Drugs for Arrhythmia's Part 2

28 Pages·2013·4.24 MB·English

by  David Fedida

Drugs Controlling Myocyte Excitability
and Conduction at the AV node
Singh and Vaughan-Williams Classification
Class III
Class I
K channel Blockers
Na Channel Blockers
Dofetilide , Dronedarone,
Flecainide
Amiodarone
Propafenone
Class II
Class VI
Beta Blockers
Ca Channel Blockers
Propranolol
Diltiazem
Metoprolol
Class V
Other
Digoxin
Two Strategies for Drugs Directly
Treating AFib
• Rhythm Control
– True antiarrhythmic drugs – designed to restore sinus
rhythm by affecting ion channels during the action potential
– Na channel blockers
• Flecainide and propafenone
• Inhibits………
– K channel blockers
• Dofetilide,
• Inhibits…….
– Multi ion channel blockers
• Amiodarone and dronedarone
• All-in-one Na, K, Ca and beta blockers (has rate control
properties)
• Vernakalant, Na and K channel blocker
Antiarrhythmic Drugs
Antiarrhythmic Cardiac Myocyte route of admini- Presumable
compound Membrane Effects stration indications
Propafenone/flecainide/vernakalant: PO/IV Parox AF
(AFI)
Amiodarone PO and (?IV) Persist AF
Dronedarone multiple effects PO Persist AF
(AFI)
Dofetilide blocks .... PO Parox and
Persistent
AFl and AF
Verapamil/Beta blocker PO AF/Afl: rate
control
History of Antiarrhythmic Therapy
Tree extracts
Beta blockers
Class I Quinidine From China
Class II
Amiodarone
1918 1700
1950s
1960s
1967
Class Ic 1980s
1989
?
1990s
1999
2005
CAST
Selective
SWORD
AFFIRM
Class III
DIAMOND
compounds
• Clinical trials: failure, failure, failure.....
Vaughan-Williams Classification..
Potential for
PROARRHYTHMIA
CLASS DRUGS ACTIVE IN EFFICACY TOXICITY
IA Quinidine Atria, Ventricles 2+ 3+ 2+
Moderately slow conduction Procainamide
Moderately prolong action potential Dispyramide
IB Lidocaine Ventricles 1+ 1+ 1+
Minimally slow conduction Mexilitine
Shorten action potential duration Phenytoin
IC Flecainide Atria, Ventricles 3+ 1+ 3+
Markedly slow conduction Propafenone
Minimally prolong action potential duration Encainide
II Beta Blockers AV node 1+ 1+ 0
Ventricles
III Amiodarone Atria, Ventricles 2+ 1+ 2+
Prolong action potential duration Bretylium
Sotalol
Ibutilide
IV Calcium Channel AV node 1+ 1+ 0
blocking drugs
Red = drug effect on action potential. Blue = normal action potential. (Purkinje fiber)
Treatment of ventricular arrhythmias
– Drugs are generally used with a great deal of care due to potential for
pro-arrhythmia (CAST trial in 1980s).
– Ectopic activity arising from DADs/EADs: Not considered serious
unless more than 4-10 beats in a row. Potentially treat with beta
blockers, amiodarone or Na or K channel blockers in a healthy heart.
– Re-entry arrhythmias: e.g. Ventricular tachycardia. Can attempt
suppression in a healthy heart, with Na channel blockers, amiodarone,
dofetilide; otherwise use implantable defribillators (ICD) + Beta
blockade.
– Inherited arrhythmias in children/adults:
The long QT interval syndromes. Tendency for torsades de pointes due
to repolarization instability. Treat with beta blockade to suppress EADs.
If recurrent insert ICD.
Brugada syndrome. Right ventricular disease, due to loss of function of
Scn5A (Na channel). Treat with ICD, or quinidine.
Catecholaminergic Paroxysmal Ventricular Tachycardia (CPVT). Beta
blocker or ICD
Quinidine Exposure can be Pro-Arrhythmic
Implantable cardiac defribrillator
Evolution
Number of Worldwide ICD Implants Per Year
(Ref: Corporate Market Share Database)
ICD Evolution
ICD Components