keyword
https://read.qxmd.com/read/37745076/integrating-distribution-kinetics-and-toxicodynamics-to-assess-repeat-dose-neurotoxicity-in-vitro-using-human-brainspheres-a-case-study-on-amiodarone
#1
JOURNAL ARTICLE
Carolina Nunes, Susana Proença, Giovanna Ambrosini, David Pamies, Aurélien Thomas, Nynke I Kramer, Marie-Gabrielle Zurich
For ethical, economical, and scientific reasons, animal experimentation, used to evaluate the potential neurotoxicity of chemicals before their release in the market, needs to be replaced by new approach methodologies. To illustrate the use of new approach methodologies, the human induced pluripotent stem cell-derived 3D model BrainSpheres was acutely (48 h) or repeatedly (7 days) exposed to amiodarone (0.625-15 µM), a lipophilic antiarrhythmic drug reported to have deleterious effects on the nervous system...
2023: Frontiers in Pharmacology
https://read.qxmd.com/read/37571970/amiodarone-induced-nystagmus-and-ataxia-case-report-and-systematic-review-of-case-reports
#2
REVIEW
Paawanjot Kaur, Ashampreet Kaur, Amitasha Sinha, Waseem Khaliq, Igor Dumic, Amteshwar Singh
Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen forms of amiodarone neurotoxicity, very few cases of nystagmus are reported. We report the case of an 86-year-old man who presented with abrupt onset ataxia, dizziness, and inability to ambulate, ten days after initiating amiodarone for atrial fibrillation. His examination revealed gaze-evoked nystagmus along with features of cerebellar dysfunction...
August 12, 2023: Journal of Clinical Pharmacology
https://read.qxmd.com/read/36171835/myoclonic-jerks-and-ataxia-a-case-of-rare-neurological-side-effects-of-amiodarone
#3
Vanessa Milan-Ortiz, Anirudh R Damughatla, Saivaishnavi Kamatham, Zain N Jawad, Shakeela Shakoor
We present the case of an 85-year-old man with a known medical history of recurrent ventricular arrhythmia and paroxysmal atrial fibrillation who was started on an amiodarone loading dose four days before presenting with tremors and balance impairment. Amiodarone's adverse effects in various systems have been well studied, although this is not the case with neurotoxic side effects. In this article, we discuss the neurotoxic side effects caused by amiodarone and the importance of a complete physical examination when starting this medication for supraventricular and ventricular arrhythmias...
August 2022: Curēus
https://read.qxmd.com/read/33606068/prediction-of-the-dose-range-for-adverse-neurological-effects-of-amiodarone-in-patients-from-an-in-vitro-toxicity-test-by-in-vitro-in-vivo-extrapolation
#4
JOURNAL ARTICLE
Engi Abd El-Hady Algharably, Emma Di Consiglio, Emanuela Testai, Reinhold Kreutz, Ursula Gundert-Remy
Amiodarone is an antiarrhythmic agent inducing adverse effects on the nervous system, among others. We applied physiologically based pharmacokinetic (PBPK) modeling combined with benchmark dose modeling to predict, based on published in vitro data, the in vivo dose of amiodarone which may lead to adverse neurological effects in patients. We performed in vitro-in vivo extrapolation (IVIVE) from concentrations measured in the cell lysate of a rat brain 3D cell model using a validated human PBPK model. Among the observed in vitro effects, inhibition of choline acetyl transferase (ChAT) was selected as a marker for neurotoxicity...
April 2021: Archives of Toxicology
https://read.qxmd.com/read/33494393/amiodarone-enhances-anticonvulsive-effect-of-oxcarbazepine-and-pregabalin-in-the-mouse-maximal-electroshock-model
#5
JOURNAL ARTICLE
Monika Banach, Monika Rudkowska, Agata Sumara, Kinga Borowicz-Reutt
Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepileptic drugs was evaluated in the maximal electroshock model in mice. Amiodarone, although ineffective in the electroconvulsive threshold test, significantly potentiated the antielectroshock activity of oxcarbazepine and pregabalin...
January 21, 2021: International Journal of Molecular Sciences
https://read.qxmd.com/read/33413942/calcium-induced-autonomic-denervation-in-patients-with-post-operative-atrial-fibrillation
#6
RANDOMIZED CONTROLLED TRIAL
Huishan Wang, Yuji Zhang, Fangran Xin, Hui Jiang, Dengshun Tao, Yan Jin, Yuanchen He, Qiang Wang, Sunny S Po
BACKGROUND: Post-operative atrial fibrillation (POAF) is associated with worse long-term cardiovascular outcomes. OBJECTIVES: This study hypothesized that injecting calcium chloride (CaCl2 ) into the major atrial ganglionated plexi (GPs) during isolated coronary artery bypass grafting (CABG) can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity. METHODS: This proof-of-concept study randomized 200 patients undergoing isolated, off-pump CABG to CaCl2 (n = 100) or sodium chloride (sham, n = 100) injection...
January 5, 2021: Journal of the American College of Cardiology
https://read.qxmd.com/read/33369922/amiodarone-associated-neurotoxicity
#7
JOURNAL ARTICLE
Anojan Pathmanathan, Lynn Cleary
No abstract text is available yet for this article.
January 2021: American Journal of Therapeutics
https://read.qxmd.com/read/32817824/levetiracetam-for-the-treatment-of-myoclonic-neurotoxicity-induced-by-amiodarone
#8
Diego Celli, Alonso Marquez, Marina Byer, Rosario Colombo
No abstract text is available yet for this article.
August 2020: HeartRhythm Case Reports
https://read.qxmd.com/read/31324950/model-based-estimation-of-lowest-observed-effect-concentration-from-replicate-experiments-to-identify-potential-biomarkers-of-in-vitro-neurotoxicity
#9
JOURNAL ARTICLE
Silvia Calderazzo, Denise Tavel, Marie-Gabrielle Zurich, Annette Kopp-Schneider
A paradigm shift is occurring in toxicology following the report of the National Research Council of the USA National Academies entitled "Toxicity testing in the 21st Century: a vision and strategy". This new vision encourages the use of in vitro and in silico models for toxicity testing. In the goal to identify new reliable markers of toxicity, the responsiveness of different genes to various drugs (amiodarone: 0.312-2.5 [Formula: see text]; cyclosporine A: 0.25-2 [Formula: see text]; chlorpromazine: 0...
July 19, 2019: Archives of Toxicology
https://read.qxmd.com/read/30029951/amiodarone-does-not-affect-brain-injury-in-a-rat-model-of-transient-forebrain-ischemia
#10
JOURNAL ARTICLE
K Yamanaka, S Inoue, Y Naito, M Kawaguchi
OBJECTIVES: Although amiodarone may cause neurotoxicity that can affect patient outcomes when used during cardiopulmonary resuscitation (CPR), it has been commonly prescribed during CPR. This study investigated the possible neurotoxic effects of amiodarone in a rat model of transient forebrain ischemia. DESIGN: A prospective laboratory animal study was carried out. SETTING: Animal laboratory. MATERIALS: Male Sprague-Dawley rats...
November 2019: Medicina intensiva
https://read.qxmd.com/read/29420339/probable-drug-drug-interaction-between-erlotinib-and-amiodarone-causes-severe-neurotoxicity-in-a-patient-with-advanced-lung-cancer
#11
JOURNAL ARTICLE
Maria López Brunsó, Cristina Toro Blanch, Elia Sais Girona, Diana Roa García, Alejandro Hernández Martínez, Angel Izquierdo Font, Silvia Guerra Prió, Huber Gunter Mas Pueyo, Joaquim Bosch-Barrera
Drug-drug interactions (DDIs) are of great concern in the treatment of cancer, especially when target therapies, such as tyrosine kinase inhibitors, are being used. Here, we report a case of probable DDI between erlotinib and amiodarone leading to severe neurotoxicity. Amiodarone inhibits P-glycoprotein (P-gp), for which erlotinib is a substrate. P-gp is an important drug transporter that is involved in limiting the blood-brain barrier penetration of erlotinib. Clinicians should be aware of emerging data characterizing the effect of the P-gp transport system on drug exposure and its potential for DDI...
April 2018: Anti-cancer Drugs
https://read.qxmd.com/read/26026931/evaluation-of-drug-induced-neurotoxicity-based-on-metabolomics-proteomics-and-electrical-activity-measurements-in-complementary-cns-in-vitro-models
#12
JOURNAL ARTICLE
Luise Schultz, Marie-Gabrielle Zurich, Maxime Culot, Anaelle da Costa, Christophe Landry, Patricia Bellwon, Theresa Kristl, Katrin Hörmann, Silke Ruzek, Stephan Aiche, Knut Reinert, Chris Bielow, Fabien Gosselet, Romeo Cecchelli, Christian G Huber, Olaf H-U Schroeder, Alexandra Gramowski-Voss, Dieter G Weiss, Anna Bal-Price
The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity...
December 25, 2015: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://read.qxmd.com/read/25795400/cell-type-specific-expression-and-localization-of-cytochrome-p450-isoforms-in-tridimensional-aggregating-rat-brain-cell-cultures
#13
JOURNAL ARTICLE
S Vichi, J Sandström von Tobel, S Gemma, S Stanzel, A Kopp-Schneider, F Monnet-Tschudi, E Testai, M G Zurich
Within the Predict-IV FP7 project a strategy for measurement of in vitro biokinetics was developed, requiring the characterization of the cellular model used, especially regarding biotransformation, which frequently depends on cytochrome P450 (CYP) activity. The extrahepatic in situ CYP-mediated metabolism is especially relevant in target organ toxicity. In this study, the constitutive mRNA levels and protein localization of different CYP isoforms were investigated in 3D aggregating brain cell cultures. CYP1A1, CYP2B1/B2, CYP2D2/4, CYP2E1 and CYP3A were expressed; CYP1A1 and 2B1 represented almost 80% of the total mRNA content...
December 25, 2015: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://read.qxmd.com/read/25696267/-white-elephants-and-a-distinguished-monkey-or-the-need-for-a-proactive-follow-up-in-amiodarone-therapy
#14
Chr van Tellingen
Two patients presented with a rather unusual form and documentation of amiodarone toxicity. General aspects on this topic are addressed with emphasis on neurotoxicity and pulmonary disease. The need for rational prescribing and a scrupulous follow-up is stressed in view of apparent unawareness of general physicians and organ-related specialists alike regarding these very phenomena.
October 2004: Netherlands Heart Journal
https://read.qxmd.com/read/25659768/amiodarone-biokinetics-the-formation-of-its-major-oxidative-metabolite-and-neurotoxicity-after-acute-and-repeated-exposure-of-brain-cell-cultures
#15
JOURNAL ARTICLE
Giuliana Pomponio, Marie-Gabrielle Zurich, Luise Schultz, Dieter G Weiss, Luca Romanelli, Alexandra Gramowski-Voss, Emma Di Consiglio, Emanuela Testai
The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices...
December 25, 2015: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://read.qxmd.com/read/25479353/in-vitro-detection-of-cardiotoxins-or-neurotoxins-affecting-ion-channels-or-pumps-using-beating-cardiomyocytes-as-alternative-for-animal-testing
#16
JOURNAL ARTICLE
Jonathan Nicolas, Peter J M Hendriksen, Laura H J de Haan, Rosella Koning, Ivonne M C M Rietjens, Toine F H Bovee
The present study investigated if and to what extent murine stem cell-derived beating cardiomyocytes within embryoid bodies can be used as a broad screening in vitro assay for neurotoxicity testing, replacing for example in vivo tests for marine neurotoxins. Effect of nine model compounds, acting on either the Na(+), K(+), or Ca(2+) channels or the Na(+)/K(+) ATP-ase pump, on the beating was assessed. Diphenhydramine, veratridine, isradipine, verapamil and ouabain induced specific beating arrests that were reversible and none of the concentrations tested induced cytotoxicity...
March 2015: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://read.qxmd.com/read/24072835/ataxia-a-diagnostic-perplexity-and-management-dilemma
#17
JOURNAL ARTICLE
Vinod K Chaubey, Lovely Chhabra, Aaysha Kapila
A 79-year-old woman presented with lower extremity weakness and unsteadiness for 2 weeks. She was recently diagnosed with refractory atrial flutter and was prescribed amiodarone. Physical examination revealed signs of cerebellar dysfunction. Neuroimaging including CT and MRI were unremarkable. Her hospital course included the development of ventricular tachycardia necessitating increment in amiodarone dose. Laboratory studies were unremarkable except mild transaminitis. Other workup including the one for paraneoplastic neurological involvement was negative...
September 26, 2013: BMJ Case Reports
https://read.qxmd.com/read/22218697/a-neonate-with-long-qt-syndrome-refractory-ventricular-arrhythmias-and-lidocaine-toxicity
#18
JOURNAL ARTICLE
Aruna T Nathan, Maryam Naim, Lisa M Montenegro, Victoria L Vetter
Long QT syndrome is characterized by electrocardiographic appearance of long QT intervals and propensity to polymorphic ventricular tachycardia. Aggressive anticipatory clinical management is required for a good outcome, especially in the symptomatic neonate. We present a neonate with a compound mutation with refractory ventricular tachycardia that necessitated multimodal pharmacotherapy with lidocaine, esmolol, and amiodarone along with ventricular pacing. Despite normal serum lidocaine levels, complex pharmacokinetic interactions resulted in presumed neurotoxicity due to lidocaine...
February 2012: Anesthesia and Analgesia
https://read.qxmd.com/read/20175957/amiodarone-induced-liver-cirrhosis-and-parkinsonism-a-case-report
#19
JOURNAL ARTICLE
S Ishida, M Sugino, T Hosokawa, T Sato, D Furutama, A Fukuda, F Kimura, H Kuwabara, Y Shibayama, T Hanafusa
BACKGROUND: Amiodarone-induced hepatotoxicity consists of mild liver test abnormalities and rare cases of acute hepatitis and chronic hepatic lesions, and histologically resembles the whole spectrum of alcoholic liver disease, i.e., non-alcoholic steatohepatitis. Amiodarone-induced neurotoxicity, including tremor, ataxia and peripheral neuropathy, is known, and some cases of parkinsonism following amiodarone use have also been reported. OBJECTIVE: To study the pathology of amiodarone-associated parkinsonism...
March 2010: Clinical Neuropathology
https://read.qxmd.com/read/19597088/frequency-characteristics-and-risk-factors-for-amiodarone-neurotoxicity
#20
JOURNAL ARTICLE
Carolyn F Orr, J Eric Ahlskog
OBJECTIVE: To assess the incidence, severity, and spectrum of neurologic toxic effects associated with administration of amiodarone hydrochloride. DESIGN: Retrospective medical record analysis of cardiac patients treated with amiodarone between January 1, 1996, and July 31, 2008. SETTING: Residents of Olmsted County, Minnesota, treated at the Mayo Clinic. PATIENTS: The Mayo Clinic medical records of all adult Olmsted County residents prescribed amiodarone between January 1, 1996, and July 31, 2008, were reviewed and all possible neurologic adverse effects that might be attributable to amiodarone were tabulated...
July 2009: Archives of Neurology
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