Amiodarone

Amiodarone 

1. CLASSIFICATION 

Amiodarone = Class III antiarrhythmic (Vaughan-Williams classification)

 2. MECHANISM OF ACTION 

1. K⁺ channel blockade (Phase 3)
   • ↑ repolarization time
   • ↑ QT interval
   • ↑ refractory period → prevents re-entry circuits

2. Na⁺ channel blockade

1. • ↓ conduction velocity (especially in ischemic tissue)

3. Ca²⁺ channel blockade

1. • ↓ AV node conduction

4. Non-competitive β-blockade

1. • ↓ sympathetic drive

 3. HEMODYNAMIC PROFILE 

• Safe in LV dysfunction / cardiogenic shock (relative)
• Much safer than other antiarrhythmics (e.g., flecainide)
• Safest antiarrhythmic in structural heart disease
• Prefer central line (peripheral → phlebitis)
• Dilute properly (avoid hypotension from solvent)
• Avoid rapid bolus in unstable BP(IV → due to solvent, vasodilation)
• Watch for drug accumulation in prolonged ICU stay

4. INDICATIONS 

 A. Cardiac Arrest (ACLS – American Heart Association)

 B. Ventricular Arrhythmias

• Sustained VT (stable/unstable)
• Electrical storm
• Post-MI VT

 Preferred when:

• Structural heart disease
• LV dysfunction

 C. Supraventricular Arrhythmias

• Atrial fibrillation (AF) with:
  • Hemodynamic instability
  • Heart failure
• Atrial flutter
• AVRT / WPW ( careful)

D. ICU-Specific Uses

• Post-cardiac surgery AF
• Sepsis-associated AF
• Rate + rhythm control when β-blockers contraindicated

 5. DOSING IN ICU

 Cardiac Arrest (VF/pVT)

• 300 mg IV bolus
• Repeat 150 mg if needed

 Stable VT / AF

Loading:–150 mg IV over 10 min

Infusion:

• 1 mg/min × 6 hrs
• then 0.5 mg/min

 Max: ~2.2 g/24 hr

 Oral Conversion

• 800–1200 mg/day (loading)
• Maintenance: 100–200 mg/day

If arrhythmia is controlled and patient can take orally

Step 1: Start oral amiodarone.

Common regimen:

• 400 mg PO twice daily for 1 week
• Then 400 mg PO once daily for 2–4 weeks
• Then maintenance 200 mg daily

Step 2: Continue IV infusion briefly

Because amiodarone has a large volume of distribution and delayed oral absorption:

• Give first oral dose.
• Continue IV infusion for 12–24 hours after starting oral therapy.
• Then discontinue infusion if rhythm remains stable.

 6. PHARMACOKINETICS 

 Clinical implication:

• Accumulates in tissues → toxicity even after stopping

7. ADVERSE EFFECTS 

 Pulmonary (MOST SERIOUS)

• Interstitial pneumonitis
• Pulmonary fibrosis
• ARDS

 Mortality high → STOP drug immediately

 Cardiac

• Bradycardia
• AV block
• QT prolongation
•  Torsades (rare vs others)

 CNS

• Tremor
• Ataxia
• Peripheral neuropathy

 Dermatological

• Photosensitivity
• Blue-gray skin discoloration

 Ocular

• Corneal deposits (common)
• Optic neuropathy (rare)

 Thyroid 

Because of iodine content:

 Hepatic

• ↑ LFTs
• Hepatitis

 8. MONITORING

 9. DRUG INTERACTIONS 

Amiodarone = CYP inhibitor

 10. CONTRAINDICATIONS

• Severe sinus node disease
• AV block (without pacemaker)
• Severe hypotension
• Thyroid disease (relative)