AB, a 56 year old male, presents to the emergency department with complaints of lightheadedness, occasional episodes of a rapid heart beat, and infrequent palpitations, that all started within the past few days. 

Past medical history:

GAD with Depression: Celexa 20mg QD

CAP: Z-Pak (day 4)

T2D: Metformin 1000mg BID

HLD: Rosuvastatin 10mg QHS

HTN: Propranolol IR 80mg BID

The patient’s laboratory findings and vitals are below:

Ht: 5’10”

Wt: 197 lbs

HR: 112 BPM

BP: 130/82 mm Hg

Temp: 98.6° F

EKG findings: normal rate and rhythm

QTc: 520ms

Na: 140 mEq/L (135 mEq/L-146 mEq/L)

K: 3.0 mEq/L (3.5 mEq/L-5.3 mEq/L)

Ca: 9.4 mg/dL (8.5 mg/dL-10.5 mg/dL)

Mg: 1.8 mg/dL (1.7 mg/dL-2.3 mg/dL)

Which of the following could be attributed to this patient’s current EKG findings? Select all that apply.

A. Hyponatremia

B. Celexa

C. Z-pak

D. Hypokalemia

E. Propranolol

F. Rosuvastatin 

Answer with rationale:

The cardiac action potential is the electrical impulse that controls heart muscle contraction. In Phase 0, the cell rapidly depolarizes when sodium (Na⁺) channels open and Na⁺ enters the cell. In phase 1, potassium ions (K⁺) exit, and sodium channels close. During the Plateau Phase (Phase 2), calcium (Ca²⁺) enters the cell, furthering muscle contraction, while potassium continues to leave. Phase 3 sees calcium channel closure while potassium, still, continues to leave, leading to repolarization. In Phase 4, the cell returns to its resting potential, fully repolarized, maintained by the Na⁺/K⁺ ATPase pump.

The QT interval on an ECG reflects the time between depolarization and repolarization, and the QTc (corrected) adjusts this time difference for heart rate. A QTc greater than 450 in males or 460 in females is considered prolonged and a clinical conversation may be necessary. Any QTc greater than 500 generally warrants an immediate cardiac consult, as there is a major increase in the risk of potentially life-threatening arrhythmias, specifically Torsades de Pointes.

Electrolytes and their manipulations have a significant impact on the action potential and QTc interval. Hypokalemia (low potassium) slows repolarization, prolonging the QTc and increasing the risk of arrhythmias, like Torsades de pointes. Similarly, hypocalcemia (low calcium) delays repolarization, also prolonging the QT interval. Magnesium helps stabilize potassium channels, and its deficiency can worsen QT prolongation. All of these electrolytes can appear normal on lab work, but still be affected by a wide variety of medications that work by altering the ion channels that affect these ions in cardiac cells. Monitoring for QTc prolonging drugs are critical for pharmacists to help aid in achieving proper heart rhythm and reducing arrhythmia risk.

Answer A is incorrect. While sodium plays a crucial role in cardiac function, it primarily affects the depolarization phase of the action potential (think soDEum). The prolonging of a QTc interval is affected mainly by electrolytes in the repolarization phase, such as potassium, magnesium, and calcium. Chronic hyponatremia may come into play with some indirect secondary or tertiary effects down the line that prolong the QTc, but this patient’s sodium levels are normal.

Answer B is correct. Citalopram is an SSRI, a class of antidepressants that are common culprits for QTc prolongation. It prolongs the QTc interval by blocking potassium channels during the repolarization phase, stretching out the time it takes for the cardiac cells to actually repolarize.  Citalopram specifically has a recommendation to avoid more than 20mg per day in patients above 60 years old due to its increased risk. 

Answer C is correct. Azithromycin (Z-pak) is a macrolide antibiotic commonly used in Community Acquired Bacterial Pneumonia (CABP) and exacerbations of COPD. Just like citalopram, macrolides (erythromycin, clarithromycin) inhibit potassium channels during the repolarization phase, prolonging the QTc. The patient’s symptoms started recently, after he started the Z-Pak, which added another QTc prolonging drug to his system.

Answer D is correct. Hypokalemia is one of the most common causes of a prolonged QTc interval. Potassium ions are essential to concluding the duration of an action potential, and not having enough can slow down the process tremendously. The effects of low potassium ions can occur through many mechanisms, including direct lowering, or as we’ve discussed above, blocking its ion channels.  

Answer E is incorrect. Propranolol is a beta-blocker capable of actually decreasing the QTc in tachycardic patients. Blocking the beta-adrenergic receptors in the heart can decrease the heart rate, giving cardiac cells in the ventricles more time to properly repolarize.

Answer F is incorrect. Statins, including rosuvastatin, have no significant effect on QTc or heart rate or rhythm. They act by inhibiting HMG-CoA reductase, an enzyme in the cholesterol production pathway. However, this is unrelated to the cardiac action potential system that can cause prolonged QTC.

Brand/generics Covered:

Citalopram (Celexa), Azithromycin (ZPak), Metformin (no brand on market), Rosuvastatin (Crestor), Propranolol IR (no brand on market)

Naplex Content Domains Covered

1.A.1 - Pharmacology

3.C.3 - Interactions

3.C.5 - Adverse drug reactions

3.D.2 - Therapeutic monitoring: Safety