Awesome lecture as usual. Quinidine is also a first line pharmacoogic agent for patients with Brugada syndrome. Incidence of Brudaga syndrome is believed to be around 1:2000, but the incidence of patients with inducible/non-monogenic/type 2/3 ECG forms may be higher, like 1:500. One of the issues in Brugada is shortened ERP, which quinidine helps prolong by blocking inward K. Studies have shown Quinidine reduces inducibility in such patients. There is a great JACC EP review article on this, came out March 2022. Thought I would share.
Question for you, regarding 1B: According to the graphic 70771 on UpToDate article discussing antiarrhythimics, it shows that 1. Sodium channels in the open state, during phase 0, have the highest current, but 2. Sodium channels in the inactivated state (essentially open, but clogged) have sodium current that is about 5% of the open state. 3. In the "closed" state, sodium channels have no conductance (late phase 3 and all of phase 4) 4. 1B antiarrhythmics bind in the inactivated (clogged but not closed) state, and block this "5-ish %" current. And then dissociate when the channel closes. Doesn't it's mechanism of action, alone, combined with physiology, explain why AP duration is shortened? Essentially, you get less inward sodium current during phase 1 and phase 2. I realize that there is some alternative splicing on the SCN5A gene to give multiple sub-types of sodium channels, but the sodium current and drug activity reflects the average of all Subtypes. In short, how is that not the reason for the shortened action potential? It's implied by the drug MOA and cellular physiology.
doi.org/10.1016/j.tcm.2015.05.006 I tried to find a way to link the figure that I referenced, above, but couldn't. This link is a good overview of what I was referring to, however.
Hmmm...Mike, your questions always make me think! I think you are probably right, though I haven't been able to find a reference that outlines it quite that clearly. Another search turned up this paper: www.ncbi.nlm.nih.gov/pubmed/2412723. It's old (1985) and dense, but the relevant highlight is as follows: "Lidocaine reduces the rapidly inactivating component of INa (cf. Bean et al., 1983) and the steady state IN, 'window* current (Colatsky, 1982) which is observed during the plateau of the action potential. The reduction of INa decreases sodium influx directly, and is responsible for the shortening of the action potential duration that we and others have observed. Although the INa seen during the plateau is small, compared to INa at its peak, the duration of the plateau is very much longer. Thus, significant sodium influx can occur during the plateau of the action potential. Eisner et al. (1983a) have concluded that, at least over plateau potentials, lidocaine's principal action is to block INa and does not markedly alter other membrane currents (but see also Colatsky, 1982). This finding of Eisner et al. (1983a) is based on a comparison of the magnitude of the rapid change in current produced by the addition of lidocaine to the change in a'N, seen at the same time. Sodium influx is therefore reduced, because lidocaine blocks some sodium channels and also because the shorter action potential decreases the time available for sodium influx through the sodium channels that are unblocked and have not inactivated." This seems to agree with your excellent thoughts. Thanks for pointing this out!
Strong Medicine I actually have to say "thank you" If you didn't mention it, in this video, I wouldn't have been intrigued to question the lessons from my Pharmacology courses; which were completely wrong. - the prior explanation didn't make sense to me, but I crammed it in view of upcoming testing. - But there's something about the feeling of an explanation that is wrong. I just don't like the way it feels. Anyhow, id rather have a "we don't know, yet." Than "yep, this is definitely the answer" when it isn't. Love your channel. Can't wait for the next series. Boards and Beyond has a lecture (from a cardiologist) on RUclips concerning antiarrhythmics. And so far, your lecture are so complementary. There are things about your presentation I wish Dr. Jason Ryan would adopt, but there is one thing about his lecture: - he has a semi-extensive section where he shows the action potential sitting directly above the ECG QRS wave, and he explains their relationship. - he also has a great way of visually explaining use dependence. All in all, you've given far more information, though. - and I admit, I get distracted on online forums like this. So I apologize; and I thank you so much for your reply. I'm raised in a lower station in life and consider MD (and PhD) something to revere. So I am always grateful when I get replies from anyone.
Strong Medicine Btw; I love your seemingly effortless ability to find the perfect study to answer a question. It usually takes me weeks, and then I go to the librarian. You should do a video on "literature search" or something to that effect: - how to answer quid pro quos - how to use clinical reasoning in search of dx - how to find answers for patients - and the list could go on. Our librarian did a lecture like this and it was largely a huge fail.
Why does the repolarization curve for Class 1C match with the repolarization curve before antiarrhythmic drug (i.e. control AP)? We know the Y axis represents time here and In all cases and also for class 1C the depolarization curve reaches peak a little later . And If plateau phase starts from that point , shouldnt we have a different repolarization curve for class 1C??
The only thing that I am struggling with is finding a connection between their mechanism of action and their therapeutic indications. Are there any sources that discuss this?
Not that I know of (and I had asked an electrophysiologist at the time I made this series if she knew of one...). Some of these mechanism-indication connections are relatively straight-forward. For example, beta blockers and calcium channel blockers for the acute treatment of reentrant rhythms dependent on the AV node. But with some of the class I and class III drugs, their indications are not always predictable from first principles, and I feel like some of it has just been empiric.
I hope somebody can answer me this....decreasing the action potential (class 1 B Drugs) how is this beneficial in arrhythmia? Wouldn't you want to PROLONG the action potential because the AV node is firing TOO fast?
Thank you for all of your outstanding videos! Quick question; when it comes to Class I antiarrhythmics are the only real indications as backups to amiodarone in the termination of tachyarrhythmias? I'm a pre-clinical medical student, and I understand the drug mechanisms from your videos and other reading, but the only real clinical use I can think of for these drugs is maybe propafenone in terminating superventricular arryhtmias in those without Hx of ischemic heart disease.
![Class I Anti-Arrhythmic Drugs (Subclasses A, B, and C) - The Sodium Channel Blockers [Explained]](http://i.ytimg.com/vi/j5eu1uBxSMk/mqdefault.jpg)
Awesome lecture as usual. Quinidine is also a first line pharmacoogic agent for patients with Brugada syndrome. Incidence of Brudaga syndrome is believed to be around 1:2000, but the incidence of patients with inducible/non-monogenic/type 2/3 ECG forms may be higher, like 1:500. One of the issues in Brugada is shortened ERP, which quinidine helps prolong by blocking inward K. Studies have shown Quinidine reduces inducibility in such patients. There is a great JACC EP review article on this, came out March 2022. Thought I would share.
this flute intro got me feeling stupendous
This video is so Power full concise and to the point that I can't explain it with words .good job sir well done,god bless you sir
Question for you, regarding 1B:
According to the graphic 70771 on UpToDate article discussing antiarrhythimics, it shows that
1. Sodium channels in the open state, during phase 0, have the highest current, but
2. Sodium channels in the inactivated state (essentially open, but clogged) have sodium current that is about 5% of the open state.
3. In the "closed" state, sodium channels have no conductance (late phase 3 and all of phase 4)
4. 1B antiarrhythmics bind in the inactivated (clogged but not closed) state, and block this "5-ish %" current. And then dissociate when the channel closes.
Doesn't it's mechanism of action, alone, combined with physiology, explain why AP duration is shortened?
Essentially, you get less inward sodium current during phase 1 and phase 2.
I realize that there is some alternative splicing on the SCN5A gene to give multiple sub-types of sodium channels, but the sodium current and drug activity reflects the average of all Subtypes.
In short, how is that not the reason for the shortened action potential? It's implied by the drug MOA and cellular physiology.
doi.org/10.1016/j.tcm.2015.05.006
I tried to find a way to link the figure that I referenced, above, but couldn't. This link is a good overview of what I was referring to, however.
Hmmm...Mike, your questions always make me think! I think you are probably right, though I haven't been able to find a reference that outlines it quite that clearly. Another search turned up this paper: www.ncbi.nlm.nih.gov/pubmed/2412723. It's old (1985) and dense, but the relevant highlight is as follows:
"Lidocaine reduces the rapidly inactivating component of INa (cf. Bean et al., 1983) and the steady state IN, 'window* current (Colatsky, 1982) which is observed during the plateau of the action potential. The reduction of INa decreases sodium influx directly, and is responsible for the shortening of the action potential duration that we and others have observed. Although the INa seen during the plateau is small, compared to INa at its peak, the duration of the plateau is very much longer. Thus, significant sodium influx can occur during the plateau of the action potential. Eisner et al. (1983a) have concluded that, at least over plateau potentials, lidocaine's principal action is to block INa and does not markedly alter other membrane currents (but see also Colatsky, 1982). This finding of Eisner et al. (1983a) is based on a comparison of the magnitude of the rapid change in current produced by the addition of lidocaine to the change in a'N, seen at the same time. Sodium influx is therefore reduced, because lidocaine blocks some sodium channels and also because the shorter action potential decreases the time available for sodium influx through the sodium channels that are unblocked and have not inactivated."
This seems to agree with your excellent thoughts. Thanks for pointing this out!
Strong Medicine
I actually have to say "thank you"
If you didn't mention it, in this video, I wouldn't have been intrigued to question the lessons from my Pharmacology courses; which were completely wrong.
- the prior explanation didn't make sense to me, but I crammed it in view of upcoming testing.
- But there's something about the feeling of an explanation that is wrong. I just don't like the way it feels.
Anyhow, id rather have a "we don't know, yet." Than "yep, this is definitely the answer" when it isn't.
Love your channel. Can't wait for the next series.
Boards and Beyond has a lecture (from a cardiologist) on RUclips concerning antiarrhythmics. And so far, your lecture are so complementary. There are things about your presentation I wish Dr. Jason Ryan would adopt, but there is one thing about his lecture:
- he has a semi-extensive section where he shows the action potential sitting directly above the ECG QRS wave, and he explains their relationship.
- he also has a great way of visually explaining use dependence.
All in all, you've given far more information, though.
- and I admit, I get distracted on online forums like this. So I apologize; and I thank you so much for your reply. I'm raised in a lower station in life and consider MD (and PhD) something to revere. So I am always grateful when I get replies from anyone.
Strong Medicine
Btw; I love your seemingly effortless ability to find the perfect study to answer a question. It usually takes me weeks, and then I go to the librarian. You should do a video on "literature search" or something to that effect:
- how to answer quid pro quos
- how to use clinical reasoning in search of dx
- how to find answers for patients
- and the list could go on. Our librarian did a lecture like this and it was largely a huge fail.
Thank you Dr Strong. This is my second listening. I seem to get .
Why does the repolarization curve for Class 1C match with the repolarization curve before antiarrhythmic drug (i.e. control AP)? We know the Y axis represents time here and In all cases and also for class 1C the depolarization curve reaches peak a little later . And If plateau phase starts from that point , shouldnt we have a different repolarization curve for class 1C??
Videos are life savers for med students.
Yes ritika
thanks for the clear explanation! i learn a lot from this video
The only thing that I am struggling with is finding a connection between their mechanism of action and their therapeutic indications. Are there any sources that discuss this?
Not that I know of (and I had asked an electrophysiologist at the time I made this series if she knew of one...). Some of these mechanism-indication connections are relatively straight-forward. For example, beta blockers and calcium channel blockers for the acute treatment of reentrant rhythms dependent on the AV node. But with some of the class I and class III drugs, their indications are not always predictable from first principles, and I feel like some of it has just been empiric.
@@StrongMed Thank you a lot for your reply doctor!
Excellent lecture! One question though: Don't they all prolong the ERP by slowing the recovery of sodium channels from inactivation?
I hope somebody can answer me this....decreasing the action potential (class 1 B Drugs) how is this beneficial in arrhythmia? Wouldn't you want to PROLONG the action potential because the AV node is firing TOO fast?
Great video! Now its so easy to learn.
Pitoleczek تتتتت
Thank you sr😊
Thank you for the videos. Would love access to a powerpoint of your finished tables in this series to have for reference.
invaluable video
Sooo simple, thank you
Thank you for all of your outstanding videos! Quick question; when it comes to Class I antiarrhythmics are the only real indications as backups to amiodarone in the termination of tachyarrhythmias? I'm a pre-clinical medical student, and I understand the drug mechanisms from your videos and other reading, but the only real clinical use I can think of for these drugs is maybe propafenone in terminating superventricular arryhtmias in those without Hx of ischemic heart disease.
Well very nice.god bless you dr.
Thanks a lot Doctor
I like your background 🎵
Thank you so much for the lecture. Excellent presentation! I would like to print out a copy of your slides. Is it possible?
Thank u. Can you give us the PowerPoint material plz
Good one
thank you very much sir for such an amazing job of making video lectures👌👌👌
thanks!