Lecture 20 - Antiarrhythmic drugs

What are the three main mechanisms of an arrhythmia? Which is most common?

1. Abnormal impulse formation

   1. Enhanced normal automaticity

   2. Abnormal

2. Triggered activity

3. Conduction disturbances

   1. Reentry (most common)

   2. Conduction delay

What is the goal of treating an abnormal impulse formation?

Slow rate of spontaneous depolarization

What is the treatment goal for triggered activity?

Shorten AP duration

What is the treatment goal of reentry?

Slow spontaneous depolarization and conduction velocity

What are the consequences of an arrhythmia?

-Hemodynamic (decreased cardiac function, hypotension, etc)

-Electrical instability (myocardial fibrillation, asystole)

What are the four classes of antiarrhythmic drugs?

1. Na+ channel blocker

2. Beta blocker

3. K channel blocker

4. Ca2+ channel blocker

How do Na+ channel blockers function?

-Inhibit fast sodium channels during depolarization

-Decrease depolarization rate and conduction velocity

-Suppress abnormal automaticity in non-nodal tissues

What should you check before starting a class 1 drug?

Electrolytes → hyperkalemia may cause increased toxicity

How does class 1a work?

Lengthen both the AP duration and effective refractory period

How does class 1b work?

Shorten AP and refractory period

How does class 1c work?

Decreases rate of phase 0 depolarization with no change in AP duration

What class is Quinidine part of? What is it used for?

-Class 1A

-Atrial fibrillation in horses

What are the adverse effects of Quinidine?

-Speeds up AV conduction

-Proarrhythmic (blocks K+ channels)

-Potentiates digoxin toxicity

-GI effects

What class is procainamide part of? How does it work?

-Class 1A

-Slows conduction velocity and abolishes reentry circuits

-Prolongs effective refractory period

What are the indications for procainamide?

-Supraventricular dysrhythmias

-Ventricular dysrhythmias refractory to lidocaine

What are the adverse effects of Procainamide?

-GI upset

-Bradycardia

-Proarrhythmia

-Hypotension

-May change coat color in some dogs

What class is lidocaine part of? What is it used for? How does it work?

-Class 1B

-Acute control of ventricular tachycardia

-Abolishes reentry circuits

What does Lidocaine require?

Normal serum K+ levels

What class does Mexiletine belong to? What is it used for?

-Class 1B

-Long term oral therapy for arrhythmias

What are the adverse effects of Mexiletine?

-Tremors

-GI upset

-Relatively expensive

What class does Beta blockers belong to? How do they function? What are they used for?

-Class II

-Decrease sympathetic nervous system (B1)

-Used for arrhythmias caused by catecholamines

What are the cardiac effects of beta blockers?

-Negative chronotropy (decreased HR) and dromotropy (decreased conduction speed)

-Depress slope of phase 4

-Reduce myocardial work and oxygen consumption

-Slow conduction through AV node

How should you give a beta blocker?

-Do not abruptly stop

-Start low, go slow, aim high

Which is the most common beta blocker used? Why?

-Atenolol

-Selective B1

What are the adverse effect of beta blockers?

-Exacerbation of heart failure or nodal dysfunction (do not use in CHF)

-Bronchoconstriction (B2)

-Prevents glycogenolysis

What class are potassium channel blockers? How do they function?

-Class 3

-Increases AP duration by delaying/prolonging repolarization

What are class III drugs used for?

Significant ventricular arrhythmias

What class does Amiodarone belong to? What is it used for?

-Class III

-Life threatening ventricular tachycardia (not a first line drug)

What are the adverse effects of Amiodarone?

-Hepatotoxicity

-GI upset

-Neutropenia

-Hypothyroid

-Anorexia

-Vomiting

-Lethargy

-Pulmonary fibrosis

-Blue skin (humans)

What class does Sotalol belong to? what is it used for?

-Class III

-First line oral drug for ventricular tachycardia

What are the adverse effects?

-Proarrhythmic

-Mild negative inotropy

-May exacerbate nodal dysfunction (weak beta blocker)

What class do Calcium channel blockers belong to? How do they function?

-Class IV

-Inhibits L-type Ca channels (delay phase 4 and phase 0)

-Slows AV node conduction and prolongs AV nodal refractory period

What are the clinical uses for class IV drugs?

-Slowing ventricular response rate in a-fib

-Terminate or prevent AV reentrant arrhythmias

What are the adverse effects for Class IV drugs?

Mild negative inotrope

What class does Diltiazem belong to? What is it used for?

-Class IV

-Used to control supraventricular tachyarrhythmias (a-fib)

What are the adverse effects of Diltiazem? What does an overdose cause?

-Bradycardia

-AV block

-Hypotension

-Overdose = 3rd degree AV block

How does Digoxin function?

-Depress AV nodal conduction and prolong refractory

-Weak antiarrhythmic

-Positive inotrope

What are the only indication for digoxin? What is it usually combined with?

-a-fib

-Diltiazem

What are the adverse side effects of digoxin?

-GI signs

-Depression

-Proarrhythmic