Antiarrhythmic drugs Mechanism of antiarrhythmic drugs is to modulate cardiac rhythm and

conduction By themselves, they can aggravate or produce arrhythmias, so caution in

their usage is needed Characterised by the Vaughan Williams’ classification system Some drugs can have multiple actions, e.g. amiodarone has class I-IV

activity

Drug Class

Uses

Class I Paroxysmal SVTs (IA, IC) Atrial fibrillation, flutter (IA,

IC) Ventricular tachycardia (IA,

IB) Digoxin-induced arrhythmias

(IB)Class II Paroxysmal SVTs

Atrial or ventricular premature beats

Atrial fibrillation, flutterClass III Ventricular tachycardia

Atrial fibrillation, flutter Atrial flutter (only

amiodarone)Class IV Paroxysmal SVTs

Atrial fibrillation, flutter

Adenosine

Paroxysmal SVTs

Cardiac glycosid

es

Atrial fibrillation Atrial flutter with

↑ventricular rate

Class I Class I antiarrhythmic drugs are based on Na+ channel blockade Results in ↓phase 0 slope of cardiomyocytes ↓conduction

velocity/reentryo Also, ↓phase 4 depolarisation ↓rate of fire/automaticityo Class IA drugs also K+ channel blocking activity = elongated

repolarisation ↓conduction velocity/reentry Use dependence (block ∝ channel activity), therefore called “membrane-

stabilising” drugs

Drug MoA Indications Other NotesClass I (Na+-channel blockers)

Disopyramide, quinidine

Na+ channel blockade (intermediate, fast or

- Ventricular dysrhythmias

- AEs include blurred vision,

Drug MoA Indications Other Notes(Class Ia)

slow) ↑AP length by ↓phase 4 depolarisation (pacemaker), ↓phase 0 slope velocity (myocytes)

- Paroxysmal AF (by vagal overactivity)

dry mouth, constipation, urinary retention (antimuscarinic)

Lidocaine (Class Ib)

- VT, VF (during and after MI)

- IV delivery due to extensive first pass metabolism

Flecainide, encanide(Class Ic)

- Paroxysmal AF- Recurrent

tachyarrhythmias

- Can be used for VEBs, but ↑risk of SCD

Class II Class II antiarrhythmic drugs include propranolol, metoprolol and timolol Antagonises β1-adrenoreceptors causing ↓Ca2+ influx at SA and AV nodes

o Blocks AP conduction with little impact on myocardium

o Decreased automaticity by ↓phase 4 slopeo Prolonged repolarisation of AV node (increases effective refractory

period) decreasing window of reentry

Drug MoA Indications Other NotesClass II (β-blockers)

Propranolol, metoprolol,

timolol

β1-adrenoceptor antagonism slow Ca2+ current blockade SA and AV node inhibition ↓automaticity and ↓reentry

- ↓mortality post-MI- Prophylaxis of recurrent

tachyarrhythmias by ↑SNS

- Ventricular- AEs include

fatigue, bronchospasm, bradycardia,

Class III Class III antiarrhythmic drugs operate mainly by K+ channel blockade

↑repolarisation time Drugs include amiodarone, dronedarone and sotalol Most drugs of this class have proarrhythmic activity (except amiodarone

and dronedarone) Amiodarone has multiple class activity and is an effective antiarrhythmic

drugo Multiple adverse effects including hypotension, heart block, bradycardia;

non-cardiac AEs include pulmonary fibrosis and thyroid abnormalities (due to iodine moiety)

Sotalol mechanism is primarily β-blockade at low dosage, K+ channel block at higher doses

Drug MoA Indications Other NotesClass III (prolong action potentials)

Amiodarone K+ channel block prolongs repolarisation and

- Wolff-Parkinson-White syndrome tachycardia

- Supraventricular and

- Multiple serious AEs

- Need to monitor

Drug MoA Indications Other Notesrefractory period;Na+ and Ca2+ channel block ↓reentry and ↓automaticity (↓phase 4 slope)

ventricular arrhythmias K+ (to prevent TdP)

Sotalol K+ channel block prolongs repolarisation and refractory period ↓reentry

- Paroxysmal SVT- VEB suppression- Some cases of VT

- Mixed class III/II action

- May trigger TdP and LQTS

Class IV Class IV drugs are L-type (slow) Ca2+-channel blockers with mixed negative

ionotropic, chronotropic or vasodilatory effects Antiarrhythmic properties require either/or negative chronotropic or

ionotropic effectso For this reason, dihydropyridines such as nifedipine and nicardipine

not used in the treatment of arrhythmias Used to slow SA and AV nodal conduction (AV node inhibition is key)

Drug MoA Indications Other NotesClass IV (Ca2+-channel blockers)

Verapamil, diltiazem

Ca2+ channel block (mainly AV node) ↓phase 0 slope (↓automaticity) and ↓phase 3 duration (↑ repolarisation and refractory period)

- Paroxysmal SVT- Prophylaxis of

junctional tachycardia (AVNRT, AVRT)

- AF to ↓ventricular beats

- Contraindicated in WPW syndrome

- Adenosine more used to terminate SVT

- Interacts with digoxin

Other/”class V” Not classified by the Vaughan Williams classification system Adenosine often used in acute settings for termination of SVTs (little-no

impact on VTs due to lack of K+ channels in ventricular myocardium) Digoxin is used to slow cardiac conduction and to increase force of

contractiono Disrupts normal rhythm by AV conduction block and ↑ectopic

activityo Used commonly in patients with heart failure

Drug MoA Indications Other NotesOther (unclassified by Vaughan Williams system, “Class V”)

Cardiac glycosides (digoxin)

Na+/K+-ATPase inhibition Na+

I

increases blocking Na+/Ca2+ exchanger ↑Ca2+

I results in increased contractile ability and longer K+

- Heart failure patients- AF and atrial flutter with

high ventricular rate

- Class II and III drugs can be used instead in some cases for treatment of arrhythmia

- Small therapeutic

Drug MoA Indications Other Notesefflux (↑hyperpolarisation)

window- Toxicity can

result in arrhythmias

Adenosine Adenosine receptor activation ↑K+

efflux (across channel) hyperpolarisation ↓rate of firing and slowed phase 4 slope (pacemaker)

- SVTs (incl. AVNRT and AVRT) termination

- Also AF and atrial flutter

- Very short half-life (t½<10s)

- Can be used to better distinguish atrial patterns

- Risk of degeneration to VF