Anti-Arrythmic Drugs Flashcards
what are the 3 goals of anti-arrhythmic therapy?
- decrease automaticity of pacemaker or non-pacemaker cells
- disrupt reentrant pathways
- eliminate triggered activity
why are action potentials slower in the SA and AV node as compared to other regions of the heart?
phase 0 is driven by calcium channels, rather than sodium channels
what is the action of Class 1 vs 2 vs 3 vs 4 antiarrhythmic drugs?
Class 1: sodium channel blockade
- 1A: prolong AP
- 1B: shorten AP, dissociate rapidly
- 1C: minimal AP effects, dissociate slowly
Class 2: sympatholytics (beta blockers)
Class 3: prolong AP by blocking Phase 2 K+ current
Class 4: calcium channel blockade
Drug X is found to block phase 2 potassium current in cardiomyocytes, prolonging the duration of action potential. What class of antiarrhythmic drugs would this fit into?
Class 3: block K+ current in phase 2, prolonging AP
A new drug is developed to treat arrhythmia that works by blocking Na+ channels with minimal effect on the duration of the action potential. Which class of antiarrhythmics does this fit into?
this drug fits in Class 1C - block sodium channels with minimal effect on AP
Class 1: sodium channel blockade
- 1A: prolong AP
- 1B: shorten AP, dissociate quickly
- 1C: minimal AP effects, dissociate slowly
Into which class of antiarrhythmics do verapamil and diltiazem fit?
these are calcium channel blockers
Class 4 antiarrhythmic drugs block calcium current
what is the mechanism of action of Class 1A antiarrhythmic drugs?
Class 1A (Procainamide): bind Na+ and K+ channels with intermediate kinetics and moderate affinity —> slow upstroke of AP to prolong AP duration
prolonged refractory period —> reentrant loop is closed because retrograde pathway has been made unavailable —> termination of arrhythmia
what kind of drug is Procainamide and how does it work?
Class 1A antiarrhythmic: bind Na+ and K+ channels with intermediate kinetics and moderate affinity —> slow upstroke of AP to prolong AP duration
prolonged refractory period —> reentrant loop is closed because retrograde pathway has been made unavailable —> termination of arrhythmia
what toxicities are associated with Procainamide? (1 class associated, 1 specific)
Procainamide: Class 1A antiarrhythmic - blocks sodium channel to prolong AP and refractory period (to block reentrant loop)
however, prolongation of AP increases risk of torsade de pointes, syncope, new arrhythmias
long-term procainamide also causes symptoms resembling lupus erythematosus
what is the mechanism of action of Class 1B antiarrhythmic drugs?
Class 1B (lidocaine): block activated and inactivated Na+ channels —> shorten AP and refractory period —> allows activated K+ channels to repolarize the cell faster
state dependent block - binds cells that are already depolarized (such as ischemic tissue during MI that doesn’t repolarize well)
rapid kinetics ensures the cell recovers before the next AP (drug has no effect on conduction)
preferentially targets cells with long AP - particularly useful for targeting ventricular tissue (slower conduction)
what kind of drug is lidocaine and how does it work?
Class 1B antiarrhythmic: block activated and inactivated Na+ channels —> shorten AP and refractory period —> allows activated K+ channels to repolarize the cell faster
state dependent block - binds cells that are already depolarized (such as ischemic tissue during MI)
rapid kinetics ensures the cell recovers before the next AP (drug has no effect on conduction)
preferentially targets cells with long AP - particularly useful for targeting ventricular tissue (slower conduction)
describe how Class 1B antiarrhythmics such as lidocaine induce “state dependent block”
Class 1B: block activated and inactivated Na+ channels —> shorten AP and refractory period —> allows activated K+ channels to repolarize the cell faster
state dependent block = binding is dependent on the voltage of the cell - binds cells that are already depolarized (like ischemic tissue during MI which doesn’t repolarize well)
preferentially targets cells with long AP - particularly useful for targeting ventricular tissue (slower conduction)
to which cardiac cells do Class 1B antiarrhtymics such as lidocaine target best?
Class 1B: block activated and inactivated Na+ channels —> shorten AP and refractory period —> allows activated K+ channels to repolarize the cell faster
preferentially targets cells with long AP - particularly useful for targeting ventricular tissue (slower conduction), and ineffective for supraventricular tachycardias or atrial fib/flutter
state dependent block - binds cells that are already depolarized
what kind of toxicities are associated with Class 1B antiarrhythmics, such as lidocaine?
Paresthesia (pins&needles), tremor, nausea, lightheaded, slurred speech, convulsions
recall Class 1B antiarrhythmics block activated and inactivated Na+ channels —> shorten AP and refractory period —> allows activated K+ channels to repolarize the cell faster
how are class 1B antiarrhythmics such as lidocaine administered?
Class 1B: block activated and inactivated Na+ channels —> shorten AP and refractory period —> allows activated K+ channels to repolarize the cell faster
extensive first-pass hepatic metabolism, given by IV (short t1/2 of 1-2 hours)
how are class 1B antiarrhythmics such as lidocaine used? (3)
Class 1B: block activated and inactivated Na+ channels —> shorten AP and refractory period —> allows activated K+ channels to repolarize the cell faster
exhibit state-dependent block for cells already depolarized - therefore, used to treat arrhythmias caused by acute MI (recall ischemic tissue will continue to depolarize)
also preferentially targets cells with long AP - therefore, useful for termination of ventricular tachycardia/prevention of ventricular fibrillation (slower conducting)
also used for digitalis-induced arrhythmias
