Page 263 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 14 Agents Used in Cardiac Arrhythmias 249

4. Question the need for therapy. The mere identification of pointes. Treatment for torsades requires recognition of the arrhyth-
an abnormality of cardiac rhythm does not necessarily require mia, withdrawal of any offending agent, correction of hypokale-
that the arrhythmia be treated. An excellent justification for mia, and treatment with maneuvers to increase heart rate (pacing
conservative treatment was provided by the Cardiac Arrhyth- or isoproterenol); intravenous magnesium also appears effective,
mia Suppression Trial (CAST) referred to earlier. even in patients with normal magnesium levels.
Drugs that markedly slow conduction, such as flecainide,
Benefits & Risks or high concentrations of quinidine can result in an increased
frequency of reentry arrhythmias, notably ventricular tachycardia
The benefits of antiarrhythmic therapy are difficult to establish. in patients with prior myocardial infarction in whom a potential
Two types of benefits can be envisioned: reduction of arrhythmia- reentry circuit may be present. Treatment here consists of recogni-
related symptoms, such as palpitations, syncope, or cardiac arrest; tion, withdrawal of the offending agent, and intravenous sodium
and reduction in long-term mortality in asymptomatic patients. to reverse unidirectional block.
Among drugs discussed here, only β blockers have been definitely
associated with reduction of mortality in relatively asymptomatic Conduct of Antiarrhythmic Therapy
patients, and the mechanism underlying this effect is not estab-
lished (see Chapter 10). The urgency of the clinical situation determines the route and
Antiarrhythmic therapy carries with it a number of risks. In rate of drug initiation. When immediate drug action is required,
some cases, the risk of an adverse reaction is clearly related to high the intravenous route is preferred. Therapeutic drug levels can be
dosages or plasma concentrations. Examples include lidocaine- achieved by administration of multiple slow intravenous boluses.
induced tremor or quinidine-induced cinchonism. In other cases, Drug therapy can be considered effective when the target arrhyth-
adverse reactions are unrelated to high plasma concentrations mia is suppressed (according to the measure used to quantify it at
(eg, procainamide-induced agranulocytosis). For many serious baseline) and toxicities are absent. Conversely, drug therapy should
adverse reactions to antiarrhythmic drugs, the combination of drug not be considered ineffective unless toxicities occur at a time when
therapy and the underlying heart disease appears important. arrhythmias are not suppressed.
Several specific syndromes of arrhythmia provocation by antiar- Monitoring plasma drug concentrations can be a useful
rhythmic drugs have also been identified, each with its underly- adjunct to managing antiarrhythmic therapy. Plasma drug con-
ing pathophysiologic mechanism and risk factors. Drugs such as centrations are also important in establishing compliance during
quinidine, sotalol, ibutilide, and dofetilide, which act—at least long-term therapy as well as in detecting drug interactions that
in part—by slowing repolarization and prolonging cardiac action may result in very high concentrations at low drug dosages or very
potentials, can result in marked QT prolongation and torsades de low concentrations at high dosages.

Antiarrhythmic Drug-Use Principles Applied to Atrial Fibrillation

Atrial fibrillation is the most common sustained arrhythmia (maintenance of ventricular rate in the range of 60–80 bpm) has
observed clinically. Its prevalence increases from approximately a better benefit-to-risk outcome than rhythm control (conversion
0.5% in individuals younger than 65 years of age to 10% in indi- to normal sinus rhythm) in the long-term health of patients with
viduals older than 80. Diagnosis is usually straightforward by atrial fibrillation. If rhythm control is deemed desirable, sinus
means of an ECG. The ECG may also enable the identification of a rhythm is usually restored by DC cardioversion in the USA. This is
prior myocardial infarction, left ventricular hypertrophy, and ven- also the preferred strategy in an emergency, eg, atrial fibrillation
tricular pre-excitation. Hyperthyroidism is an important treatable associated with hypotension or angina. For the elective restora-
cause of atrial fibrillation, and a thyroid panel should be obtained tion of sinus rhythm, a single large oral dose of propefenone or
at the time of diagnosis to exclude this possibility. With the clini- flecainide may be used, provided that safety is initially docu-
cal history and physical examination as a guide, the presence and mented in a monitored setting. Intravenous ibutilide can also
extent of the underlying heart disease should be evaluated, pref- restore sinus rhythm promptly.
erably using noninvasive techniques such as echocardiography. The selection of a drug to maintain normal sinus rhythm
Treatment of atrial fibrillation is initiated to relieve patient depends on the presence and type of underlying heart disease.
symptoms and prevent the complications of thromboembolism An example of an algorithm for drug selection is given in
and tachycardia-induced heart failure, the result of prolonged Figure 14–11.
uncontrolled heart rates. The initial treatment objective is con- Antiarrhythmic drugs remain the preferred rhythm control
trol of the ventricular rate. This is usually achieved by use of a strategy. However, a comparison of initial strategies for the mainte-
calcium channel-blocking drug alone or in combination with a nance of normal sinus rhythm is currently undergoing clinical trial.
β-adrenergic blocker. Digoxin may be of value in the presence of The pivotal role of oral anticoagulation in the prevention of stroke
heart failure. A second objective is a restoration and maintenance is established. Currently guidelines identify patients who are at
of normal sinus rhythm. Several studies show that rate control particular risk and should undergo long-term anticoagulation.