Physiological basis of action of antiaarhythmic drugs

There are 4 classes of antiarrhythmic drugs depending on which channels or receptors they block.

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

 We should know first where on the cardiac action potentials, different classes of antiarrhthymic drugs will act…

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..
   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 occur either due to
Enhanced automaticty
Triggered automaticity
Reentry

Physiological basis of treatment of arrhythmias

 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

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 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.