why do Class Ia/b/c anti arrythmics affect APD differently?

[tarsuc]

Class IA increases, Class IB decreases and Class IC creates no change in Action potential duration.

All of these block Na channel, though at different states, i understand; but how can this be correlated to the change in Action potential duration.

Anti arrythmics are so confusing.

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[image187]

Class IA increases, Class IB decreases and Class IC creates no change in Action potential duration.

All of these block Na channel, though at different states, i understand; but how can this be correlated to the change in Action potential duration.

Anti arrythmics are so confusing.

true that, you're better off just reading this Wikipedia page, section "antiarrythmics" http://en.wikipedia.org/wiki/Sodium_channel_blocker lol

I don't even think cardiology fellows know how antiarrythmics work

 

[Phloston]

The class-I drugs, in addition to inhibiting Na+ channels directly, also directly carry varied effects on the potassium channels.

Class-Ia's merely slow K+ efflux (increase QT). Ib's hasten efflux (decrease QT). Ic's don't affect K+ efflux (QT constant).

The point is, they all inhibit Na+ channels, so you know they also have direct effects on the K+ channels. The MOA of class-I drugs is held constant, so you know the K+ effects can't be indirect, because if they were, they'd all be the same.

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This is where I had originally learned this from:

http://www.pharmacorama.com/en/Sections/Sodium-6.php

 

[tarsuc]

damn. awesome. thanks.

 

[Charles_Carmichael]

To add on to what's already been discussed, in Kaplan pharm, they also mention that during phase 0, 1, 2, and 3, there is an additional inward Na+ current (via slow channels, NOT the fast ones) called the "window current." This current helps in establishing the action potential duration (APD) and messing with it can affect APD.

So, the way I think about it, class Ia drugs block the fast Na+ channel and K+ channels, so you have slower repolarization and thus, an increased APD. Class Ib drugs block the fast Na+ channels and the slow Na+ window current -- since you're taking away an inward current that helps maintain the normal APD, you now end up with a decreased APD. Class Ic drugs block only the fast Na+ channels and don't mess with the slow Na+ window current or the K+ channels -- so they don't change APD.

It's pretty similar to what Pholston wrote. I just never knew that class Ib drugs sped up repolarization -- I thought it was simply due to the inhibition of the window current.

 

[Phloston]

To add on to what's already been discussed, in Kaplan pharm, they also mention that during phase 0, 1, 2, and 3, there is an additional inward Na+ current (via slow channels, NOT the fast ones) called the "window current." This current helps in establishing the action potential duration (APD) and messing with it can affect APD.

So, the way I think about it, class Ia drugs block the fast Na+ channel and K+ channels, so you have slower repolarization and thus, an increased APD. Class Ib drugs block the fast Na+ channels and the slow Na+ window current -- since you're taking away an inward current that helps maintain the normal APD, you now end up with a decreased APD. Class Ic drugs block only the fast Na+ channels and don't mess with the slow Na+ window current or the K+ channels -- so they don't change APD.

It's pretty similar to what Pholston wrote. I just never knew that class Ib drugs sped up repolarization -- I thought it was simply due to the inhibition of the window current.

In terms of your second paragraph, I just don't see how Na+ influx via slow channels would have anything to do with AP duration. AP duration (as far as I'm aware) is dictated by QT-interval (K+ channels).

 

[Charles_Carmichael]

In terms of your second paragraph, I just don't see how Na+ influx via slow channels would have anything to do with AP duration. AP duration (as far as I'm aware) is dictated by QT-interval (K+ channels).

Well, the QT-interval includes both ventricular depolarization and repolarization, right? So I'm not sure why only K+ channel activity would influence its length. Messing with any of the major ionic fluxes during this period should influence the length of the QT-interval.

Here's my line of thinking:

Inward Ca2+ current + slow inward window current = K+ efflux in a normal plateau phase. The balance between these currents helps maintain that plateau.

With class Ib drugs, you're taking away the slow inward window current. So now, you have: inward Ca2+ current < K+ efflux. Thus, you have a shortened APD.

FWIW, regarding class Ib drugs, Lilly's section on antiarrhythmics states the following:

"Class IB drugs inhibit the fast sodium channel, but unlike IA agents, they typically shorten the action potential duration and the refractory period. Such shortening is attributed to blockade of small sodium currents that normally continue through phase 2 of the action potential."

Presumably, it's referring to the slow inward Na+ current that I learned about from Kaplan pharm.

 

[Phloston]

"Class IB drugs inhibit the fast sodium channel, but unlike IA agents, they typically shorten the action potential duration and the refractory period. Such shortening is attributed to blockade of small sodium currents that normally continue through phase 2 of the action potential."

Presumably, it's referring to the slow inward Na+ current that I learned about from Kaplan pharm.

Thanks so much for posting that. That helps a lot.

 

[tarsuc]

Thanks a lot kaushik

 

[donkeykong1]

The way I was taught in lecture:

Class 1a (moderate na channel blochade): slows phase 0 depolarization+increases ERP (class III effect)=increase in APD

Class 1b (weak na channel blockade): slows phase 3 repolarization+decreased in ERP since there drugs increase the efflux of K+=decrease in APD

Class 1c (strong na channel blockade): slows phase 0 depolarization+minimal effect on ERP=minimal effect on APD

hopefully this makes it bit simpler to understand

 

[goal270]

The class-I drugs, in addition to inhibiting Na+ channels directly, also directly carry varied effects on the potassium channels.

Class-Ia's merely slow K+ efflux (increase QT). Ib's hasten efflux (decrease QT). Ic's don't affect K+ efflux (QT constant).

The point is, they all inhibit Na+ channels, so you know they also have direct effects on the K+ channels. The MOA of class-I drugs is held constant, so you know the K+ effects can't be indirect, because if they were, they'd all be the same.

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This is where I had originally learned this from:

Class I antiarrhythmics - Pharmacorama

You are THE man! I am learning so much because of you. Thank you!!

 

[navigator]

To piggyback off this thread, from my understanding, whenever there is prolonged QT interval (bc of blocked K+ current, extending Phases 1, 2, and 3), there's also extended ERP and AP duration.

Thus, for 1A, there's longer QT interval bc of the K+ channel block and for 1B there's shorter QT interval bc of the enhanced K+ channel activity. QT interval is normal for 1C bc there's no effect on K+ channels.

However, FA says that 1C drugs have significantly prolonged ERP in AV node and bypass tracts. I'm so confused about this. Shouldn't ERP only be prolonged if there's a prolonged QT interval?