What medications can cause palpitations, sweating, and arrhythmia in a general adult population with no specified medical history?

Medications That Cause Palpitations, Sweating, and Arrhythmia

Multiple drug classes can cause this triad of symptoms through sympathomimetic stimulation, cardiac ion channel effects, or autonomic dysregulation, with stimulants, antiarrhythmics, bronchodilators, and certain antibiotics being the most common culprits.

Stimulant Medications

Amphetamines and related stimulants are among the most potent causes of palpitations, sweating, and arrhythmias through direct sympathomimetic effects. 1

• Amphetamines cause modest increases in heart rate (3-6 bpm) and blood pressure (2-4 mmHg) on average, but individual patients may experience much larger increases 1
• These agents can precipitate sudden death, stroke, and myocardial infarction in adults, particularly those with underlying structural cardiac abnormalities, cardiomyopathy, or serious heart rhythm abnormalities 1
• Patients may develop exertional chest pain, unexplained syncope, or other cardiac symptoms requiring prompt cardiac evaluation 1

Bronchodilators

Theophylline-containing compounds (like Deriphyllin) directly stimulate the myocardium and can cause significant tachycardia, sweating, and arrhythmias. 2

• The American College of Cardiology warns that theophylline increases atrial automaticity, shortens atrial action potential duration/effective refractory period, and predisposes to arrhythmias 2
• Theophylline has a narrow therapeutic window, making toxicity common with symptoms including marked tachycardia, multifocal atrial tachycardia, premature ventricular contractions, hypotension, and seizures 3
• In severe toxicity cases, propranolol and verapamil have been useful in controlling supraventricular tachycardia 3
• Patients with hyperthyroidism are at particularly high risk as it potentiates theophylline's cardiovascular effects 2

Antiarrhythmic Drugs (Paradoxical Pro-arrhythmia)

Class Ia, Ic, and III antiarrhythmic drugs frequently cause pro-arrhythmic effects including palpitations and life-threatening arrhythmias. 4

• Class Ia and Ic antiarrhythmics (flecainide, propafenone, quinidine) induce torsades de pointes, with most arrhythmias occurring within the first few days of therapy 4
• D-sotalol causes dose-dependent pro-arrhythmias and increased mortality in post-myocardial infarction patients 4
• Dofetilide caused torsades de pointes in 3.3% of patients with severe heart failure during the first 72 hours of therapy 4
• Amiodarone, despite prolonging QT interval, has surprisingly low incidence of torsades de pointes compared to other class III agents 4

Antibiotics

Macrolide antibiotics and fluoroquinolones block cardiac potassium channels and significantly increase risk of ventricular arrhythmias and sudden death. 4

• Erythromycin, clarithromycin, and azithromycin directly block IKr channels, causing excessive QT prolongation and torsades de pointes 4
• The risk is particularly elevated in women and when combined with cytochrome P450 3A4 inhibitors 4
• Co-trimoxazole combined with renin-angiotensin system inhibitors has been associated with sudden death due to unrecognized hyperkalemia 4

Tricyclic Antidepressants

Imipramine and other tricyclic antidepressants cause cardiovascular toxicity including arrhythmias, tachycardia, and conduction defects through anticholinergic and sodium channel blocking effects. 5

• These agents require cardiac surveillance at all dosage levels due to risk of conduction defects, arrhythmias, myocardial infarction, and tachycardia 5
• Extreme caution is needed in patients with cardiovascular disease, hyperthyroidism (which increases cardiovascular toxicity), or history of seizure disorder 5
• Tricyclic antidepressants can produce QRS prolongation and unmask Brugada syndrome ECG patterns 4

Cardiac Glycosides

Digoxin toxicity produces characteristic arrhythmias with enhanced automaticity combined with AV block. 4

• Typical digoxin toxicity arrhythmias include enhanced atrial, junctional, or ventricular automaticity often combined with AV block 4
• Anorexia, nausea, vomiting, and visual changes accompany cardiac arrhythmias when levels exceed 2 ng/mL 4
• Risk is increased with renal dysfunction, hypokalemia, and drug interactions with amiodarone, verapamil, clarithromycin, and erythromycin 4

Non-Cardiac Drugs with Potassium Channel Effects

Numerous non-cardiac medications inhibit potassium channels and cause QT prolongation with risk of torsades de pointes. 4

• Older antihistamines (terfenadine, astemizole) block cardiac K+ channels and prolong repolarization, particularly when co-administered with CYP3A4 inhibitors like ketoconazole 4
• Antifungals (ketoconazole) both inhibit drug metabolism and directly block cardiac potassium channels 4
• Even grapefruit juice can inhibit metabolism of certain drugs, leading to toxic levels and arrhythmias 4

High-Risk Clinical Scenarios

Certain patient populations and drug combinations dramatically increase arrhythmia risk. 4, 1

• Patients with structural heart disease, cardiomyopathy, or pre-existing conduction abnormalities are at highest risk 1
• Drug-drug interactions involving CYP3A4 inhibitors (ketoconazole, erythromycin, grapefruit juice) can cause toxic accumulation 4
• Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia) potentiate QT-prolonging effects 4
• Bradycardia and female sex are independent risk factors for drug-induced torsades de pointes 4

Management Approach

Immediate discontinuation of the offending agent is the primary intervention, with specific antiarrhythmic treatment based on the arrhythmia type. 4, 3

• For QT prolongation and torsades de pointes: discontinue drug, correct electrolytes (maintain potassium >4.5 mEq/L, magnesium >2 mg/dL), and administer intravenous magnesium 4
• Isoproterenol can increase heart rate and shorten ventricular action potential duration to eliminate torsades de pointes 4
• For supraventricular tachycardia from theophylline toxicity: propranolol or verapamil are effective 3
• Temporary pacing may be necessary for severe bradyarrhythmias from beta-blockers, calcium channel blockers, or digoxin 4
• In severe toxicity with delayed drug elimination, charcoal hemoperfusion should be considered only when conservative measures fail 3