Anoion Mechanism of Action

Pharmacology: Pharmacodynamics and Pharmacokinetics: Amiodarone is a Class III antiarrhythmic agent prolonging the action potential duration and hence refractory period of atrial, nodal and ventricular tissues, thereby giving a very broad spectrum of activity. An increase in the refractory period of the atrial cells is a major contributing action to the control of atrial tachyarrhythmias.
A reduction in the permeability of the AV node, both anterograde and retrograde, explains the efficacy of the drug in nodal tachycardias caused by re-entry through the AV node. Its action on ventricular arrhythmias is explained by a number of mechanisms. The effect on the atrium and AV node results in a reduction in the frequency of stimuli reaching the ventricle thus giving the ventricular cell mass time to repolarise in cases where there has been desynchronization of the refractory periods. Furthermore, a lengthening of the refractory period of the His-Purkinje system and ventricular contractile fibers reduces or prevents micro re-entry. Amiodarone increases coronary blood flow, decreases cardiac oxygen requirements without producing negative inotropic effects and also suppresses ectopic pacemakers, and this is particularly valuable in arrhythmias associated with ischaemic damage or angina pectoris.
Amiodarone is absorbed variably and erratically from the gastrointestinal tract; the average bioavailability is about 50%, but varies widely, and both the rate and extent of absorption are increased by food. It is extensively distributed to body tissues and accumulates notably in fat as well as in skeletal muscle and highly perfused tissues such as liver, lungs, and spleen; it has been reported to be about 96% bound to plasma proteins. The terminal elimination half- life is about 50 days with a range of about 20 to 100 days due to its extensive tissue distribution. On stopping prolonged amiodarone therapy, a pharmacological effect is evident for a month or more. A major metabolite, desethylamiodarone, has antiarrhythmic properties. There is very little urinary excretion of amiodarone or its metabolites, the major route of excretion being in faeces via the bile; some enterohepatic recycling may occur. Amiodarone and desethylamiodarone are reported to cross the placenta and to be distributed into breast milk.