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II. SELECTION OF AN ANTIARRHYTHMIC DRUG

Selection of a drug in a complicated arrhythmia is often
difficult because of the lack of knowledge regarding the exact
mechanism of the arrhythmia. In some cases, certain agents will
be excluded by the existence of contraindications to their use.
Choice of an agent may be aided or narrowed by testing the
candidate drugs with programmed electrical stimulation (PES) in
the clinical electrophysiology laboratory, or with prolonged (48
hr) Holter monitoring; by knowledge of prior efficacy of a drug
in that patient; by presence of nodal dysfunction; and by
presence of congestive heart failure. The drugs available are
commonly classified into 4 groups. These groups are discussed be-
low and listed in the following tables:
Group IA:
Group IB:
Group IC:
Groups II, III, and IV:
Miscellaneous agents (amiodarone, digoxin, phenytoin):



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1. Sodium channel blockers (Group I). Quinidine and its
congeners have a local anesthetic-like action on ventricular
muscle and on the rapid conduction system. Conduction is
slowed and ectopic pacemaker discharge rate is reduced.
* Group IA agents (eg, quinidine, see ) produce a dose-
dependent prolongation of the QRS duration, reflecting
slowing of intraventricular conduction even in normal
myocardium. They also increase the QTc duration.

* Group IB agents (lidocaine, etc ) produce little ECG
effect; their action on normal myocardium is minimal, but
they have significant effects on abnormal tissue, especially
in the conducting system and the ventricular myocardium.

* Group IC drugs (flecainide, encainide, ) are potent
depressants of conduction and prolong the QRS and PR interval
but have little effect on QTc duration.





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2. Sympathetic nervous system blockers (Group II). Propranolol
and other beta blockers act by this mechanism and, to a
lesser extent, through sodium channel blockade. Some of the
effect of bretylium probably results from this mechanism.
Esmolol is an new ultra-short-acting beta blocker that has
been used successfully to reduce heart rate and suppress
arrhythmias during cardiac surgery. The ECG effects of the
beta-adrenoceptor blocking agents are not dramatic but often
include sinus rate slowing and PR prolongation.
3. Drugs that prolong of the action potential (Group III). Drugs
in this class, eg, bretylium, probably block potassium
channels in myocardial cells in addition to other effects.
Quinidine and amiodarone also significantly prolong the
action potential. This action is reflected in the ECG by QTc
prolongation. Sotalol and clofilium are investigative group
III drugs.
4. Calcium channel blockers (Group IV). The calcium channel
blockers reduce pacemaker activity and conduction in the SA
and AV nodes, and significantly prolong AV nodal
refractoriness. The ECG manifestations include PR
prolongation.

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Major indications for selected drugs (see also ):
* Isolated atrial premature depolarizations: seldom require
therapy. If associated with symptoms, Group IA agents or
beta-blockers may be used.

* Paroxysmal supraventricular tachycardia (including sinus node
reentry, atrial reentry, AV nodal reentry, or
atrioventricular tachycardia involving a bypass tract):
- Acute therapy: vagal maneuvers (eg,carotid sinus massage);
IV verapamil; IV adenosine (investigational); IV
propranolol (if calcium channel blocker has not been
used); IV procainamide; direct current countershock
- Chronic maintenance therapy: Digoxin, beta-blockers,
calcium channel blockers, group IA agents, flecainide, or
amiodarone have all been used. Diltiazem (investigational
use) may be useful. Digoxin is contraindicated in WPW
syndrome. If drugs are ineffective or not tolerated,
surgical procedures, antitachycardia pacing, or catheter
ablation procedures may be considered.


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* Atrial flutter or fibrillation:
- Acute therapy: IV digoxin, IV verapamil, IV beta-blockers,
or DC countershock. Digoxin and verapamil are
contraindicated in patients with WPW syndrome and atrial
fibrillation. These patients should be treated with IV
procainamide and DC shock.
- Maintenance therapy: Group IA drugs, or amiodarone
(investigational). Diltiazem (investigational use) may be
useful in ventricular rate control. Consider surgery for
patients with WPW syndrome and fibrillation.

* Ventricular premature depolarizations: quinidine,
procainamide, disopyramide, lidocaine, mexiletine, tocainide,
propranolol, acebutolol, flecainide, (amiodarone, unlabelled)

* Unsustained ventricular tachycardia: quinidine, procainamide,
disopyramide, lidocaine, mexiletine, tocainide, flecainide,
(amiodarone, unlabelled)



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* Sustained ventricular tachycardia and recurrent ventricular
fibrillation:
- Acute therapy: DC countershock, IV lidocaine, IV
procainamide, IV bretylium, (or IV amiodarone,
investigational)
- Chronic therapy: Drug selection should be guided by
programmed stimulation electrophysiologic testing. For
refractory cases, consider cardiac electrosurgery,
catheter ablation procedures, or insertion of automatic
internal cardioverter defibrillator.

* Drug or hormone-related arrhythmias: may be caused by any
Group IA antiarrhythmic agent (pattern may be polymorphous
ventricular tachycardia or torsade de pointes), digitalis
excess, catecholamine excess, or thyrotoxicosis. Therapy
includes prompt cessation of the causative agent, IV
lidocaine, IV phenytoin, or beta-blockers in the case of
thyrotoxicosis. Resistant cases may require IV magnesium and
cardiac pacing.


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Drugs of Special Importance
* Quinidine is the prototype antiarrhythmic and still perhaps
the single most useful drug for oral therapy of cardiac
arrhythmias. Procainamide and disopyramide have similar
efficacy profiles but are less well tolerated in chronic oral
therapy than quinidine.
* Lidocaine is one of the most useful agents for the rapid
control of life-threatening arrhythmias, especially those
associated with myocardial infarction and digitalis
intoxication. It has the lowest toxicity of all the
antiarrhythmic drugs but it must be used parenterally.
Tocainide and mexiletine are orally active drugs with similar
actions.
* Amiodarone is one of the most efficacious of all the
antiarrhythmic agents, but it is also one of the most toxic.
It is therefore reserved for use only when other agents fail.
Flecainide is less toxic overall than amiodarone but is more
proarrhythmic and has a much more restricted spectrum of
action.
* Verapamil is considered the drug of choice for acute
management of narrow QRS supraventricular tachycardia.

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