25:36and I noticed that it'll actually cause

1:25:38a longer it'll actually cause a longer

1:25:41repolarization period so it'll increase

1:25:42what's called your effective refractory

1:25:44period and that will increase your

1:25:47action potential duration

1:25:49so again what is the overall effect with

1:25:51this drug it will decrease the slope

1:25:56of phase zero but also increase the

1:26:01reflective refractory period

1:26:03so that will increase the action

1:26:04potential duration this is primarily

1:26:06which drugs again

1:26:08procainamide disoperamide quinitine I

1:26:10can't stress this enough this is the

1:26:13only one out of the sodium channel

1:26:14blockers that increases the effect of

1:26:16refractor bear to increase the action

1:26:17potential duration okay so so far we

1:26:20have the most sodium Channel blockade

1:26:22the middle sodium Channel blockade with

1:26:24a little bit of potassium blockade

1:26:25that's what's really interesting about

1:26:27this drug

1:26:28because this will decrease the upstroke

1:26:29of phase zero the most this will

1:26:31decrease the upstroke of phase zero like

1:26:33in the moderate middle amount but it

1:26:35also prolong the effect of refractory

1:26:37period increase action potential

1:26:38duration type 1B so this is going to be

1:26:40lidocaine this one's weird

1:26:43it'll have the least amount of

1:26:46the least amount of so here we'll just

1:26:48put one Arrow so this had three arrows

1:26:49for type one C two errors for type one

1:26:52um a this will only have one Arrow so it

1:26:55has a little bit of sodium blockade the

1:26:57least amount out of all three of these

1:26:59subclasses

1:27:00so because of that if we were to look

1:27:02here it's really not going to have a

1:27:03very profound effect here on the of the

1:27:06upstroke so this one had a very powerful

1:27:07this one at a very powerful kind of

1:27:09delay and this one's going to have a

1:27:10little bit of a delay here all right but

1:27:12here's what's also really interesting

1:27:13look what happens to the action

1:27:14potential duration

1:27:16oh you're like man I can't remember all

1:27:19this stuff I'm supposed to remember all

1:27:20this stuff what I noticed here is that

1:27:22my phase zero

1:27:25is decreased slope not as powerful but

1:27:28there is a decrease upstroke of phase

1:27:30zero

1:27:31but what I noticed is that my refractory

1:27:33period kind of like decreases a little

1:27:34bit

1:27:35so now I notice that I shift this thing

1:27:37a little bit towards the left

1:27:39this has nothing to do with the

1:27:40potassium channels it's that you know

1:27:42usually with sodium channel blockers

1:27:43there's different phases when you can

1:27:44block them so you have different faces

1:27:46you have What's called the resting state

1:27:48so

1:27:49when you go through these channels here

1:27:51let's say that this is a it's in the

1:27:52resting membrane potential there's two

1:27:55gates usually and whenever these

1:27:57patients are in What's called the

1:27:58resting state their their voltage-gated

1:28:00sodium channels let's say resting

1:28:01membrane potential this is when it's

1:28:03active

1:28:04and this is when it's inactive

1:28:07and then usually it kind of Cycles back

1:28:09up to this point so it's kind of like a

1:28:10circle here it's a cycle right and the

1:28:12resting membrane potential you have

1:28:14what's called your inactivation Gates

1:28:15these are usually open but your

1:28:17activation gate is closed

1:28:20what happens is once this cell becomes

1:28:23stimulated it goes into this active

1:28:25configuration which is where the

1:28:26activation gate is open and the

1:28:28inactivation gate is open and this is

1:28:31really the phase where lots of sodium

1:28:32ions are flooding in

1:28:34and then you have the inactive state

1:28:36which is basically where the again the

1:28:39inactivation gate closes here but you

1:28:41still have the activation gate open so

1:28:43this is the three configurations what we

1:28:45see with the type 1B is that it might be

1:28:48able to kind of block this state the

1:28:51type 1B so the one B's can block here

1:28:53and they've also been shown to block

1:28:55here which really none of the other ones

1:28:57can do

1:28:58and so this may alter to some degree the

1:29:00plateau phase

1:29:02so it may alter the plateau phase and

1:29:04the repolarization period a little bit

1:29:05and shorten the action potential

1:29:07duration which is really interesting

1:29:10so that's one of the big things to

1:29:11remember here is that with this drug

1:29:12type 1B or the class would be the

1:29:14lidocaine it will block the sodium

1:29:16channels and if you do block the sodium

1:29:18channels very moderately you will

1:29:20decrease the slope

1:29:22of phase

1:29:25zero but it also will decrease the

1:29:28action potential

1:29:30duration

1:29:31and the way it may do that is by kind of

1:29:34keeping the sodium channels inhibited in

1:29:36both the active and inactive state

1:29:38and so look at the action potential

1:29:40duration here now the action potential

1:29:42duration

1:29:44is decreased

1:29:46and that's what's really interesting

1:29:47about this drug category so to quickly

1:29:49recap

1:29:50sodium channel blockers we're utilizing

1:29:53these this is a Class one you got the

1:29:54drugs class 1A class 1B class 1C Double

1:29:57Quarter Pounder again with lettuce and

1:29:59fries please disappear myquinidine

1:30:01procainamide lidocaine flecanide

1:30:04propofenone that's how you remember

1:30:05those what do they utilize for they're

1:30:07utilized to cardiovert or to kind of

1:30:09shift people from these abnormal rhythms

1:30:11that are generated by these abnormal

1:30:12atrial or ventricular cells into a

1:30:15normal sinus rhythm so we use this in

1:30:17afib a flutter v-tac maybe even torsos

1:30:19to points okay when we talk about these

1:30:22how do they work they block these so a

1:30:23voltage-gated sodium channels and

1:30:25decrease the slope of phase zero

1:30:28but on top of them all decreasing the

1:30:31slope of phase zero some of them do it a

1:30:33little bit more powerfully than others

1:30:34you can remember the strength of it by

1:30:36cab so when c one a one B strongest with

1:30:40one C Middle with one a the weakest with

1:30:43one b

1:30:44but then don't forget

1:30:46that with one C it has no effect on the

1:30:50actual potential duration it doesn't

1:30:51affect the plateau phase it doesn't

1:30:52affect the actual effect of refractory

1:30:54period And so because of that it only

1:30:56just strongly decrease the slope of

1:30:59phase zero with one a it has sodium

1:31:03Channel blockade so it decreased the

1:31:04slope of phase zero but it also has a

1:31:06little bit of potassium Channel blockade

1:31:08so it prolongs the refractory period of

1:31:10the repolarization period And so you may

1:31:12get an increase in action potential

1:31:14duration

1:31:14whereas lidocaine weakest sodium channel

1:31:17blocker but because it may inhibit the

1:31:19sodium channels in both the active and

1:31:21inactive state

1:31:23it may be able to not only decrease the

1:31:25upstroke of phase zero but shorten the

1:31:28action potential duration so it may

1:31:30affect the plateau phase and it may also

1:31:33to some degree affect the effect of

1:31:34refractory period

1:31:36and so because you shorten that kind of

1:31:37plateau phase a little bit you shorten

1:31:39the action potential duration and so

1:31:41that is another cool concept of these

1:31:43structs

1:31:44now that we've talked about the sodium

1:31:46channel blockers let's finish up with

1:31:48the last type of drug category here

1:31:50which is your potassium channel blockers

1:31:52your class III drugs all right my

1:31:55friends class three antarrhythmic drugs

1:31:57okay so these ones are really cool the

1:31:59potassium channel blockers one of these

1:32:01I really really like but when we talk

1:32:02about the names of these like because

1:32:04there's a lot of names right so I think

1:32:05it helped you guys remember maybe the

1:32:06sodium channel blockers with the Double

1:32:08Quarter Pounder with lettuce you know

1:32:10fries please with these ones is not the

1:32:12best mnemonic but it works it comes out

1:32:14from the first aid USMLE one but usually

1:32:17you can remember AIDS so it's terrible

1:32:19but this is amiodarone

1:32:22amiod around for the a a butylied

1:32:26for the I

1:32:29and then do fetalide and there's even

1:32:31another one called draneterone

1:32:33do fetalide

1:32:35and then s for so to law

1:32:39so this is you can remember these again

1:32:40with the mnemonic AIDS

1:32:43terrible one but it works

1:32:45so

1:32:46when we talk about these particular

1:32:49drugs what are they actually going to be

1:32:50utilized for it's the same concept we

1:32:53talked about with the Sodium channel

1:32:54blockers we're utilizing this in

1:32:56particular diseases where you have an

1:32:58atrial Focus or a ventricular Focus that

1:33:00are not a pacemaker tissue that are

1:33:02generating these triggered activity or

1:33:05re-entrant circuits and what you're

1:33:07trying to do is to shut down the

1:33:08ventricular atrial tissue from

1:33:10generating these abnormal rhythms so

1:33:12when diseases such as atrial

1:33:14fibrillation atrial flutter you're

1:33:17utilizing these two Rhythm control these

1:33:19patients are to cardiovert them in some

1:33:20particular way to either maintain normal

1:33:23sinus rhythm or switch them back to

1:33:25normal sinus rhythm that's what you're

1:33:26trying to utilize it for and the other

1:33:28one is vtac and again you're trying to

1:33:30cardiovert these patients you're trying