Step I class 1B antiarrhythmics

[Dr.serotonin]

how dose class 1B drugs decrease action potential duration ? isn't it proarrhythmic to do so ?

 

[zhopv10]

You are correct that they are potentially proarrhythmic but all of the antiarrythmic have potential proarrhythmic side effects. In the case of class 1B's I think we first should keep in mind the indication as it helps drive understanding of why we would want AP shortening: they are used post MI, in digoxin toxicity, and open heart surgery. So why? In all of these states there is a decrease in ATP (except digoxin it directly inhibits the sodium potassium atpase). Low ATP prevents the sodium potassium pump from working, sodium builds up, leads to a state of relative refractoriness if you will because the fast sodium channels need the membrane potential to be quite low to become ready to fire again (remember they are deactivated when depolarizers). So, this creates an area where conduction is slowed, which could lead to arrhythmias. So then the 1B's could potentially help this out.

Mech: 2 parts to the mech 1. these drugs block inactivated sodium channels increasing the threshold for excitation (not what we are looking for yet pharmacologically). 2. These drugs block the late window sodium channels that are still allowing sodium to come in during the plateau phase therefore decreasing the depolarizing effect that is Working with calcium intake to balance the potassium outflow that is polarizing the cell. Thus, the balance becomes more in favor of potassium and the cell polarized more quickly.

Now remember they this drug is working on the cardiac muscle tissue not the SA or AV node as the channels are different.

Now what's interesting is in normal tissue the first mechanism seems to be more important because the CV side effects of lidocaine that has gone systemic are more bradycardia, hypotension etc. not sure why this is, but w/e I think the mechanism and how it would look on a tracing (decreases plateau phase) is more important.


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[worldbeater]

It's a sodium channel blocker that acts on the ventricle (which uses sodium to depolarize). In terms of strength, it's "CAB" from right to left on the x-axis, B is the weakest, meaning it holds for the shortest time. Tocainide, Phenytoin (gingival hyperplasia), Lidocaine (attracted to ischemic tissue), Mexintide (I am butchering spellings here - upset stomach) are the associated drugs and side effects. The questions aren't going to go any deeper than that.

 

[Dr.serotonin]

these are such nice explanations. thanks for the inputs

 

[Oh_Gee]

You are correct that they are potentially proarrhythmic but all of the antiarrythmic have potential proarrhythmic side effects. In the case of class 1B's I think we first should keep in mind the indication as it helps drive understanding of why we would want AP shortening: they are used post MI, in digoxin toxicity, and open heart surgery. So why? In all of these states there is a decrease in ATP (except digoxin it directly inhibits the sodium potassium atpase). Low ATP prevents the sodium potassium pump from working, sodium builds up, leads to a state of relative refractoriness if you will because the fast sodium channels need the membrane potential to be quite low to become ready to fire again (remember they are deactivated when depolarizers). So, this creates an area where conduction is slowed, which could lead to arrhythmias. So then the 1B's could potentially help this out.

Mech: 2 parts to the mech 1. these drugs block inactivated sodium channels increasing the threshold for excitation (not what we are looking for yet pharmacologically). 2. These drugs block the late window sodium channels that are still allowing sodium to come in during the plateau phase therefore decreasing the depolarizing effect that is Working with calcium intake to balance the potassium outflow that is polarizing the cell. Thus, the balance becomes more in favor of potassium and the cell polarized more quickly.

Now remember they this drug is working on the cardiac muscle tissue not the SA or AV node as the channels are different.

Now what's interesting is in normal tissue the first mechanism seems to be more important because the CV side effects of lidocaine that has gone systemic are more bradycardia, hypotension etc. not sure why this is, but w/e I think the mechanism and how it would look on a tracing (decreases plateau phase) is more important.


Sent from my iPhone using SDN mobile app

in sketchy, they say that class IB shortens phase 2 and 3 and the effective refractory period, but if IB is blocking the inactivated Na+ channels from becoming resting Na+ channels, doesn't that mean IB lengthens effective refractory period (ERP)?

"Of major importance is the effect of all Class I drugs (1a, 1b & 1c) to increase the ERP of cardiac tissue in depolarized & ischemic tissue" (intro_to_antiarrhythmics [TUSOM | Pharmwiki])

so is ERP lengthened in ischemic/depolarized tissue, but ERP is shortened in normal functioning tissue?