· 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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