Arrhythmia Adverse Effects

Ivabradine — adverse effects

Cardiovascular: • Bradycardia • QT prolongation with risk of severe ventricular arrhythmias • Atrial fibrillation (discontinue if it develops)

Visual: • Phosphenes (transient enhanced brightness, typically within 2 months)

Ivabradine — adverse-effect-related action

• Decrease dose if HR <50 bpm • Discontinue if atrial fibrillation develops

Beta-blockers — adverse effects

• Bradycardia • AV block • Bronchospasm (caution in asthma/COPD) • Can mask hypoglycemia-induced tachycardia

Beta-blockers — abrupt withdrawal warning

• Abrupt discontinuation after long-term use can exacerbate angina and cause myocardial infarction • Gradually reduce dose over 1–2 weeks and monitor

Non-DHP CCBs (diltiazem/verapamil) — adverse effects

• Peripheral edema • Constipation (especially verapamil) • Gingival hyperplasia • Headache • Flushing

Non-DHP CCBs — major cardiac safety concerns

Negative inotropy and AV nodal suppression.

Contraindications: • HFrEF/cardiogenic shock • 2nd/3rd-degree AV block • Severe hypotension • AF/AFL with WPW • Sustained VT • Concurrent/recent IV beta-blockers

Digoxin — GI adverse effects

• Nausea • Vomiting • Abdominal pain • Anorexia

Digoxin — visual adverse effects

• Halos • Photophobia • Altered color perception (red-green or yellow-green) • Scotomata

Digoxin — CNS adverse effects

• Fatigue • Weakness • Dizziness • Headache • Neuralgia • Confusion • Delirium • Psychosis

Digoxin — cardiac and electrolyte adverse effects

• Ventricular arrhythmias from delayed afterdepolarizations (DADs) • Sinus bradycardia • 1st-, 2nd-, or 3rd-degree AV block • Hyperkalemia in toxicity

Digoxin — factors increasing toxicity risk

• Hypokalemia • Hypomagnesemia • Hypothyroidism

Toxicity can occur at lower serum concentrations with these conditions.

Lecture notes increasing risk above 1.2 ng/mL

Adenosine — adverse effects

• Chest pain • Transient AV block • Flushing • Dyspnea • Headache • Transient feeling of impending doom

Adenosine — respiratory/cardiac precautions

• Monitor for bronchoconstriction, particularly with COPD • Contraindicated in reactive airway disease • Contraindicated in AV block >1st degree or sick sinus syndrome (per lecture)

Class Ia sodium-channel blockers — shared proarrhythmic effect

• Quinidine, procainamide and disopyramide prolong QTc • All three can cause torsades de pointes

Quinidine — distinctive adverse effects

• Cinchonism: tinnitus, CNS symptoms and GI effects • CNS symptoms: scotomata, dizziness, fatigue, confusion, headache • Hemolytic anemia in G6PD deficiency • Torsades de pointes

Procainamide — distinctive adverse effects

• Drug-induced lupus-like syndrome • Agranulocytosis • Hypotension during infusion • Torsades de pointes

Procainamide — adverse-effect monitoring

• CBC with differential and platelets (agranulocytosis) • ANA titers (lupus-like syndrome) • ECG and BP • Assess hepatic and renal impairment

Disopyramide — distinctive adverse effects

Anticholinergic effects: • Constipation • Dry mouth • Urinary retention • Tachycardia

Monitor for signs and symptoms of heart failure

Class Ib sodium-channel blockers — shared CNS toxicity

Lidocaine and mexiletine: • Dizziness • Sedation • Confusion • Paresthesia • Blurred vision • Slurred speech • Seizures • Psychosis • Tremors • Agitation

Lidocaine — adverse-effect monitoring

• Monitor CNS effects • Monitor LFTs • Continuous ECG during IV administration (including QTc per lecture)

Mexiletine — distinctive adverse effects

• Prominent GI effects, especially nausea/vomiting (up to 41%) • Class Ib CNS toxicity • Narrow therapeutic-to-toxic range

Mexiletine — serious warnings

• Blood dyscrasias: leukopenia, agranulocytosis, thrombocytopenia • Drug reaction with eosinophilia and systemic symptoms (DRESS)

Class Ic sodium-channel blockers — shared major risk

Flecainide and propafenone: • Serious proarrhythmia/conduction disturbances

Contraindicated in structural heart disease: • CAD • HF • Valvular heart disease • LVH

Flecainide — adverse effects

• Dizziness (14%) • Dyspnea (10%) • Headache (10%) • Tremor (5%) • 2nd/3rd-degree heart block • Ventricular arrhythmias • Prolonged QT/TdP as listed in lecture

Fatal proarrhythmia typically occurs within the first 1–3 weeks

Propafenone — distinctive adverse effects

• Unusual metallic/salty taste (14%) • Nausea/vomiting (11%)

Monitoring: • ECG for QRS widening • BP and pulse, especially at initiation

Class III potassium-channel blockers — shared risk

• Proarrhythmia from QT prolongation, including torsades de pointes • Correct K+, Mg2+ and Ca2+ abnormalities before and during administration

Ibutilide — major adverse effect

• Serious ventricular arrhythmias, including torsades de pointes • Lecture reports 1.7% fatal arrhythmia incidence

Monitoring: • Continuous cardiac/hemodynamic monitoring during infusion and for 4 hours afterward

Amiodarone — pulmonary adverse effect

• Pulmonary toxicity

Lecture monitoring: • Baseline and periodic chest radiograph • Pulmonary function testing

Amiodarone — thyroid adverse effects

• Hyperthyroidism • Hypothyroidism

Lecture notes interference with T4-to-T3 conversion.

Monitoring: • TSH and free T4 at baseline and every 6 months

Amiodarone — hepatic and ocular adverse effects

• Hepatotoxicity • Optic neuropathy

Monitoring: • Liver enzymes at baseline and every 6 months • Baseline ophthalmologic exam

Amiodarone — skin and GI adverse effects

• Photosensitivity • Blue skin discoloration • Nausea • Anorexia

Amiodarone — cardiac adverse effects

• Proarrhythmia, including torsades de pointes • Bradycardia, mainly with IV administration

Amiodarone — overall toxicity pattern

Multiorgan toxicity: • Lungs • Thyroid • Liver • Eyes • Skin • GI tract • Heart

Adverse effects can accumulate over time due to its long half-life

Dronedarone — adverse effects

• Worsening heart failure • Increased serum creatinine • QTc prolongation/proarrhythmia • Hepatic injury • Interstitial lung disease • Skin rash • GI distress

Dronedarone — important adverse-effect monitoring

• ECG every 3 months • BP, HR and rhythm • LFTs and bilirubin, especially during the first 6 months

Dofetilide — adverse effects

• Ventricular tachycardia (4%) • Torsades de pointes (≤3%) • Headache • Chest pain • Dyspnea • Respiratory tract infection

Dofetilide — safety monitoring

• QT/QTc monitoring for a minimum of 3 days • Baseline ECG and repeat 2–3 hours after each administration • Renal function affects dosing and toxicity risk

Sotalol — adverse effects

• Bradycardia • Dizziness • Fatigue • Dyspnea • Ventricular tachycardia (≤1%) • Torsades de pointes (≤4%)

Sotalol — safety monitoring

• QT/QTc monitoring for a minimum of 3 days • Baseline ECG and repeat 2–4 hours after each administration • Renal impairment increases half-life

Distinguish the classic Class Ia adverse effects

• Quinidine → Cinchonism • Procainamide → Lupus-like syndrome/agranulocytosis • Disopyramide → Anticholinergic effects

All three → Torsades risk

Distinguish the classic Class III adverse effects

• Ibutilide → Acute ventricular arrhythmia/TdP risk • Amiodarone → Multiorgan toxicity • Dronedarone → HF, creatinine rise, liver/lung toxicity • Dofetilide → Torsades • Sotalol → Torsades plus beta-blocker effects