Welcome to USMLE practice question #134! Today’s question covers cardio/pharm.
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A 60-year-old woman with a history of depression and atrial fibrillation presents to the emergency department after experiencing an episode of syncope. Her medications include sertraline, amiodarone, and rivaroxaban. Vital signs are normal, but ECG reveals a prolonged QT interval with occasional premature ventricular contractions. Serum potassium and magnesium levels are within normal limits. Which of the following best explains the mechanism underlying her symptoms?
A) Blockade of L-type calcium channels during the plateau phase of the cardiac action potential
B) Inhibition of voltage-gated sodium channel inactivation during the depolarization phase
C) Enhanced activation of inward rectifier potassium channels during late repolarization
D) Blockade of delayed rectifier potassium channels prolonging repolarization
E) Competitive inhibition of sodium-potassium ATPase leading to altered ion gradients
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following best explains the mechanism underlying her symptoms?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Diagnose the patient’s condition; 2nd: Identify the underlying mechanism responsible for her symptoms.
Step 3: Read the vignette carefully and ask yourself: “Based on this patient’s presentation and history, the underlying mechanism is most likely ______________.”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
This 60-year-old woman presents with syncope, a prolonged QT interval, and premature ventricular contractions (PVCs) on ECG. Her medications include amiodarone, an antiarrhythmic drug known to prolong the QT interval by blocking potassium channels. Laboratory studies show normal potassium and magnesium levels, ruling out electrolyte abnormalities as a cause. The clinical presentation strongly suggests that the QT prolongation.
ANSWER CHOICES:
CHOICE A: Blockade of L-type calcium channels during the plateau phase of the cardiac action potential
Explanation: L-type calcium channels are responsible for the plateau phase (phase 2) of the cardiac action potential. Blocking these channels reduces calcium influx, which can decrease contractility and conduction through the AV node.
CHOICE B: Inhibition of voltage-gated sodium channel inactivation during the depolarization phase
Explanation: Voltage-gated sodium channels mediate the rapid depolarization phase (phase 0) of the cardiac action potential. Inhibition of sodium channel inactivation would prolong depolarization and potentially widen the QRS complex.
CHOICE C: Enhanced activation of inward rectifier potassium channels during late repolarization
Explanation: Inward rectifier potassium channels contribute to maintaining resting membrane potential and help terminate repolarization. Enhanced activation would shorten the action potential duration and QT interval.
CHOICE D: Blockade of delayed rectifier potassium channels prolonging repolarization
Explanation: The delayed rectifier potassium current (IKr) is critical for phase 3 (repolarization) of the cardiac action potential. Amiodarone blocks these potassium channels, delaying repolarization and prolonging the QT interval. This mechanism underlies its antiarrhythmic effects but also increases the risk of torsades de pointes (TdP) in some cases.
CHOICE E: Competitive inhibition of sodium-potassium ATPase leading to altered ion gradients
Explanation: Sodium-potassium ATPase maintains intracellular sodium and potassium gradients, which are essential for normal cell function and electrical activity. Inhibition of this pump (e.g., by digoxin) can lead to arrhythmias but does not directly cause QT prolongation.
FINAL VERDICT…
CORRECT ANSWER: D) Blockade of delayed rectifier potassium channels prolonging repolarization
Amiodarone causes QT prolongation by blocking delayed rectifier potassium channels (IKr), which delays phase 3 repolarization of the cardiac action potential. This mechanism increases action potential duration and can predispose to arrhythmias like torsades de pointes in some cases.
KEY CONCEPTS:
Mechanism of Amiodarone-Induced QT Prolongation:
Amiodarone is a Class III antiarrhythmic that primarily blocks delayed rectifier potassium channels (IKr).
This blockade delays phase 3 repolarization, prolonging the action potential duration and QT interval.
Unlike other Class III agents, amiodarone has a lower risk of torsades de pointes due to its additional effects on L-type calcium channels and beta-blocking properties.
Phases of Cardiac Action Potential Affected by Ion Channels:
Phase 0 (Depolarization): Mediated by voltage-gated sodium channels.
Phase 2 (Plateau): Mediated by L-type calcium channels.
Phase 3 (Repolarization): Mediated by delayed rectifier potassium currents (IKr).
Clinical Features of Drug-Induced QT Prolongation:
Prolonged QT interval on ECG (>450 ms in men or >470 ms in women).
Risk factors for torsades de pointes include bradycardia, hypokalemia, hypomagnesemia, and use of multiple QT-prolonging drugs.
Amiodarone's Unique Properties:
Broad-spectrum antiarrhythmic effects (blocks sodium, potassium, and calcium channels; beta-blocking effects).
Long half-life (~58 days), leading to prolonged drug effects even after discontinuation.
Relatively low risk of torsades de pointes compared to other Class III agents.
Management Considerations for QT Prolongation:
Avoid co-administration with other QT-prolonging drugs (e.g., sertraline in this case).
Monitor electrolytes (potassium, magnesium) and correct abnormalities.
Regular ECG monitoring for patients on high-risk medications like amiodarone.