Antiarryythmic Drugs

Question 1

Proarrhythmic

Answer 1

increase automaticity and excitability
conduction block or slowing
increase/decrease ERP
heterogeneity of ERPs
afterdepolarization

Question 2

Antiarrhythmic

Answer 2

decrease automaticity and excitability
restoration of conduction or block of conduction
increase/decrease ERP
homogeneity of ERPs

Question 3

Classification of Antiarrhythmic Drugs

Answer 3

Class I: state-dependent block of Na+ channels
Class II: inhibition of beta-adrenergic receptors
Class III: homogenous prolongation of APD & ERP
Class IV: inhibition of Ca channels

Question 4

Class I drugs

Answer 4

Class Ia: modest dissociation with moderate depression - Procainamide

Class Ib: fast dissociation with little depression - Lidocaine and Mexilitine

Class Ic: slow dissociation with marked depression - Flecainide and Propafenone

Question 5

Class IA - Procainamide

Answer 5

modest
decrease automaticity and conduction velocity
increase APD and ERP

AVOID in prolonged QT syndrome (may cause torsades de pointes)
may cause an increase in AV nodal conduction

Used for: Life threatening ventricular arrhythmias

Kinetics: well absorbed orally, also IV, RE and HM creating an active metabolite (NAPA)

Adverse: +ANA lupus like syndrome with chronic treatment, agranulocytosis/leukopenia, proarrhythmic, conduction block, decrease myocardial contractility, hypotension, and GI

Contraindications: prolonged QT syndrome, hypokalemia, and SLE

Question 6

Class IB - Lidocaine and Mexilitine

Answer 6

minimal effects in normal tissues, similar to IA in diseased tissue

Lidocaine
use: life threatening ventricular arrhythmias and digoxin induced arrhythmia
Kinetics: first pass HM, IV only, decrease dose in liver disease and CHF
Adverse effects: *CNS disorientation and seizures**, hypotension, decreased myocardial contractility
Contraindications: hypersensitivity to amides, severe hepatic dysfunction, history of lidocaine induced seizures

Mexilitine
use: life threatening ventricular arrhythmias
similar to lidocaine but effective orally
Adverse: GI, tremors, thrombocytopenia, and CNS

Question 7

Class IC - Flecainide and Propafenone

Answer 7

Use: Life threatening ventricular arrhythmias in absence of organic heart disease and disabling supraventricular arrhythmias in absence of disease

Flecainide
Adverse: increase mortality with preexisting heart disease, conduction block, precipitation of CHF, AV block, and proarrhythmic effects
Contraindications: preexisting heart disease

Propafenone
generally similar to flecainide
has weak Beta blockade so don’t use if bronchospastic disease is present

rarely used class

Question 8

Class II - Beta Blockers

Answer 8

due to beta receptor blockade, prominent effet in SA and AV node
decrease automaticity, decrease conduction velocity, and increase refractoriness, decrease myocardial contractility

Use: supraventricular arrhythmias, control of V rate in A flutter and A fib, symptomatic PVCs, post MI, CHF

Adverse effects: related to beta blockade (bronchoconstriction, etc)

Esmolol - cardioselective, short t1/2, IV only, short term Tx, use in emergency control of V rate in A flutter and A fib, sinus tachycardia, use post CABG and cardiac surgeries

Question 9

Class III

Answer 9

homogenous prolongation of APD and ERP, proarrhythmic

Question 10

Amiodarone

Answer 10

Class III
Effects: Class III, I, and IV

Use: DOC for acute suppression of V arrhythmias, refractory life threatening V tach, and highly efficacious in sustained V tach

Pharmacokinetics - extremely lipid soluble, very long half life (26-107 days)

Adverse: pulmonary fibrosis, hyper/hypothyroidism, hepatic dysfunction
monitor hepatic, pulmonary, and thyroid function
AV blocks, sinus bradycardia, corneal micro deposits, photosensitivity, blue-gray nose and cheeks

Question 11

Dronedarone

Answer 11

Class III
Effects: Class III and I
prevent A fib and flutter
increase mortality in CHF
half life = 24 hours
can cause liver injury and failure

Question 12

Ibutilide and Dofetilide

Answer 12

Class III - clean
prolong APD and ERP
terminate A flutter and A fib
proarrhythmic –> torsades de pointes

Question 13

Sotalol

Answer 13

**
Class III
prolong APD and ERP as well as non selective beta receptor block
life threatening ventricular arrhythmias, prevents the recurrence of symptomatic A flutter and A fib
Proarrhythmic –> torsades de pointes

back up for Amiodarone

Question 14

Class IV - Verapamil

Answer 14

Ca-Channel Blockers
Effects: decrease Ca influx at SA and AV node leading to a decrease HR (decrease slope of phase 0) decreased conduction in AV node, and an increased APD and ERP (increasing refractoriness); also decreases contractility with action in A and V muscle, and vasodilation by decreasing TPR
Use: control V rate in A flutter and A fib, supraventricular tachyarrhythmias, PSVT due to AV nodal reentry

Adverse: in other lectures
Don’t use with beta-blockers

Question 15

Adenosine

Answer 15

decreases automaticity and AV conduction
metabolized by adenosine deaminase
short half life ( IV ONLY)
terminate PSVT
avoid in asthmatics

Question 16

Vagomimetics

Answer 16

decrease AV nodal conduction to terminate PSVT and control ventricular rate in A fib and flutter

Carotid massage increases vagal tone can be used for PSVT
Digoxin is also vagomimetic

Question 17

Tx of Bradyarrhythmias and AV Block

Answer 17

Atropine: vagolytic and increases sinus rate and AV conduction

Isoproterenol: increase AV conduction used for Tx of secondary and tertiary Av block prior to pacing