INTRODUCTION Amiodarone is an iodinated Benzofuran. Structurally similar to THYROXINE and PROCAINAMIDE. It is a class-3 antiarrhythmic drugs of Vaughan Williams classification It was used initallyas a treatment for angina pectoris.– coronary vasodilation.
MECHANISM OF ACTION Blocks K+ channels,thus increasing the effective refractory period. Effective blocker of Na+ channels with high affinity for inactivated channels. Anti adrenergic effects by non competitively blocking α and β receptors. Weak calcium channel blocker. Slows sinus rate and AV conduction,slightly prolongs the QT interval.
CLINICAL PHARMACOLOGY Highly lipid soluble compound. DESETHYL AMIODARONE is the active metabolite. ON ORAL ADMINISTRATION Slowly absorbed Low bioavailability Large volume of distribution Extensively metabolised
ON INTRAVENOUS ADMINISTRATION 100% bioavailability Large volume of distribution Variable t½ ranging from 4.8hr to 68.2hrs
INDICATIONS It is primarily indicated for atrial fibrillations and flutter. Effective in maintaining sinus rhythm. Not useful as prophylactic in Pt. with risk of sudden cardiac death after MI. It is indicated when other treatments are ineffective or have not been tolerated esp. in recurrent life threatening vent.arrhythmias.
In ventricular arrhythmias after ablation to suppress recurrences.
It is the only drug available for treatment of Pt. with reduced ejection fraction who are at risk of SCD.
In followup of Pt. with an ICD for secondary prevention.
DOSAGE AND ADMINSTRATION Large oral or iv loading doses are required to hasten the onset of therapeutic action. Loading dosage varies from 600 to 1400 mg/day for 2 to 21 days. Usual maintenance dose varies from 200 to 600 mg/day Plasma concentrations of AMIDARONE are usually b/w 1 to 2mcg/ml during effective therapy. Levels of drug >3-4mcg/ml,for prolonged periods of time are associated with adverse effects.
ADVERSE REACTIONS HEART : bradycardia and AV conduction disturbances. Thyroid : HYPOTHYROIDISM : it inhibits the enzyme 5-deiodinase. Amiodarone and DEA the entry of thyroid hormone into cells and binding to its receptor. The high iodine content results in WOLFF-CHAIKOFF effect. HYPERTHYROIDISM: In the case of autonomic nodus,where autoregulation is lost,intake of a large amount of iodine can induce Thyrotoxicosis. cont…..
LUNG: Chemical pneumonitis. SKIN : Photosensitivity with susceptibility to sun burns. OCULAR CHANGES: Micro depositions of Amiodarone in the cornea. OTHERS: Neurological changes like peripheral neuropathy,tremor,ataxia
DRUG INTERACTIONS It inhibits hepatic and renal metabolism of drugs like DIGOXIN. It inhibits several cytochrome P450 pathways ,thus increasing serum concentrations of drugs such as statins,quinidine,flecainide. It inhibits the metabolism of Coumadin derivatives. It has got an additive proarrhythmic effect with other drugs that prolong the QT interval, such as class 1a anti arrhythmics, TCA, erythromycin ,thiazide diuretics and Sotalol.