The effects of disopyramide are very similar to those of procainamide and quinidine. Its cardiac antimuscarinic effects are even more marked than those of quinidine. Therefore, a drug that slows AV conduction should be administered with disopyramide when treating atrial flutter or fibrillation.
Toxic concentrations of disopyramide can precipitate all of the electrophysiologic disturbances described under quinidine. As a result of its negative inotropic effect, disopyramide may precipitate heart failure de novo or in patients with preexisting depression of left ventricular function. Because of this effect, disopyramide is not used as a first-line antiarrhythmic agent in the USA. It should not be used in patients with heart failure.
Disopyramide’s atropine-like activity accounts for most of its symptomatic adverse effects: urinary retention (most often, but not exclusively, in male patients with prostatic hyperplasia), dry mouth, blurred vision, constipation, and worsening of preexisting glaucoma.
These effects may require discontinuation of the drug.
In the USA, disopyramide is only available for oral use. The typical oral dosage of disopyramide is 150 mg three times a day, but up to 1 g/d has been used. In patients with renal impairment, dosage must be reduced. Because of the danger of precipitating heart failure, loading doses are not recommended.
Although disopyramide has been shown to be effective in a variety of supraventricular arrhythmias, in the USA, it is approved only for the treatment of ventricular arrhythmias.
Lidocaine has a low incidence of toxicity and a high degree of effectiveness in arrhythmias associated with acute myocardial infarction. It is used only by the intravenous route.
Lidocaine blocks activated and inactivated sodium channels with rapid kinetics (Figure 14–10); the inactivated state block ensures greater effects on cells with long action potentials such as Purkinje and ventricular cells, compared with atrial cells. The rapid kinetics at normal resting potentials result in recovery from block between action potentials and no effect on conduction. In depolarized cells, the increased inactivation and slower unbinding kinetics result in the selective depression of conduction. Little effect is seen on the ECG in normal sinus rhythm.
Lidocaine is one of the least cardiotoxic of the currently used sodium channel blockers. Proarrhythmic effects, including SA node arrest, worsening of impaired conduction, and ventricular arrhythmias, are uncommon with lidocaine use. In large doses, especially in patients with preexisting heart failure, lidocaine may cause hypotension—partly by depressing myocardial contractility.