Key result
Certain drugs, including ketoconazole and fluoxetine, can induce long QT syndrome indirectly by reducing hERG channel expression at the cell surface rather than direct pore blockade.
Highlights an under-explored indirect mechanism (hERG channel trafficking inhibition) by which commonly prescribed drugs cause long QT syndrome.
Alerts prescribers to QT risk from trafficking inhibitors like ketoconazole; leaves open clinical impact and need for prospective validation.
hERG channel trafficking inhibition leads to QT prolongation: Drugs that cause long QT syndrome usually do so by directly blocking the hERG channel through binding in the pore domain. However, an increasing number of drugs, including the widely prescribed antifungal ketoconazole and the antidepressant fluoxetine, can induce long QT syndrome by an indirect effect in which hERG channel expression at the cell surface is reduced.
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Yeung et al. (2008) conducted a review in Drug-induced QT prolongation. Drugs inhibiting hERG channel trafficking (e.g., ketoconazole, fluoxetine) was evaluated on QT prolongation. Certain drugs, including ketoconazole and fluoxetine, can induce long QT syndrome indirectly by reducing hERG channel expression at the cell surface rather than direct pore blockade.
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