Seizing child recieving IN treatmentTherapeutic Intranasal Drug Delivery

Needleless treatment options for medical problems

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Miscellaneous intranasal medications

The number of potential applications for intranasal medications is enormous.  Potential uses that may enhance or provide alternative treatment modalities include headache therapy,[1-15, 32] anti-nausea medication delivery in patients intolerant of oral medications and patients suffering from diabetic gastroparesis,[16-19, 44] chronic pain therapy,[20-25] insulin therapy (avoid multiple daily shots),[26,37] vaccine administration (enhance immune response by delivery via a more natural exposure route),[27-29] antipsychotic medications (reduce chance or injury to patient and provider),[45,46] prevention of abnormal nasal blood vessel growth (Avastin) and even the delivery of medications and drug antidotes such as hydroxocobalamin (antidote to cyanide poisoning)[11, 30, 31, 54]. Another topic investigated in intranasal B-2 agonists for asthma - something that could use further investigation.[33] More recently interest is developing on delivery of a number of peptides and other drugs to the nose for direct transport into the brain to treat neurodegenerative disorders such as Alzheimer's (click here for an article on the topic). Intranasal insulin is being investigated for treatment of neurodegenerative disorders such as Alzheimer's disease.[36]

IN ketamine is becoming an area of significant research interest for the treatment of bipolar disease and major depressive disorder with early results suggesting a strong and prolonged antidepressant effect following a single subdissociative dose (50 mg) of ketamine[34, 42-43, 47, 48,49]. One of the better studies I have seen on the topic was by Domany et al.[53] It is a small but well designed study that encapsulates the concept. They found that I single dose of nasal ketamine given in the emergency reduced SI in patients by 80% compared to 33% in the patients who simply had ED counseling. (Free from the internet - Click here for the full article). Intranasal oxytocin is also being actively investigated for many psychiatric conditions including alcohol withdrawal, anorexia nervosa, PTSD, autism, anxiety disorders, pain sensation and schizophrenia.[35,38-41]

Scopalamine can also be given intranasally to suppress motion sickness faster that the oral or transdermal route. The results are preliminary but show definite effect at reducing/suppressing motion sickness.[51]

 Intranasal atropine can be delivered and lead to significant systemic effects as demonstrated accidentally by Alaula et al.[52] This insight might be useful for rapidly treating a multi-casualty neurotoxin exposure event if proper dosing could be determined.

More unusual articles entail IN dexmedetomidine for converting supraventricular tachycardia [50].

Some of these concepts are fully developed and commercially available pharmaceutical products are already available on the market such as intranasal dihydroergotamine for headaches[13] and nasal vaccines for influenza.[27-29] Other concepts, such as intranasal hydroxocobalamin are purely conjecture and may or may not be viable concepts.

The area of intranasal medication delivery provides a huge opportunity for research – both for specifically developed pharmaceutical drugs designed for intranasal treatment, as well as for investigating off label uses of commonly available generic medications.
Link to separate web site listing ongoing intranasal research into many drugs - insulin, viral particles, glucagon, flu, etc - click here


Bibliography (click here for abstracts)

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2.  Maizels, M., et al., Intranasal lidocaine for treatment of migraine: a randomized, double-blind, controlled trial [see comments]. Jama, 1996. 276(4): p. 319-21.

3.   Maizels, M. and A.M. Geiger, Intranasal lidocaine for migraine: a randomized trial and open-label follow-up. Headache, 1999. 39(8): p. 543-51.

4.   Costa, A., et al., The effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks in cluster headache. Cephalalgia, 2000. 20(2): p. 85-91.

5.    Buckley, R., T. McCurry, and J. Gera, Intranasal lidocaine for migraine using a metered-dose spray. Headache, 2000. 40(6): p. 498.

6.   Maizels, M., et al., Intranasal lidocaine for treatment of migraine: a randomized, double-blind, controlled trial. Jama, 1996. 276(4): p. 319-21.

7.   Robbins, L., Intranasal lidocaine for cluster headache. Headache, 1995. 35(2): p. 83-4.

8.   Quadir, M., H. Zia, and T.E. Needham, Development and evaluation of nasal formulations of ketorolac. Drug Deliv, 2000. 7(4): p. 223-9.

9.   Markley, H.G., Topical agents in the treatment of cluster headache. Curr Pain Headache Rep, 2003. 7(2): p. 139-43.

10.    Kudrow, L., D.B. Kudrow, and J.H. Sandweiss, Rapid and sustained relief of migraine attacks with intranasal lidocaine: preliminary findings. Headache, 1995. 35(2): p. 79-82.

11.  van der Kuy, P.H., et al., Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an open, pilot study. Cephalalgia, 2002. 22(7): p. 513-9.

12.  Rapoport, A. and P. Winner, Nasal delivery of antimigraine drugs: clinical rationale and evidence base. Headache, 2006. 46 Suppl 4: p. S192-201.

13.  Weintraub, J., Repetitive dihydroergotamine nasal spray for treatment of refractory headaches: an open-label pilot study. Curr Med Res Opin, 2006. 22(10): p. 2031-6.

14.   Rapoport, A.M., et al., Intranasal medications for the treatment of migraine and cluster headache. CNS Drugs, 2004. 18(10): p. 671-85.

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16.   Ormrod, D. and K.L. Goa, Intranasal metoclopramide. Drugs, 1999. 58(2): p. 315-22; discussion 323-4.

17.   Wagner, B.K., et al., A double-blind, placebo-controlled evaluation of intranasal metoclopramide in the prevention of postoperative nausea and vomiting. Pharmacotherapy, 1996. 16(6): p. 1063-9.

18.  Tomirotti, M., et al., Efficacy and tolerability of nasally administered compared to parenterally administered metoclopramide in the symptomatic treatment of chemotherapy-induced emesis in cancer outpatients. A controlled clinical study. Support Care Cancer, 1994. 2(6): p. 389-92.

19. Cho, E., H. Gwak, and I. Chun, Formulation and evaluation of ondansetron nasal delivery systems. Int J Pharm, 2008. 349(1-2): p. 101-7.

20. Flood, P. and D. Daniel, Intranasal nicotine for postoperative pain treatment. Anesthesiology, 2004. 101(6): p. 1417-21.

21. Zeppetella, G., An assessment of the safety, eff icacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain. A pilot study. J Pain Symptom Manage, 2000. 20(4): p. 253-8.

22.  Cleary, J.F., Pharmacokinetic and pharmacodynamic issues in the treatment of breakthrough pain. Semin Oncol, 1997. 24(5 Suppl 16): p. S16-13-9.

23.    Goudas, L.C., et al., Efficacy and safety of intranasal ketamine for the management of breakthrough pain in chronic pain. A randomized, double-blind, placebo-controlled, cross-over trial. American Society of Clinical Oncology Meeting, 2002. Abstract No: 450.

24.  Bell, Rf, and Kalso, Is intranasal ketamine an appropriate treatment for chronic non-cancer breakthrough pain? Pain, 2004. 108(1-2): p. 1-2.

25.  Carr, D.B., et al., Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study. Pain, 2004. 108(1-2): p. 17-27.

26.  Lassmann-Vague, V. and D. Raccah, Alternatives routes of insulin delivery. Diabetes Metab, 2006. 32(5 Pt 2): p. 513-22.

27.  Eyles, J.E., E.D. Williamson, and H.O. Alpar, Intranasal Administration of InfluenzaVaccines: Current Status. BioDrugs, 2000. 13(1): p. 35-59.

28.  Lin, K., Intranasal influenza vaccine may be a safe, effective option for many children. J Pediatr, 2007. 151(1): p. 102-3.

29.  Dean, H.J., Alternative routes of influenza vaccine delivery. Expert Opin Drug Deliv, 2006. 3(5): p. 557-61.

30.  Slot, W.B., et al., Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients. Gastroenterology, 1997. 113(2): p. 430-3.

31.  van Asselt, D.Z., et al., Nasal absorption of hydroxocobalamin in healthy elderly adults. Br J Clin Pharmacol, 1998. 45(1): p. 83-6.

32.  Giraud, P, et al. "Cluster Headache During Pregnancy: Case Report and Literature Review." Headache Jan 2009: 136-139

33. Weksler, N., S. Brill, et al. (1999). "Intranasal salbutamol instillation in asthma attack." Am J Emerg Med 17(7): 686-688.

34. Papolos, D. F., M. H. Teicher, et al. (2013). "Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype." J Affect Disord 147(1-3): 431-436.

35. Pedersen, C. A., K. L. Smedley, et al. (2013). "Intranasal oxytocin blocks alcohol withdrawal in human subjects." Alcohol Clin Exp Res 37(3): 484-489.

36. Claxton, A., et al., Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia. J Alzheimers Dis, 2014.

37. Dash, S., et al., Intranasal insulin suppresses endogenous glucose production in humans compared to placebo, in the presence of similar venous insulin concentration. Diabetes, 2014.

38. Guastella, A.J., et al., The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. J Child Psychol Psychiatry, 2014.

39. Kim, Y.R., et al., The impact of intranasal oxytocin on attention to social emotional stimuli in patients with anorexia nervosa: a double blind within-subject cross-over experiment. PLoS One, 2014. 9(6): p. e90721.

40. Koch, S.B., et al., Intranasal oxytocin as strategy for medication-enhanced psychotherapy of PTSD: salience processing and fear inhibition processes. Psychoneuroendocrinology, 2014. 40: p. 242-56.

41. Rash, J.A. and T.S. Campbell, The effect of intranasal oxytocin administration on acute cold pressor pain: a placebo-controlled, double-blind, within-participants crossover investigation. Psychosom Med, 2014. 76(6): p. 422-9.

42. Lapidus, K.A., et al., A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder. Biol Psychiatry, 2014.

43. McGirr, A., et al., A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med, 2014: p. 1-12.

44. Parkman, H.P., M.R. Carlson, and D. Gonyer, Metoclopramide nasal spray is effective in symptoms of gastroparesis in diabetics compared to conventional oral tablet. Neurogastroenterol Motil, 2014. 26(4): p. 521-8.

45. Piazza, J., et al., Intranasally administered lectin functionalized poly(ethylene glycol)-block-poly(d,l)-lactic-co-glycolic acid (PEG-PLGA) nanoparticles for the treatment of schizophrenia. Eur J Pharm Biopharm, 2014.

46. Miller, J.L., et al., Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: a pilot pharmacokinetic study. Pharmacotherapy, 2008. 28(7): p. 875-82.

47. McGirr A, Berlim MT, Bond DJ, Fleck MP, Yatham LN, Lam RW. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychological medicine 2015;45:693-704.

48. Andrade, C. (2015). "Intranasal drug delivery in neuropsychiatry: focus on intranasal ketamine for refractory depression." J Clin Psychiatry 76(5): 628-631.

49. Papolos, D., M. Frei, et al. (2018). "Clinical experience using intranasal ketamine in the longitudinal treatment of juvenile bipolar disorder with fear of harm phenotype." J Affect Disord 225: 545-551.

50. Hultin, M. and E. Sundberg (2018). "Spontaneous Conversions of Supraventricular Tachycardia to Sinus Rhythm in Children After Premedication With Intranasal Dexmedetomidine: A Case Report." A A Pract 11(8): 219-220.

51. Stankovic, A. S., D. L. Alvarenga, et al. (2019). "Intranasal Scopolamine for Motion Sickness." Aerosp Med Hum Perform 90(11): 917-924.

52. Alaula, L. S., M. Al-Kadi, et al. (2019). "Atropine toxicity caused by erroneous intranasal administration in a pediatric patient: case report." Ann Saudi Med 39(4): 279-282.

53. Domany, Y., J. Lord, et al. (2020). "Intranasal Ketamine for Alleviation of Acute Suicidal Ideation. An Emergency Department, Trans-Diagnostic Approach: Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial " SSRN(

54. Estourgie-van Burk, G. F., P. H. M. van der Kuy, et al. (2020). "Intranasal treatment of vitamin B12 deficiency in children." Eur J Pediatr 179(2): 349-352.