The Q-T interval and antimuscarinic drugs

Antimuscarinic drugs form the mainstay of pharmacotherapy for the treatment of overactive bladder. The primary sites of activity of the agents for the desired therapeutic effect are the M3 and M2 receptors of the bladder. Drug interaction with other non-vesical muscarinic receptors produces a range of undesired adverse events. In general, certain adverse effects associated with antimuscarinic agents such as dry mouth (salivary) and constipation (colon) may be considered only bothersome, and somnolence and confusion (central nervous system) may be considered more serious in nature. However, effects on the myocardium are considered to be more significant safety issues and increased awareness and understanding of the effect of drugs on the myocardium, including the additional effects of drug-drug interaction, has increased a need for the evaluation of new drugs for cardiac safety. The role of genetics (and the identification of populations at risk) in the causation of congenital dysrhythmias has received specific attention in this area. New drugs now must undergo more intense scrutiny and cardiac testing to evaluate their effects on cardiac rate and rhythm, especially the QT interval. The recently approved agents (trospium, solifenacin, darifenacin) used for the treatment of overactive bladder have been rigorously evaluated for these effects.