Review of Pharmacology - 9E (2015)

Cardiovascular System
depolarized cells with fast response action potential. They either do not change or decrease
the APD in non-depolarized tissues. These drugs are used only for ventricular arrhythmia.
• Lignocaine is the most commonly used local anaesthetic agent. It has very high
first pass metabolism, therefore administered only by i.v. route. Excessive dose
can lead to neurological toxicity (drowsiness, paraesthesia, convulsions and coma)
and myocardial depression. It is the drug of choice for the treatment of ventricular
arrhythmias due to digitalis toxicity. (ineffective in atrial arrhythmias).
• Mexiletine is an orally active lignocaine derivative with all the properties of
lignocaine.
• Phenytoin is a popular antiepileptic drug. It can be used as an alternative to
lignocaine for digitalis induced ventricular arrhythmias.
• Tocainide (group Ib drug having similar name as group Ic drugs like encainide
and flecainide) can be given orally but not used widely because of risk of
agranulocytosis.
Lignocaine is drug of choice
for digitals-induced ventricular
arrhythmias
Procainamide is metabolized in
liver by acetylation
Treatment of choice for WPW
syndrome is radiofrequency
ablation of the aberrant pathway
CLASS IC AGENTS
These agents have the most potent sodium channel blocking effects with negligible effect on
K + channels (therefore no effect on APD). These have slow kinetics (τ > 10s). Drugs in this
group include encainide, moricizine, flecainide and propafenone. These drugs have maximum proarrhythmic
property, therefore indicated only for the resistant and life-threatening ventricular
tachycardia or ventricular fibrillation and for the treatment of refractory supraventricular
tachycardia. Flecainide can be used for acute treatment of Wolff Parkinson White (WPW)
syndrome. [Treatment of choice for WPW syndrome is radiofrequency ablation of the aberrant
pathway].
Class II Agents
Class II agents are conventional beta blockers. They act by blocking the effects of adrenaline
and nor-adrenaline at the β 1
receptors, thereby decreasing the sympathetic activity on the
heart. These agents are particularly useful in the treatment of supraventricular tachycardia.
These drugs decrease the slope of phase 4 (responsible for automaticity) and conduction through
the AV node. Important β blockers used as antiarrhythmic agents are esmolol, propranolol, and
metoprolol. Esmolol is the shortest acting beta blocker. It can be used i.v. for the emergency
control of ventricular rate in atrial fibrillation or flutter.
General Cardiovascular Pharmacology System
Class III Agents
Class III agents predominantly block the potassium channels, thereby prolonging repolarization
(prolongation of APD). These drugs may precipitate torsades de’pointes due to prolongation of
QT interval.
Fig. 5.7: Action of class III antiarrhythmic
agents (shown by
dotted line)
These drugs exhibit reverse use dependent prolongation of the action potential duration (Reverse
use-dependence). This means that the refractoriness increases at lower heart rates, therefore
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