Skip to main content
SpringerLink
Log in
Book cover

Therapeutic Intranasal Delivery for Stroke and Neurological Disorders pp 135–147Cite as

Intranasal Medication Delivery in Children for Brain Disorders

  • Chapter
  • First Online:

  • 359 Accesses

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Intranasal administration is an attractive option for the delivery of many therapeutic agents especially for the treatment of central nervous system (CNS). In contrast to drugs that require delivery by peripheral injection, which requires blood brain barrier permeability of the injected drug for CNS delivery and may cause anxiety and infection, the intranasal route allows drugs to bypass the BBB due to its highly specialized nasal anatomy and the olfactory pathway. Due to its non-invasive nature and easy procedure, intranasal drug delivery is particularly suited for use in children and may be performed by medical staff or family members. This article will review the use of intranasal medications with a focus on their utility in children. We will provide an overview of the nasal anatomy and its impact on drug delivery, the side effects of drugs specific to intranasal delivery, and a list of the medications which are currently administered intranasally. The most common drug classes for intranasal delivery in pediatrics include sedatives and analgesia, drugs for seizure control, opioid antagonists, and antimigraine medications. In summary, intranasal delivery is a versatile method for drug application with a wide range of clinical utility, and especially effective in the pediatric population.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Guennoun R, et al. Intranasal administration of progesterone: a potential efficient route of delivery for cerebroprotection after acute brain injuries. Neuropharmacology. 2018;145(Pt B):283–91.

    PubMed  Google Scholar 

  2. Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010;126(3):532–7.

    Article  PubMed  Google Scholar 

  3. Talon MD, et al. Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery. J Burn Care Res. 2009;30(4):599–605.

    Article  PubMed  Google Scholar 

  4. Corrigan M, Wilson SS, Hampton J. Safety and efficacy of intranasally administered medications in the emergency department and prehospital settings. Am J Health Syst Pharm. 2015;72(18):1544–54.

    Article  CAS  PubMed  Google Scholar 

  5. Bitter C, Suter-Zimmermann K, Surber C. Nasal drug delivery in humans. Curr Probl Dermatol. 2011;40:20–35.

    Article  CAS  PubMed  Google Scholar 

  6. Barash PG, et al. Is cocaine a sympathetic stimulant during general anesthesia? JAMA. 1980;243(14):1437–9.

    Article  CAS  PubMed  Google Scholar 

  7. Fantacci C, et al. Intranasal drug administration for procedural sedation in children admitted to pediatric emergency room. Eur Rev Med Pharmacol Sci. 2018;22(1):217–22.

    CAS  PubMed  Google Scholar 

  8. Kanazawa T. [Development of noninvasive drug delivery systems to the brain for the treatment of brain/central nervous system diseases]. Yakugaku Zasshi. 2018;138(4):443–50.

    Article  CAS  PubMed  Google Scholar 

  9. Chamanza R, Wright JA. A review of the comparative anatomy, histology, physiology and pathology of the nasal cavity of rats, mice, dogs and non-human primates. Relevance to inhalation toxicology and human health risk assessment. J Comp Pathol. 2015;153(4):287–314.

    Article  CAS  PubMed  Google Scholar 

  10. Stenner M, Rudack C. Diseases of the nose and paranasal sinuses in child. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2014;13:Doc10.

    PubMed  PubMed Central  Google Scholar 

  11. Grassin-Delyle S, et al. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther. 2012;134(3):366–79.

    Article  CAS  PubMed  Google Scholar 

  12. Koskenkorva T, Kristo A. [It’s normal—structural and functional variations of nose and paranasal sinuses]. Duodecim. 2012;128(2):225–9.

    Google Scholar 

  13. Ooi EH, Wormald PJ, Tan LW. Innate immunity in the paranasal sinuses: a review of nasal host defenses. Am J Rhinol. 2008;22(1):13–9.

    Article  PubMed  Google Scholar 

  14. Imamura F, Hasegawa-Ishii S. Environmental toxicants-induced immune responses in the olfactory mucosa. Front Immunol. 2016;7:475.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Yeh CY, et al. Activated human nasal epithelial cells modulate specific antibody response against bacterial or viral antigens. PLoS One. 2013;8(2):e55472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Petrov VV, Tepliy DL. [The functional state of nasal cavity in the aspect of structural-functional changes of the human organism in postnatal ontogenesis.]. Adv Gerontol. 2017;30(5):739–44.

    Google Scholar 

  17. Dahl R, Mygind N. Anatomy, physiology and function of the nasal cavities in health and disease. Adv Drug Deliv Rev. 1998;29(1–2):3–12.

    CAS  PubMed  Google Scholar 

  18. Pires A, et al. Intranasal drug delivery: how, why and what for? J Pharm Pharm Sci. 2009;12(3):288–311.

    Article  CAS  PubMed  Google Scholar 

  19. Snidvongs K, Thanaviratananich S. Update on intranasal medications in rhinosinusitis. Curr Allergy Asthma Rep. 2017;17(7):47.

    Article  PubMed  CAS  Google Scholar 

  20. Phukan K, et al. Nanosized drug delivery systems for direct nose to brain targeting: a review. Recent Pat Drug Deliv Formul. 2016;10(2):156–64.

    Article  CAS  PubMed  Google Scholar 

  21. Mistry A, Stolnik S, Illum L. Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm. 2009;379(1):146–57.

    Article  CAS  PubMed  Google Scholar 

  22. Crowe TP, et al. Mechanism of intranasal drug delivery directly to the brain. Life Sci. 2018;195:44–52.

    Article  CAS  PubMed  Google Scholar 

  23. Marianecci C, et al. Drug delivery in overcoming the blood-brain barrier: role of nasal mucosal grafting. Drug Des Devel Ther. 2017;11:325–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Khan AR, et al. Progress in brain targeting drug delivery system by nasal route. J Control Release. 2017;268:364–89.

    Article  CAS  PubMed  Google Scholar 

  25. Freitag FG, Shumate DA. The efficacy and safety of sumatriptan intranasal powder in adults with acute migraine. Expert Rev Neurother. 2016;16(7):743–7.

    Article  CAS  PubMed  Google Scholar 

  26. Au CC, Branco RG, Tasker RC. Management protocols for status epilepticus in the pediatric emergency room: systematic review article. J Pediatr. 2017;93(Suppl 1):84–94.

    Article  Google Scholar 

  27. DeMayo MM, et al. A review of the safety, efficacy and mechanisms of delivery of nasal oxytocin in children: therapeutic potential for autism and Prader-Willi syndrome, and recommendations for future research. Paediatr Drugs. 2017;19(5):391–410.

    Article  PubMed  Google Scholar 

  28. Borland ML, Clark LJ, Esson A. Comparative review of the clinical use of intranasal fentanyl versus morphine in a paediatric emergency department. Emerg Med Australas. 2008;20(6):515–20.

    PubMed  Google Scholar 

  29. Young VN, Smith LJ, Rosen CA. Comparison of tolerance and cost-effectiveness of two nasal anesthesia techniques for transnasal flexible laryngoscopy. Otolaryngol Head Neck Surg. 2014;150(4):582–6.

    Article  PubMed  Google Scholar 

  30. Parvizrad R, et al. Comparing the analgesic effect of intranasal with intravenous ketamine in isolated orthopedic trauma: a randomized clinical trial. Turk J Emerg Med. 2017;17(3):99–103.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Luthringer R, et al. Rapid absorption of sumatriptan powder and effects on glyceryl trinitrate model of headache following intranasal delivery using a novel bi-directional device. J Pharm Pharmacol. 2009;61(9):1219–28.

    Article  CAS  PubMed  Google Scholar 

  32. Charalambous M, et al. Intranasal midazolam versus rectal diazepam for the management of canine status epilepticus: a multicenter randomized parallel-group clinical trial. J Vet Intern Med. 2017;31(4):1149–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Maglalang PD, et al. Rescue therapies for seizure emergencies: new modes of administration. Epilepsia. 2018;59:207–15.

    Article  CAS  PubMed  Google Scholar 

  34. Nunley S, et al. Healthcare utilization characteristics for intranasal midazolam versus rectal diazepam. J Child Neurol. 2018;33(2):158–63.

    Article  PubMed  Google Scholar 

  35. Zelcer M, Goldman RD. Intranasal midazolam for seizure cessation in the community setting. Can Fam Physician. 2016;62(7):559–61.

    PubMed  PubMed Central  Google Scholar 

  36. Campbell C, et al. Drug development of intranasally delivered peptides. Ther Deliv. 2012;3(4):557–68.

    Article  CAS  PubMed  Google Scholar 

  37. Fortuna A, et al. Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules. Eur J Pharm Biopharm. 2014;88(1):8–27.

    Article  CAS  PubMed  Google Scholar 

  38. Al Bakri W, et al. Overview of intranasally delivered peptides: key considerations for pharmaceutical development. Expert Opin Drug Deliv. 2018;15(10):991–1005.

    Article  PubMed  CAS  Google Scholar 

  39. Borland M, et al. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med. 2007;49(3):335–40.

    Article  PubMed  Google Scholar 

  40. Miller JL, et al. Sedation and analgesia using medications delivered via the extravascular route in children undergoing laceration repair. J Pediatr Pharmacol Ther. 2018;23(2):72–83.

    PubMed  PubMed Central  Google Scholar 

  41. Adelgais KM, et al. Intranasal fentanyl and quality of pediatric acute care. J Emerg Med. 2017;53(5):607–615 e2.

    Article  PubMed  Google Scholar 

  42. Baldwa NM, et al. Atomised intranasal midazolam spray as premedication in pediatric patients: comparison between two doses of 0.2 and 0.3 mg/kg. J Anesth. 2012;26(3):346–50.

    Article  PubMed  Google Scholar 

  43. Hosseini Jahromi SA, et al. Comparison of the effects of intranasal midazolam versus different doses of intranasal ketamine on reducing preoperative pediatric anxiety: a prospective randomized clinical trial. J Anesth. 2012;26(6):878–82.

    Article  CAS  PubMed  Google Scholar 

  44. Mellion SA, et al. Evaluating clinical effectiveness and pharmacokinetic profile of atomized intranasal midazolam in children undergoing laceration repair. J Emerg Med. 2017;53(3):397–404.

    Article  PubMed  Google Scholar 

  45. Sulton C, et al. The use of intranasal dexmedetomidine and midazolam for sedated magnetic resonance imaging in children: a report from the pediatric sedation research consortium. Pediatr Emerg Care. 2017. https://doi.org/10.1097/PEC.0000000000001199.

  46. Tsze DS, et al. Intranasal ketamine for procedural sedation in pediatric laceration repair: a preliminary report. Pediatr Emerg Care. 2012;28(8):767–70.

    Article  PubMed  Google Scholar 

  47. Bahetwar SK, et al. A comparative evaluation of intranasal midazolam, ketamine and their combination for sedation of young uncooperative pediatric dental patients: a triple blind randomized crossover trial. J Clin Pediatr Dent. 2011;35(4):415–20.

    Article  CAS  PubMed  Google Scholar 

  48. Fisgin T, et al. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol. 2002;17(2):123–6.

    Article  PubMed  Google Scholar 

  49. Holsti M, et al. Prehospital intranasal midazolam for the treatment of pediatric seizures. Pediatr Emerg Care. 2007;23(3):148–53.

    Article  PubMed  Google Scholar 

  50. Arya R, et al. Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study. Epilepsia. 2011;52(4):788–93.

    Article  CAS  PubMed  Google Scholar 

  51. Merlin MA, et al. Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses. Am J Emerg Med. 2010;28(3):296–303.

    Article  PubMed  Google Scholar 

  52. Vanky E, et al. Pharmacokinetics after a single dose of naloxone administered as a nasal spray in healthy volunteers. Acta Anaesthesiol Scand. 2017;61(6):636–40.

    Article  CAS  PubMed  Google Scholar 

  53. Winner P, et al. A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents. Pediatrics. 2000;106(5):989–97.

    Article  CAS  PubMed  Google Scholar 

  54. Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev. 2017;1:CD002052.

    PubMed  Google Scholar 

  55. Thomas A, et al. Non-intravenous sedatives and analgesics for procedural sedation for imaging procedures in pediatric patients. J Pediatr Pharmacol Ther. 2015;20(6):418–30.

    PubMed  PubMed Central  Google Scholar 

  56. Theroux MC, et al. Efficacy of intranasal midazolam in facilitating suturing of lacerations in preschool children in the emergency department. Pediatrics. 1993;91(3):624–7.

    CAS  PubMed  Google Scholar 

  57. Ljungman G, et al. Midazolam nasal spray reduces procedural anxiety in children. Pediatrics. 2000;105(1 Pt 1):73–8.

    Article  CAS  PubMed  Google Scholar 

  58. Saunders M, Adelgais K, Nelson D. Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain. Acad Emerg Med. 2010;17(11):1155–61.

    Article  PubMed  Google Scholar 

  59. Furyk JS, Grabowski WJ, Black LH. Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: a randomized controlled trial. Emerg Med Australas. 2009;21(3):203–9.

    PubMed  Google Scholar 

  60. Nielsen BN, et al. Intranasal sufentanil/ketamine analgesia in children. Paediatr Anaesth. 2014;24(2):170–80.

    Article  PubMed  Google Scholar 

  61. Hitt JM, et al. An evaluation of intranasal sufentanil and dexmedetomidine for pediatric dental sedation. Pharmaceutics. 2014;6(1):175–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. AlSarheed MA. Intranasal sedatives in pediatric dentistry. Saudi Med J. 2016;37(9):948–56.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Roelofse JA, et al. Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison. Anesth Prog. 2004;51(4):114–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Henry RJ, et al. A pharmacokinetic study of midazolam in dogs: nasal drop vs. atomizer administration. Pediatr Dent. 1998;20(5):321–6.

    CAS  PubMed  Google Scholar 

  65. Malinovsky JM, et al. Plasma concentrations of midazolam after i.v., nasal or rectal administration in children. Br J Anaesth. 1993;70(6):617–20.

    Article  CAS  PubMed  Google Scholar 

  66. Lahat E, et al. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ. 2000;321(7253):83–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Mahmoudian T, Zadeh MM. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav. 2004;5(2):253–5.

    Article  CAS  PubMed  Google Scholar 

  68. Ahmad S, et al. Efficacy and safety of intranasal lorazepam versus intramuscular paraldehyde for protracted convulsions in children: an open randomised trial. Lancet. 2006;367(9522):1591–7.

    Article  CAS  PubMed  Google Scholar 

  69. Wilson MT, Macleod S, O’Regan ME. Nasal/buccal midazolam use in the community. Arch Dis Child. 2004;89(1):50–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Harbord MG, et al. Use of intranasal midazolam to treat acute seizures in paediatric community settings. J Paediatr Child Health. 2004;40(9–10):556–8.

    Article  CAS  PubMed  Google Scholar 

  71. Weiner SG, et al. Use of intranasal naloxone by basic life support providers. Prehosp Emerg Care. 2017;21(3):322–6.

    Article  PubMed  Google Scholar 

  72. Warrington SE, Kuhn RJ. Use of intranasal medications in pediatric patients. Orthopedics. 2011;34(6):456.

    Article  PubMed  Google Scholar 

  73. Costantino HR, et al. Intranasal delivery: physicochemical and therapeutic aspects. Int J Pharm. 2007;337(1–2):1–24.

    Article  CAS  PubMed  Google Scholar 

  74. Centers for Disease Control and Prevention (CDC). Integrated prevention services for HIV infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use drugs illicitly: summary guidance from CDC and the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2012;61(RR-5):1–40.

    Google Scholar 

  75. Barton ED, et al. Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting. J Emerg Med. 2005;29(3):265–71.

    Article  PubMed  Google Scholar 

  76. Robertson TM, et al. Intranasal naloxone is a viable alternative to intravenous naloxone for prehospital narcotic overdose. Prehosp Emerg Care. 2009;13(4):512–5.

    Article  PubMed  Google Scholar 

  77. Bailey AM, et al. Review of intranasally administered medications for use in the emergency department. J Emerg Med. 2017;53(1):38–48.

    Article  PubMed  Google Scholar 

  78. Miyake MM, Bleier BS. The blood-brain barrier and nasal drug delivery to the central nervous system. Am J Rhinol Allergy. 2015;29(2):124–7.

    Article  PubMed  Google Scholar 

  79. Lipton RB, et al. DFN-02 (sumatriptan 10 mg with a permeation enhancer) nasal spray vs placebo in the acute treatment of migraine: a double-blind, placebo-controlled study. Headache. 2018;58(5):676–87.

    Article  PubMed  Google Scholar 

  80. Ahonen K, et al. Nasal sumatriptan is effective in treatment of migraine attacks in children: a randomized trial. Neurology. 2004;62(6):883–7.

    Article  CAS  PubMed  Google Scholar 

  81. Lewis DW, et al. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics. 2007;120(2):390–6.

    Article  PubMed  Google Scholar 

  82. Priprem A, et al. Intranasal melatonin nanoniosomes: pharmacokinetic, pharmacodynamics and toxicity studies. Ther Deliv. 2017;8(6):373–90.

    Article  CAS  PubMed  Google Scholar 

  83. Maizels M, Geiger AM. Intranasal lidocaine for migraine: a randomized trial and open-label follow-up. Headache. 1999;39(8):543–51.

    Article  CAS  PubMed  Google Scholar 

  84. Maizels M, et al. Intranasal lidocaine for treatment of migraine: a randomized, double-blind, controlled trial. JAMA. 1996;276(4):319–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Children’s Hospital of Nanjing Medical University, Nanjing, China

    Gang Zhang

  2. Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA

    Gang Zhang, Myles R. McCrary & Ling Wei

  3. Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA

    Ling Wei

Authors
  1. Gang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myles R. McCrary
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ling Wei .

Editor information

Editors and Affiliations

  1. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    Jun Chen

  2. Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jian Wang

  3. Departments of Anesthesiology and Neurology, Emory University School of Medicine, Atlanta, GA, USA

    Ling Wei

  4. Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA

    John H. Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zhang, G., McCrary, M.R., Wei, L. (2019). Intranasal Medication Delivery in Children for Brain Disorders. In: Chen, J., Wang, J., Wei, L., Zhang, J. (eds) Therapeutic Intranasal Delivery for Stroke and Neurological Disorders. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-030-16715-8_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-16715-8_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-16713-4

  • Online ISBN: 978-3-030-16715-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation