2. Amiodarone
• Type III antiarrhythmic agent.
• Contains alpha- & beta-receptor blocking properties
as well as sodium-, potassium-, & calcium- channel
blocking properties.
• Indicated for ventricular & atrial dysrhythmias.
3. Classification of Antiarrhythmic Agents
IA Quinidine IC Flecainide
Procainamide
Propafenone
Disopyramide Encainide
IB Lidocaine I? Moricizine
Mexiletine
Tocainide
4. Classification of Antiarrhythmic Agents
II Beta-adrenergic blockers
III Amiodarone Ibutilide
Dronedarone Dofetilide
Sotalol Bretylium
IV Calcium channel blockers
Diltiazem & Verapamil
5. Amiodarone Historical Landmarks (1)
1962: Synthesized as an anti-anginal compound .
1968: Novel action with new biological profile.
1970: Unusual electrophysiology profile.
74/76: Unusual clinical potency as an
antiarrhythmic drug
6. Amiodarone Historical Landmarks (2)
1983: First US Symposium on Amiodarone .
1984: FDA Approval.
1993: Efficacy Unparalleled; Mode of Action
Unknown.
1995: Amiodarone IV approved
7. Unique Features of Amiodarone
as an Anti-arrhythmic Drug
• Long elimination half-life.
• Can be administered to anephric patients on dialysis.
• Well tolerated in advanced CHF.
• Manageable drug-drug interactions .
(ie, digoxin)
• Very low incidence of torsades de pointes even
with diuretic therapy.
8. Unique Features of Amiodarone
(Cont’d.)
• Has Class 1 properties without the associated
proarrhythmic actions or negative impact on
mortality.
• Has antisympathetic actions without beta-blocker
side effects.
• Increases LVEF and improves CHF.
• Antifibrillatory actions in the ventricles may be
augmented by addition of beta-blockade.
10. Significant Electropharmacologic Effects -
Effect IV Amiodarone
• Prolonged action potential duration +
• Blockade of inactivated Sodium channels ++
• Slowed phase 4 depolarization in the SA node +
• Calcium channel blockade +++
• AV Node – effective refractory period
• Atrial – effective refractory period
• Ventricle – effective refractory period
• Noncompetitive blockade of and receptors +
• Heart rate -/
= increase or decrease; + = effect present;
11. Amiodarone I.V.
Indication
Amiodarone I.V ---for of treatment and
prophylaxis of frequently recurring
ventricular fibrillation and
hemodynamically unstable ventricular
tachycardia in patients refractory to
other therapy.
12. Contraindication
• Amiodarone I.V. is contraindicated in patients
with cardiogenic shock, marked sinus
bradycardia, and second- or third-degree AV
block in the absence of a functioning
pacemaker.
• An allergy to iodine is contraindication to
amiodarone therapy.
13. Pharmakokinetics
• Large volume of distribution.
• Half-life: 30 - 100 days.
• Metabolized primarily by CYP 3A4.
• Active metabolite : N- des-ethyl-amiodarone
- Half-life: ~60 days
14. Intravenous Amiodarone Pharmacokinetics
• Peak levels after single 5 mg/kg 15 min infusions
: 5-41 mg/L .
• After 10 min 150 mg load for VF/VT : 7-26
mg/L.
• Levels decline to 10 % of peak within 30-45 min
at the end of the infusion.
• After 48 hrs of continued infusions, levels 0.7 to 1.4
mg/L.
15. Pharmacokinetics of
Oral Amiodarone
•Absorption : Tmax: 2-12 h (lab 0.4-3 h).
• Extent of absorption : Poor and slow.
• Bioavailability : Variable (22-86%).
• Protein binding : 96.3 ± 0.6%.
• Volume of distribution : 1.3-65.8 L/kg.
• Negligible renal excretion
• Biotransformation : Hepatic and intestinal.
• Elimination half-life : 3 -20 h (acute),
15-50day (chronic).
16. Pharmacokinetics of
Oral Amiodarone
•Total body clearance : 0.10-0.77 l/min.
•Pattern of elimination : First order.
• Metabolites :
Major : mono N-des-ethyl-amiodarone,
Minor: bis-N-des-ethyl-amiodarone, deiodinated
•Therapeutic levels : 1.0-2.5 µg/mL range.
•Special factors : Slow onset & offset of action
17. Actions of IV Amiodarone vs Chronic
Amiodarone
Actions IV Amio Chronic Amio
Repolarization (QT
interval) prolongation
(atria & ventricles)
± ++++
Conduction velocity
(atria & vent)
reduced
++ ++
(function of
rate)
Sinus rates reduced + +++
AV nodal
conduction slowed
+ ++
18. Actions of IV Amiodarone vs Chronic
Amiodarone
Actions IV Amio Chronic Amio
AV nodal
refactoriness
increased
++ ++++
Atrial refactoriness
increased
± +++
Ventricular
refactoriness
increased
± +++
Noncompetitive
alpha and beta
blocking activity
+ +
20. AMIODARONE DOSING
•An oral dosing protocol
- 15 mg/kg/day x 1 week
- 10 mg/kg/day x 2 weeks
- 5 mg/kg/day
- Eventually reduce to 100-200 mg daily
•Oral bioavailability: ~50%
21. •General IV load
- 150 mg over 10 minutes.
- 1 mg/min x 6 hours.
- 0.5 mg/min x 18 hours or longer.
Monitor heart rate & blood pressure
•Ventricular fibrillation
- 300 mg IV ; may repeat 150 mg IV.
•Ventricular tachycardia
- 150 mg over 10 min; repeat as needed to a total
of 2.2 gm in 24 hours.
22. Adverse Effect
• Hypotension is the most common adverse effect seen
with amiodarone I.V. and may be related to the rate
of infusion.
• Hypotension should be treated by slowing the infusion
or with standard therapy : vasopressor drugs, positive
inotropic agents, and volume expansion.
23. Other emergent adverse effects are;
• Hypotension (16%)
• Bradycardia (4.9%),
• Liver function test abnormalities (3.4%),
• Cardiac arrest (2.9%),
• Ventricular Tachycardia (2.4%),
• Chronic heart failure
• Cardiogenic shock (1.3%),
• AV block (0.5%).
26. Pulseless VT/VF
Shock x 3
Persistent or recurrent
VT/VF
Continue CPR
Intubate
Obtain IV access
Epinephrine 1 mg I.V.
q 3 to 5 minutes
amiodarone I.V. 300 mg
rapid peripheral infusion
DF 360 J within
30 to 60 sec after each drug
“Drug-Shock”, “Drug-Shock”
IIb Medications, e.g.,
Lidocaine
Procainamide
etc.
*Due to persistent VF/pulseless VT
27. Dronedarone
• A “less toxic” amiodarone.
• Half-life: 13-19 hours.
• Only FDA-approved for atrial
fibrillation/flutter
- Not as effective as amiodarone.
