Pleiotropic actions of amiodarone: still puzzling after half a century

Heijman, Jordi; Dobrev, Dobromir

doi:10.1007/s00210-013-0865-0

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…Similar to amiodarone, 27,28 dronedarone has a wide range of pleiotropic electrophysiological effects, either by directly inhibiting atrial ion channels or indirectly by inhibiting G-protein-coupled receptors (Fig. 2 and Table 2).…”

Section: Pleiotropic Actions Of Dronedaronementioning

confidence: 99%

Pleiotropic Effects of Antiarrhythmic Agents: Dronedarone in the Treatment of Atrial Fibrillation

Heijman

Heusch

Dobrev

2013

Clin Med Insights Cardiol

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Atrial fibrillation remains the most common arrhythmia in clinical practice. Dronedarone is an antiarrhythmic drug for the maintenance of sinus rhythm in patients with atrial fibrillation. Dronedarone is an amiodarone derivative developed to reduce the number of extracardiovascular side effects. Dronedarone has undergone extensive experimental and clinical testing during the last decade. On the aggregate, these studies have highlighted a complex set of pleiotropic actions that may contribute to dronedarone’s antiarrhythmic effects. In this review, we summarize the clinical studies that have evaluated dronedarone and provide an overview of dronedarone’s electrophysiological and nonelectrophysiological pleiotropic actions.

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Section: Pleiotropic Actions Of Dronedaronementioning

confidence: 99%

Pleiotropic Effects of Antiarrhythmic Agents: Dronedarone in the Treatment of Atrial Fibrillation

Heijman

Heusch

Dobrev

2013

Clin Med Insights Cardiol

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“…For instance, flecainide, an antiarrhythmic drug primarily inhibiting Na ϩ channels in the plasma membrane, can inhibit intracellular Ca 2ϩ channels such as the ryanodine receptor (128). Similarly, amiodarone, a frequently used antiarrhythmic drug also inhibiting Na ϩ channels, can also block several types of K ϩ and Ca 2ϩ channels and inhibit ␣and ␤-ARs (83,157) and additionally is a receptor-independent direct G protein activator (79). The frequently used Ca 2ϩ channel inhibitors diltiazem and verapamil additionally are ␣and/or ␤-AR antagonists (62,146), and this apparently even affects their clinical profile (131).…”

Section: C511mentioning

confidence: 99%

Selectivity of pharmacological tools: implications for use in cell physiology. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms

Michel

Seifert

2015

American Journal of Physiology-Cell Physiology

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Pharmacological inhibitors are frequently used to identify the receptors, receptor subtypes, and associated signaling pathways involved in physiological cell responses. Based on the effects of such inhibitors conclusions are drawn about the involvement of their assumed target or lack thereof. While such inhibitors can be useful tools for a better physiological understanding, their uncritical use can lead to incorrect conclusions. This article reviews the concept of inhibitor selectivity and its implication for cell physiology. Specifically, we discuss the implications of using inhibitor vs. activator approaches, issues of direct vs. indirect pathway modulation, implications of inverse agonism and biased signaling, and those of orthosteric vs. allosteric, competitive vs. noncompetitive, and reversible vs. irreversible inhibition. Additional problems can result from inconsistent estimates of inhibitor potency and differences in potency between cell-free systems and intact cells. These concepts are illustrated by several examples of inhibitors displaying affinity for related but distinct targets or even unrelated targets. Of note, many of the issues being addressed are also applicable to genetic inhibition strategies. The main practical conclusion following from these concepts is that investigators should be critical in the choice of inhibitor, its concentrations, and its mode of application. When this advice is adhered to, small-molecule pharmacological inhibitors can be important experimental tools in the hand of physiologists.

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Section: Introductionmentioning

confidence: 99%

“…Amiodarone is among the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, while also being important for maintaining sinus rhythm in patients with atrial fibrillation (AF) [ 5 ]. Although it does not decrease all-cause mortality in the primary prevention population, amiodarone is the most effective antiarrhythmic drug to prevent SCD [ 5 ]. Importantly, amiodarone reduces automatic implantable cardioverter defibrillator (ICD) shocks, being a first relatively easily available treatment option in patients experiencing electrical storm and repeated ventricular arrhythmias leading to recurrent ICD shocks [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, amiodarone possesses anti-inflammatory and antioxidant properties [ 7 , 8 ], i.e. pleiotropic effects, which can indirectly suppress ventricular arrhythmias [ 5 ]. However, amiodarone is not free of secondary adverse effects, contraindications and interactions with other drugs, including the potential to cause pulmonary toxicity and fibrosis, thyroid disease, hepatic toxicity, increased creatine levels, QT interval prolongation, and bradyarrhythmia [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Amiodarone in the COVID-19 Era: Treatment for Symptomatic Patients Only, or Drug to Prevent Infection?

Sanchís-Gomar

Lavie

Morin

et al. 2020

Am J Cardiovasc Drugs

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Amiodarone, one of the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, has been identified as a candidate drug for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present the rationale of using amiodarone in the COVID-19 scenario, as well as whether or not amiodarone administration represents a potential strategy to prevent SARS-CoV-2 infection, rather than simply used to treat patients already symptomatic and/or with severe coronavirus disease 2019 (COVID-19), based on current evidence.

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Pleiotropic actions of amiodarone: still puzzling after half a century

Cited by 10 publications

References 36 publications

Pleiotropic Effects of Antiarrhythmic Agents: Dronedarone in the Treatment of Atrial Fibrillation

Pleiotropic Effects of Antiarrhythmic Agents: Dronedarone in the Treatment of Atrial Fibrillation

Selectivity of pharmacological tools: implications for use in cell physiology. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms

Amiodarone in the COVID-19 Era: Treatment for Symptomatic Patients Only, or Drug to Prevent Infection?

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