Rozaimah Zain-Hamid & Tri Widyawati

Department Pharmacology and Therapeutics

Faculty of Medicine
Universitas Sumatera Utara
 Normal conduction pathway

SA node
Generates action
potential

AV node
Delivers the impulse
to purkinje fibers

Purkinje fibers
Conduct the impulse
to the ventricles
 Cardiac arrhythmia

Any disorder of rate, rhythm, origin,

or conduction of impulses within the heart

Results from abnormalities

of pacemaker activity or cardiac conduction

80-90 % in case of myocard infarction

20-50 % during general anaesthesia
10-25 % in patients being treated with digitalis
(hospitalized)
Types therapy for cardiac arrhythmia

 Drugs  modify or substitute

for autonomic cardiac control mechanism

 Drugs act directly on cardiac cells

 Electrical pacemakers
& direct current (DC) electroshock or
“cardioversion”
 Schematic representation of the heart
& normal cardiac electrical activity
(intracellular recordings from areas indicated & ECG)
The action potentialgoverned by both
Na+ & K+ ion transport

 Inward Na+ flow (phase 0) influence depolarization

& outward K+ flow (phase 3) influences
repolarization

 Blocking Na+ influx   impulse conduction

 Blocking K+ efflux  prolonged refractory period

 Enhancing K+ efflux  shortened refractory period

 Ca++ influx during phase 2

& is primary responsible for muscle contractility
 Dominant cations
of the cardiac conduction pathway

Site Dominant cation

SA node Ca++

Atrium Na + / K+

AV node Ca ++

Ventricle Na + / K+
 Drugs for cardiac arrhythmia

1. Class I : Local anesthetic action

(Sodium channel blockers)
2. Class II :  - adrenergic blockers.
3. Class III : Inhibitors / prolonged
of repolarization
4. Class IV : Calcium channel blockers.
5. Others : Adenosine, K+ and Mg++
Class Ia antiarrhythmics
Mechanism: Local anesthetic action
Moderate sodium channel blockade,
prolongation of repolarisation
(prolonged refractory period)
Drug: Quinidine
Location of action : Atrial and ventricle
Clinical Uses :  atrial & ventricular arrhythmia
Side Effects/Toxicities: Cinchonism, headache,
tinnitus, hemolytic anemia, thrombocytopenia,
torsades de pointes, syncope.
Others of class Ia antiarrhythmics: procainaide,
disopyramide
Class Ib antiarrhythmics
Mechanism: Mild sodium channel blockade,
shortening of repolarization
(shortening refractory period)
Drug: Lidocaine
Location of action: ventricle
Clinical Uses : Acute ventricular arrhythmias,
digitalis-induced arrhythmias
Side Effects/Toxicities: Confusion, dizziness,
seizures
Others of class Ib antiarrhythmics: phenytoin
Notes: Lidocaine also used as a local anesthetic
Class Ic antiarrhythmics
Mechanism : Strong sodium channel blockade
 conduction
Drug: Flecainide
Location of action : Ventricle
Clinical Uses: ventricular arrhythmia
& supraventricular arrhythmia
Side Effects/Toxicities: Proarrhythmic.
Others of class Ib antiarrhythmics: propafenone,
moricizine
Notes:
Due to serious proarrhythmic effects,
used only as a last resort
Class II antiarrhythmics
Mechanism:  adrenergic receptor blockade
Blocking Ca++ (indirect sympatholytic)
Drug: Propranolol
Location of action: SA node & AV node
Clinical Uses :  SA initiation &  AV conduction
 VT & SVT
Side Effects/Toxicities: Bronchospasm, impotence,
bradycardia, heart block, insomnia, depression
Contra indications: Nonselective -blockers 
relatively contraindicated in asthmatics
Others of class II antiarrhythmics: Esmolol
Notes: May mask signs of hypoglycemia
Class III antiarrhythmics
Mechanism: Prolonged repolarization,
mainly through potassium channel blockade
Drug: Bretylium
Location of action: atrium & ventricle
Clinical uses: Life-threatening VF and VT unresponsive
to lidocaine and defibrillation.
Side Effects/Toxicities: Orthostatic hypotension,
new arrhythmias
Others of class II antiarrhythmics: sotalol,
amidarone
Notes: Also an antihypertensive agent
Class III Antiarrhythmics
Mechanism: Prolongation of action potential,
mainly through K++ channel blockade
Drug: Sotalol
Location of action: atrium & ventricle
Clinical Uses : Supraventricular and ventricular
tachycardia
Side Effects/Toxicities: Predisposes to torsades
de pointes, excessive  blockade
Contraindications:Preexisting prolonged QT interval
Notes: Also a nonselective -adrenergic receptor
antagonist
Class III Antiarrhythmics
Mechanism : Prolongation of action potential,
mainly through potassium channel
blockade.
Drug: Amiodarone
Location of action: atrium & ventricle
Clinical Uses : - Atrial fibrillation, hypertrophic
cardiomyopathy, SVT.
- Chemical cardioversion of malignant
ventricular arrhythimia, VF,
pulseless VT
Side Effects/Toxicities: Pulmonary fibrosis,
hepatotoxicity, thyroid dysregulation,
corneal deposits, skin deposits leading
to photodermatitis, neurological effects
Drug: amiodarone (con’t)

Contraindications: LV dysfunction, second or third

degree AV block, atrial fib/flutter with bypass tract,
sick sinus syndrom
Class IV Antiarrhythmics
Mechanism: Calcium channel blockade
Drug: Verapamil
Location of action: SA node & AV node
Clinical Uses: supraventricular tachycardia,
atrial fibrillation and flutter, angina,
hypertension
Side Effects/Toxicities: CHF (especially verapamil),
AV block, sinus node depression, constipation,
flushing, edema.
Contraindications: LV dysfunction, 2nd or 3rd degree
AV block, atrial fibrillation/flutter with bypass tract,
sick sinus syndrome.
Other antiarrhythmia
Mechanism : Enhances K+ conductance and
inhibits Ca2+ influx in SA and AV
nodal cells.
Drug: Adenosine
Clinical Uses : Paroxysmal Supraventricular
Tachycardia (PSVT)
Side Effects/Toxicities
Arrhythmia, flushing, hypotension.
 Conclusions

 Classification of antiarrhythmics :
Mechanism & location of action

 The site of action of antiarrhythmics :

sympathetic activity, myocardial energy
metabolism, calcium hemostasis,
contractile protein
Thank You