Amiodarone is a unique antiarrhythmic drug that is classified as class III but also possesses class I, II, and IV properties. It works by blocking sodium, calcium, and potassium channels to prolong the action potential duration. Amiodarone has a slow onset due to its high lipid solubility and storage in adipose tissues, resulting in a very long half-life. It can have serious side effects involving the lungs, thyroid, and interactions with other drugs. Amiodarone is effective for treating atrial fibrillation and ventricular arrhythmias when other options are not appropriate. Close monitoring is required due to risks of pulmonary toxicity and QT prolongation.

1. Amiodarone

2. Class III drugs
↑APD & ↑RP by
blocking the K+ channels

3. Vm
(mV)
-80mV
0mV
↑ APD
Block IK

4. Amiodarone (Cordarone) is a unique “wide-
spectrum” antiarrhythmic agent, chiefly class III
but also with powerful class I activity and
ancillary class II and class IV activity. Thus it
blocks Na+,Ca++, and repolarizing K+ channels

5. Its established antiarrhythmic beneftis and potential for
mortality reduction need to be balanced against several
considerations:
- First, the slow onset of action of oral therapy may require large
intravenous or oral loading doses to achieve effects rapidly
- Second, the many serious side effects, especially pulmonary
infiltrates and thyroid problems, dictate that there must be a fine
balance between the maximum antiarrhythmic effect of the drug
and the potential for side effects
- Third, the half-life is extremely long
- Fourth, there are a large number of potentially serious drug
interactions, some of which predispose to torsades de pointes,
which is nonetheless rare when amiodarone is used as a single
agent
For recurrent AF, amiodarone may be strikingly effective with little risk
of side effects.
Otherwise the use of amiodarone in as low a dose as possible should
be restricted to selected patients with refractory ventricular
arrhythmias in which an ICD is not appropriate

6. Electrophysiologic characteristics
Predominantly class III, that shares at least some of the properties of each of
the other three EP classes of antiarrhythmics
- The class III activity means that amiodarone lengthens the effective
refractory period by prolonging the APD in all cardiac tissues, including bypass
tracts
- It also has a powerful class I antiarrhythmic effect inhibiting inactivated
sodium channels at high stimulation frequencies
- Its benefits in AF may be explained at least in part by prolongation of the
refractory periods of both the left and right superior pulmonary veins, and
inhibition of the AV node
- it is “uniquely effective” against AF in experimental atrial remodeling
- Amiodarone noncompetitively blocks a- and b-adrenergic receptors (class
II effect), and this effect is additive to competitive receptor inhibition by b-
blockers
- The weak calcium antagonist (class IV) effect might explain bradycardia
and AV nodal inhibition and the relatively low incidence of torsades de
pointes
- Furthermore, there are relatively weak coronary and peripheral
vasodilator actions

7. Pharmacokinetics
• highly lipid soluble drug differ markedly from other
cardiovascular agents : After variable (30% to 50%) and
slow gastrointestinal (GI) absorption, amiodarone
distributes slowly but very extensive into adipose
tissues
 amiodarone must fill an enormous peripheral-tissue
depot to achieve adequate blood and cardiac
concentrations, accounting for its slow onset of action .
 In addition, when oral administration is stopped, most
of the drug is in peripheral stores unavailable to
elimination systems, causing very slow elimination with
a very long half-life, up to 6 months

8. Dose (Amiodarone: Guidelines for Use and Monitoring, Am Fam Physician. 2003)

11. Dose: Adults
• Ventricular arrhythmias: IV: 15 mg/min × 10 min, then
1 mg/min × 6 h, maint 0.5-mg/min cont Inf or PO:
Load: 800–1600 mg/d PO × 1–3 wk Maint: 600–800
mg/d PO for 1 mo, then 200–400 mg/d
• Supraventricular arrhythmias: IV: 300 mg IV over 1 h,
then 20 mg/kg for 24 h, then 600 mg PO daily for 1
wk, maint 100–400 mg daily or PO: Load 600–800
mg/d PO for 1–4 wk Maint: Slow ↓ to 100–400 mg
daily
ECC 2010
- VF/VT cardiac arrest refractory to CPR, shock and
pressor: 300 mg IV/IO push; can give additional 150 mg
IV/IO once;
- Life-threatening arrhythmias: Max dose: 2.2 g IV/24 h;
rapid Inf: 150 mg IV over first 10 min (15 mg/min); can
repeat 150 mg IV q10min PRN; slow Inf: 360 mg IV over
60 min (1 mg/min); maint: 540 mg IV over 18 h (0.5
mg/min)

12. ESC 2016 - atrial fibrillation

13. Rate control
In critically ill patients and those with severely impaired LV systolic
function, intravenous amiodarone can be used where excess heart
rate is leading to haemodynamic instability. Urgent cardioversion
should be considered in unstable patients

14. Pharmacological cardioversion
Selection of antiarrhythmic drugs for long-term therapy: safety first

15. • The most serious potential adverse effect of amiodarone therapy is
pulmonary toxicity. The most common clinical presentation is subacute
cough and progressive dyspnea, with associated patchy interstitial
infiltrates on chest radiographs and reduced diffusing capacity on
pulmonary function tests.

16. - Although QTc prolongation
occurred frequently in patients
receiving amiodarone I.V., torsades
de pointes or new-onset VF occurred
infrequently (less than 2%). Patients
should be monitored for QTc
prolongation during infusion with
amiodarone I.V
- Patients with hypokalemia or
hypomagnesemia should have the
condition corrected whenever
possible before being treated with
amiodarone I.V., as these disorders
can exaggerate the degree of QTc
prolongation and increase the
potential for TdP. Special attention
should be given to electrolyte and
acid-base balance in patients
experiencing severe or prolonged
diarrhea or in patients receiving
concomitant diuretics