Amiodarone pharmacological effects

C. Clinical Use and Toxicities Calcium channel blockers are effective for converting atrioventricular nodal reentry (also known as nodal tachycardia) to normal sinus rhythm. Their major use is in the prevention of these nodal arrhythmias in patients prone to recurrence. These drugs are orally active verapamil is also available for parenteral use (Table 14—2). The most important toxicity of verapamil is excessive pharmacologic effect, since cardiac contractility, AV conduction, and blood pressure can be significantly depressed. See Chapter 12 for additional discussion of toxicity. Amiodarone has moderate calcium channel-blocking activity. 

Waldhauser KM, Torok M, Ha HR, Thomet U, Konrad D, Brecht K, Follath F, Krahenbuhl S (2006) Hepatocellular toxicity and pharmacological effect of amiodarone and amiodarone derivatives. J Pharmacol Exp Ther 319(3) 1413-1423 Wang Y, Singh R, Lefkowitch JH, Rigoli RM, Czaja MJ (2006) Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway. J Biol Chem 281(22) 15258-15267 Watkins PB (2005) Idiosyncratic liver injury challenges and approaches. Toxicol Pathol 33 (l) l-5... 

The pharmacological profile of amiodarone is extremely complex. On acute exposure the compound slows conduction (indicative of Class I elec-trophysiological activity) [17], exhibits both a- and y9-adrenergic antagonism [18], and may have an effect on calcium channels [19]. The Class III elec-trophysiological activity is generally not manifest on acute exposure but may take several days to weeks to reach maximal effect in patients [20,21]. 

Pharmacology Amiodarone possesses electrophysiologic characteristics of all 4 Vaughan Williams Classes but has predominantly Class III antiarrhythmic effects. The antiarrhythmic effect may be due to at least 2 major properties Prolongation of the myocardial cell-action potential duration and refractory period, and noncompetitive - and -adrenergic inhibition. 

Sotalol, as the racemate (a 1 1 mixture of the d- and 1-enantiomers), has a well-documented class Ill-antiarrhythmic activity, without showing the various side-effects of amiodarone. The -adrenoceptor blockade by this agent, however, limits its use in patients with heart failure. Dofetilide is an example of a newer, rather pure class in-antiarrhythmic, virtually devoid of other pharmacological properties. 

Watanabe, Y. and Kimura,). Inhibitory effect of amiodarone on Na+/Ca2+ exchange current in guinea-pig cardiac myocytes. British Journal of Pharmacology 2000,131 80-84. 

Amiodarone is highly effective in treating both ventricular and supraventricular dysrhythmias (1). Its pharmacology, therapeutic uses, and adverse effects and interactions have been extensively reviewed (2-14). 

Somani P. Basic and clinical pharmacology of amiodarone relationship of antiarrhythmic effects, dose and drug concentrations to intracellular inclusion bodies. J Chn Pharmacol 1989 29(5) 405-12. 

Type III antiarrhythmics include agents that specifically prolong refractoriness in atrial and ventricular tissue. This class includes very different drugs bretylium, amiodarone, sotalol, ibutilide, and recently, dofetilide they share the common effect of delaying repolarization by blocking potassium channels. The electrophysiologic actions of bretylium are related to its multifaceted pharmacology. 

Hohnloser SH, Dorian P, Roberts R, Gent M, Israel CW,Fain E, Champagne J, and Connolly SJ. Effect of amiodarone and sotalol on ventricular defibrillation threshold the optimal pharmacological therapy in cardioverter defibrillator patients (OPTIC) trial. Circulation 2006 114 104-109. 

---