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Quinidine, procainamide (Pronestyl), and disopyramide (Norpace) are type Ia antiarrhythmic agents. These agents are used primarily for suppression of supraventricular arrhythmias. Disopyramide is also used to treat hypertrophic obstructive cardiomyopathy. Procainamide oral preparations are not available in the United States but are available in some other countries. All three agents have a low toxic-to-therapeutic ratio and may produce fatal intoxication (Table II–55). See the description of other antiarrhythmic agents.



  1. 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. Type Ia agents also inhibit the outward potassium channel, delaying repolarization, and resulting in a prolonged QT interval that may be associated with polymorphic ventricular tachycardia (torsade de pointes).

  2. Quinidine and disopyramide also have anticholinergic activity; quinidine has alpha-adrenergic receptor–blocking activity, and procainamide has ganglionic and neuromuscular blocking activity.

  3. Pharmacokinetics (see Table II–66)


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.


The primary manifestations of toxicity involve the cardiovascular and central nervous systems.

  1. 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. Anticholinergic effects may result in a rapid ventricular response with emergence of atrial fibrillation or flutter.

  2. 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.

  3. 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. Anticholinergic effects of type Ia drugs can result in urinary retention and precipitation of acute glaucoma.


Is based on a history of exposure and typical ...

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