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Neurotoxicity of Drugs in Children During Antenatal and Postnatal Development Periods

Received: 8 November 2019     Accepted: 14 February 2020     Published: 28 February 2020
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Abstract

Neurotoxicity is not rare and periodically severe and even life-threatening adverse effect (AE) of drugs belonging to many therapeutic groups. Manifestations of neurotoxicity are variable: disturbances of peripheral nervous system (ototoxicity and ophtalmotoxicity, visceral neuropathy, neuromuscular blockade), involving of central nervous system (CNS) (developmental brain malformations, seizures, impairment of consciousness, nonspecific encephalopathy). In the way of its consequences central nervous system damage is the most severe manifestation of drug neurotoxicity but the main predisposing factor is related to immature but growing intensively child brain of first years of life; the primary factor for neurotoxic effect is the capacity of drugs to transfer through brain-blood barrier and cumulate into CNS. The principal mechanism of neurotoxicity is dysfunction/apoptosis of nervous cells. Aim of this survey is to provide data and attract once again the professionals attention to the neurological complications of those drugs in the first place that are mainly targeted to the CNS effects (anticonvulsants, antidepressants, antipsychotic drugs, anesthetics) among the mostly sensitive groups – pregnant women, newborns, infants. Results. Based on analyzed data it was revealed high incidence of CNS complications both transient (seizures, temporarily impairment of consciousness) and persistent (developmental brain malformations, decrease of cognitive functions) in case of use of the drugs of current interest (anticonvulsants, antidepressants, antipsychotics, anesthetics (general and local), antibiotics) in risk groups – fetus, newborns, infants. Population risk of neurotoxicity includes also ethnic and genetic special features, renal and hepatic failure, background neuropsychic diseases except determined age groups. Conclusion. Neurotoxicity is one of the most severe manifestations of drug intolerance that depends on different aspects. The youngest targeted group is children of 0 – 3 years old due to their developmental immature brain and age-dependent specific characteristics of pharmacodynamics and pharmacokinetics that could result in drug overdose as a particular case of neurotoxicity due underestimation of the mentioned above factors.

Published in American Journal of Pediatrics (Volume 6, Issue 1)
DOI 10.11648/j.ajp.20200601.21
Page(s) 62-67
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Neurotoxicity, Anticonvulsants, Psychotropic Agents, Anesthetics, Antibiotics, Pregnancy, Lactation

References
[1] Mira Harrison-Woolrich, Juan Garcia-Quiroga, Jahella Ashton and Peter Herbison “Safety and Usage of Atypical Antipsychotic Medicines in Children” Drug Safety, 2007; 30 (7): 569-79.
[2] Stephen Toovey, Craig Rayner, Eric Prinssen et al “Assessment of Neuropsychiatric Adverse Events in Influenza Patients Treated with Oseltamivir: A Comprehensive Review”. Drug Safety, 2008; 31 (12): 1097-1114.
[3] Stephanie Cham, Hayley J. Koslik, Beatrice A. Golomb “Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series”. Drug Safety - Case Reports. December 2016, 3: 1-13.
[4] Kwan P., Brodie MJ «Neuropsychological effects of epilepsy and antiepileptic drugs» The Lancet v. 357, № 9251. January 2001.
[5] Rezvani M, Finkelstein Y, Verjee Z, Railton C, Koren G “Generalized seizures following topical lidocaine administration during circumcision: establishing causation”. Paediatric drugs, 2007; 9 (2): 125-127.
[6] Marco Mula, Josemir W. Sander “Negative Effects of Antiepileptic Drugs on Mood in Patients with Epilepsy”. Drug Safety, July 2007, Volume 30, Issue 7, pp 555–567.
[7] James E Tisdale, Douglas A. Miller “Drug induced diseases”. American Society of Health-system Pharmacists. Bethesda, 2010, p 179-316.
[8] Bleggi-Torres LF, de Medeiros BC, Werner B. “Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases”. Bone Marrow Transplant. 2000; 25 (3): 301.
[9] Patrick A. Forcelli. “Short- and Long-Term Neurological and Psychiatric Sequelae of Developmental Exposure to Antiepileptic and Anesthetic Drugs”. Front Neurol. 6: 41, 2015.
[10] Nie Q, Su B, Wei J et al. “Neurological teratogenic effects of antiepileptic drugs during pregnancy”. Exp Ther Med. 2016 Oct; 12 (4): 2400–2404. Epub 2016; Aug 29.
[11] O. A. Pylaeva, K. Y. Mukhin, A. S. Petrukhin « Side effects of antiepileptic therapy ». Publishing house “Garant”, 2016.
[12] L. V. Ushkalova, E. A. Ushkalova «Safety of psychotic drugs during lactation ». Pharmateka 2013, N1, pp 55-63.
[13] Payne JL. Psychopharmacology in Pregnancy and Breastfeeding. Med Clin North Am. 2019 Jul; 103 (4): 629-650.
[14] Gedzelman E, Meador K. “Neurological and psychiatric sequelae of developmental exposure to antiepileptic drugs”. Front Neurol (2012) 3: 182. doi: 10.3389/fneur.2012.00182.
[15] Turski CA, Ikonomidou C. “Neuropathological sequelae of developmental exposure to antiepileptic and anesthetic drugs”. Front Neurol (2012) 3: 120. doi: 10.3389/fneur.2012.00120.
[16] Johnson EL, Burke AE, Wang A, Pennell PB. Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women with epilepsy. Neurology. 2018 Sep 11; 91 (11): e1031-e1039.
[17] Korotaeva N. V., Ippolitova L. I., Nastausheva T. L., Ivanova O. A., Kogutnitskaya M. I., Pershina E. S. Psychological features of mothers who have given birth to premature infants. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2019; 64 (4): 38-44. (In Russ.)
[18] Weisskopf E, Fischer CJ, Bickle Graz M, Morisod Harari M, Tolsa JF, Claris O, Vial Y, Eap CB, Csajka C, Panchaud A. Risk-benefit balance assessment of SSRI antidepressant use during pregnancy and lactation based on best available evidence. Expert Opin Drug Saf. 2015 Mar; 14 (3): 413-27.
[19] Wainer C. P., Mason C. Drugs for pregnant and lactating women. Third edition, 2019. Elsvier.
[20] Anderson KN, Ailes EC, Lind JN, Broussard CS, Bitsko RH, Friedman JM, Bobo WV, Reefhuis J, Tinker SC; National Birth Defects Prevention Study. Atypical antipsychotic use during pregnancy and birth defect risk: National Birth Defects Prevention Study, 1997-2011. Schizophr Res. 2019 Nov 21.
[21] Brown R. E., Agarwal R. AAP responds to FDA warning jn anesthesia use in children. AAP News, 2017.
[22] Creeley, C. E. From Drug-Induced Developmental Neuroapoptosis to Pediatric Anesthetic Neurotoxicity—Where Are We Now? Brain Sci. 2016, 6, 32.
[23] Postnikov S. S., Kostyleva M. N., Linkova T. V., Lopatin A. V. “Usual and unusual side effects of ropivacaine (naropine) in child of 6 months old”. Children Hospital 2009; 3 (37), pp. 19-21.
[24] El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives. Local Reg Anesth. 2018 Aug 8; 11: 35-44.
[25] Zeljko J Bosnjak, Sarah Logan, Yanan Liu “Recent Insights Into Molecular Mechanisms of Propofol-Induced Developmental Neurotoxicity: Implications for the Protective Strategies” Anesthesia and analgesia August 2016; 123 (5): 1286-1296.
[26] Kashirskaya E. I. «Clinical biochemical assessment and forecast for health of children who develop under psychoactive drugs influence». Summary of doctoral dissertation. Astrakhan, 2010.
[27] Ferrajolo C, Capuano A, Trifiro G. “Pediatric drug safety surveillance in Italian pharmacovigilance network: an overview of adverse drug reactions in the years 2001–2012”. Expert opinion on drug safety. 2014; 13 Suppl 1: S9–20. Epub 2014/08/30. doi: 10.1517/14740338. 2014.939581PMID: 25171155.
[28] Rama K Maganti. “Neurotoxic effects associated with antibiotic use: Management considerations”. British Journal of Clinical Pharmacology 72 (3): 381-93 April 2011.
[29] Charlotte Durand-Maugard, Anne-Sophie Lemaire-Hurtel, Valérie Gras-Champel “Blood and CSF monitoring of cefepime-induced neurotoxicity: Nine case reports”. Feb 2012. Journal of Antimicrobial Chemotherapy, 67 (5): 1297-9.
[30] Ki Bae Kim, Sun Moon Kim, Woori Park et al. “Ceftiaxone-Induced Neurotoxicity: Case Report, Pharmacokinetic Considerations, and Literature Review”. Journal of Korean medical science 27 (9): 1120-3 • September 2012.
[31] E. N. Padeyskaya “New fluoroquenolones: successes and failures”. In the book “Gold pages”. Moscow, 2016, pp. 235-43.
[32] S. S. Postnikov, M. N. Kostyleva, G. P. Brusov. “Case of infusion syndrome in child of 10 years old”. Safety and risk in pharmacotherapy. - 2016. - N4, pp. 5-10.
[33] Renbarger JL, McCammack KC, Rouse CE, Hall SD. “Effect of race on vincristine associated neurotoxicity in pediatric acute lymphoblastic leukemia patients” Pediatric Blood and Cancer 2008 April; 50 (4): 769‐71. PMID: 18085684.
[34] Postnikov S. S., Strykov V. A., Kostyleva M. N., Ilina E. S., Gracianskaya A. N., Strock A. B. The case of dynamic intestinal obstruction, caused by an individual intolerance to vincristine in a child of 5 years. Safety and Risk of Pharmacotherapy. 2018; 6 (1): 32-35. https://doi.org/10.30895/2312-7821-2018-6-1-32-35.
[35] Manikoth P., Subramanyan R., Menon S., Al Khusaiby S. M. «A child with cardiac arrhythmia and convulsions» The Lancet, v354, December 11, 1999, p 2046.
Cite This Article
  • APA Style

    Sergey Postnikov, Natalia Teplova, Aleksey Ermilin, Marya Kostyleva, Anna Gratzhianskaya, et al. (2020). Neurotoxicity of Drugs in Children During Antenatal and Postnatal Development Periods. American Journal of Pediatrics, 6(1), 62-67. https://doi.org/10.11648/j.ajp.20200601.21

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    ACS Style

    Sergey Postnikov; Natalia Teplova; Aleksey Ermilin; Marya Kostyleva; Anna Gratzhianskaya, et al. Neurotoxicity of Drugs in Children During Antenatal and Postnatal Development Periods. Am. J. Pediatr. 2020, 6(1), 62-67. doi: 10.11648/j.ajp.20200601.21

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    AMA Style

    Sergey Postnikov, Natalia Teplova, Aleksey Ermilin, Marya Kostyleva, Anna Gratzhianskaya, et al. Neurotoxicity of Drugs in Children During Antenatal and Postnatal Development Periods. Am J Pediatr. 2020;6(1):62-67. doi: 10.11648/j.ajp.20200601.21

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  • @article{10.11648/j.ajp.20200601.21,
      author = {Sergey Postnikov and Natalia Teplova and Aleksey Ermilin and Marya Kostyleva and Anna Gratzhianskaya and Galina Chervyakova and Yulia Eremina},
      title = {Neurotoxicity of Drugs in Children During Antenatal and Postnatal Development Periods},
      journal = {American Journal of Pediatrics},
      volume = {6},
      number = {1},
      pages = {62-67},
      doi = {10.11648/j.ajp.20200601.21},
      url = {https://doi.org/10.11648/j.ajp.20200601.21},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20200601.21},
      abstract = {Neurotoxicity is not rare and periodically severe and even life-threatening adverse effect (AE) of drugs belonging to many therapeutic groups. Manifestations of neurotoxicity are variable: disturbances of peripheral nervous system (ototoxicity and ophtalmotoxicity, visceral neuropathy, neuromuscular blockade), involving of central nervous system (CNS) (developmental brain malformations, seizures, impairment of consciousness, nonspecific encephalopathy). In the way of its consequences central nervous system damage is the most severe manifestation of drug neurotoxicity but the main predisposing factor is related to immature but growing intensively child brain of first years of life; the primary factor for neurotoxic effect is the capacity of drugs to transfer through brain-blood barrier and cumulate into CNS. The principal mechanism of neurotoxicity is dysfunction/apoptosis of nervous cells. Aim of this survey is to provide data and attract once again the professionals attention to the neurological complications of those drugs in the first place that are mainly targeted to the CNS effects (anticonvulsants, antidepressants, antipsychotic drugs, anesthetics) among the mostly sensitive groups – pregnant women, newborns, infants. Results. Based on analyzed data it was revealed high incidence of CNS complications both transient (seizures, temporarily impairment of consciousness) and persistent (developmental brain malformations, decrease of cognitive functions) in case of use of the drugs of current interest (anticonvulsants, antidepressants, antipsychotics, anesthetics (general and local), antibiotics) in risk groups – fetus, newborns, infants. Population risk of neurotoxicity includes also ethnic and genetic special features, renal and hepatic failure, background neuropsychic diseases except determined age groups. Conclusion. Neurotoxicity is one of the most severe manifestations of drug intolerance that depends on different aspects. The youngest targeted group is children of 0 – 3 years old due to their developmental immature brain and age-dependent specific characteristics of pharmacodynamics and pharmacokinetics that could result in drug overdose as a particular case of neurotoxicity due underestimation of the mentioned above factors.},
     year = {2020}
    }
    

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  • TY  - JOUR
    T1  - Neurotoxicity of Drugs in Children During Antenatal and Postnatal Development Periods
    AU  - Sergey Postnikov
    AU  - Natalia Teplova
    AU  - Aleksey Ermilin
    AU  - Marya Kostyleva
    AU  - Anna Gratzhianskaya
    AU  - Galina Chervyakova
    AU  - Yulia Eremina
    Y1  - 2020/02/28
    PY  - 2020
    N1  - https://doi.org/10.11648/j.ajp.20200601.21
    DO  - 10.11648/j.ajp.20200601.21
    T2  - American Journal of Pediatrics
    JF  - American Journal of Pediatrics
    JO  - American Journal of Pediatrics
    SP  - 62
    EP  - 67
    PB  - Science Publishing Group
    SN  - 2472-0909
    UR  - https://doi.org/10.11648/j.ajp.20200601.21
    AB  - Neurotoxicity is not rare and periodically severe and even life-threatening adverse effect (AE) of drugs belonging to many therapeutic groups. Manifestations of neurotoxicity are variable: disturbances of peripheral nervous system (ototoxicity and ophtalmotoxicity, visceral neuropathy, neuromuscular blockade), involving of central nervous system (CNS) (developmental brain malformations, seizures, impairment of consciousness, nonspecific encephalopathy). In the way of its consequences central nervous system damage is the most severe manifestation of drug neurotoxicity but the main predisposing factor is related to immature but growing intensively child brain of first years of life; the primary factor for neurotoxic effect is the capacity of drugs to transfer through brain-blood barrier and cumulate into CNS. The principal mechanism of neurotoxicity is dysfunction/apoptosis of nervous cells. Aim of this survey is to provide data and attract once again the professionals attention to the neurological complications of those drugs in the first place that are mainly targeted to the CNS effects (anticonvulsants, antidepressants, antipsychotic drugs, anesthetics) among the mostly sensitive groups – pregnant women, newborns, infants. Results. Based on analyzed data it was revealed high incidence of CNS complications both transient (seizures, temporarily impairment of consciousness) and persistent (developmental brain malformations, decrease of cognitive functions) in case of use of the drugs of current interest (anticonvulsants, antidepressants, antipsychotics, anesthetics (general and local), antibiotics) in risk groups – fetus, newborns, infants. Population risk of neurotoxicity includes also ethnic and genetic special features, renal and hepatic failure, background neuropsychic diseases except determined age groups. Conclusion. Neurotoxicity is one of the most severe manifestations of drug intolerance that depends on different aspects. The youngest targeted group is children of 0 – 3 years old due to their developmental immature brain and age-dependent specific characteristics of pharmacodynamics and pharmacokinetics that could result in drug overdose as a particular case of neurotoxicity due underestimation of the mentioned above factors.
    VL  - 6
    IS  - 1
    ER  - 

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Author Information
  • Chair of Clinical Pharmacology, Russian National Research Medical University Named After Pirogov, Moscow, Russian Federation

  • Chair of Clinical Pharmacology, Russian National Research Medical University Named After Pirogov, Moscow, Russian Federation

  • Chair of Clinical Pharmacology, Russian National Research Medical University Named After Pirogov, Moscow, Russian Federation

  • Chair of Clinical Pharmacology, Russian National Research Medical University Named After Pirogov, Moscow, Russian Federation

  • Chair of Clinical Pharmacology, Russian National Research Medical University Named After Pirogov, Moscow, Russian Federation

  • Chair of Clinical Pharmacology, Russian National Research Medical University Named After Pirogov, Moscow, Russian Federation

  • Chair of Clinical Pharmacology, Russian National Research Medical University Named After Pirogov, Moscow, Russian Federation

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