---

Antiarrhythmic Drugs - Simplified for MD Emergency Medicine Exam

The Cardiac Action Potential - Foundation You Must Know

---

Vaughan-Williams Classification - The Big Picture

---

CLASS I - Sodium Channel Blockers

General rule: All class I agents block fast Na+ channels → increase excitability threshold → slow conduction velocity → can break re-entry circuits.

Class Ia - "Moderate Blockers" (Procainamide, Quinidine, Disopyramide)

Procainamide (Most EM-relevant Class Ia)

• Actions: Intermediate Na+ channel block + K+ channel block; active metabolite NAPA (blocks only K+)
• EM Indications:
  • Hemodynamically stable VT - drug of choice in stable monomorphic VT (PROCAMIO trial: 68% conversion vs amiodarone 48%, fewer adverse events)
  • WPW with AF (pre-excited AF) - PREFERRED over adenosine/verapamil
  • AF of <48 hours duration
• Dose: 10 mg/kg IV; or 1g in 250 mL D5W over 60-120 minutes. Stop if BP <100 mmHg, HR <60, or QRS widens >50%
• Avoid in: Prolonged QT, symptomatic CHF, lupus
• Adverse effects: Hypotension, QT prolongation, TdP, lupus-like syndrome (chronic use), agranulocytosis

Quinidine

• Historically important; now mostly oral/chronic use
• Side effects: Cinchonism (tinnitus, headache, visual disturbances), hemolytic anemia, thrombocytopenia, TdP

Disopyramide

• Strong anticholinergic effects (urinary retention, constipation, dry mouth)
• Negative inotrope - avoid in heart failure

---

Class Ib - "Weak Blockers" (Lidocaine, Mexiletine)

Lidocaine (The EM Workhorse)

• Actions: Preferentially suppresses ischemic myocardial tissue; local anesthetic properties
• EM Indications: Ventricular arrhythmias - VT/VF (especially in acute MI setting); alternative when amiodarone unavailable
• Dose: 1-1.5 mg/kg IV bolus; repeat 0.5-0.75 mg/kg every 5-10 min; infusion 1-4 mg/min
• Adverse effects (CNS dose-dependent): Tremor → paresthesias → confusion → seizures → respiratory arrest
• Hepatic metabolism - reduce dose in liver disease/low cardiac output states

Mexiletine

• Oral lidocaine analog; used for chronic VT suppression
• Side effects: nausea, vomiting, dyspepsia

---

Class Ic - "Strong Blockers" (Flecainide, Propafenone)

Flecainide

• EM Use: "Pill-in-pocket" for paroxysmal AF (lone AF, no structural heart disease)
• CAST trial warning: Increased mortality in post-MI patients with PVCs - never use in ischemic heart disease
• Adverse effects: Proarrhythmia, visual disturbances

Propafenone

• Also has mild beta-blocking properties
• Similar indications and contraindications to flecainide

EM Pearl on Class I overall: Class Ic drugs are "use-dependent" - they bind more to open channels during tachycardia, so they're better at rate-related arrhythmia suppression.

---

CLASS II - Beta-Blockers

• EM Indications: Rate control in AF/atrial flutter; AVNRT; post-MI arrhythmia suppression; thyrotoxicosis-induced arrhythmias
• Contraindications: Decompensated HF, cardiogenic shock, severe bradycardia, 2nd/3rd degree AV block, reactive airway disease (propranolol)
• Adverse effects: Bradycardia, AV block, bronchospasm, hypotension

---

CLASS III - Potassium Channel Blockers

Amiodarone - "The King of Class III" (and the most EM-critical drug)

• Pulmonary toxicity - most serious (pneumonitis → fibrosis)
• Thyroid - hypo or hyperthyroidism (contains iodine)
• Hepatotoxicity
• Corneal microdeposits (most patients on chronic therapy)
• Photosensitivity, blue-grey skin discoloration
• Bradycardia, AV block (acute IV)
• Hypotension (IV formulation contains polysorbate 80)

---

Sotalol

• Has BOTH Class II (beta-blocker) and Class III (K+ channel block) effects
• EM Use: AF/flutter; monomorphic VT
• Risk: TdP (must monitor QT); avoid if QTc >500 ms or CrCl <40 mL/min
• Requires inpatient initiation (QT monitoring)

Ibutilide

• IV only; acute cardioversion of AF/flutter
• Big risk: TdP in 3-8% of patients - monitor for at least 4 hours post-infusion
• Dose: 1 mg IV over 10 min; repeat once if needed; correct electrolytes first

Dofetilide

• Oral only; AF/flutter conversion and maintenance of sinus rhythm
• Renally cleared - dose adjust for renal impairment
• Requires inpatient initiation (QT monitoring x 3 days)

Dronedarone

• Amiodarone analog without iodine (less thyroid/pulmonary toxicity)
• Only for paroxysmal/persistent AF that has converted to sinus rhythm
• Contraindicated in: Permanent AF, HF with NYHA III-IV, severe liver disease
• Increases digoxin levels and doubles serum creatinine (not true renal impairment)

---

CLASS IV - Calcium Channel Blockers

• WPW with AF/flutter - NEVER use (can accelerate conduction down accessory pathway → VF)
• Hypotension, cardiogenic shock
• Decompensated HF with systolic dysfunction
• Wide-complex tachycardia of unknown origin (may be VT)

---

OTHER ANTIARRHYTHMICS (Non-Vaughan-Williams)

Adenosine - "The Reset Button"

• EM Indication: Drug of choice for acute SVT (AVNRT, AVRT) - terminates re-entry through AV node
• Dose: 6 mg rapid IV push + flush; repeat 12 mg x2 if no response
  • Use central line or antecubital vein (distal veins give unreliable delivery)
  • Higher doses needed if patient on theophylline/caffeine (adenosine antagonists)
  • Halve the dose if on dipyridamole/carbamazepine (potentiate adenosine) or after heart transplant
• Adverse effects (transient, last seconds): Flushing, chest tightness, dyspnea, "sense of impending doom" - warn the patient!
• Contraindicated in: WPW with pre-excited AF, 2nd/3rd degree AV block, sick sinus syndrome (without pacemaker), severe reactive airway disease

Digoxin

• Mechanism: Inhibits Na+/K+-ATPase → intracellular Na+ rises → Ca2+ accumulates → increased contractility; also increases vagal tone → slows AV conduction
• EM Use: Rate control in AF (especially in HF with reduced EF); not for acute AF cardioversion
• Limitation: Sympathetic activation overcomes digoxin's AV-slowing effect (unreliable rate control in high-adrenergic states)
• Toxicity: Nausea, vomiting, yellow-green visual halos, bradycardia, any arrhythmia (PVCs, junctional tachycardia, AF with slow ventricular response are classic)
  • Risk factors: Hypokalemia (most important), hypomagnesemia, renal impairment
  • Toxic levels: >2.0 ng/mL (but toxicity can occur at lower levels)
  • Treatment: Digoxin-specific antibody fragments (Digibind/DigiFab)
• Therapeutic range for AF: 1.0-2.0 ng/mL; for HFrEF: 0.5-0.9 ng/mL

Magnesium Sulfate

• Mechanism: Blocks Ca2+ channels; inhibits early afterdepolarizations
• EM Indications:
  • Torsades de Pointes (drug of choice) - 1-2 g IV over 1-2 min (even if Mg level is normal)
  • Digoxin toxicity arrhythmias
  • Arrhythmias associated with hypomagnesemia
• Dose for TdP: 1-2 g IV bolus over 1-2 min, then infusion if recurrent

Atropine

• Mechanism: Muscarinic antagonist → blocks vagal tone → increases SA and AV node rate/conduction
• EM Use: Symptomatic bradycardia (sinus bradycardia, AV block)
• Dose: 0.5 mg IV; repeat every 3-5 min; max 3 mg
• Avoid in: High degree (Mobitz II, complete) AV block - may worsen infranodal block

Isoproterenol

• Mechanism: Non-selective β-agonist → increases HR and conduction
• EM Use: Pharmacologic pacing for symptomatic bradycardia refractory to atropine; TdP with bradycardia
• Contraindicated in: Ischemic heart disease (worsens ischemia)

---

Drug-Arrhythmia Quick Reference Map

---

High-Yield EM Exam Summary Table

---

Critical "NEVER DO" Pearls for the EM Exam

1. Never give adenosine, verapamil, diltiazem, beta-blockers, or digoxin in WPW + AF - can precipitate VF
2. Never give Class Ic drugs (flecainide, propafenone) post-MI or with structural heart disease - CAST trial
3. Never give verapamil/diltiazem for wide-complex tachycardia unless you are 100% sure it is SVT with aberrancy (assume VT first)
4. Never use procainamide/quinidine when QT is already prolonged - TdP risk
5. Correct K+ and Mg2+ before giving any QT-prolonging antiarrhythmic
6. Sotalol + dofetilide must be started inpatient with QT monitoring

---

Proarrhythmia Risk Summary

Why amiodarone has low TdP risk despite prolonging QT: It also blocks Ca2+ and Na+ channels, which offset the proarrhythmic effects of K+ channel block. This is why amiodarone is preferred in structural heart disease.

---