Amiodarone: A Comprehensive Guide for Clinicians

Hamilton, David; Nandkeolyar, Shuktika; Lan, Howard Haw-Chang; Desai, Pooja; Evans, Jonathan; Hauschild, Christopher; Choksi, Dimpa; Abudayyeh, Islam; Contractor, Tahmeed; Hilliard, Anthony

doi:10.1007/s40256-020-00401-5

Cited by 65 publications

(57 citation statements)

References 60 publications

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“…Amiodarone was first approved by the U.S. FDA in 1985. It is orally or parenterally used to manage life-threatening recurrent ventricular fibrillation or recurrent ventricular tachycardia refractory to other antiarrhythmic agents or in patients intolerant of other agents used for these conditions [ 212 ]. It inhibits adrenergic stimulation and affects endogenous mono and di-cation channels.…”

Section: Potential Small Molecule Inhibitors Of Early Viral Eventsmentioning

confidence: 99%

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Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

Al‐Horani

Kar

Aliter

2020

IJMS

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The ongoing pandemic of coronavirus disease-2019 (COVID-19) is being caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease continues to present significant challenges to the health care systems around the world. This is primarily because of the lack of vaccines to protect against the infection and the lack of highly effective therapeutics to prevent and/or treat the illness. Nevertheless, researchers have swiftly responded to the pandemic by advancing old and new potential therapeutics into clinical trials. In this review, we summarize potential anti-COVID-19 therapeutics that block the early stage of the viral life cycle. The review presents the structures, mechanisms, and reported results of clinical trials of potential therapeutics that have been listed in clinicaltrials.gov. Given the fact that some of these therapeutics are multi-acting molecules, other relevant mechanisms will also be described. The reviewed therapeutics include small molecules and macromolecules of sulfated polysaccharides, polypeptides, and monoclonal antibodies. The potential therapeutics target viral and/or host proteins or processes that facilitate the early stage of the viral infection. Frequent targets are the viral spike protein, the host angiotensin converting enzyme 2, the host transmembrane protease serine 2, and clathrin-mediated endocytosis process. Overall, the review aims at presenting update-to-date details, so as to enhance awareness of potential therapeutics, and thus, to catalyze their appropriate use in combating the pandemic.

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Section: Potential Small Molecule Inhibitors Of Early Viral Eventsmentioning

confidence: 99%

“…Noteworthy is the fact that amiodarone has a U.S. boxed warning because it precipitates life-threatening arrhythmias, pulmonary toxicity, and hepatotoxicity. It is possible that its derivative, i.e., dronedarone, serves as a better alternative [ 212 ].…”

Section: Potential Small Molecule Inhibitors Of Early Viral Eventsmentioning

confidence: 99%

Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

Al‐Horani

Kar

Aliter

2020

IJMS

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“…This feature can become clinically relevant if such difference in the pharmacological potency prevents or at least, significantly attenuates the AMIO-class I activity, which may lower the efficacy of AMIO in treating ventricular or supraventricular arrhythmias in individuals harboring these polymorphisms. This also can be particularly important when considering the lower bioavailability and dosing of long-term oral treatments with AMIO (Hamilton et al, 2020). Following this rationale, some long-term AMIO antiarrhythmic effects were partially associated with the prevention of triggered mechanisms (Singh et al, 1984), and the blockage of I Na is known to create stabilization of the membrane potential, driven by the reduction of overall cell excitability (Kahlig et al, 2014), (Shaw and Rudy, 1997a), (Shaw and Rudy, 1997b).…”

Section: Usementioning

confidence: 99%

Ethnic-Related Sodium Voltage-Gated Channel α Subunit 5 Polymorphisms Shape the In Vitro Pharmacological Action of Amiodarone upon Na_v1.5

et al. 2021

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Nav1.5-derived Na + current (I Na ) exerts a pivotal role in the depolarization phase of cardiomyocytes' action potential, and therefore, changes in I Na can contribute to fatal arrhythmias. Nav1.5 displays naturally occurring ethnic-related polymorphisms, which might alter the functioning and pharmacology of the channel. Some studies have shown how single nucleotide polymorphism can change the response to antiarrhythmic drugs. Investigations on the role of Nav1.5 in arrhythmogenesis, associated with its functional polymorphisms, are currently growing, as well as the possible variability in the antiarrhythmic pharmacotherapy among ethnic-groups. The influence of the ethnic-related polymorphisms (S524Y, S1103Y, R1193Q, V1951L) on the responsiveness, selectivity, and pharmacological efficacy of the clinically used antiarrhythmic, amiodarone (AMIO), is not completely known. Our objectives were to analyze biophysical and pharmacological aspects of four ethnic-related polymorphisms before and after exposure to AMIO. Polymorphisms caused reduced AMIO potency compared to wild-type (WT) that can vary up to 4x between them.AMIO shifted the voltage dependency for current inactivation, without significant effect in voltage-dependent activation to a similar extend in WT and polymorphisms.The recovery from inactivation was altered between the polymorphisms when compared to WT. Finally, the use-dependency of AMIO differed between studied groups, especially at a more depolarized cell membrane. Thus, our work may guide future studies focusing on the efficiency of AMIO in treating different arrhythmias and to establish more individualized guidelines for its use depending on the Nav1.5polymorphism, after validating our findings using in vivo studies.

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“…Furthermore, the clinical application of amiodarone is limited by its marked extracardiac toxicity. Amiodarone has been associated with hepatic transaminitis, thyroid dysfunction, and pulmonary toxicity, although these adverse effects are directly related to the duration of treatment (amiodarone toxicity is cumulative and dose-dependent) [ 25 ]. Amiodarone’s iodine moieties and extreme lipophilic character importantly contribute to its toxicity.…”

Section: Rationale For Amiodarone Usementioning

confidence: 99%

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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Amiodarone: A Comprehensive Guide for Clinicians

Cited by 65 publications

References 60 publications

Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

Ethnic-Related Sodium Voltage-Gated Channel α Subunit 5 Polymorphisms Shape the In Vitro Pharmacological Action of Amiodarone upon Na_v1.5

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

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Amiodarone: A Comprehensive Guide for Clinicians

Cited by 65 publications

References 60 publications

Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

Ethnic-Related Sodium Voltage-Gated Channel α Subunit 5 Polymorphisms Shape the In Vitro Pharmacological Action of Amiodarone upon Nav1.5

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

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Product

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Ethnic-Related Sodium Voltage-Gated Channel α Subunit 5 Polymorphisms Shape the In Vitro Pharmacological Action of Amiodarone upon Na_v1.5