creation date: 2025-10-28 15:01
tags: Pharmacology
Antiarrhythmics
Background
Antiarrhythmics are a class of medications used to treat or prevent arrhythmias. These medications are classified by their primary mechanism of action under the Vaughan-Williams (VW) classification system.
Normal Physiology (Cardiac Action Potential)
Ion movement results in the depolarization and repolarization of cardiac myocytes which results in muscle contraction, with a resting membrane potential of -80 to -90 mV at baseline.
Phase 0
Depolarization phase: sodium rapidly moves into the cell via voltage-gated channels, bringing membrane potential to approximately +30 mV.
Phase 1
Notch: efflux of potassium occurs resulting in slight repolarization (early repolarization phase).
Phase 2
Plateau: inwards calcium movement offsets outwards potassium movement, balancing membrane potential.
Phase 3
Repolarization phase: movement of potassium out of the cell (and deactivation of Ca channels) restores negative action potential.
Phase 4
Na/K-ATPase restores resting membrane potential. Three sodium ion is pumped outwards and 2 potassium inwards. This also drives the Na/Ca exchanger (extrudes 2Ca for 3 Na inwards). This in addition to leaky potassium channels maintains resting membrane potential.
Classes
Class I - Fast Sodium Channel Blockers
Mechanism of Action (shared among class I)
Sodium channel blockers act on phase 0 of the cardiac action potential, reducing or blocking conduction in depolarized tissue. Characteristics of action include:
- State-dependent (greater effect the faster the heart rate)
- Decreases slope of phase 0 depolarization
- Membrane is stabilized and excitability decreases
Subgroups of class I is based on the effect on Na channels and the action potential (AP) duration.
Class Ia
Mechanism of Action
- Blockage of Na channels: moderate
- AP duration: prolongs
Additional characteristics:
- Slows conduction velocity
- Prolongs effective refractory period in ventricular APs
- Weak blockade of K channels
Indications
- Paroxysmal SVTs (AVNRT and AVRT)
- Ectopic SVTs
- Antidromic AVRT and WPW (procainamide)
- Atrial fibrillation and atrial flutter
- Ventricular arrhythmias
Adverse Effects
- QT prolongation (risk of TdP)
- Cinchonism (quinine-related)
- Thrombocytopenia
- Drug-induced lupus erythematosus (procainamide)
- Drug fever (procainamide)
- Heart failure (disopyramide)
- Anticholinergic effects (disopyramide)
Examples
- Quinidine
- Procainamide
- Disopyramide
- Ajmaline
Class Ib
Mechanism of Action
- Blockage of Na channels: weak
- AP duration: shortens
Additional characteristics:
- Slows conduction velocity
- No effect or slight prolongation of effective refractory period in ventricular APs
- Strongest effect on ischemic or depolarized Purkinje cells and ventricular myocardium
Indications
- Ventricular arrhythmias (especially post-MI)
- Digitalis-induced arrhythmias
Adverse Effects
- CNS depression or excitation
- AV conduction block or ventricular extrasystoles
Examples
- Lidocaine
- Mexiletine
- Phenytoin
Class Ic
Mechanism of Action
- Blockage of Na channels: strong
- AP duration: no effect
Additional characteristics:
- Slows conduction velocity
- Prolongs effective refractory period in AV node and accessory tracts
- No effect on effective refractory period in Purkinje cells and ventricular myocardium
Indications
- Paroxysmal SVTs
- Atrial fibrillation (cardioversion)
- Atrial flutter
- Last resort in refractory ventricular tachycardia
Adverse Effects
- Proarrhythmogenic (contraindicated post-MI)
- Possible QT prolongation
Examples
- Flecainide
- Propafenone
Class II - Beta Blockers
Mechanism of Action
Beta blockers inhibit beta-adrenergic activation, reducing SA and AV node activity.
- Prolongation of AV node repolarization prolongs PR interval
- Decrease slope of phase 4 in cardiac pacemaker cells suppresses aberrant pacemakers
- Slows conduction velocity
Indications
- Atrial fibrillation (rate control)
- Atrial flutter
- Paroxysmal SVT
- Premature ventricular contractions
- Ventricular arrhythmias
- Atrial premature complexes
Adverse Effects
- AV block, bradycardia, heart failure
- Exacerbation of asthma, COPD
- Sedation, CNS depression, sleep disturbances
- Impotence (increased vasoconstriction)
- Masking symptoms of hypoglycemia
- Hyperkalemia
- Dyslipidemia (metoprolol)
- Vasospasm worsening if preexisting vasopastic angina (propanolol)
- Caution in patients with cocaine use or pheochromocytoma
Examples
- Metoprolol
- Esmolol (short-acting)
- Propranolol
- Atenolol
- Timolol
- Carvedilol
- Sotalol
Class III - Potassium Channel Blockers
Mechanism of Action
Potassium channel blockers prevent potassium efflux which delays repolarization.
- Prolong QT interval
- Prolong AP duration and ERP
- No effect on conduction velocity
Indications
- Atrial fibrillation (cardioversion and rhythm control)
- Atrial flutter
- Sotalol and amiodarone: supraventricular arrhythmias and ventricular arrhythmias)
Adverse Effects
- QT prolongation (risk of TdP)
- Amiodarone:
- Heart failure, heart block, bradycardia, hypotension
- Pulmonary fibrosis
- Thyroid dysfunction (hypo- or hyperthyroidism due to high iodine)
- Liver dysfunction
- Neurologic side effects (eg. peripheral neuropathy)
- Photodermatitis and photosensitivity
- Constipation
- Sotalol: see [[#Class II - Beta Blockers#Adverse Effects|above]]
Examples
- Amiodarone (class I, II, III, IV properties)
- Dronedarone
- Sotalol
- Bretylium
- Ibutilide
- Dofetilide
Class IV - Calcium Channel Blockers
Mechanism of Action
Calcium channel blockers inhibit slow calcium channels which decrease the slope of phase 0 and 4 of the cardiac conduction.
- Decreases conduction velocity (increasing ERP)
- Prolongs AV node repolarization
- Prolongs PR interval
Indications
- Atrial fibrillation (rate control)
- Atrial flutter
- Prophylaxis of nodal arrhythmias
- Multifocal atrial tachycardia
- Hypertension (nifedipine)
Adverse Effects
Verapamil
- AV block
- Bradycardia
- Sinus node depression
- Heart failure
- Constipation
- Flushing
- Edema
Nifedipine - Headache
- Flushing
- Pitting edema
- Reflex tachycardia
Diltiazem - milder forms of above two
Examples
Class V - Others (Variable Mechanism)
Adenosine
Mechanism of Action
Adenosine activates Gi protein which deactivates L-type Ca channels resulting in transient AV node block. The action lasts for a very short duration (~15 sec)
Indications
- Diagnosis and termination of certain forms of paroxysmal SVT
Adverse Effects
- Chest pain
- Flushing
- Hypotension
- Bronchospasm
- Sense of impending doom
- Effect weakened by adenosine receptor antagonists (eg. caffeine)
Magnesium sulfate
Mechanism of Action
Decreases calcium influx preventing early afterdepolarizations.
Indications
- Torsades de pointes (TdP)
- Digoxin toxicity
Adverse Effects
- Hypotension
- Asystole
- Drowsiness
- Flushing
- Loss of reflexes
- Respiratory depression
Digoxin
Mechanism of Action
Inhibition of NaK-ATPases resulting in higher intracellular Na. This reduces Na/Ca exchanger activity which results in higher intracellular Ca.
- Increases cardiac contractility
- Decreases heart rate
Indications
- Atrial fibrillation
- Atrial flutter
- Chronic systolic heart failure
Adverse Effects
- Nausea, vomiting
- Abdominal pain
- Blurry vision with yellow tint and halos
Ivabradine
Mechanism of Action
Selective inhibition of If channels in pacemaker cells of SA node.
- Prolongs slow depolarization (phase 4)
- Slows heart rate
Indications
- Chronic stable coronary heart disease if beta-blockers are not tolerated
- Chronic HFrEF
Adverse Effects
- Vision changes (luminous phenomena; enhanced brightness)
- Bradycardia
- Hypertension