Polymorphic ventricular tachycardia can occur when terfenadine(antihistaminic):
**Core Concept**
Polymorphic ventricular tachycardia, specifically Torsades de Pointes, is a life-threatening arrhythmia linked to prolonged cardiac repolarization, measured by a prolonged QT interval. Terfenadine, a first-generation antihistamine, inhibits hERG potassium channels, delaying ventricular repolarization and increasing risk of torsades when its effect is amplified.
**Why the Correct Answer is Right**
Terfenadine itself has a high risk of causing QT prolongation and polymorphic ventricular tachycardia due to its blockade of the hERG potassium channel. When given in **higher doses**, the degree of hERG blockade increases, leading to greater QT prolongation and a significantly elevated risk of torsades de pointes. This dose-dependent effect is the primary mechanism, not drug interactions or interval shortening.
**Why Each Wrong Option is Incorrect**
Option A: Azithromycin increases hERG blockade, but terfenadine is contraindicated with azithromycin due to additive QT prolongation — this is a known interaction, not the cause of polymorphic VT in terfenadine alone.
Option B: Fluconazole is a strong CYP3A4 inhibitor, which increases terfenadine levels, but the main risk is due to hERG blockade, not metabolism — this is a secondary factor, not the primary cause.
Option D: Terfenadine **prolongs**, not reduces, the QT interval; reducing QT would be protective, not dangerous.
**Clinical Pearl / High-Yield Fact**
Terfenadine is a classic example of a drug with a narrow therapeutic index and a high risk of torsades de pointes due to hERG blockade. Always avoid high-dose terfenadine and monitor QT intervals closely — it is now withdrawn from most markets due to safety concerns.
✓ Correct Answer: C. Is given in higher doses