Antiarrhythmic Agents I: Mechanisms of Action and Clinical Pharmacology

In the application of antiarrhythmic drugs in patients, a thorough knowledge of their pharmacological effects greatly aids the clinician in the more rational selection of the drug or combination of drugs in terms of expected benefits, favourable additive actions, and contra-indications. Each of the agents depresses disorders of rapid impulse formation (repetitive ectopic pacemaker activity) by reducing diastolic depolarisation and thereby diminishing automaticity, and inhibits disorders of impulse conduction (re-entry tachyarrhythmias) by altering conduction velocity and refractory period and thereby interrupting reciprocal excitation pathways. Concerning unidirectional block perpetuating re-entry mechanisms, group I drugs (quinidine, procainamide, propranolol, bretylium and potassium) produce bidirectional block by slowing conduction velocity, while group II drugs (lignocaine and phenytoin or diphenylhydantoin) abolish localised block by enhancing conduction velocity. In addition to depression of automaticity, agents in both groups increase functional refractoriness relative to action potential duration due to alterations in membrane responsiveness. Quinidine, procainamide and bretylium directly prolong refractory period; in contrast, lignocaine, phenytoin, and propranolol directly reduce this period. Both propranolol and bretylium possess powerful antiadrenergic actions, while quinidine and procainamide produce anticholinergic effects. Accompanying their antiarrhythmic actions, quinidine, procainamide, and propranolol worsen atrioventricular block, whereas this property in the atrioventricular node usually is not influenced by lignocaine and is accelerated by phenytoin. Quinidine and procainamide are broad-spectrum antiarrhythmic drugs which are effective in both supraventricular and ventricular tachyarrhythmia while propranolol and phenytoin are useful in supraventricular and ventricular disorders. Propranolol is particularly efficacious against supraventricular arrhythmias and phenytoin more beneficial in disturbances of ventricular rhythm. Lignocaine has little action in atrial disorders but markedly suppresses ventricular irritability. Bretylium may successfully terminate refractory ventricular rhythm abnormalities. Phenytoin propranolol lignocaine and potassium possess the most favourable electrophysiological properties for correction of tachyarrhythmias due to digitalis toxicity.