How do phenothiazine antipsychotic medications prolong the QRS?
Phenothiazines are a class of antipsychotics with chemical structures that include three rings that closely resemble the structure of tricyclic antidepressants (TCA). Phenothiazines bind to the inactivated sodium channels and are associated with a use dependent sodium channel blockade. Phenothiazine block the influx of sodium into the cardiac myocytes which prolongs the depolarization period or slows the recovery of the sodium channels. As a result, they are associated with QRS prolongation in the setting of an overdose.
Bolotina V, Courtney KR, Khodorov B. Gate-dependent blockade of sodium channels by phenothiazine derivatives: structure-activity relationships. Mol Pharmacol. 1992;42(3):423-431.
Contributed by: Cedric White, PharmD (Cedric.White@bmc.org) with oversight from Natalija Farrell, PharmD, BCPS, DABAT (Natalija.Farrell@bmc.org)