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CHAPTER 14 Agents Used in Cardiac Arrhythmias 237

Polymorphic ventricular tachycardia
(torsade de pointes)

NSB

Prolonged QT interval

FIGURE 14–8 Electrocardiogram from a patient with the long QT syndrome during two episodes of torsades de pointes. The polymorphic
ventricular tachycardia is seen at the start of this tracing and spontaneously halts at the middle of the panel. A single normal sinus beat (NSB)
with an extremely prolonged QT interval follows, succeeded immediately by another episode of ventricular tachycardia of the torsades type.
The usual symptoms include dizziness or transient loss of consciousness. (Reproduced, with permission, from Basic and Clinical Pharmacology, 10th edition,
McGraw-Hill, 2007. Copyright © The McGraw-Hill Companies, Inc.)

the number of available unblocked channels, which reduces the have minimal effects on the APD and dissociate from the
excitatory currents to a level below that required for propagation channel with slow kinetics.
(Figure 14–4, left); and (2) prolongation of recovery time of the 2. Class 2 action is sympatholytic. Drugs with this action reduce
channels still able to reach the rested and available state, which β-adrenergic activity in the heart.
increases the effective refractory period (Figure 14–4, right). As 3. Class 3 action manifests as prolongation of the APD. Most
a result, early extrasystoles are unable to propagate at all; later drugs with this action block the rapid component of the
impulses propagate more slowly and are subject to bidirectional delayed rectifier potassium current, I .
Kr
conduction block. 4. Class 4 action is blockade of the cardiac calcium current. This
By these mechanisms, antiarrhythmic drugs can suppress ecto-
pic automaticity and abnormal conduction occurring in depolar- action slows conduction in regions where the action potential
upstroke is calcium dependent, eg, the SA and AV nodes.
ized cells—rendering them electrically silent—while minimally
affecting the electrical activity in normally polarized parts of the A given drug may have multiple classes of action as indicated
heart. However, as dosage is increased, these agents also depress by its membrane and ECG effects (Tables 14–2 and 14–3). For
conduction in normal tissue, eventually resulting in drug-induced example, amiodarone shares all four classes of action. Drugs are
arrhythmias. Furthermore, a drug concentration that is therapeu- usually discussed according to the predominant class of action.
tic (antiarrhythmic) under the initial circumstances of treatment Certain antiarrhythmic agents, eg, adenosine and magnesium, do
may become “proarrhythmic” (arrhythmogenic) during fast heart not fit readily into this scheme and are described separately.
rates (more development of block), acidosis (slower recovery from
block for most drugs), hyperkalemia, or ischemia.
SODIUM CHANNEL-BLOCKING
DRUGS (CLASS 1)
■ SPECIFIC ANTIARRHYTHMIC Drugs with local anesthetic action block sodium channels and
AGENTS reduce the sodium current, I . They are the oldest group of anti-
Na
arrhythmic drugs and are still widely used.
The most widely used scheme for the classification of antiarrhyth-
mic drug actions recognizes four classes:
PROCAINAMIDE (SUBGROUP 1A)
1. Class 1 action is sodium channel blockade. Subclasses of this
action reflect effects on the action potential duration (APD)
and the kinetics of sodium channel blockade. Drugs with class Cardiac Effects
1A action prolong the APD and dissociate from the channel By blocking sodium channels, procainamide slows the upstroke
with intermediate kinetics; drugs with class 1B action shorten of the action potential, slows conduction, and prolongs the QRS
the APD in some tissues of the heart and dissociate from the duration of the ECG. The drug also prolongs the APD (a class 3
channel with rapid kinetics; and drugs with class 1C action action) by nonspecific blockade of potassium channels. The drug