Home | | Pharmacology | Principles in the Clinical Use of Antiarrhythmic Agents

Chapter: Basic & Clinical Pharmacology : Agents Used in Cardiac Arrhythmias

Principles in the Clinical Use of Antiarrhythmic Agents

The margin between efficacy and toxicity is particularly narrow for antiarrhythmic drugs. Risks and benefits must be carefully considered (see Box: Antiarrhythmic Drug-Use Principles Applied to Atrial Fibrillation).


The margin between efficacy and toxicity is particularly narrow for antiarrhythmic drugs. Risks and benefits must be carefully considered (see Box: Antiarrhythmic Drug-Use Principles Applied to Atrial Fibrillation).

Pretreatment Evaluation

Several important steps must be taken before initiation of any antiarrhythmic therapy:

1. Eliminate the cause. Precipitating factors must be recognized and eliminated if possible. These include not only abnormali-ties of internal homeostasis, such as hypoxia or electrolyte abnormalities (especially hypokalemia or hypomagnesemia), but also drug therapy and underlying disease states such as hyperthyroidism or cardiac disease. It is important to separate this abnormal substrate from triggering factors, such as myo-cardial ischemia or acute cardiac dilation, which may be treat-able and reversible by different means.

2. Make a firm diagnosis. A firm arrhythmia diagnosis should beestablished. For example, the misuse of verapamil in patients with ventricular tachycardia mistakenly diagnosed as supraven-tricular tachycardia can lead to catastrophic hypotension and cardiac arrest. As increasingly sophisticated methods to charac-terize underlying arrhythmia mechanisms become available and are validated, it may be possible to direct certain drugs toward specific arrhythmia mechanisms.


3. Determine the baseline condition. Underlying heart disease isa critical determinant of drug selection for a particular arrhyth-mia in a particular patient. A key question is whether the heart is structurally abnormal. Few antiarrhythmic drugs have docu-mented safety in patients with congestive heart failure or isch-emic heart disease. In fact, some drugs pose a documented proarrhythmic risk in certain disease states, eg, class 1C drugs in patients with ischemic heart disease. A reliable baseline should be established against which to judge the efficacy of any subsequent antiarrhythmic intervention. Several methods are now available for such baseline quantification. These include pro-longed ambulatory monitoring, electrophysiologic studies that reproduce a target arrhythmia, reproduction of a target arrhyth-mia by treadmill exercise, or the use of transtelephonic monitor-ing for recording of sporadic but symptomatic arrhythmias.


4. Question the need for therapy. The mere identification of anabnormality of cardiac rhythm does not necessarily require that the arrhythmia be treated. An excellent justification for conser-vative treatment was provided by the Cardiac Arrhythmia Suppression Trial (CAST) referred to earlier.


Antiarrhythmic Drug-Use Principles Applied to Atrial Fibrillation

Atrial fibrillation is the most common sustained arrhythmia observed clinically. Its prevalence increases from ~ 0.5% in indi-viduals younger than 65 years of age to 10% in individuals older than 80. Diagnosis is usually straightforward by means of an ECG. The ECG may also enable the identification of a prior myocardial infarction, left ventricular hypertrophy, and ventricular pre-exci-tation. Hyperthyroidism is an important treatable cause of atrial fibrillation, and a thyroid panel should be obtained at the time of diagnosis to exclude this possibility. With the clinical history and physical examination as a guide, the presence and extent of the underlying heart disease should be evaluated, preferably using noninvasive techniques such as echocardiography.

Treatment of atrial fibrillation is initiated to relieve patient symptoms and prevent the complications of thromboembolism and tachycardia-induced heart failure, the result of prolonged uncontrolled heart rates. The initial treatment objective is con-trol of the ventricular rate. This is usually achieved by use of a calcium channel-blocking drug alone or in combination with a β-adrenergic blocker. Digoxin may be of value in the presence of heart failure. A second objective is a restoration and mainte-nance of normal sinus rhythm. Several studies show that rate control (maintenance of ventricular rate in the range of 60–80 bpm) has a better benefit-to-risk outcome than rhythm control (conversion to normal sinus rhythm) in the long-term health of patients with atrial fibrillation. If rhythm control is deemed desir-able, sinus rhythm is usually restored by DC cardioversion in the USA; in some countries, a class 1 antiarrhythmic drug is used initially. For patients with paroxysmal atrial fibrillation, normal sinus rhythm may be restored with a single large oral dose of propafenone or flecainide, provided that safety is initially docu-mented in a monitored setting. Intravenous ibutilide can restore sinus rhythm promptly. For restoration of sinus rhythm in an emergency, eg, atrial fibrillation associated with hypotension or angina, DC cardioversion is the preferred modality. A class 1 or class 3 antiarrhythmic drug is then used to maintain normal sinus rhythm.

Benefits & Risks

The benefits of antiarrhythmic therapy are actually relatively dif-ficult to establish. Two types of benefits can be envisioned: reduc-tion of arrhythmia-related symptoms, such as palpitations, syncope, or cardiac arrest; and reduction in long-term mortality in asymptomatic patients. Among drugs discussed here, only blockers have been definitely associated with reduction of mor-tality in relatively asymptomatic patients, and the mechanism underlying this effect is not established .

Antiarrhythmic therapy carries with it a number of risks. In some cases, the risk of an adverse reaction is clearly related to high dosages or plasma concentrations. Examples include lidocaine-induced tremor or quinidine-induced cinchonism. In other cases, adverse reactions are unrelated to high plasma concentrations (eg, procainamide-induced agranulocytosis). For many serious adverse reactions to antiarrhythmic drugs, the combination of drug ther-apy and the underlying heart disease appears important.

Several specific syndromes of arrhythmia provocation by anti-arrhythmic drugs have also been identified, each with its underly-ing pathophysiologic mechanism and risk factors. Drugs such asquinidine, sotalol, ibutilide, and dofetilide, which act—at least in part—by slowing repolarization and prolonging cardiac action potentials, can result in marked QT prolongation and torsades de pointes. Treatment for torsades requires recognition of the arrhythmia, withdrawal of any offending agent, correction of hypokalemia, and treatment with maneuvers to increase heart rate (pacing or isoproterenol); intravenous magnesium also appears effective, even in patients with normal magnesium levels.

Drugs that markedly slow conduction, such as flecainide, or high concentrations of quinidine, can result in an increased frequency of reentry arrhythmias, notably ventricular tachycardia in patients with prior myocardial infarction in whom a potential reentry circuit may be present. Treatment here consists of recognition, withdrawal of the offending agent, and intravenous sodium.

Conduct of Antiarrhythmic Therapy

The urgency of the clinical situation determines the route and rate of drug initiation. When immediate drug action is required, the intravenous route is preferred. Therapeutic drug levels can be achieved by administration of multiple slow intravenous boluses. Drug therapy can be considered effective when the target arrhyth-mia is suppressed (according to the measure used to quantify it at baseline) and toxicities are absent. Conversely, drug therapy should not be considered ineffective unless toxicities occur at a time when arrhythmias are not suppressed.

Monitoring plasma drug concentrations can be a useful adjunct to managing antiarrhythmic therapy. Plasma drug concentrations are also important in establishing compliance during long-term therapy as well as in detecting drug interactions that may result in very high concentrations at low drug dosages or very low concen-trations at high dosages.

Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail
Basic & Clinical Pharmacology : Agents Used in Cardiac Arrhythmias : Principles in the Clinical Use of Antiarrhythmic Agents |

Privacy Policy, Terms and Conditions, DMCA Policy and Compliant

Copyright © 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.