Amiodaraon

1. Amiodarone: Introduction
• Class III antiarrhythmic agent with multiple
channel-blocking actions
• Derived from benzofuran, structurally similar
to thyroid hormone
• Used for life-threatening arrhythmias

2. Chemical Structure and Properties
• Contains iodine – contributes to thyroid and
pulmonary toxicity
• Highly lipophilic – accumulates in tissues
(lungs, liver, skin)
• Long half-life: 40-60 days

3. Pharmacokinetics
• Oral bioavailability: 35-65%
• Extensive tissue binding → large volume of
distribution
• Metabolized in liver by CYP3A4 to
desethylamiodarone (DEA)
• Excretion mainly via bile

4. Mechanism of Action Overview
• Multi-class antiarrhythmic: I, II, III, IV
• Prolongs action potential duration and
refractory period
• Reduces conduction velocity and automaticity

5. Class III Effect (Primary)
• Blocks potassium channels
• Prolongs repolarization and action potential
duration
• Lengthens QT interval

6. Class I Effect
• Inhibits sodium channels
• Slows intraventricular conduction

7. Class II and IV Effects
• Noncompetitive beta-blocker activity (Class II)
• Calcium channel inhibition (Class IV)
• Suppresses SA and AV node conduction

8. Electrophysiological Effects
• SA node: ↓ automaticity → bradycardia
• AV node: ↓ conduction → PR prolongation
• Ventricles: ↑ refractory period → prevents
reentry arrhythmias

9. Clinical Indications
• Ventricular fibrillation (VF) – FDA approved
• Unstable ventricular tachycardia (VT) – FDA
approved
• Atrial fibrillation/flutter – off-label use
• Supraventricular tachycardia (SVT) – off-label

10. Use in Atrial Fibrillation
• Used for rhythm control in persistent AF
• Effective in patients with structural heart
disease
• Better tolerated than other antiarrhythmics in
HF patients

11. Use in Ventricular Arrhythmias
• Effective in monomorphic and polymorphic VT
• Drug of choice in cardiac arrest due to
VF/pulseless VT unresponsive to defibrillation

12. Oral Dosage Regimen
• Loading: 800–1600 mg/day in divided doses
for 1–3 weeks
• Intermediate: 600–800 mg/day for 1 month
• Maintenance: 200–400 mg/day

13. IV Dosage Regimen
• 150 mg over 10 minutes
• 1 mg/min for 6 hours, then 0.5 mg/min for 18
hours
• Switch to oral once stable

14. Drug Interactions: Enzyme
Inhibition
• Inhibits CYP3A4, CYP2C9, and P-glycoprotein
• ↑ levels of digoxin, warfarin, phenytoin,
cyclosporine
• ↓ dose of interacting drugs required

15. Drug Interactions: Additive Effects
• Increased bradycardia with beta-blockers,
verapamil, diltiazem
• ↑ QT prolongation with other QT-prolonging
drugs
• Caution with statins – risk of myopathy

16. Common Side Effects
• Bradycardia, hypotension
• Photosensitivity, skin discoloration (blue-gray)
• Corneal microdeposits (benign)

17. Pulmonary Toxicity
• Interstitial pneumonitis (most serious
complication)
• Pulmonary fibrosis with chronic use
• Requires PFT and chest X-ray monitoring

18. Thyroid Dysfunction
• Hypothyroidism (more common) – blocks T4
to T3 conversion
• Hyperthyroidism – Jod-Basedow effect or
thyroiditis
• Monitor TSH every 6 months

19. Hepatic Toxicity
• Elevated transaminases, hepatitis
• Rarely fulminant hepatic failure
• Monitor LFTs at baseline and during therapy

20. Ocular and Neurologic Effects
• Corneal deposits (common, reversible)
• Optic neuritis/neuropathy (rare, may cause
blindness)
• Tremor, ataxia, peripheral neuropathy with
long-term use

21. Contraindications
• Sinus node dysfunction causing bradycardia
• AV block (2nd or 3rd degree) without
pacemaker
• Cardiogenic shock
• Hypersensitivity to amiodarone or iodine

22. Black Box Warnings
• Pulmonary toxicity – potentially fatal
• Hepatotoxicity – can be severe
• Proarrhythmia – especially torsades de
pointes
• Reserved for life-threatening arrhythmias

23. Monitoring Parameters
• Baseline: LFTs, TFTs, PFTs, CXR, ECG
• Repeat every 6 months or if symptomatic
• Ophthalmologic exam annually

24. Special Populations
• Use with caution in elderly – risk of
bradycardia and hypotension
• Pregnancy Category D – crosses placenta, risk
of fetal thyroid dysfunction
• Lactation – excreted in breast milk, avoid use

25. Summary and Key Points
• Potent antiarrhythmic with multi-class actions
• Extensive side effect profile requires regular
monitoring
• Reserved for life-threatening arrhythmias or
refractory AF/VT
• Use lowest effective dose for shortest duration

26. References
• FDA Label (2018): Cordarone (Amiodarone)
• Goodman & Gilman's The Pharmacological
Basis of Therapeutics
• StatPearls, DrugBank, ACC/AHA Guidelines