Amiodarone toxicity: Myopathy and neuropathy

Roth, Ram; Itabashi, Hideo H.; Louie, James S.; Anderson, Thomas F.; Narahara, Kenneth A.

doi:10.1016/s0002-8703(05)80264-9

Cited by 50 publications

(6 citation statements)

References 5 publications

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“…Amiodarone is an antiarrhythmic medication that may cause a tremor or ataxia and neuromyopathy (39,40). The neuromyopathy is characterized by severe proximal and distal weakness along with distal sensory loss and reduced muscle stretch reflexes.…”

Section: Amphiphillic Drug Myopathy (Drug-induced Autophagic Lysosomamentioning

confidence: 99%

Toxic Myopathies

2014

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Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, as they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features and possible underlying cellular mechanisms.

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Section: Amphiphillic Drug Myopathy (Drug-induced Autophagic Lysosomamentioning

confidence: 99%

Toxic Myopathies

2014

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“…Adverse neurologic effects of this amphiphilic drug commonly include tremor, ataxia, and a peripheral neuropathy 3, 116. In humans, amiodarone‐induced peripheral neuropathy is well‐documented, whereas only a few instances of myopathy have been reported 43, 140. Interestingly, animal experiments showed an increase in the amount of amiodarone and its metabolite in denervated muscles compared with normally innervated muscles 29.…”

Section: Lysosomal Storage Myopathymentioning

confidence: 99%

Iatrogenic and toxic myopathies

Sieb

Gillessen

2002

Muscle and Nerve

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There has been increasing awareness of the adverse effects of therapeutic agents and exogenous toxins on the structure and function of muscle. The resulting clinical syndrome varies from one characterized by muscle pain to profound myalgia, paralysis, and myoglobinuria. Because toxic myopathies are potentially reversible, their prompt recognition may reduce their damaging effects or prevent a fatal outcome. Interest in the toxic myopathies, however, derives not only from their clinical importance but also from the fact that they serve as useful experimental models in muscle research. Morphological and biochemical studies have increased our understanding of the basic cellular mechanisms of myotoxicity. Toxins may produce, for instance, necrotizing, lysosomal-related, inflammatory, anti-microtubular, mitochondrial, hypokalemia-related, or protein synthesis-related muscle damage.

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“…Less is known on the effects of amiodarone on muscle cell lysosome morphology and function. Several case reports demonstrate the occurrence of skeletal muscle vacuolarization with or without the presence of inclusion bodies upon chronic amiodarone therapy, interpreted as lysosomal defects by the authors . In myocardial fibres from the left and right ventricle, and right atrium derived from dogs chronically treated with amiodarone, abnormal lysosomal structures with often dense lamellar inclusion bodies were found .…”

Section: Discussionmentioning

confidence: 93%

ClassIIIantiarrhythmic drugs amiodarone and dronedarone impairK_IR2.1 backward trafficking

Yuan¹,

Takanari²,

Qile³

et al. 2017

J Cellular Molecular Medi

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Drug‐induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK 1), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late‐endosome/lysosome system. Here we defined the potential interference in KIR2.1 backward trafficking by amiodarone and dronedarone. Both drugs inhibited IK 1 in isolated rabbit ventricular cardiomyocytes at supraclinical doses only. In HK‐KWGF cells, both drugs dose‐ and time‐dependently increased KIR2.1 expression (2.0 ± 0.2‐fold with amiodarone: 10 μM, 24 hrs; 2.3 ± 0.3‐fold with dronedarone: 5 μM, 24 hrs) and late‐endosomal/lysosomal KIR2.1 accumulation. Increased KIR2.1 expression level was also observed in the presence of Nav1.5 co‐expression. Augmented KIR2.1 protein levels and intracellular accumulation were also observed in COS‐7, END‐2, MES‐1 and EPI‐7 cells. Both drugs had no effect on Kv11.1 ion channel protein expression levels. Finally, amiodarone (73.3 ± 10.3% P < 0.05 at −120 mV, 5 μM) enhanced IKIR 2.1 upon 24‐hrs treatment, whereas dronedarone tended to increase IKIR 2.1 and it did not reach significance (43.8 ± 5.5%, P = 0.26 at −120 mV; 2 μM). We conclude that chronic amiodarone, and potentially also dronedarone, treatment can result in enhanced IK 1 by inhibiting KIR2.1 degradation.

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Amiodarone toxicity: Myopathy and neuropathy

Cited by 50 publications

References 5 publications

Toxic Myopathies

Toxic Myopathies

Iatrogenic and toxic myopathies

ClassIIIantiarrhythmic drugs amiodarone and dronedarone impairK_IR2.1 backward trafficking

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Amiodarone toxicity: Myopathy and neuropathy

Cited by 50 publications

References 5 publications

Toxic Myopathies

Toxic Myopathies

Iatrogenic and toxic myopathies

ClassIIIantiarrhythmic drugs amiodarone and dronedarone impairKIR2.1 backward trafficking

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ClassIIIantiarrhythmic drugs amiodarone and dronedarone impairK_IR2.1 backward trafficking