The QT interval on ECG is measured as 480 ms at a heart rate of 60 bpm (QTc by Bazett formula = QT/√RR interval). This patient is started on haloperidol. What is the PRIMARY mechanism by which haloperidol prolongs the QT interval?
- A Blockade of hERG (IKr) potassium channels in ventricular myocytes delaying repolarization ✓
- B Activation of the late sodium current (INaL) prolonging the action potential plateau
- C Inhibition of the calcium-independent transient outward K+ current (Ito) in phase 1
- D Direct inhibition of the Na+/K+-ATPase reducing membrane potential stability
Explanation
QT prolongation by antipsychotics (haloperidol, thioridazine) and many other drugs (including some antibiotics and antiarrhythmics) occurs via blockade of hERG (human ether-à-go-go related gene) channels, which carry the rapid delayed rectifier potassium current (IKr). IKr is the dominant repolarizing current in phase 3 of the ventricular action potential; its blockade delays repolarization, prolonging APD and the QT interval. This predisposes to torsades de pointes. The late INaL mechanism (option B) is relevant to ranolazine/certain Na channel conditions; Ito blockade (option C) affects phase 1 notch; Na+/K+-ATPase inhibition (option D) is the mechanism of digitalis.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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