What drugs can affect ECG (electrocardiogram) readings?

Drugs Affecting ECG

Numerous medications can significantly alter ECG readings, most importantly by prolonging the QT interval and increasing the risk of life-threatening ventricular arrhythmias including torsades de pointes (TdP), with antiarrhythmic drugs, antipsychotics, certain antibiotics, and antidepressants being the most clinically significant offenders. 1, 2

Major Drug Categories That Affect ECG

Antiarrhythmic Agents

• Class IA antiarrhythmics (quinidine, procainamide, disopyramide) prolong the QT interval by blocking IKr potassium channels and are frequently associated with TdP 1, 3
• Class III antiarrhythmics (sotalol, dofetilide, amiodarone) markedly prolong QT interval through potassium channel blockade 1
• Amiodarone is unique: despite causing marked QT prolongation, it rarely causes TdP because it uniformly delays repolarization across all myocardial layers rather than creating transmural heterogeneity 1
• Class IC agents (flecainide, propafenone) widen the QRS complex through sodium channel blockade 1
• Verapamil and diltiazem prolong the PR interval through calcium channel blockade 1

Psychiatric Medications

• Antipsychotics carry dose-related risk of sudden cardiac death, with both typical (haloperidol, thioridazine) and atypical agents (quetiapine) prolonging QT interval 1, 2, 4
• Quetiapine causes moderate QT prolongation (approximately 6 ms) 2
• Thioridazine requires special caution in CYP2D6 poor metabolizers (5-10% of white and black populations) or when combined with CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine) due to drug accumulation 1
• Tricyclic antidepressants (amitriptyline) cause TdP and also produce wide QRS complexes through sodium channel blockade in overdose 1
• SSRIs (citalopram, sertraline) have lower TdP risk than tricyclics but can still prolong QT, particularly in overdose 1, 2

Antibiotics

• Macrolides (erythromycin, clarithromycin) prolong QT interval, especially with intravenous administration, high doses, or when combined with CYP3A4 inhibitors 1, 4
• Fluoroquinolones are associated with QT prolongation 4
• Azithromycin has lower interaction risk compared to other macrolides 5

Other High-Risk Medications

• Methadone causes QT prolongation, particularly with high doses or recent dose increases; guidelines recommend baseline ECG, follow-up within 30 days, and annual monitoring 1, 2
• Antiemetics (ondansetron, metoclopramide, domperidone, 5HT3 antagonists) prolong QT interval 2, 4
• Antihistamines: terfenadine (withdrawn from market) caused TdP especially with CYP3A4 inhibitors; fexofenadine does not block IKr channels 1

Critical Risk Factors for Drug-Induced QT Prolongation and TdP

Patient-Specific Factors

• Female sex increases risk significantly 1, 5, 6
• Advanced age prolongs elimination half-life of many QT-prolonging drugs 1, 5, 6
• Bradycardia (heart rate <60 bpm) increases TdP risk 1, 5, 6
• Cardiac disease (heart failure, acute MI, structural heart disease) 1, 5, 6
• Genetic predisposition (congenital long QT syndrome, CYP2D6 poor metabolizers) 1, 7, 6

Electrolyte Abnormalities (Modifiable Risk Factors)

• Hypokalemia is the most critical modifiable risk factor 1, 5, 6
• Hypomagnesemia increases TdP risk 5, 6
• Hypocalcemia contributes to prolonged repolarization 7, 5

Drug-Related Factors

• Renal dysfunction: dofetilide and sotalol are renally cleared; procainamide's active metabolite NAPA accumulates in renal failure 1
• Hepatic dysfunction: affects metabolism of drugs cleared by CYP450 enzymes 1, 7
• High-risk drug interactions: CYP3A4 inhibitors (ketoconazole, erythromycin) with terfenadine; CYP2D6 inhibitors with thioridazine 1, 5
• Rapid IV administration increases risk compared to oral dosing 1

ECG Monitoring Protocol

Baseline Assessment

• Obtain baseline 12-lead ECG before initiating any QT-prolonging medication 1, 2, 6
• Measure QTc interval using Bazett's or Fridericia's formula 2, 6
• Correct all electrolyte abnormalities (potassium, magnesium, calcium) before drug initiation 1, 2, 6
• Document baseline PR interval (for flecainide, propafenone, sotalol, amiodarone), QRS duration (for flecainide, propafenone), and QT interval (for dofetilide, sotalol, amiodarone) 1

During Treatment Monitoring

• Repeat ECG 7 days after starting therapy and after any dose change 2, 6
• For high-risk situations, document QTc every 8 hours using rhythm strip examples 2
• Monitor heart rate weekly by pulse check, event recorder, or office ECG 1
• Reassess ECG after each dose adjustment of antiarrhythmic drugs 1

Critical Thresholds for Action

Reduce dose or discontinue drug when:

• QTc reaches >500 ms 1, 2, 6
• QTc increases ≥60 ms from baseline 2, 5, 6
• QRS widens to 130% of baseline duration 8
• PR interval prolongs to 130% of baseline 8
• Patient develops symptomatic bradycardia or hypotension 8

For males: consider intervention at QTc 470-500 ms; for females: at QTc 480-500 ms 6

When QTc ≥500 ms:

• Immediately discontinue the offending drug 2, 6
• Initiate continuous telemetry monitoring OR repeat 12-lead ECG every 2-4 hours until QT normalizes 6
• Correct all electrolyte abnormalities urgently 2, 6

Special Considerations for Specific Drug Classes

Antiarrhythmic Initiation

• Sotalol: may be started outpatient only if baseline uncorrected QT <450 ms, electrolytes normal, and patient has little/no heart disease; safest to start in sinus rhythm 1
• Dofetilide: out-of-hospital initiation is not permitted 1
• Quinidine, procainamide, disopyramide: should never be started out of hospital 1
• Amiodarone: can usually be started outpatient even in persistent AF due to minimal myocardial depression and low proarrhythmic potential; reduce doses of digoxin and warfarin in anticipation of drug interactions 1

Drug Overdose Management

• Assess ECG in all drug overdose victims for prolonged QT, QT-U distortion, and signs of impending TdP 1
• Tricyclic overdoses may show both QT prolongation and wide QRS/sinusoidal ventricular tachycardia from sodium channel toxicity 1
• SSRI overdoses (citalopram, trazodone) have been reported to cause TdP 1

High-Risk Drug Combinations to Avoid

• Never combine multiple QT-prolonging drugs unless absolutely necessary 2
• Highest-risk pharmacokinetic interactions: antifungals or macrolides (except azithromycin) with amiodarone, disopyramide, dofetilide, or pimozide 5
• Antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) with flecainide, quinidine, or thioridazine 5
• Domperidone with chlorpromazine should be avoided whenever possible 2

Management of Torsades de Pointes

Immediate interventions:

• Administer magnesium sulfate 2g IV as first-line therapy regardless of serum magnesium level 2, 5
• Non-synchronized defibrillation for hemodynamically unstable patients 2
• Overdrive pacing at 90-110 bpm to shorten QTc 2
• Isoproterenol IV titrated to heart rate >90 bpm when temporary pacemaker unavailable 2
• Discontinue all QT-prolonging medications immediately 2, 5
• Correct all electrolyte abnormalities (potassium, magnesium, calcium) 2, 5

Common Pitfalls to Avoid

• Do not assume amiodarone is high-risk for TdP despite marked QT prolongation—it rarely causes TdP due to uniform repolarization delay 1
• Do not overlook renal function when dosing sotalol, dofetilide, or procainamide—accumulation dramatically increases TdP risk 1
• Do not ignore drug interactions involving CYP3A4 (macrolides, azole antifungals) or CYP2D6 (SSRIs with thioridazine) 1, 5
• Do not forget to monitor potassium levels during antipsychotic treatment—hypokalemia is the most modifiable risk factor 2, 5, 6
• Do not use Class IA antiarrhythmics in torsades de pointes—they are contraindicated and will worsen the arrhythmia 3