Amiodarone
1. CLASSIFICATION
Amiodarone = Class III antiarrhythmic (Vaughan-Williams classification)
|
Class |
Action |
|
Class I |
Na⁺ channel blockade |
|
Class II |
β-blocking effect |
|
Class III |
K⁺ channel blockade (main) |
|
Class IV |
Ca²⁺ channel blockade |
2. MECHANISM OF ACTION
- K⁺ channel blockade (Phase 3)
- ↑ repolarization time
- ↑ QT interval
- ↑ refractory period → prevents re-entry circuits
- Na⁺ channel blockade
- ↓ conduction velocity (especially in ischemic tissue)
- Ca²⁺ channel blockade
- ↓ AV node conduction
- Non-competitive β-blockade
- ↓ sympathetic drive
3. HEMODYNAMIC PROFILE
|
Parameter |
Effect |
|
HR |
↓ |
|
AV conduction |
↓ |
|
BP |
↓ (IV → due to solvent, vasodilation) |
|
Contractility |
Mild ↓ |
|
Coronary flow |
↑ |
- 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
- Watch for drug accumulation in prolonged ICU stay
4. INDICATIONS
A. Cardiac Arrest (ACLS – American Heart Association)
|
Scenario |
Role |
|
VF / pulseless VT (shock refractory) |
Drug of choice |
|
After 3rd shock |
300 mg IV bolus |
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
6. PHARMACOKINETICS
|
Feature |
Details |
|
Lipophilicity |
Very high |
|
Volume of distribution |
Massive |
|
Half-life |
20–60 days (!!) |
|
Onset (IV) |
Rapid |
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:
|
Type |
Mechanism |
|
Hypothyroidism |
Wolff-Chaikoff effect |
|
Hyperthyroidism |
Jod-Basedow / thyroiditis |
Hepatic
- ↑ LFTs
- Hepatitis
8. MONITORING
|
System |
Test |
|
Thyroid |
TSH (baseline + 6 monthly) |
|
Liver |
LFT |
|
Lung |
CXR / PFT |
|
Cardiac |
ECG (QT interval) |
|
Eye |
Ophthalmology if symptoms |
9. DRUG INTERACTIONS
Amiodarone = CYP inhibitor
|
Drug |
Effect |
|
Warfarin |
↑ INR |
|
Digoxin |
↑ toxicity |
|
Simvastatin |
↑ myopathy |
|
QT drugs |
↑ torsades risk |
10. CONTRAINDICATIONS
- Severe sinus node disease
- AV block (without pacemaker)
- Severe hypotension
- Thyroid disease (relative)
|
Arrhythmia |
Amiodarone Role |
|
Torsades de pointes |
Contraindicated |
|
Pre-excited AF (WPW) |
Avoid |
|
MAT |
Not preferred |
|
Digoxin toxicity arrhythmias |
Avoid |
