Antiarrhythmic Pharmacology
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Transcript of Antiarrhythmic Pharmacology
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