Poisoning Due to Class IA Antiarrhythmic Drugs Quinidine, Procainamide and Disopyramide

Abstract

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of ATP-Sensitive K+ Channels and L-Type Ca2+ Channels by Amiodarone Elicits Contradictory Effect on Insulin Secretion in MIN6 Cells

“…It is well-known that class Ia antiarrythmic drugs such as quinidine, disopyramide, and cibenzoline induce a hypoglycemia (1,2,27,28). Several studies have indicated that these drugs increase insulin secretion from pancreatic β-cells by inhibiting K ATP channels in a manner similar to sulfonylurea antidiabetic drugs (3,4,25).…”

“…It has been reported that antiarrhythmic drugs with Vaughan Williams class Ia action such as quinidine, cibenzoline and disopyramide induce a hypoglycemia (1,2). Several studies have indicated that the drug-induced hypoglycemia can be ascribed to insulin secretion from pancreatic β-cells resulting from ATP-sensitive K + (K ATP )-channel inhibition (3,4).…”

Amiodarone Versus Procainamide for the Acute Treatment of Recurrent Supraventricular Tachycardia in Pediatric Patients

“…The use of procainamide in the management of adult ventricular arrhythmias and atrial fibrillation is well established, as well as the potential for adverse effects with class IA agents. 11 However, safe dosing regimens have been reported in pediatric patients. Using an intravenous dosing regimen similar to that used for older children and adults to achieve therapeutic levels, Moffett et al 12 demonstrated that neonatal recipients did not have hypotension, heart block, GI disturbances, rash, or lupus-like reactions.…”

New Potential Antimalarial Agents: Therapeutic-Index Evaluation of Pyrroloquinazolinediamine and Its Prodrugs in a Rat Model of Severe Malaria

“…There are no effective malaria vaccines, and the efficacies of antimalarial drugs continue to decrease as a consequence of the emergence of drugresistant parasites. In addition, the first-line antimalarial drugs, such as quinine, quinidine, and mefloquine (18), are still in use and are reported to have from mild to severe adverse effects (7,10,11,20). Fortunately, many academic centers and organizations, including the U.S. Army, are seeking new antimalarial products (26).…”