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 Uses Paroxysmal SVTs (IA, IC) Atrial fibrillation, flutter (IA, IC) Ventricular tachycardia (IA, IB) Digoxin-induced arrhythmias (IB) Paroxysmal SVTs Atrial or ventricular premature beats Atrial fibrillation, flutter Ventricular tachycardia Atrial fibrillation, flutter Atrial flutter (only amiodarone) Paroxysmal SVTs Atrial fibrillation, flutter Paroxysmal SVTs Atrial fibrillation Atrial flutter with ventricular rate

Drug Class Class I

Class II

Class III

Class IV

Adenosine Cardiac glycosides

Class I
Class I antiarrhythmic drugs are based on Na+ channel blockade Results in phase 0 slope of cardiomyocytes conduction velocity/reentry o Also, phase 4 depolarisation rate of fire/automaticity o Class IA drugs also K+ channel blocking activity = elongated repolarisation conduction velocity/reentry Use dependence (block channel activity), therefore called membranestabilising drugs Drug Disopyramide, quinidine (Class Ia) Lidocaine (Class Ib) Flecainide, encanide MoA Indications Class I (Na+-channel blockers)
- Ventricular dysrhythmias - Paroxysmal AF (by vagal overactivity) - VT, VF (during and after MI) - Paroxysmal AF - Recurrent

Other Notes
- AEs include blurred vision, dry mouth, constipation, urinary retention (antimuscarinic) - IV delivery due to extensive first pass metabolism - Can be used for VEBs, but risk of

Na+ channel blockade (intermediate, fast or slow) AP length by phase 4 depolarisation (pacemaker), phase 0 slope velocity (myocytes)

Drug (Class Ic)

MoA

Indications
tachyarrhythmias

Other Notes
SCD

Class II
Class II antiarrhythmic drugs include propranolol, metoprolol and timolol Antagonises 1-adrenoreceptors causing Ca2+ influx at SA and AV nodes o Blocks AP conduction with little impact on myocardium o Decreased automaticity by phase 4 slope o Prolonged repolarisation of AV node (increases effective refractory period) decreasing window of reentry Drug Propranolol, metoprolol, timolol MoA Indications Class II (-blockers)
- mortality post-MI - Prophylaxis of recurrent tachyarrhythmias by SNS

Other Notes
- Ventricular - AEs include fatigue, bronchospasm, bradycardia,

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

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 drug
o Multiple adverse effects including hypotension, heart block, bradycardia; noncardiac AEs include pulmonary fibrosis and thyroid abnormalities (due to iodine moiety)

Sotalol mechanism is primarily -blockade at low dosage, K+ channel block at higher doses Drug MoA Indications Class III (prolong action potentials)
- Wolff-Parkinson-White syndrome tachycardia - Supraventricular and ventricular arrhythmias

Other Notes
- Multiple serious AEs - Need to monitor K+ (to prevent TdP)

Amiodarone

Sotalol

K+ channel block prolongs repolarisation and refractory period; Na+ and Ca2+ channel block reentry and automaticity (phase 4 slope) 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 effects o 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 Verapamil, diltiazem MoA Indications 2+ Class IV (Ca -channel blockers) Ca2+ channel block - Paroxysmal SVT (mainly AV node) - Prophylaxis of junctional
phase 0 slope (automaticity) and phase 3 duration ( repolarisation and refractory period)

Other Notes
- Contraindicated in WPW syndrome - Adenosine more used to terminate SVT - Interacts with digoxin

tachycardia (AVNRT, AVRT) - AF to ventricular beats

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 contraction o Disrupts normal rhythm by AV conduction block and ectopic activity o Used commonly in patients with heart failure Drug Cardiac glycosides (digoxin) MoA Indications Other Notes Other (unclassified by Vaughan Williams system, Class V)
Na+/K+-ATPase inhibition Na+I increases blocking Na+/Ca2+ exchanger Ca2+I results in increased contractile ability and longer K+ efflux (hyperpolarisation) Adenosine receptor activation K+ efflux (across channel) hyperpolarisation rate of firing and slowed phase 4 slope (pacemaker) - 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 window - Toxicity can result in arrhythmias - Very short half-life (t<10s) - Can be used to better distinguish atrial patterns - Risk of degeneration to VF

Adenosine

- SVTs (incl. AVNRT and AVRT) termination - Also AF and atrial flutter