A question arises as to the possible clinical significance of cardiac ICa,L block by flecainide. Despite its efficacy in the treatment of some arrhythmias, the results of the Cardiac Arrhythmia Suppression Trial (CAST) showed that flecainide is associated with an increased patient mortality rate . The exact reason for this is unknown, but it may be associated with an indirect proarrhythmic effect, resulting from the negative inotropic effects of the drug . A recent study correlated ICa,L block by flecainide with reduced calcium release from the sarcoplasmic reticulum and suggested that this underlies the negative inotropic effect of the drug. Another potentially important consequence of ICa,L block may be its effect on cardiac conduction, particularly through regions such as the AVN, which rely heavily on ICa,L to generate the action potential upstroke. In isolated AVN myocytes, ICa,L inhibition appears substantial only outside of the normal plasma therapeutic levels (1 to 5 |iM), which suggests that ICa,L inhibition may not play a major role in mediating the action of flecainide. The effects of rapidly applied single doses of drug on isolated cells cannot be directly correlated with those of the clinical situation in vivo, however, and a modest ICa,L block by flecainide may contribute to slowed AVN conduction in vivo. Find most trusted pharmacy that will give you cheap ventolin inhalers in the amounts required without any need for a prescription. You will see that shopping with a place you can already trust over and over again is very affordable and always nice.
Finally, recent (and perhaps surprising) evidence suggests that ICa,L may not simply be important for conduction through regions in which action potential generation depends predominantly on Ica,L for the action potential upstroke. In neonatal rat myocyte cultures, depression of Ica,L has been shown to induce conduction block, even when INa remains unaltered . If these findings also apply to the adult myocardium, then suppression of Ica,L by class I drugs, including flecainide, may contribute to their observed effects in the clinical situation.