| Indication |
Intravenously, for initiation of treatment and prophylaxis of
frequently recurring ventricular fibrillation and hemodynamically
unstable ventricular tachycardia in patients refractory to other
therapy. Orally, for the treatment of life-threatening recurrent
ventricular arrhythmias such as recurrent ventricular fibrillation and
recurrent hemodynamically unstable ventricular tachycardia. |
| Pharmacodynamics |
Amiodarone belongs to a class of drugs called Vaughan-Williams
Class III antiarrhythmic agents. It is used in the treatment of a wide
range of cardiac tachyarhthmias, including both ventricular and
supraventricular (atrial) arrhythmias. After intravenous administration
in man, amiodarone relaxes vascular smooth muscle, reduces peripheral
vascular resistance (afterload), and slightly increases cardiac index.
Amiodarone prolongs phase 3 of the cardiac action potential. It has
numerous other effects however, including actions that are similar to
those of antiarrhythmic classes Ia, II, and IV. Amiodarone shows beta
blocker-like and calcium channel blocker-like actions on the SA and AV
nodes, increases the refractory period via sodium- and potassium-channel
effects, and slows intra-cardiac conduction of the cardiac action
potential, via sodium-channel effects. |
| Mechanism of action |
The antiarrhythmic effect of amiodarone may be due to at least two
major actions. It prolongs the myocardial cell-action potential (phase
3) duration and refractory period and acts as a noncompetitive a- and
b-adrenergic inhibitor. |
| Absorption |
Slow and variable (about 20 to 55% of an oral dose is absorbed). |
| Volume of distribution |
Not Available |
| Protein binding |
>96% |
| Metabolism |
Amiodarone is extensively metabolized in the liver via CYP2C8
(under 1% unchanged in urine), and can effect the metabolism of numerous
other drugs. The major metabolite of amiodarone is desethylamiodarone
(DEA), which also has antiarrhythmic properties. The metabolism of
amiodarone is inhibited by grapefruit juice, leading to elevated serum
levels of amiodarone. |
| Route of elimination |
Amiodarone is eliminated primarily by hepatic metabolism and
biliary excretion and there is negligible excretion of amiodarone or DEA
in urine. |
| Half life |
58 days (range 15-142 days) |
| Clearance |
- 90-158 mL/h/kg [Healthy with a single dose IV (5 mg/kg over 15 min)]
- 100 mL/h/kg [Normal subjects > 65 yrs]
- 150 mL/h/kg [younger subjects]
- 220 and 440 mL/h/kg [patients with VT and VF]
|
| Toxicity |
Intravenous, mouse: LD50 = 178 mg/kg. Some side effects
have a significant mortality rate: specifically, hepatitis,
exacerbation of asthma and congestive failure, and pneumonitis. |
