Pharmacology · Year 2 · from Pharmacology
Case 1: Drug-Induced QT Prolongation and Torsades de Pointes
Clinical Scenario
A 72-year-old female presents to the emergency department after a syncopal episode while taking multiple medications, including a recently started antibiotic.
Patient Demographics
- Age: 72 years
- Sex: Female
- Weight: 62 kg
Chief Complaint
Syncope without warning while standing in the kitchen
History of Present Illness
The patient has a history of atrial fibrillation (on amiodarone 200 mg daily for 5 years), hypertension, and type 2 diabetes. She was recently started on levofloxacin 750 mg daily for a urinary tract infection 3 days ago. Today, she experienced sudden loss of consciousness without prodrome, witnessed by her husband who described "shaking" lasting approximately 30 seconds. She has also been taking ondansetron for nausea.
Medications
- Amiodarone 200 mg daily
- Levofloxacin 750 mg daily (started 3 days ago)
- Ondansetron 4 mg PRN (2-3 times daily)
- Metformin 1000 mg twice daily
- Lisinopril 10 mg daily
Physical Examination
- Vital Signs: BP 128/78 mmHg, HR 82 bpm (irregular), RR 16, T 37.0C
- General: Alert, oriented, slightly fatigued
- Cardiovascular: Irregular rhythm, no murmurs
- Neurological: No focal deficits, no post-ictal state
Workup and Results
| Test | Result | Reference Range |
|---|---|---|
| Potassium | 3.1 mEq/L | 3.5-5.0 mEq/L |
| Magnesium | 1.4 mEq/L | 1.5-2.5 mEq/L |
| Calcium | 9.0 mg/dL | 8.5-10.5 mg/dL |
| TSH | 2.8 mIU/L | 0.4-4.0 mIU/L |
| Creatinine | 1.3 mg/dL | 0.6-1.2 mg/dL |
ECG on arrival: Atrial fibrillation, QTc 580 ms (prolonged)
Telemetry recording during syncopal episode: Torsades de pointes degenerating to ventricular fibrillation with spontaneous conversion
Diagnosis
Drug-induced QT prolongation with Torsades de Pointes from multiple QT-prolonging drugs (amiodarone, levofloxacin, ondansetron) and electrolyte abnormalities
Cardiovascular Pharmacology Principles Illustrated
- QT prolongation mechanism: Multiple drugs block the hERG (IKr) potassium channel, delaying ventricular repolarization.
- Additive risk: Combining multiple QT-prolonging drugs dramatically increases risk of torsades.
- Risk factors: Hypokalemia and hypomagnesemia lower the threshold for torsades.
- Drug classes implicated: Fluoroquinolones, Class III antiarrhythmics (amiodarone), antiemetics (ondansetron), many antipsychotics.
- Female sex: Women have inherently longer QTc and higher torsades risk.
Treatment
- Immediate: IV magnesium sulfate 2 g over 10 minutes (first-line for torsades)
- Discontinue all QT-prolonging agents: Stop levofloxacin, ondansetron
- Electrolyte repletion: IV potassium to K+ >4.0 mEq/L, magnesium to Mg2+ >2.0 mEq/L
- Overdrive pacing or isoproterenol: If recurrent torsades (increases heart rate, shortens QT)
- Alternative antibiotic: Nitrofurantoin or amoxicillin-clavulanate for UTI
- Review all medications for QT-prolonging potential
- Cardiology consultation for amiodarone risk-benefit discussion
Clinical Image
Torsades de pointes ("twisting of the points") - a polymorphic ventricular tachycardia characterized by QRS complexes that twist around the baseline. This arrhythmia occurs in the setting of prolonged QT interval and can degenerate to ventricular fibrillation.
Image Source: Wikimedia Commons License: Public Domain URL: https://commons.wikimedia.org/wiki/File:Torsades_de_pointes.svg