1 - Antiarrhythmics: Review, Class I(a-c)

Define arrhythmia

any disturbance in the rate, regulatory, site of origin, or conduction of the cardiac electrical impulse

Define transmembrane/membrane potential

electrical charge across the plasma membrane of cardiac cell; difference in electrical potential between interior of the cell

Define action potential

change in electrical potential associated with the propagation of an impulse along the membrane of a cell

Define refractory period

period of time in which a cell is incapable of firing an action potential to prevent overlapping impulses; occurs from depolarization to halfway through repolarization

Define electrocardiogram

measures the overall electrical activity of the heart

Define Torsades de pointes and the typical cause

polymorphic ventricular tachycardia with a long QT interval, often drug induced

What are the two goals of antiarrhythmic therapy?

1. terminate ongoing arrhythmia

2. prevent future/recurrent arrhythmia

How do antiarrhythmics suppress arrhythmias?

1. blocking flow through specific ion channels

2. altering autonomic nervous system function

What 4 ways can antiarrhythmics generally work?

1. automaticity of slope of phase 4 depolarization

2. threshold potential increase/decrease

3. maximum diastolic potential

4. AP duration

All antiarrhythmics are ____________.

proarrhythmic

Provide examples of how antiarrhythmics can be proarrhythmic.

• decreased conduction velocity → bradycardia and/or heart block

• slowed heart rate → prolonged QT interval → TDP

What is the common classification system for antiarrhythmics?

Vaughan Williams

What is the dominant action of class Ia antiarrhythmics?

Na+ channel block (intermediate)

What is the dominant action of class Ib antiarrhythmics?

Na+ channel block (fast on-off)

What is the dominant action of class Ic antiarrhythmics?

Na+ channel block (slow on-off)

What is the dominant action of class II antiarrhythmics?

beta blockade (indirect Ca²⁺ block)

What is the dominant action of class III antiarrhythmics?

K+ channel block

What is the dominant action of class IV antiarrhythmics?

Ca²⁺ channel block

What 3 drugs are classified as Ia?

quinidine, procainamide, disopyramide

What 2 drugs are classified as Ib?

lidocaine, mexiletine

What 2 drugs are classified as Ic?

flecainide, propagenone

What drugs are classified as II?

various: metoprolol, labetalol, etc.

What 5 drugs are classified as III?

amiodarone, dronedarone, dofetilide, sotalol, ibutilide

What 2 drugs are classified as IV?

diltiazem, verapamil

Which class(es) of antiarrhythmics do not lower conduction velocity?

class III

Which class(es) of antiarrhythmics prolong refractory period?

Ia, II

Which class(es) of antiarrhythmics do not prolong refractory period?

Ib, Ic

What class(es) of antiarrhythmics do not lower automaticity?

III

What is the MOA of class I antiarrhythmics (sodium channel blockers)?

block open/inactivated Na+ channels

Which type of Na+ channels do class I antiarrhythmics bind and not bind?

readily activated (phase 0 depolarization) or inactivated (phase 2 refractory) channels

not closed channels (phase 4 resting membrane potential)

How are class I antiarrhythmics subclassified?

• Ia - moderate Na+ channel blockage

• Ib - mild Na+ channel blockage

• Ic - marked (strong) Na+ channel blockage

What is the AP duration/QT duration of each subclass of class I antiarrhythmics?

• Ia - prolonged

• Ib - shortened

• Ic - no effect

What is the dissociation rate of each subclass of class I antiarrhythmics?

• Ia - intermediate

• Ib - fast

• Ic - slow

What ingredient is a class Ia antiarrhythmic?

disopyramide

What ingredient is a class Ib antiarrhythmic?

lidocaine

What ingredient is a class Ic antiarrhythmic?

flecainide

What effect does disopyramide have in addition to Na+ channel blockade?

prominent anticholinergic

For what scenario is disopyramide useful for?

arrhythmias vagally mediated, for example atrial fibrillation in athletes

What are the ADE of dysopyramide?

1. anticholinergic - constipation, dry mouth, urinary retention, worsening glaucoma

2. TDP risk

3. decreases force of contraction

What are contraindications for disopyramide?

• heart failure

• BPH or glaucoma

In what situation is lidocaine used?

• coronary eschemia due to lack of oxygen

• used as acute IV therapy

Why must lidocaine be reduced with infusions >24 hours?

accumulation due to competition between parent drug & less potent metabolites for clearance

What are the ADE of lidocaine?

dose/accumulation related neurologic effects: perioral, tingling, tinnitus, tremor, nystagmus, confusion, altered conscioiusness, seizures

Why does flecainide have slowed conduction, even in normal tissues at normal rates?

has a long rate of recovery due to slowed dissociation from Na+ channels

What situation is flecainide typically ideal for?

supraventricular arrhythmias in patients with structurally normal hearts (arrhythmia is the only thing wrong)

What are the ADE of flecainide?

very well tolerated

• dose-relate

• arrhythmias

• exacerbates heart failuree

What is a patient care consideration for patients taking flecainide?

increased risk in patients with structural heart disease, presumably from proarrhythmic properties