The clinical results of amiodarone in cardiac arrhythmias: optimal dosing.
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| Abstract |
Amiodarone hydrochloride is a relatively new antiarrhythmic agent, the properties of which differ in a significant manner electrophysiologically, pharmacokinetically and structurally from those of conventional as well as other investigational antidysrhythmic compounds. It is also pharmacologically unique in so far as its fundamental action on cardiac muscle following chronic therapy differs markedly from that found during the intravenous administration; its I.V. action is dominated by the lengthening of intranodal (AV) conduction time and the effective refractory period of the AV node, the electrophysiologic basis for which is unclear but accounts for the slowing of the ventricular response in atrial flutter and fibrillation and the variable conversion rate of narrow QRS reentrant paroxysmal supraventricular tachycardia. Intravenous amiodarone is ineffective in most other arrhythmias; it does not lengthen repolarization, nor does it prolong the effective refractory period of atria, ventricle, His-Purkinje system or the accessory pathways of the heart in the WPW syndrome. In contrast, chronically administered amiodarone lengthens repolarization and the effective refractory period of all cardiac tissues as a function of dose and duration of therapy consistent with its wide spectrum of antiarrhythmic activity in the prophylactic control of supraventricular and ventricular tachyarrhythmias. The nature of the slow onset of action of the oral drug is not well-understood; it may be due to the slow formation of active metabolites or the gradual and selective inhibition of T3 action on the myocardium since the effects of amiodarone on cardiac repolarization are identical to those of hypothyroidism and are negated by the concomitant administration of thyroxine. Serum reverse T3 levels increase as a function of dose and duration of amiodarone therapy and tentative data indicate that serial measurements of rT3 levels may provide a reliable index for gauging efficacy and toxicity of amiodarone during chronic therapy. The role of serum drug and metabolite levels appears less reliable in this regard. The exceedingly long and variable elimination half-life of amiodarone necessitates individualized loading and maintenance dosage regimens, and the latency of onset of antiarrhythmic action during oral therapy is not shortened by intravenous bolus injections or sustained infusions. However, the judicious choice of oral dosage as discussed herein permits the development of an effective prophylactic regimen for most patients with supraventricular and ventricular tachyarrhythmias; when the lowest dosage regimen to control a particular arrhythmia is identified, limiting side
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| Authors | B N Singh, K Nademanee, R Kannan, N Ikeda |
| Journal | Pacing and clinical electrophysiology : PACE (Pacing Clin Electrophysiol) Vol. 7 Issue 1 Pg. 109-24 (Jan 1984) ISSN: 0147-8389 [Print] United States |
| PMID | 6199755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.) |
| Chemical References |
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