Amiodarone

Bramah N. Singh, MD, PhD

	May 13, 1999 - Along with sotalol, amiodarone
was the start of controlling heart arrhythmias by 
prolonging repolarization - the so-called class 3 anti-
arrhythmic action. It has many complex actions.
	Amiodarone affects *all* heart tissues, such
as the sinus node, the AV node, atrial cells, 
Purkinje fibers and the ventricular myocardium. 
These effects differ when the drug is given acutely 
from when it is given over a long period of time.
	It is effective in restoring and maintaining 
sinus rhythm in a-fib and it can prevent ventricular 
tachycardia and fibrillation. It slows heart rate and
conduction. Amiodarone blocks the sodium-channel
(class 1 effect), inhibits sympathetic stimulation 
(class 2 action), blocks potassium channels (class 3 
action) and calcium channels (class 4 actions).
	Amiodarone does not lessen the heart's ability 
to contract and rarely causes arrhythmia so it can
be used in patients with heart failure and in those who
need large doses of diuretics.
	Amiodarone is a powerful suppressant of 
premature ventricular contractions (PVCs), runs of 
ventricular tachycardia, and can prevent onset of
ventricular fibrillation. Unlike class 1 drugs, it does
not very often prevent EPS rfom inducing tachycardia.
It may reduce sudden death and prolong survival in 
certain groups of patients.
	ICDs have caused a change in the use of anti-
arrhythmic drugs. It is now generally agreed that for 
many patients with ventricular tachycardia and 
fibrillation, the preferred therapy is ICD but 
amiodarone as well as sotalol or beta-blockers may also
be required.
	There are data suggesting that when the 
ejection fraction is not severely depressed,
amiodarone may be as effective as ICD in some patients.
Such a possibility needs to be explored.

Intravenous Amiodarone

	Intravenous amiodarone may control ventricular
tachycardia and fibrillation in hospitalized heart 
attack patients who do not respond to other therapies.
Such patients are treated with IV lidocaine, 
procainamide and bretylium. Some studies suggest that
IV amiodarone in this setting is an important addition
to anti-arrhythmia therapy in these patients. Three 
doses (125mg, 500mg, 1000mg per 24 hours) of amiodarone
were recently compared in this group of patients.
The highest dose was best in preventing arrhythmia 
recurrence and was well tolerated.
	In a recent trial from Seattle, heart attack
patients were given standard ACLS treatment and were
then randomized to placebo or IV amiodarone. More 
patients could be resuscitated to reach a hospital 
with amiodarone. This is the first controlled trial
of its kind showing that an IV drug, in this case 
amiodarone, is better than placebo for increasing 
survival in heart attack patients. This may be of 
major interest for arrhythmic patients having heart
surgery.
	Intravenously administered amiodarone reduces
the a-fib that is seen in more than 30% of patients 
having open-heart surgery. A preventive regimen for 
high-risk groups in this setting might be considered.

Maintaining Sinus Rhythm

	While most patients with supraventricular 
arrhythmias, including atrial flutter, now have ablation,
few a-fib patients are currently considered for it.
A-fib has become the most common arrhythmia requiring
hospitalization. Its incidence is rising as people live
longer. A-fib treatment is still not standardized.
	Amiodarone in low-doses might be appropriate
for maintaining sinus rhythm. The drug might ease 
electrical conversion in some patients for whom 
cardioversion may be difficult. Given orally for a 
week, amiodarone reduces episodes of a-fib and flutter
in patients having heart surgery. It reduces the
number of episodes of paroxysmal a-fib and may be most
effective in patients who have persistent 
a-fib which can be converted to sinus rhythm.
	While most anti-arrhythmic drugs maintain sinus
rhythm in 40-50% of patients, amiodarone is effective in
more than 60%. A number of trials are now in progress 
comparing amiodarone to other anti-arrhythmic drugs.
	One area where the drug is clearly first line
for control of a-fib is in congestive heart failure.
Here, the drug is effective in a significant number 
of patients of all heart classes.

Possible Side Effects

	There is an increasing tendency for the use of 
lower and more standardized doses of amiodarone to control
arrhythmias. While the side effect potential of the drug
cannot be eliminated, it can be reduced. The drug does 
have a large potential for drug interactions. A beneficial
interaction is with beta-blockers. They may prolong 
survival in certain patients without producing bradycardia
or heart block.
	The major bad side effects are pulmonary toxicity
(probably 3-4%), serious liver toxicity (probably less 
than 1%), skin changes (reversible), and eye changes,
which rarely may become serious. The effects of amiodarone 
on thyroid function needs to be monitored regularly, since
it can induce hypo- and hyperthyroidism. This is related 
to the effects of the iodine in the molecule. Amiodarone 
rarely produces torsades de pointes.