Lippincott

Illustrated Reviews:
Pharmacology
DR NESAR A. ZAHIER, MD (KUMS), PGD (MOPH)
ECHOCARDIOLOGIST, SONOLOGIST, LECTURER & TRAINER SPECIALIST (KUMS & ALI ABAD TEACHING HOSPITAL)
‫بسم هللا الرحمن‬
‫الرحیم‬
Antiarrhythmics
Cardiac conduction system & Action
potential
Action potential in different parts
Arrhythmias

 Anatomical sites
1. Atrial
2. Supraventricular
3. Ventricular
Causes of arrhythmias

 Abnormal authomaticity
 Abnormal conduction
Reentry is example of abnormal
conduction
Anti-arrhythmic drugs
Anti arrhythmic drugs & its effect
Proarrhythmic action of
antiarrhythmics

 K+ channel blocker activity  prolong QT interval  torsades de

pointes

QT prolongation
1. Drugs: class III, macrolids, antisychotics, cisapride & terfenadine
2. Ischemia
3. Hypokalemia
4. Genetic profile
 So nowadays  implantable cardioverter defibrillators are widely
used
 CLASS I ANTIARRHYTHMIC DRUGS

 Action: block voltage-sensitive Na+ channels in frequently

depolarizing tissues
 Not used widely, & not used in ventricular dysfunction & IHD

 According to the duration of action potential

1. Class IA  moderate Na+ blocker & prolong action potential
2. Class IB  weak Na+ blocker & shorten action potential
3. Class IC  strong Na+ blocker & no change action potential
 Class IA antiarrhythmic drugs

 Quinidine, procainamide, and disopyramide

 Concomitant class III activity (prolong action potential) 
arrhythmias
 Action: block frequently activating Na channel in fast tissues,
decrease the slope of phase 4 (SAN), inhibit K+ channels, & blocks
Ca++ channels
 Quinidine also anticholinergic action and alpha blocking
 Disopyramide  negative inotropic and peripheral
vasoconstriction
Continued…

 Uses: atrial, AV junctional & ventricular tachyarrhythmias

Adverse effects:
 Quinidine  quinism or cinchonism (blurred vision, tinnitus,
headache, disorientation, & psychosis
 Disopyramide  anticholinergic effects (dry mouth, urinary
retention, blurred vision, constipation)
Class IB antiarrhythmic drugs

 Lidocaine and mexiletine

 Action: block Na+ channel & decrease action potential
 Uses: ventricular arrhythmias (VF, pulseless VT, polymorphic VT) and
because of no effect on conduction  no value in atrial and AV
junctional arrhythmias
 Side effects:
 Lidocaine  CNS effects: nystagmus, drowsiness, slurred speech,
paresthesia, agitation, confusion, and convulsions
 Mexiletine  Nausea, vomiting, and dyspepsia
Class IC antiarrhythmic drugs

 Flecainide and propafenone

 Slow rate of dissociation from resting Na channels  not safe in structural
heart disease
 Action: strongly suppress phase 0 depolarization, decrease authomaticity
by increasing threshold of phase 4 in SAN
 Uses: maintenance of sinus rhythm in atrial flutter & fibrillation without
structural heart disease, and treating refractory ventricular arrhythmias
 Propafenone has beta blocking activities, contraindicated in asthma
 Side effects: blurred vision, dizziness, and nausea.
 CLASS II ANTIARRHYTHMIC DRUGS

 β-adrenergic antagonists, or β-blockers

 Action: Diminish phase 4 depolarization and depress
automaticity, prolong AV conduction, and
decrease heart rate and contractility
 Uses: Treating tachyarrhythmias caused by
increased sympathetic Activity, atrial flutter and
fibrillation and for AV nodal reentrant tachycardia
 Prevent life-threatening ventricular arrhythmias
following a myocardial infarction
Continued…

Metoprolol
 Widely used in the treatment of cardiac arrhythmias with less risk of
broncho-spasm
 CNS penetration (less than propranolol, but more than atenolol
Esmolol
 Very-short-acting β-blocker used for intravenous administration in acute
arrhythmias that occur during surgery or emergency situations
 Fast onset of action and a short half-life rapidly metabolized by esterases in
red blood cells
CLASS III ANTIARRHYTHMIC DRUGS

 Block K+ channels  prolong action potential  proarrhythmic effects

 Increase refractory period

 Amiodarone: all classes activity and alpha blocking also, has Iodine
 Dronedarone: all classes activity
 Sotalol: class III and beta blocker activity
 Dofetilide: pure K+ channel blocker
 Ibutilide: class IA and III activity
CLASS IV ANTIARRHYTHMIC DRUGS

 Nondihydropyridine calcium channel blockers verapamil & diltiazem

 Action: Block voltage-sensitive calcium channels occur in many
different tissues, like vascular smooth muscle and the heart
 Verapamil  greater action on the heart than on vascular smooth
muscle
 Decreased rate of phase 4 spontaneous depolarization
 Slow conduction in AV and SA nodes
 Uses: more effective against atrial than against ventricular arrhythmias
 Reentrant supraventricular tachycardia and in reducing the ventricular
rate in atrial flutter and fibrillation
OTHER ANTIARRHYTHMIC DRUGS

Digoxin
3
 Block Na-K ATPase  shortening refractory 2
period in atrial & myocardial cells
 Prolong effective refractory period &
diminish conduction velocity in AVN
 Uses: control ventricular response in AF &
Atrial flutter, systolic heart failure
 Toxic doses: VT & VF
Continued…

Adenosine
 Action: Decreases conduction velocity, prolongs the refractory
period, and decreases automaticity in the AV node
 Uses: acute supraventricular tachycardia
 Side effects: flushing, chest pain, and hypotension
 Extremely short duration of action (approximately 10 to 15 seconds)
due to rapid uptake by erythrocytes and endothelial cells
Continued…

Magnesium sulfate
 Magnesium is necessary for the transport of sodium,
calcium, and potassium across cell membranes
 It slows the rate of SA node impulse formation and
prolongs conduction time along the myocardial tissue
 Uses: torsades de pointes and digoxin-induced
arrhythmias
Thanks