Therapeutic drug monitoring: antiarrhythmic drugs

Abstract

Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

Amiodarone, Unlike Dronedarone, Activates Inflammasomes via Its Reactive Metabolites: Implications for Amiodarone Adverse Reactions

“…The fact that the physical properties of dronedarone and amiodarone such as volume of distribution are so different may contribute to the difference in the spectrum of adverse reactions. 6,7 Although dronedarone appears to be safer than amiodarone, it can cause adverse reactions including liver injury. 4 Amiodarone also causes liver injury; however, the major serious adverse reaction associated with amiodarone is interstitial lung disease and pulmonary fibrosis.…”

“…23 Therefore, bioactivation of amiodarone and inflammasome activation by these macro-phages may play an important role in amiodarone-induced interstitial lung disease. The terminal half-life of amiodarone elimination is usually 35−40 days, but may exceed 100 days, 6 which is so long that stopping the drug administration may not be effective when severe adverse events are observed. Therefore, drugs such as canakinumab to block the effects of IL-1β, or belnacasan to prevent activation of caspase-1 may provide a more specific treatment of serious amiodarone-induced adverse reactions.…”

“…The amiodarone and DEA concentrations used in this study were similar to their therapeutic concentrations (0.3−3 μM). 6 Although the therapeutic plasma concentration of dronedarone is about a tenth that of amiodarone, the concentration used in this study was same as the amiodarone concentration so that a direct comparison between amiodarone and dronedarone could be made. 17 ABT (1 mM) was used to inhibit cytochrome P450 activities, 18,19 and Ac-YVAD-cmk (YVAD, 1 μM) was used to inhibit caspase-1 activity.…”

“…4 It is not associated with the same risk of interstitial lung disease as amiodarone, 5 and although cases of liver injury have been reported and there are a few direct comparisons, 4 the risk of liver injury appears lower than that of amiodarone. In addition, the volume of distribution is much lower and the half-life of dronedarone much shorter than that of amiodarone, 6,7 which may contribute to the difference in the spectrum of adverse reactions.…”

Prevention and Treatment of Iodine-Induced Thyrotoxicosis

“…The long half-life of both amiodarone and his active metabolite, DEA, contributes to his toxicity. For a therapeutic effect, a plasma concentration between 0.5 and 2.5 μg/mL is required; however, serum levels do not correlate well with efficacy or with adverse effects [45,[48][49][50].…”