Antiarrhythmic drugs | Cardiovascular Pharmacology | mechanism of action
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- Опубликовано: 7 фев 2025
- Mechanisms of cardiac arrhythmia: Mechanisms of cardiac arrhythmias | Pathophysiology
• Mechanisms of cardiac ...
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4 classes of antiarrhythmic drugs
Class I drugs block sodium channels
Class II drugs are beta blockers
Class III drugs block K+ channels
and Class IV drugs are calcium channel blockers
Class I antiarrhythmic drugs: Sodium channel blocker i.e class I anti arrhythmic drugs increase the threshold for phase 0 of contractile cell action potential increases, …it also decreases the slope of phase 0.
In class I there are 3 subclasses of drugs.. see there are different states of sodium channels …closed, open and inactivated. Class Ia drugs block sodium channels in open state
Class Ib drugs block sodium channels in inactivated state… most important effect on already depolarised tissue as seen in ischemia
Class Ic drugs block sodium channels in open state and also prolong the recovery time of channels
Class II antiarrhythmic drugs: act on phase 4 of pacemaker action potential
Class III drugs i.e potassium channel blockers will act on the repolarization phase and prolong the duration of action potential
Class IV drugs i.e L type calcium channel blockers will act in phase 0 of action potential of pacemaker cells.
Tachyarrhythmias may occurdue to
1. Enhanced automaticity: In arrhythmias due to enhanced automaticity, the slope of the prepotential becomes steeper may be due to enhanced sympathetic activity or the maximum diastolic potential becomes less negative
Basically to treat these arrhythmias you will want to decrease the rate of generation of impulse either by:
a. decreasing the slope of this drift of phase 4 : beta blockers (Class II)
b. Increasing the threshold for excitation… so phase 0 will start much above than usual threshold: Class IV for pacemaker cells or class I for contractile cells
c. Prolonging action potential duration: by potassium channel blockers
d. Increasing the negativity of RMP: by acetylcholine and adenosine
2. Triggered automaticity: these arrhythmias occur due to after depolarizations which occur either due to prolonged Action potential duration i.e early after depolarization or due to increased intracellular calcium load i.e delayed after depolarization
These can be treated by:
a. not allowing EADs and DADs to develop: by isoproteronol infusion for EAD and blocking calcium entry for DADs ( by class IV drugs i.e calcium channel blockers or class II drugs )
b. If they develop, by not allowing upstroke of the action potential to happen: by sodium channel blockers
3. Reentry mechanisms
Reentry of impulse may occur when it has 2 conducting pathways but they differ electrically with one pathway slower and the other pathway having fast conduction
So what can you do to treat these arrhythmias….
1. Keep the cells refractory for longer time: for ventricular cells use class IC drugs while for conducting pathway cells use calcium channel blockers i.e. class IV drugs.
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#cardiovascularpharmacology
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This is a wonderful video! Most useful explanation of why we use what we use instead of just memorizing. Bringing this vid to the wards!
Glad it was helpful! Will be happy if you share it with others.
I simply love you as a teacher. You deserve the best in life. I discovered you yesterday and only watched your video on refractory periods, I knew right away you are the one for this job. Appreciate you, sincerely. Subscribed, of course! Thanks again dear sister. From a Palestinian ❤.
Edit: I also love the fact that you use the color YELLOW as the background. This is something important for me that I'm sure goes unappreciated and overlooked on this channel. So THANK YOU FOR THAT as well haha. Peace be with you.
Ohhh my god…thank you…and yeah I liked hello too…but too many negative feedback’s made me switch to white now
@@PhysiologyOpen Oh dang, sorry to hear that haha. Hope you are doing well, and thank you again for these wonderful videos. You have a gift for this!
Thanks
This channel is underrated! Thank you u're the best teacher
Everybody keeps on saying this...but somehow the channel remains like that. Anyways thanks for the compliment...hopefully one day !
Thank you so much Ma'am 😊 I have seen many of your videos.. They all are just wonderful .. I am an mpharm 1st year student in jamia hamdard and on this Monday I have to give a presentation on antiarrhythmics.. And this video had helped me a lot.. Thank you 😊😊😊
I am really helpful when my videos help anybody who are in real need 😊. Do share the videos with others . Help them and help me. Thank you
Mam
Please make the similar summary of anti epileptic drugs if possible
Very simple explanation of complicated topics 😃
Will surely do…thanks for the topic..will do next week
this channel is underrated
I know😅
this is such a great video..it deserves a lot more views and likes and subscription to the channel
Thank you so much 😀
Very nice explanation 👌👌. Thank you mam.
Thanks for liking
Hi Maam How will drugs dissociate if the state of channel changes ??
also in inactivated state there will be no sodium influx why do you want to block it then it will be futile?? do we do it to prolong the recovery time?? 8:15
so that it doesnt open next time
Good job it really helps thannk you
Most welcome
Nice video mam....... Thank you so much......
Most welcome 😊
Mam, lidocaine binds to inactivated na channels and it seems that it doesn't allow them to go to closed state (and hence again to open state) and don't allow next potential to generate.... But at the same time it's given that it doesn't delay channel recovery.... Then what's the effect.?
Yes but what is the use of blocking an inactive na channel do you have any answer bro
Can you help me explain why blocking sodium and calcium channels can increase the action potential threshold?
These channels open at threshold...but there is something known as probability of opening of channels...with increased no. Of channels there is a high probability of opening sufficient no. Of channels....but if some channels are blocked...lesser no. of channels will open....the entry of ions will not be able to counter exit of potassium which is continuously occurring (due to leaky channels)...hence it requires a little more potential change to increase the probability of opening of the channels which are not blocked
Did you get it? A follow up question is most welcome
@@PhysiologyOpen I was having the same doubt.. Thanku maam I got the answer... But can you please explain why the probability of opening of channels is affected by the number of channels??
@@ansarialhazamohammedarif9762 actually probability of single channel is not affected as such...however if each channel has a 25% probability of opening and there is only a single channel, it will open 25% of times..but there are 4 channels , with each stimulus, each channel has 25% probability of evening, so the probabilities in total add up. Now apply that to 100s or 1000s of channels..
@@PhysiologyOpen What i dont understand though is that the funny current of sodium entering should already more than counter exit of potassium which is why the pacemaker cell has automaticity in the first place. So surely even if fewer calcium channels open at a given potential that will still cause depolarisation of the cell, it wouldnt just be countered.
To make my point clearer, i will lay out my logic a bit.
1. prior to threshold potential there is both sodium influx through funny channels and potassium efflux through leaky channels
2. the sodium influx is greater than potassium efflux, hence the membrane potential slowly rises
3. at threshold potential some calcium channels opens (yes, probably less than if there was no blocker present)
4. the opening of any number of channels at all will increase the net influx of ions which will further raise potential which will open more channels etc
5. this positive feedback loop will result in depolarisation regardless, so the threshold potential is still the same, there is just perhaps a reduction in the slope of the phase 0 as maximum calcium channel opening will not occur.
Could you please explain where i am wrong
Thank you soo much❤
Pleasure is all mine
Mam, how class 1 b drugs helping in arrhythmia as sodium channels are inactivated they can't take in sodium channels, so why using a drug that bind to inactivated channel, and as inactivation diminish they also diminish. So why to use Ib blocker in already inactivated state, if 1b not used then also inactivated sodium channels will not allow sodium entry.
Maa'm please upload pharmacology videos 🙏🙏
will surely do ...currently busy making physiology notes
Okk maam 🙏
Mam.. Antiarythmic (class 1)drugs binds to voltage gated na channels, then how do they affect phase 4 of sa node which is due to na "leaky channels"
It’s not leaky channels. They are HCN channels.. check out the video on pacemaker potential
Mam please. Explain the. Reverse use dependence phenomena of class 3 drugs
Will try
@@PhysiologyOpen definitely ma'am
Mam please make a detailed video on reentry arrthymia ..please mam
Will try
@@PhysiologyOpen thanks mam😀
Ma'am you said sodium channel blocking drugs are going to bind to sodium channels only as long as they are in inactivated state , and as in ventricular myocytes they are inactivated for longer time than atrial ones they will bind to them more effectively . But I wonder what is the use of blocking already inactivated channels as they are already not contributing to ion conduction ??
Because as soon as the channels come to " closed " state the drug is going to dissociate anyways
Also it's written in book that because partially depolarised cells as in ischemia have more inactivated sodium channels so they will primarily target those cells but again the question is what is the use of blocking inactivated channels??? They are already inactivated or kindof useless already
It doesnt allow it to change the state. So that new action potential is not generated
@@PhysiologyOpenma'am it would be of really great help if you could respond to this particular problem I am encountering
I had adopted a concept that particular ion channels are either inactivated or " closed " or open at a particular value of transmembrane potential because of their inherent physicochemical nature . I mean to say that there is a sodium channel named A that is inactivated at -55 mv and needs to come to a potential more negative than -55 mv( say -67 mv ) to reach closed state , so if in ischemic tissue the membrane potential gets depolarised to -55 mv it will never reach closed state .Because there will be many sodium ion channels that will need to return to more negative values of transmembrane potential for reaching closed state , many channels will be inactivated in this partially depolarised cell .
But now it seems like actually all channels are continuously changing their states , like in above example the channel A can also be inactivated at at a potential of -67 mv sometime or it may be closed at -55 mv too (or even -20mv ) at other time . So What actually decreases the number of ion channels at partially depolarised potential is something like rate constant of transition which is dependent on transmembrane potential . Meaning at membrane potential -90 mv , the rate of transition of sodium channels from closed to inactivated state and vice versa will be equal when large number of channels are in closed state and only few are in inactivated state . Meaning ;at a membrane potential of -90 mv , 140 channels are closed and 5 are inactivated not because 5 channels have physicochemical property of being closed at -90 mv and other 140 channels have property of remaining in closed state . But this is because at -90 mv the rate constant of transition of channels from one state to the other is such that the rate of transition from inactivated to closed and vice versa becomes equal when there are 140 channels in inactivated and 5 channels in activated state .This is the state of dynamic equilibrium and it happens because initially a total of 145 sodium channels in the membrane will transition at faster rate to closed state but at much slower rate to inactivated state .As a result number of channels in closed state will keep increasing and number of channels in inactivated sttate will keep decreasing . When number of channels in closed state increases , the total rate of transition to inactivated state will progressively increase. Similarly as the number of channels in inactivated state decreases rate of their transition to closed state will decrease progressively until they reach a dynamic equilibrium.
This probably accounts for the greater magnitude of effect of sodium blockers in partially depolarised cells compared with the cells with normal rmp.
I want you to read this and comment on my recent concept , pls do correct if I am wrong because I have been focusing on this thing only for almost one day now and am not able to focus on other topics for my coming exam
@@abhinashsharma3456 hmmm...quite a question
I will try to tell in simple term
It’s not essential that a particular membrane potential channel will definitely be in closed state or inactivated state...it’s explained in terms of probability (what you call rate of transition) . As membrane becomes more and more repolrized, more probability that channels will move to closed state...and hence will be ready to open again...but if it is in depolarised state...the probability of moving to closed state is very less...
Also , I think channels don’t move back to inactivated state directly from closed state...closed channels open which become inactivated..again as repolarization occurs, channels move from inactivated to closed state ( with the concept of probability)
Mam for EAD to decre ase ap duration we must use k channel openers mam then why your saying k blocker mam also cant accept why 1b blocking inactive N channel is helpfull as already ap is spreaded then what is the use in blocking an blocked channel it is ideal to block open na channel but in every other source saying same without good explanition do you have one
Blocking Kchannel means...it can’t relolarize, for next action potential repolarization should occur
Again blocking inactive sodium channels means , they can’t go to open state again..
@@PhysiologyOpen mam cant accept mam if blocking action potential is our aim mean then we could give na blockers in EAD this will to prevent action potential popagation mam see mam in EAD longer ap duration is culprit as it correspond to QT interval(torsa) so long ap ling qt as refractory increased so our aim to reduce ap duration which is done by increasing heaet rate... totally confusing these topics 🤦🤦🚶🚶🚶🚶
@@PhysiologyOpen also 1b are specifically use in ca loaded cell seen in MI cell,digoxin toxicity where na channels are trapped at inactive gate due to ca loading in celll and membrane accomodatiion so 1b are effective here do this make sence to you mam
Can you please also watch video on nechanisms of cardiac arrhythmia and then link this video with that.
How do class 1b drugs act?
As when they bind to inactivated state already the Na+ has entered the cell so what is the effect when they bind to inactivated channels
For sodium channels to open again, the state of channels should change from inactivated to closed state..which these drugs delay and thus delay the generation of next action potential
Check out this video for states of sodium channel : m.ruclips.net/video/1uDgpkEHeoI/видео.html
Thanks a lot!
I ist had this doubt as why these drugs of class 1b has no effect on refractory period of the channels?
As they make the channel stay in inactivated state don't they increase there refractory period?
They don’t increase the duration of action potential since that will be affected by slow opening of sodium channels, or decrease in the rate of repolarization. So they don’t effect refractory period. Instead, they increase the duration between two action potentials and hence decreasing the rate
@@PhysiologyOpen but how come apd and erp decreases ?
Mam pls try to answer my questions..it will be your most kindness
I think I answered right!!
You are a goddess! ❤️
Oh lord ! Thank you 🙏😊❤️
Too fast go slow
Okk. Thanks for feedback. Will correct in future videos. You can listen at little less speed