Torsades

[aspiringmd1015]

When you speed up the AV conduction (anti muscuranic blockade), this will cause the Ventricles to depolarize sooner. (conduction reaches ventricles faster, so ventricles depolarized earlier)

So on the EKG, the QRS starts sooner. Also, the cell will be maintained in this depolarized state for longer, so that means the T wave will occur much later than normal. So, my question is, with the increase in conduction velocity, i undersatnd that the qrs complexes will occur earlier as the ventricles are being depolarized sooner, but why are they depolarized LONGER? which then leads to the t wave occuring later?

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[seminoma]

When you speed up the AV conduction (anti muscuranic blockade), this will cause the Ventricles to depolarize sooner. (conduction reaches ventricles faster, so ventricles depolarized earlier)

So on the EKG, the QRS starts sooner. Also, the cell will be maintained in this depolarized state for longer, so that means the T wave will occur much later than normal. So, my question is, with the increase in conduction velocity, i undersatnd that the qrs complexes will occur earlier as the ventricles are being depolarized sooner, but why are they depolarized LONGER? which then leads to the t wave occuring later?

I'm thinking by "anti muscarinic blockade" you mean "anti-muscarinic" or "muscarinic blockade" and my explanation is based off that assumption. I'm also assuming you are talking about Class 1A antiarrhythmics in particular. Class 1A also block potassium channels --> prolong the AP --> more opportunity for early after depolarizations --> torsades.

 

[aspiringmd1015]

those cause torsade, understandable, bc k efflux is delayed so thus repolarization is delayed. Fair enough, but what about other pure antimuscuranic effects of different drugs causing torsade? they dont have K channel blockade effect. My thinking would be by blocking m2 on the heart, k efflux couldnt occur, and thus torsades?

 

[Jabbed]

Can you give an example of a specific drug? afaik the LQTS associated with 'anti-muscarinic' drugs is not due to the anti-muscarinic effect per se.

 

[aspiringmd1015]

TCA's

 

[Jabbed]

TCA's

The long QT isn't due to the anticholinergic effect, TCAs directly inhibit the fast Na channels in the His purkinje system and myocardium.

 

[seminoma]

those cause torsade, understandable, bc k efflux is delayed so thus repolarization is delayed. Fair enough, but what about other pure antimuscuranic effects of different drugs causing torsade? they dont have K channel blockade effect. My thinking would be by blocking m2 on the heart, k efflux couldnt occur, and thus torsades?

TCA's

TCAs aren't pure antimuscarinic. I don't know the mechanism, but I doubt antimuscarinic is it. If antimuscarinic alone could cause torsades, then atropine would definitely be associated with torsades, but it isn't.

 

[aspiringmd1015]

atropine cant cause torsades? i believe all anticholingerics(leads to unopposed sympathetic response) can cause torsades no?

 

[aspiringmd1015]

so the prolonged QT in quindine is only due to the potassium blockade effect? not bc of the anti-muscuranic effect to increase heart rate and av conduction?

 

[aspiringmd1015]

I understand anything which prevents K efflux will prolong the APD and thus QT interval promoting torsades, but not 100% on the antimuscuranic effect if there is one

 

[aspiringmd1015]

anyone?

 

[dfib slim]

atropine cant cause torsades? i believe all anticholingerics(leads to unopposed sympathetic response) can cause torsades no?

so the prolonged QT in quindine is only due to the potassium blockade effect? not bc of the anti-muscuranic effect to increase heart rate and av conduction?

The long QT effect from quinidine is from potassium channel blockade.
I haven't heard of anti-muscarinics causing long QT but it's discussed here.
http://www.usmleforum.com/files/forum/2014/1/791253.php
What I'm unsure of is why they say in increased in heart rate will lead to torsades. Bradycardia can cause QT prolongation and you would decrease the risk for torsades by giving atropine. http://www.ncbi.nlm.nih.gov/pubmed/9505930.

Also there is this one saying atropine caused QT prolongation.
http://www.ncbi.nlm.nih.gov/pubmed/8251290

 

[aspiringmd1015]

from my understanding, antimuscruanics like atropine, via inhibitting Gi M2 receptors lead to increased cyclic amp levels inside the cells, which activates Protein Kinase A, which then phosphorylates calcium, sodium, and potassium channels, allowing efflux of sodium, and calcium causing their efflux to allow depolarization, yet phosphroylating the potassium channel effectively blocks the K channel, allowing potassium to be retained inside, contributing to futher depolarization, and delayed repolarization leading to a prolonged QT. I thought the antimuscuranic effect of TCAs also led to torsades because of this, but then again this could be wrong.

 

[Instatewaiter]

The long QT effect from quinidine is from potassium channel blockade.
I haven't heard of anti-muscarinics causing long QT but it's discussed here.
http://www.usmleforum.com/files/forum/2014/1/791253.php
What I'm unsure of is why they say in increased in heart rate will lead to torsades. Bradycardia can cause QT prolongation and you would decrease the risk for torsades by giving atropine. http://www.ncbi.nlm.nih.gov/pubmed/9505930.

Also there is this one saying atropine caused QT prolongation.
http://www.ncbi.nlm.nih.gov/pubmed/8251290

With all of these meds that cause Torsade, you have QT prolongation. The etiology of torsade is usually an R on T from a PVC landing onto of the T (You are more likely to have a PVC landing on the T when there is QT prolongation).

Bradycardias predispose you to Torsade when you have a long QT which is why overdrive pacing or isoproterenol are some of the treatments of choice. Slowing down the HR in someone with a long QT is a recipe for disaster. However, atropine is so short acting that it is unlikely to change your rate of torsade.

 

[aspiringmd1015]

atropine is short acting? isnt its effect long lasting? ie mydraisis in the eye lasting for 24 hours

 

[seminoma]

atropine is short acting? isnt its effect long lasting? ie mydraisis in the eye lasting for 24 hours

Different doses, different administration, different exposure to systemic circulation and metabolism.

 

[Instatewaiter]

atropine is short acting? isnt its effect long lasting? ie mydraisis in the eye lasting for 24 hours

Roughly 6 seconds