The side effect profile of class III antiarrhythmic drugs: focus on d,l-sotalol.
Class III antiarrhythmic drugs have been under extensive clinical investigation as safer, more effective alternatives to class I drugs, which have recognized risks in selected populations. Class III drugs prolong the action potential duration of myocardial cells, resulting in a lengthening of the effective refractory period. This pharmacologic activity has antiarrhythmic properties, but it may induce a distinctive form of proarrhythmia known as torsades de pointes. Amiodarone and d,l-sotolol are class III drugs that have been available for many years. In addition to their ability to prolong refractoriness, these drugs have other pharmacodynamic properties. Recent antiarrhythmic drug discovery has focused on the identification and development of selective or so-called pure class III drugs that are devoid of additional actions. Investigators have hoped that these drugs would be as effective as sotalol and amiodarone but have fewer adverse effects. Accumulating data, however, indicate that complex compounds exhibiting antiadrenergic and other electrophysiologic properties may be superior to pure class III agents.
MacNeil
D J
DJ
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000009:adverse effects; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006333:Heart Failure / Q000401:mortality; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007231:Infant, Newborn; D010627:Phenethylamines / Q000009:adverse effects; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D013015:Sotalol / Q000009:adverse effects*; D013449:Sulfonamides / Q000009:adverse effects; D015996:Survival Rate; D016171:Torsades de Pointes / Q000139:chemically induced*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; D013015:Sotalol; D000638:Amiodarone; C063533:dofetilide