Pharmacology of Anti-Arrhythmic Drugs

Vaughan Williams Classification: Class I Agents

Na+ channel blockers

Class IA

Disopyramide, Quinidine, Procainamide

Class IB

Lidocaine, Mexiletine

Class IC

Flecainide, Propafenone

Vaughan Williams Classification: Class II Agents

Beta-adrenergic receptor antagonists

Vaughan Williams Classification: Class III Agents

K+ channel blockers

Amiodarone

Dronedarone

Sotalol

Dofetilide

Ibutilide

Vaughan Williams Classification: Class IV Agents

Non-dihydropyridine calcium channel blockers

Class I Agents: Clinical Pearls

All agents have potential to be pro-arrhythmic

Prolonged repolarization time = prolonged QT interval

Can lead to Torsades de Pointes (TdP)

Caution use of concomitant QT-prolonging medications

Avoid in patients with structural heart disease (i.e., HF) and/or CAD

Disopyramide

ADEs:

Anticholinergic effects (e.g., dry mouth, urinary retention, constipation)

QT prolongation/TdP

Contraindicated in glaucoma

Quinidine

ADEs:

GI upset/nausea/vomiting/diarrhea (30%)

QT prolongation/TdP

Procainamide

Dosed as IV

ADEs: Drug-induced lupus (positive ANA titer in up to 50% of patients), QT prolongation/TdP

Lidocaine

ADEs: CNS effects (e.g., seizure, confusion, blurry vision, tinnitus)

Dosed as IV

Mexiletine

ADEs: CNS effects (e.g., tremor, dizziness, ataxia, nystagmus)

Class IB Agents Pearls

Relatively higher amount of CNS-related adverse effects compared to other anti-dysrhythmic agents

Class IC Agents Pearls

Useful in the outpatient setting for selected patients

Flecainide

ADEs: CNS effects (e.g., visual disturbances, dizziness, headache, tremor), QT prolongation/TdP

CIs/Precautions: HF, CAD/ACS (increases mortality post-MI)

Propafenone

ADEs: CNS effects (e.g., dizziness, fatigue, blurred vision, metallic taste/taste disturbances), QT prolongation/TdP

CIs/Precautions: HF, CAD/ACS

Class II Agents: Clinical Pearls

CIs: 2nd/3rd degree HB (unless pacemaker present), severe bradycardia (<45 BPM), ADHF, cardiogenic shock/SBP <100 mmHg

Commonly used to treat arrhythmias associated with: Comorbidities where BB improve outcomes (e.g., HFrEF, CAD)

Class III Agents: Clinical Pearls

Most can be given safely in patients with CAD and/or HFrEF

All drugs in this class can cause QT prolongation

Amiodarone

Half-life: ~55 days, with chronic oral therapy

Dosed as IV

ADEs: MANY that can affect several organ systems; QT prolongation/TdP (low risk; <1%)

SAFE to use in CAD/HF!

PK: MANY!!! (e.g., warfarin, digoxin, statins, other AADs)

Amiodarone Adverse Effects

Endocrine: thyroid dysfunction (mostly hypo)

Skin: photosensitivity/discoloration (blue)

Respiratory: pneumonitis, pulmonary fibrosis

CNS: peripheral neuropathy, optic neuritis

Liver: acute and/or chronic impairment

Dronedarone

ADEs: QT prolongation/TdP (low risk; <1%); ADHF

CIs/Precautions: QT >500 msec, NYHA IV HF or NYHA II-III with recent ADHF, permanent Afib, strong CYP3A4 inhibitors

PK: MANY!!! (e.g., warfarin, digoxin, other AADs, CYP3A4 inhibitors)

Sotalol

ADEs: QT prolongation/TdP, ADHF

CIs/Precautions: baseline QT interval >450 msec

Sotalol Dosing Considerations

BOXED WARNING: Can cause life-threatening QT interval prolongation/TdP

Initiation/re-initiation/titration done on inpatient basis

Do not initiate if baseline QTc interval >450 msec

If QTc interval ever ≥500 msec during therapy, must reduce dose, prolong interval between doses, or discontinue

Dofetilide

ADEs: QT prolongation/TdP

SAFE to use in CAD/HF!

CIs/Precautions: baseline QT interval >440 msec

Dofetilide Dosing

BOXED WARNING : can cause life-threatening QT interval prolongation/TdP

Initiation/re-initiation/titration done on inpatient basis

QTc should be determined prior to first dose

If QTc >440 msec, dofetilide is contraindicated!

Dofetilide Dosing Modification

QTc interval should be measured 2-3 hours after initial dose

If QTc increases >15% above baseline and/or >500 msec, dofetilide dose should be reduced by 50%

If QTc >500 msec at any time after second dose, dofetilide should be discontinued

Ibutilide

ADEs: QT prolongation/TdP

CIs/Precautions: LVEF ≤40%, baseline QT interval >440 msec, chronic AFib

Class IV Agents: Clinical Pearls

CIs/Precautions: Hypotension (SBP <90 mmHg) or cardiogenic shock

2nd/3rd degree HB

Avoid in HFrEF!!!