Quinidine, procainamide (Pronestyl), and disopyramide (Norpace) are type Ia antiarrhythmic agents. Quinidine and procainamide are used commonly for suppression of supraventricular and ventricular arrhythmias. Disopyramide is used for ventricular arrhythmias. All three agents have a low toxic-to-therapeutic ratio and may produce fatal intoxication (Table II–51). See the description of other antiarrhythmic agents in Amphetamines.
Table II-51 Quinidine and Type Ia Antiarrhythmic Drugs |Favorite Table|Download (.pdf)
Table II-51 Quinidine and Type Ia Antiarrhythmic Drugs
Serum Half-life (h)
Usual Adult Daily Dose (mg)
Therapeutic Serum Levels (mg/L)
B, V, H
B, V, H
S, B, V, H
Mechanism of toxicity
Type Ia agents depress the fast sodium-dependent channel, slowing phase zero of the cardiac action potential. At high concentrations, this results in reduced myocardial contractility and excitability and severe depression of cardiac conduction velocity. Repolarization is also delayed, resulting in a prolonged QT interval that may be associated with polymorphic ventricular tachycardia (torsade de pointes).
Quinidine and disopyramide also have anticholinergic activity; quinidine has alpha-adrenergic receptor–blocking activity, and procainamide has ganglionic and neuromuscular blocking activity.
Pharmacokinetics (see Table II–61)
Toxic dose. Acute adult ingestion of 1 g of quinidine, 5 g of procainamide, or 1 g of disopyramide and any ingestion in children should be considered potentially lethal.
Clinical presentation. The primary manifestations of toxicity involve the cardiovascular and central nervous systems.
Cardiotoxic effects of the type Ia agents include sinus bradycardia; sinus node arrest or asystole; PR-, QRS-, or QT-interval prolongation; sinus tachycardia (caused by anticholinergic effects); polymorphous ventricular tachycardia (torsade de pointes); and depressed myocardial contractility, which, along with alpha-adrenergic or ganglionic blockade, may result in hypotension and occasionally pulmonary edema.
Central nervous system toxicity. Quinidine and disopyramide can cause anticholinergic effects such as dry mouth, dilated pupils, and delirium. All type Ia agents can produce seizures, coma, and respiratory arrest.
Other effects. Quinidine commonly causes nausea, vomiting, and diarrhea after acute ingestion and, especially with chronic doses, cinchonism (tinnitus, vertigo, deafness, and visual disturbances). Procainamide may cause GI upset and, with chronic therapy, a lupus-like syndrome.
Diagnosis is based on a history of exposure and typical cardiotoxic features such as QRS- and QT-interval prolongation, atrioventricular (AV) block, and polymorphous ventricular tachycardia.
Specific levels. Serum levels for each agent are generally available. Serious toxicity with these drugs usually occurs only with levels above the therapeutic range; however, some complications, such as QT prolongation and polymorphous ventricular tachycardia, may occur at therapeutic levels.
Methods for detecting quinidine may vary in specificity, with some also measuring metabolites and contaminants.
Procainamide has an active metabolite, N-acetylprocainamide (NAPA); with therapeutic procainamide dosing, NAPA levels can range ...