Phenytoin: an old but effective antiarrhythmic agent for the suppression of ventricular tachycardia

Risk of cardiac events in Long QT syndrome patients when taking antiseizure medications

“…In contrast to the dual efficacy of many drugs, numerous drugs (e.g., some antihistamines, antipsychotics, antidepressants, and antimicrobials agents) exert substantial off-target cardiac effects including QT c prolongation and increased risk for developing lethal ventricular arrhythmias. (3, 18, 30) Despite numerous cellular studies(13, 14), patient case studies(9–11), and a recent review,(12) it remains unclear, with often competing results, whether ASMs are associated with changes in ECG measures, and the risk of arrhythmias and SUDEP. For example, cellular expression studies indicate that lamotrigine, phenytoin, and phenobarbital inhibit I Kr , which is mutated in LQTS2 and critical for cardiomyocyte repolarization.…”

“…(9) Yet other studies report phenytoin has no effect on the QT c duration or risk of arrhythmias,(10) or even that it suppresses arrhythmias. (11) Therapeutic serum levels of carbamazepine promote bradycardia and induce atrio-ventricular delay/block. (31, 32) Several ASMs, carbamazepine and lamotrigine in particular, suppress autonomic tone, and thus, predispose patients to arrhythmias.…”

“…In contrast, since LQTS2 patients already have a reduction in I Kr , an additional ASM-mediated reduction in I Kr (e.g., phenytoin & lamotrigine(13, 14)) may serve as a “double hit” to reduce the repolarization reserve sufficient to promote the initiation of an arrhythmia. In LQTS, late Na + channel blockers (e.g., ranolazine and phenytoin) restore the balance between depolarizing and repolarizing current, reduce the rate of triggered activity, and thus exert anti-arrhythmic effects(11, 26). Future studies will be needed to determine the interplay between these proposed pro-/anti-arrhythmic mechanisms.…”

Phenytoin as an effective treatment for polymorphic ventricular tachycardia due to QT prolongation in a patient with multiple drug intolerances

“…It reduces the rate of calcium-dependent depolarisation in the plateau phase of the cardiac action potential and increases the refractory period 4. This prevents EADs, thus inhibiting ventricular ectopy and halting a potential tachyarrhythmia,5 which is the most likely reason for arrhythmia resolution in our patient. Phenytoin's anticholinergic effects may have beneficial effects in preventing bradycardia 5…”

“…Phenytoin has been used in treatment of torsades de pointes 4 5. It reduces the rate of calcium-dependent depolarisation in the plateau phase of the cardiac action potential and increases the refractory period 4.…”