desethylamiodarone (dea). there is 10-50% transfer of amiodarone and dea in the placenta as well as a presence in breast milk. accumulation of amiodarone and dea occurs in adipose tissue and highly perfused organs (i.e. liver, lungs), therefore, if an individual was taking amiodarone on a chronic basis, if it is stopped it will remain in the system for weeks to months. pharmacology amiodarone is categorized as a class iii antiarrhythmic agent, and prolongs phase 3 of the cardiac action potential, the repolarization phase where there is normally decreased calcium permeability and increased potassium permeability. it has numerous other effects, however, including actions that are similar to those of antiarrhythmic classes ia, ii, and iv. amiodarone is a blocker of voltage gated potassium (kcnh2) and voltage gated calcium channels (cacna2d2). amiodarone slows conduction rate and prolongs the refractory period of the sa and av nodes. it also prolongs the refractory periods of the ventricles, bundles of his, and the purkinje fibres without exhibiting any effects on the conduction rate. amiodarone has been shown to prolong the myocardial cell action potential duration and refractory period and is a non-competitive β-adrenergic inhibitor. it also 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. it is suggested that amiodarone may also exacerbate the phenotype associated with long qt-3 syndrome causing mutations such as ∆kpq. this effect is due to a combination of blocking the peak sodium current, but also contributing to an increased persistent sodium current. amiodarone chemically resembles thyroxine (thyroid hormone), and its binding to the nuclear thyroid receptor might contribute to some of its pharmacologic and toxic actions. history the original observation that amiodarone's progenitor molecule, khellin, had cardioactive properties, was made by the russian physiologist gleb von anrep while working in cairo in 1946. khellin is obtained from a plant extract of khella or ammi visnaga, a common plant in north africa. anrep noticed that one of his technicians had been cured of anginal symptoms after taking khellin, then used for various, non-cardiac ailments. this led to efforts by european pharmaceutical industries to isolate an active compound. amiodarone was initially developed in 1961 at the labaz company, belgium, by chemists tondeur and binon, who were working on preparations derived from khellin. it became popular in europe as a treatment for angina pectoris. as a doctoral candidate at oxford university, bramah singh determined that amiodarone and sotalol had antiarrhythmic properties and belonged to a new class of antiarrhythmic agents (what would become the class iii antiarrhythmic agents). today the mechanisms of action of amiodarone and sotalol have been investigated in more detail. both drugs have been demonstrated to prolong the duration of the action potential, prolonging the refractory period, by interacting among other cellular function with k+ channels. based on singh's work, the argentinian physician mauricio rosenbaum began using amiodarone to treat his patients who have supraventricular and ventricular arrhythmias, with impressive results. based on papers written by rosenbaum developing singh's theories, physicians in the united states began prescribing amiodarone to their patients with potentially life-threatening arrhythmias in the late 1970s. by 1980, amiodarone was commonly prescribed throughout europe for the treatment of arrhythmias, but in the u.s. amiodarone remained unapproved by the food and drug administration, and physicians were forced to directly obtain amiodarone from pharmaceutical companies in canada and europe. the fda was reluctant to officially approve the use of amiodarone since initial reports had shown increased incidence of serious pulmonary side-effects of the drug. in the mid-1980s, the european pharmaceutical companies began putting pressure on the fda to approve amiodarone by threatening to cut the supply to american physicians if it was not approved. in december 1985, amiodarone was approved by the fda for the treatment of arrhythmias. this makes amiodarone one of the few drugs approved by the fda without rigorous randomized clinical trials. name amiodarone may be an acronym for its iupac name (2-butyl-1-benzofuran-3-yl)--3,5-diiodophenyl]methanone, where ar is a placeholder for phenyl. this is partially supported by dronedarone which is noniodinated benzofuran derivative of amiodarone, where the arylmethanone is conserved. dosing amiodarone is available in oral and intravenous formulations. orally, it is available under the brand names pacerone (produced by upsher-smith laboratories, inc.) and cordarone (produced by wyeth-ayerst laboratories). it is also available under the brand name aratac (produced by alphapharm pty ltd) in australia and new zealand, and further in australia under the brands cardinorm and rithmik as well as a number of generic brands. also arycor in south africa (produced by winthrop pharmaceuticals.). in south america, it is known as atlansil and is produced by roemmers. in india, amiodarone is marketed (produced by cipla pharmaceutical) under the brand name tachyra. it is also available in intravenous ampules and vials. the dose of amiodarone administered is tailored to the individual and the dysrhythmia that is being treated. when administered orally, the bioavailability of amiodarone is quite variable. absorption ranges from 22 to 95%, with better absorption when it is given with food. administration amiodarone iv should be administered via a central venous catheter. it has a ph of 4.08. if administered outside of the standard concentration of 900 mg/500ml it should be administered using a 0.22 micron filter to prevent precipitate from reaching the patient. amiodarone iv is a known vesicant. for infusions of longer than 1 hour, concentrations of 2 mg/ml should not be exceeded unless a central venous catheter is used.