An "autonomic" classification of antiarrhythmic drugs

An alternative classification schema for antiarrhythmic drugs is proposed based primarily on the autonomic "side effects" of these drugs in addition to their electrophysiologic actions. In this new schema, Class I (local anesthetics) is subdivided into 1A (quinidine-like agents with cholinergic blocking actions) and 1B (agents such as lidocaine without autonomic activity). Class II comprises the digitalis glycosides which have vagotonic effects. Class III contains drugs with antiadrenergic activity, subdivided into IIIA (beta-blockers such as propranolol), IIIB (norepinephrine-release inhibitors such as bretylium) and IIIC (non-specific adrenergic blockers such as amiodarone). Class IV includes the calcium channel blockers. Thus, with the exception of Classes IB and IV, all antiarrhythmics possess important autonomic properties. A possible link between autonomic and electrophysiologic effects is suggested by this schema. Classical pharmacologic theory separates the anticholinergic and membrane-active effects of quinidine-like (1A) drugs. An alternative theory is that the anticholinergic effects of 1A agents are germane to the antiarrhythmic actions of drugs in this class. A unifying hypothesis is that the acetylcholine receptor or a site with similar structure may participate directly in the binding of 1A drugs to the ventricular conduction system. This hypothesis is supported by: 1) the anti-muscarinic effects of all Class 1A agents; 2) previous data showing binding of these agents to atrial cholinergic receptors; 3) prominent His-Purkinje cholinergic innervation; 4) striking structural similarity between cocaine, the prototypical membrane anesthetic, and atropine; and 5) quinidine-like effects of tricyclic antidepressants and phenothiazines which have cholinergic properties. Additional ramifications of this autonomic classification are discussed.