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3. ANTIARRHYTHMIC DRUGS
BG Katzung & MM Scheinman
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I. General principles of arrhythmia treatment
II. Drug selection
III. Adverse reactions and drug interactions
Tables
Group IA
Group IB, IC
Group II, III, IV
Miscellaneous
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I. GENERAL PRINCIPLES OF ARRHYTHMIA TREATMENT
Cardiac arrhythmias are among the most common and serious
medical emergencies. A few are relatively easy to treat; many
are very difficult. All antiarrhythmic drugs are potentially
toxic. The pharmacologic management of difficult arrhythmias is
most successful if first, the nature of the arrhythmia is
properly documented by clinical, electrocardiographic, and
electrophysiologic examination; second, the efficacy of the
candidate drug (or drugs) is adequately ascertained; and third,
the adequacy of dosage is determined by measuring the drug
concentration in the blood (see Hondeghem and Mason ref). In
most arrhythmias, selection of a drug is empiric and often,
several agents must be tried before finding one that is
effective and well tolerated by the patient.
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Pathophysiology. Arrhythmias that are associated with organic
heart disease and/or significant symptoms are generally
considered for treatment. The major mechanisms of arrhythmias
include:
* Abnormal conduction, especially reentry, which probably
causes atrial and ventricular flutter and fibrillation,
supraventricular tachycardia involving accessory pathways or
nodal reentry, and many ventricular tachycardias.
* Abnormal automaticity, which probably causes many atrial and
ventricular tachycardias, and catecholamine- and digitalis-
induced arrhythmias. Triggered arrhythmia is a form of
abnormal repetitive firing that resembles automaticity.
* Combinations of the above, which are probably responsible for
many post-infarction arrhythmias.
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Therapeutic Rationale
* Prevention of deterioration from a nonfatal into a fatal
arrhythmia, eg, from ventricular tachycardia into ventricular
fibrillation.
* Improvement of hemodynamic function, by slowing and
regularizing the cardiac rhythm, or by synchronizing atrial
and ventricular contractions.
* Prevention of intrachamber clotting that would otherwise
result from stasis (in atrial fibrillation).
* Relief of symptoms, eg those due to premature ventricular
depolarizations or supraventricular tachycardia.
Mechanisms of Drug Action
* Selective Depression: Useful antiarrhythmic drugs are usually
depressants of cardiac function. Safe and effective therapy
requires depression of the arrhythmic tissue with minimal
interference with normal tissue. Fortunately, most sites of
arrhythmogenesis are more susceptible than normal myocardium
to antiarrhythmic drugs by virtue of depolarization, rapid
discharge, or both.
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Nevertheless, all antiarrhythmic drugs
are potentially arrhythmogenic or proarrhythmic. The membrane
actions of the major antiarrhythmic drugs are summarized in
. The most important clinical effects of the agents
are listed in . Furthermore, all antiarrhythmic
agents are, to some extent, negatively inotropic, a factor of
considerable importance in patients with marginal cardiac
output.
Pharmacokinetics and Dosage
These drugs are chemically heterogeneous and therefore
vary markedly in their pharmacokinetic properties:
For Group IA drugs (quinidine, procainamide,etc)
For Groups IB and IC (lidocaine, flecainide, etc)
For Groups II, III, and IV (á-blockers, calcium channel
blockers, etc)
For drugs with multiple actions (amiodarone, etc)
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References:
1. Cheitlin MD, Abbott JA: Cardiac emergencies. In: Current
Emergency Diagnosis & Treatment, Mills J et al, eds, Lange,
1985,pp 490-500.
2. Heger JJ, et al: Amiodarone. Clinical efficacy and
electrophysiology during long-term therapy for recurrent
ventricular tachycardia or ventricular fibrillation. N Engl J
Med 1981; 305:539.
3. Hondeghem LM, Mason JW: Agents used in cardiac arrhythmias.
In: Basic & Clinical Pharmacology, BG Katzung, ed, Lange,
1987, pp 151-168.
4. Somberg, J: Antiarrhythmic drug therapy. Recent advances and
current status. Cardiology 1985; 72: 329.
5. Schmidt, G, et al: Long term efficacy of class I
antiarrhythmic agents and amiodarone in patients with
malignant ventricular arrhythmias. Drugs 1985; 29 (Suppl
3):37.
6. Woosley, RL, Echt DS, Roden DM: Treatment of ventricular
arrhythmias in the failing heart: Pharmacologic and clinical
considerations. Rational Drug Therapy 1985; 19: 1.
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