Antiarrhythmics

Antiarrhythmic Drugs
Mechanism Effect on Action Potential Examples Additional Actions Side Effects Indications
I Ia Na+ channel blocker ↓↓ upstroke rate
↑ AP duration		 Quinidine Procainamide Class III activity
  • Prolonged QT
  • Quinidine: cinchonism
  • Procainamide: drug-induced lupus
  • Quinidine: Brugada syndrome
  • Procainamide: AVRT and preexcited a-fib / a-flutter
Ib ↓ upstroke rate
↓ AP duration		 Lidocaine Mexiletine None
  • Various CNS effects (predominantly lidocaine)
  • Suppression of VT (typically in acute ischemia)
Ic ↓↓↓ upstroke rate
Ø AP duration		 Propafenone Flecainide Class II activity
(propafenone only)
  • Increased risk of death when used in patients post-MI
  • Maintenance of sinus rhythm in paroxysmal a-fib (PAF), but only if no CAD/HF
II β blocker Slows rate of depolarization in slow AP cells Metoprolol Esmolol Acebutolol Pindolol None
  • Bronchospasm
  • Depression
  • Exercise intolerance
  • Sexual dysfunction
  • Rate control of a-fib/flutter
  • Suppression of PVCs, PACs, and VT
III K+ channel blocker ↑↑↑ AP duration Amiodarone Class I, II, and IV activity
  • Pulmonary fibrosis
  • Thyroid disease
  • Hepatic dysfunction, ↑ LFTs
  • Cardioversion of a-fib/flutter
  • Maintenance of sinus rhythm in PAF
  • Suppression of VT
Dronedarone Class I, II, and IV activity
  • Prolonged QT
  • Contraindicated in permanent a-fib and decompensated heart failure
  • Maintenance of sinus rhythm in PAF
Sotalol Class II activity
  • Prolonged QT
  • Maintenance of sinus rhythm in PAF
  • Suppression of VT
Dofetilide None
  • Prolonged QT
  • Cardioversion of a-fib/flutter
  • Maintenance of sinus rhythm in PAF
IV Ca2+ channel blocker Slows rate of depolarization in slow AP cells Verapamil Diltiazem Vasodilation
  • Negative inotropy
  • Rate control of a-fib/flutter
  • Prevention of AVNRT
Digoxin ↑ vagal tone, inhibits Na+/K+ pump Slows rate of depolarization in slow AP cells N/A Strengthens myocardial contraction
  • Very proarrhythmic
  • Rate control of a-fib (2nd line)
Adenosine Induces AV block ↑ refractory period
↑ threshold potential
↓ upstroke rate 		N/A Vasodilation
  • “Dying-like” sensation
  • Termination of AVNRT, AVRT
  • “Uncovering” a-flutter, AT

What's the physiology?

  • What is the rhythm?
    • AF / flutter
    • AVNRT / AVRT
    • Atrial tachycardia
    • Monomorphic VT (scar)
    • Polymorphic VT / torsades
  • What is the substrate?
    • Prior MI / scar
    • LV dysfunction
    • LVH
    • Cardiomyopathy
    • Channelopathies (LQT, Brugada)
    • CKD / liver disease
    • Conduction disease
  • What is driving this right now?
    • Sepsis
    • Hypoxia
    • Ischemia
    • Electrolytes
    • Volume status

Most antiarrhythmics can worsen the arrhythmia you are trying to treat.

Class I – Sodium Channel Blockers

Ia (procainamide, quinidine, disopyramide)

  • Use:
    • Procainamide
      • Afib/AFlutter
      • Stable VT
    • Quinidine
      • ****
  • Contraindications
    • Infranodal conduction disease → progress to CHB
    • Prolonged QT
    • History of Torsades
    • Uncorrected hypokalemia or hypomagnesemia
    • QT prolongation → torsades
    • Severe heart failure/hypotension → negative isotropy
  • Side effects
    • Hypotension, reduced CO
    • Torsades
  • Unique
    • Procainamide → lupus
    • Quinidine → myasthenia gravis
    • Disopyramide → anticholinergic/ myasthenia

Ib (lidocaine, mexiletine)

  • Use:
    • Ventricular arrhythmias only
    • Best in ischemia-related VT/VF
  • Key concept (EMCrit):
    • Lidocaine works best in acute ischemic myocardium
    • Often does NOT terminate scar-mediated monomorphic VT
  • Mexiletine:
    • Oral lidocaine equivalent
    • Adjunct, not strong monotherapy
  • Side effects:
    • Neurotoxicity

Ic (flecainide, propafenone)

  • Use:
    • AF rhythm control
    • Pill-in-pocket
  • ONLY if:
    • No structural heart disease
  • Key risk:
    • Post-MI → increased mortality (CAST)

Class II – Beta-Blockers

  • Use:
    • AF rate control
    • SVT
    • VT suppression
    • Long QT / CPVT
  • High-yield:
    • Often first-line safest antiarrhythmic
  • Side effects:
    • Bradycardia
    • AV block
    • Bronchospasm

Class III – Potassium Channel Blockers

Amiodarone

  • Use:
    • AF (especially structural disease / HFrEF)
    • VT/VF
  • Strength:
    • Works in almost anything
  • Weakness:
    • Toxicity:
      • Lung
      • Thyroid
      • Liver

Dofetilide

  • Use:
    • AF / flutter only
    • Safe in HFrEF
  • Must:
    • Start inpatient
  • Risk:
    • Torsades

Sotalol

  • Use:
    • AF prevention
    • VT suppression
  • Avoid:
    • CKD
    • QT prolongation

Dronedarone

  • Use:
    • Select AF patients
  • Avoid:
    • Permanent AF
    • HF (especially unstable)

Ibutilide

  • Use:
    • Chemical cardioversion (flutter > AF)
  • Risk:
    • Torsades

Class IV – Diltiazem, Verapamil

  • Use:
    • AF rate control
    • SVT
  • Avoid:
    • HFrEF
    • Pre-excited AF

Other Drugs

Adenosine

  • Use:
    • AVNRT / AVRT
    • Diagnostic
  • Avoid:
    • Asthma
    • Irregular wide-complex tachycardia

Digoxin

  • Use:
    • AF rate control (adjunct, especially HF)
  • Weakness:
    • Not effective for active patients
  • Risk:
    • Toxicity with renal dysfunction

AF / Flutter

Rate Control

  • Beta-blocker
  • Diltiazem / verapamil
  • Digoxin (adjunct)

Rhythm Control

  • No structural heart disease
    • Flecainide
    • Propafenone
    • Dronedarone
    • Sotalol
    • Dofetilide
  • Structural disease/ HFrEF
    • Amiodarone
    • Dofetilide

Ventricular Arrhythmias

Monomorphic VT (scar-mediated)

  • Amiodarone
  • Procainamide
  • Sotalol
  • Beta-blocker
  • Mexiletine (adjunct)
  • Lidocaine typically least effective if VT scar=mediated

Ischemic VT/VF

  • Lidocaine is most useful here
  • Amiodarone
  • Beta-blocker

VT Storm

  • Treat cause first:
    • Ischemia
    • Electrolytes
    • Sympathetic surge
  • Then:
    • Beta-blockade + amio
    • Sedation
Electrical Risk

Low-risk patients

  • Hemodynamically stable VA
  • Functioning ICD
  • VA terminated by ATP
  • Limited number of episodes
  • No prior AAD therapy

Step 1: initial therapies

  • Oral beta-blocker (eg propranolol)
  • Amiodarone IV ± oral loading
  • Benzodiazepine
Recurrent arrhythmias

High-risk patients

  • Hemodynamically unstable VA
  • No functioning ICD
  • VA not terminated by ATP
  • Incessant arrhythmias
  • Failure of AAD therapy

Step 2: add-on therapies

  • IV beta-blocker (eg esmolol)
  • Lidocaine IV
  • Dexmedetomidine
Recurrent arrhythmias

Step 3: rescue therapies

  • Stellate ganglion block
  • IV procainamide
  • General anesthesia
  • Urgent ablation

Definitive therapy

  • Catheter ablation
  • Heart transplant/LVAD
  • Palliative care
Intensity Antiarrhythmic Drugs Adrenergic Blockade Sedation/Anxiolysis Hemodynamic Support
Step 1 Amiodarone IV
  • Bolus 300 mg (max 5 mg/kg) over 20 min
  • Repeat 150 mg bolus over 10 min for recurrent VA
  • Infusion 1 mg/min until free from VA ≥6 hours (may continue for longer)
  • Continue 0.5 mg/min until ES resolves
 Oral beta-blocker
  • Propranolol 20-40 mg Q6h (preferred)
  • Metoprolol tartrate 25-50 mg Q6h (may be less effective)
  • May instead increase GDMT beta-blocker (eg, bisoprolol, carvedilol, metoprolol succinate) for selected low-risk patients
 Benzodiazepine
  • Lorazepam 1 mg Q4-6h PRN
  • Diazepam 5 mg Q4-6h PRN
  • Midazolam 2 mg Q1-2h PRN
 Vasopressors
  • Phenylephrine 0.1-2.0 μg/kg/min
  • Vasopressin 0.01-0.04 U/min
  • Norepinephrine 0.02-0.2 μg/kg/min
Step 2 Lidocaine IV
  • Bolus 1-1.5 mg/kg (max 100-120 mg)
  • May repeat 0.5-0.75 mg/kg Q5-10 min ×1-2 doses (max 300 mg or 3 mg/kg)
  • Infusion 1-2 mg/min (max 4 mg/min)
  • Goal serum procainamide concentration: 1.5-5 μg/mL
 IV beta-blocker
  • Esmolol
    • Bolus 0.5 mg/kg (may repeat Q5 min ×2)
    • Infusion 50-300 μg/kg/min
  • Propranolol 1-3 mg Q5 min (max 5 mg)
  • Metoprolol 2.5-5 mg Q5 min (max 15 mg)
 Dexmedetomidine
  • Bolus (optional) 0.5-1 μg/kg over 10 min (typically not recommended due to risk of hypotension)
  • Infusion 0.2-0.7 μg/kg/h
  • Maximum 1.0-1.5 μg/kg/h
 Intra-aortic balloon pump
  • Contraindicated with aortic aneurysm/dissection, severe aortic insufficiency, or peripheral vascular disease
  • Less effective with tachycardia or atrial fibrillation
Step 3 Procainamide IV
  • Bolus 10-15 mg/kg (max 17-20 mg/kg, usually 1 g total) over 30-60 min
  • Infusion 1-2 mg/min (max 4 mg/min)
  • Goal serum procainamide concentration: 4-8 μg/mL (up to 10 μg/mL)
 Stellate ganglion blockade
  • Left stellate ganglion blockade
  • 20 mL of 0.25% bupivacaine without epinephrine
  • Bilateral blocks if intubated
 General anesthesia
  • Endotracheal intubation
  • Propofol infusion often used, titrated to RAAS goal of −3
  • Opioid typically added (eg, fentanyl infusion)
 Advanced MCS
  • ECMO preferred
  • Percutaneous LVAD can be considered for selected patients
  • Contraindicated with severe aortic insufficiency or peripheral vascular disease

Torsades / Long QT

  • Magnesium
  • Stop offending drugs
  • Overdrive pacing or isoproterenol

High-Yield Contraindications

  • Flecainide / propafenone → structural disease
  • Dronedarone → permanent AF, HF
  • Dofetilide → QT prolongation, severe CKD
  • Sotalol → CKD, QT
  • Diltiazem / verapamil → HFrEF, pre-excited AF
  • Adenosine → asthma, irregular wide complex
  • Digoxin → renal failure, electrolyte issues