Amiodarone
·
Amiodarone (3,5-Diiodophenyl ketone
hydrochloride) is an iodinated benzofuran derivative with a structural
similarity to thyroxine. Each 200 mg contains 75 mg of iodine. Amiodarone is a
class III antiarrhythmic agent that primarily prolongs cardiac action potential
duration. It also possesses vasodilatory and non-competitive antiadrenergic
activity.
·
Treatment of
·
Resistant, life-threatening
supraventricular and ventricular arrhythmias.
·
Intractable congestive heart
failure.
·
Amiodarone can be given orally or
intravenously. Bioavailability on oral administration is low (28 to 50%), with
peak plasma levels achieved 3 to 8 (range 2 to 12) hours after therapeutic
doses. Absorption is slow and variable (22 to 86%). First pass metabolism in
the gut wall or liver may be the cause. Amiodarone is extensively distributed,
with concentrations in the skin, skeletal muscle, adipose tissue, lung, liver,
and myocardium. Tissue concentrations generally exceed that of plasma. The
volume of distribution is large (9–17 L/kg), protein binding is to the extent
of 98%, and the elimination half-life varies from 3 to 21 hours. Its major
metabolite is desethylami-odarone, and the principal route of elimination is by
hepatic excretion into the bile where it may get concentrated upto 50 times
that of the serum. Less than 1% is excreted by the kidneys.
■■ Prolongs the action
potential duration of myocardial cells without altering the resting membrane
potential.
■■ Non-competitive
alpha and beta sympathetic receptor blockade resulting in vasodilation.
· Rapidly progressive adult
respiratory distress syndrome. Symptoms develop either acutely, resembling an
infec-tious pneumonitis, or slowly with cough, dyspnoea, and weight loss.
Pulmonary toxicity (interstitial pneumonitis or pulmonary fibrosis) may
manifest as dyspnoea, cough, fever, chest pain, malaise, weakness, anorexia, weight
loss, and abnormal pulmonary function tests following amiodarone therapy.
Clinical and radiologic findings have included exertional or progressive
dyspnoea, tachypnoea, cough, pleuritic chest pain, fever, malaise, elevated
ESR, leukocytosis, hypoxaemia, decreased total lung capacity, diffuse
interstitial or alveolar infiltrates, and pleural thick-ening. Pulmonary
function studies have shown a decrease in carbon monoxide diffusing capacity
(DCO). Haemoptysis, an unusual adverse effect of amiodarone therapy, is
associ-ated with amiodarone-induced pulmonary toxicity.
·
Proarrhythmias, ventricular arrhythmias, bradycardia, heart
block.
·
Hypotension has been reported with rapid IV infusion.
·
A metallic or salty taste may occur with chronic therapy.
·
Hypo- or hyperthyroidism: Both hypo-and hyperthyroidism have
been reported during chronic therapy. Amiodarone has been demonstrated to cause
congenital myxoedema in infants born of amiodarone-treated women.
·
Hepatotoxicity: Transient liver enzyme elevations may occur
with chronic use, but are often asymptomatic. Signs and symptoms may include
hepatomegaly, ascites, abdominal pain, nausea, vomiting, anorexia, and weight
loss. Chronic amiodarone therapy may induce alcohol-like cirrhotic liver
changes.
·
Acute pancreatitis has been reported following therapeutic
use of amiodarone.
·
Epididymitis has occurred in some male patients. Blue-green
discolouration of skin and nails, alopecia. Prolonged exposure to sunlight
after 6 to 39 months of chronic amiodarone therapy may result in blue or purple
skin discolouration (pseudocyanosis). Cutaneous hyperpig- mentation occurs in 1
to 5% of patients taking therapeutic doses of amiodarone. Photosensitivity
reactions consisting of burning, flushing, urticaria, maculopapular eruptions,
alopecia, erythema and skin blisters have been reported after brief exposure to
sunlight in patients receiving amiodarone for as little as one week.
·
Peripheral neuropathy: Proximal muscle weakness, myopathy,
and myalgias have been noted in conjunction with neuropathies.
·
Malaise, fatigue, tremors, lack of co-ordination, abnormal
gait, ataxia, dizziness, and/or paraesthesia can occur in up to 4 to 9% of
patients receiving amiodarone.
·
Corneal microdeposits: Benign pigmented corneal
micro-deposits occur in 76 to 100% of patients receiving chronic therapy.
Visual disturbances such as blurred vision, coloured halos or photophobia may
accompany these changes. Optic neuropathy has also been reported.Severity is
related to dosage and duration of treatment. A typical symptom is described as
blue-green coloured rings or halos around surrounding light sources. Optic
examination shows opacities of the cornea, retina, lens and optic nerves.
Blue-white opacities can occur in the ante-rior subcapsular region of the lens
following amiodarone therapy. These changes may develop in 50 to 60% of the
patients receiving therapy and are not reversible with drug cessation. The
opacities, however, rarely interfere with visual acuity.
·
Bone marrow granulomas may develop after months of therapy with
amiodarone. Initial symptoms include: inter- mittent fever, night sweats and
fatigue.
·
Overdose experience with amiodarone is limited. Adults
ingesting 2.6 to 8 grams developed asymptomatic slight bradycardia and QT
prolongation with a delayed onset of 1 to 3 days post-ingestion. No other toxic
effects have been noted in overdose. In substantial overdose, bradycardia and/
or heart block, torsades de pointes and hypotension should be anticipated.
■■ Potentiates the
effect of oral anticoagulants and other antiarrhythmics.
■■ Increases digoxin
concentration by 70 to 100%.
■■ Additive effect with
beta blockers and Calcium channel blockers.
■■ Amiodarone
administration in pregnancy may result in neonatal hypothyroidism and
prematurity.
·
Although a therapeutic range is
approximately 1 to 2.5 mcg/ ml, several authors question the usefulness of
serum levels to predict either clinical efficacy or toxicity.
·
Decontamination measures may be
effective upto several hours post-ingestion. Perform stomach wash only while
cardiac monitoring is done, since profound bradycardia can occur.
·
Oral cholestyramine (4 grams every
hour for 4 hours) may help in reducing the half-life of amiodarone.
·
Pulmonary toxicity responds to
corticosteroids, but rapid withdrawal may lead to recurrence. Chest X-ray
findings in patients with amiodarone-induced pulmonary toxicity are
nonspecific, including areas of consolidation, infiltrates, and interstitial
disease. Chest CT may be helpful in evaluating patients with suspected
amiodarone-induced pulmonary toxicity.
·
Monitoring of ECG is essential and
may need to be continued for several days postingestion. Severe cardio-vascular
collapse is treated with isoprenaline and DC cardioversion.
·
Bradycardia responds to beta-adrenergic
agonists or pacemaker. With chronic therapy, bradycardia has been unresponsive
to atropine, presumably due to the noncom-petitive nature of amiodarone’s
antiadrenergic effects. Beta-adrenergic agonists such as isoproterenol or
ephedrine may be helpful in cases of sinus arrest.
·
Intravenous magnesium sulfate has
been successfully used to treat nonsustained polymorphous ventricular
tachycardia with prolonged QT interval due to amiodarone therapy.
·
Hypotension responds to
vasopressors. Infuse 10 to 20 ml/ kg of isotonic fluid and place in
Trendelenburg position. If hypotension persists, administer dopamine or
noradrena-line. Consider central venous pressure monitoring to guide further
fluid therapy.
·
Haemodialysis and haemoperfusion do
not appear to be beneficial.
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