Antiarrhythmics

Question 1

Procainamide

Answer 1

• Class 1A
• MOA
• I_Na (primary) and I_Kr (secondary) blockade
• Effects
• slows conduction and rate
• prolongs AP duration, dissociates from I_Na channel with intermediate kinetics
• direct depressant effects on SA and AV nodes
• Clinical
• most atrial and ventricular arrhythmias
• drug of 2nd choice for most sustained ventricular arrhythmias associated with acute MI
• Kinetics, tox, int.
• oral, IV, IM
• eliminated by hepatic metabolism to NAPA and renal elimination
• NAPA implicated in torsades de pointes in pts with renal failure
• tox: hypotension, long-term therapy produces reversible lupus-like syndrome

Question 2

Lidocaine

Answer 2

• Class 1B
• MOA
• I_Na blockade
• Effects
• blocks activated and inactivated channels with fast kinetics
• does not prolong and may shorten AP
• Clinical
• terminates ventricular tachycardias and prevents VF after cardioversion
• Kinetics, tox, int.
• IV, first-pass hepatic metabolism
• reduce dose in pts with heart failure or liver disease
• tox: neurologic symptoms

Question 3

Flecainide, propafenone

Answer 3

• Class 1C
• MOA
• I_Na blockade
• Effects
• dissociates from channel with slow kinetics
• no change in AP duration
• Clinical
• SV arrhythmias in pts with normal heart
• do not use in ischemic conditions (eg. post-MI)
• Kinetics, tox, int.
• oral, hepatic & kidney metabolism
• t_1/2 approx 20h
• tox: proarrhythmic
• Propafenone
• orally active, weak β-blocking activity; SV arrhythmias; hepatic metabolism

Question 4

Propranolol

Answer 4

• Class 2
• MOA
• β-blocker
• Effects
• direct membrane effects (Na ch. block) and prolongation of AP duration
• slows SA node automaticity and AV node conduction velocity
• Clinical
• atrial arrhythmias and prevention of recurrent infarction and sudden death
• Kinetics, tox, int.
• oral, parenteral, duration 4-6h
• tox: asthma, AV-block, acute heart failure
• int: with other cardiac depressants and hypotensive drugs

Question 5

Amiodarone, sotalol

Answer 5

• Class 3
• MOA
• blocks I_Kr, I_Na, I_Ca-L channels, β receptors
• Effects
• prolongs AP duration and QT interval
• slows heart rate and AV node conduction
• low incidence of torsades de pointes
• Clinical
• serious ventricular arrhythmias and SV arrhythmias
• Kinetics, tox, int.
• oral, IV, variable absorption and tissue accumulation
• hepatic metabolism, elimination complex and slow
• tox: bradycardia and heart block in diseased heart, peripheral vasodilation, pulmonary and hepatic toxicity, hyper/hypothyroidism
• int: many, CYP-related
• Sotalol
• β and I_Kr blocker; direct AP prolongation; use for ventricular arrhythmias and AF

Question 6

Verapamil

Answer 6

• Class 4
• MOA
• I_Ca-L blockade
• Effects
• slows SA node automaticity and AV node conduction velocity
• decreases cardiac contractility
• reduces blood pressure
• Clinical
• SVT, hypertension, angina
• Kinetics, tox, int.
• oral, IV, hepatic metabolism - caution in pts with hepatic dysfunction

Question 7

Adenosine

Answer 7

• MOA
• activates inward rectifier I_K
• blocks I_Ca
• Effects
• very brief, usually complete AV block
• Clinical
• paroxysmal SVT
• Kinetics, tox, int.
• IV, duration 10-15s
• tox: flushing, chest tightness, dizziness
• minimal interactions

Question 8

Magnesium

Answer 8

• MOA
• poorly understood
• interacts with Na/K-ATPase, K, and Ca channels
• Effects
• normalizes or increases plasma Mg
• Clinical
• torsades de pointes
• digitalis-induced arrhythmias
• Kinetics, tox, int.
• IV, duration dependent on dosage
• tox: muscle weakness in overdose

Question 9

Potassium

Answer 9

• MOA
• increases K permeability, K currents
• Effects
• slows ectopic pacemakers
• slows conduction velocity
• Clinical
• digitalis-induced arrhythmias
• arrhythmias associated with hypokalemia
• Kinetics, tox, int.
• oral, IV
• tox: reentrant arrhythmias, fibrillation or arrest in overdose