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{{Short description|Administration of drugs through the nose}}
[[File:Instilling nasal medication.jpg|thumb|A medical professional applies nose drops.]]

'''Nasal administration''', popularly known as '''snorting''', is a [[route of administration]] in which [[drug]]s are [[insufflation (medicine)|insufflated]] through the [[nose]]. It can be a form of either [[topical administration]] or [[systemic administration]], as the drugs thus locally delivered can go on to have either purely local or systemic effects. Nasal sprays are locally acting drugs, such as [[decongestant]]s for cold and allergy treatment, whose systemic effects are usually minimal. Examples of systemically active drugs available as nasal sprays are [[Migraine#Management|migraine drugs]], rescue medications for overdose and seizure emergencies, [[hormone therapy|hormone treatments]], [[nicotine nasal spray]], and [[nasal vaccine]]s such as [[live attenuated influenza vaccine]].

==Risks==

===Nasal septum perforation===
[[File:Cocaine nose.jpg|thumb|200px|"Cocaine nose" refers to [[nasal septum perforation]] from cocaine use (pictured), or to [[cocaine-induced midline destructive lesions]] (CIMDL), which may develop as the damage progresses.]]

{{main|Nasal septum perforation}}

A [[nasal septum perforation]] is a medical condition in which the [[nasal septum]], the [[cartilage|bony/cartilaginous]] wall dividing the [[nostrils|nasal cavities]], develops a hole or fissure.<ref>{{Citation |last1=Downs |first1=Brian W. |title=Septal Perforation |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK537208/ |work=StatPearls |access-date=2023-10-17 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30725893 |last2=Sauder |first2=Haley M.}}</ref> Nasal administration may cause nasal septum perforation by gradually injuring and ulcerating the epithelium, causing cartilage exposure and [[necrosis]].<ref>{{Cite journal |last1=Brake |first1=Daniela A. |last2=Hamilton |first2=Grant S. |last3=Bansberg |first3=Stephen F. |date=2023-12-01 |title=Nasal Septal Perforation Due to Desmopressin Nasal Spray Use |journal=Ear, Nose & Throat Journal |language=en |volume=102 |issue=12 |pages=NP621–NP624 |doi=10.1177/01455613211026425 |issn=0145-5613|doi-access=free |pmid=34233494 }}</ref>

===Risk factors for shared drug paraphernalia===
[[File:Cocaine lines 2.jpg|thumb|left|Lines of cocaine prepared for snorting. [[Contaminated currency]] such as banknotes might serve as a [[fomite]] of diseases like [[hepatitis C]]<ref name="LV">{{cite web |url=http://cocaine.org/cokemoney/banknotes.html |title='Shared banknote' health warning to cocaine users |accessdate=2008-07-26 |author=Laureen Veevers |date=1 October 2006 |work=The Observer }}</ref>]]

Sharing snorting equipment (nasal spray bottles, straws, banknotes, bullets, etc.) has been linked to the transmission of [[hepatitis C]]. In one study, the University of Tennessee Medical Center researchers warned that other blood-borne diseases such as [[HIV]] could be transmitted as well.<ref>{{Citation | year=2016 | title=Sharing Drug "Snorting Straws" Spreads Hepatitis C | work=Consumer Health News | HealthDay | url=https://consumer.healthday.com/infectious-disease-information-21/hepatitis-news-373/sharing-drug-snorting-straws-spreads-hepatitis-c-713114.html}}</ref>

== Advantages ==
The nasal cavity is covered by a thin mucosa which is well vascularised.<ref>D.F. Proctor and I. Andersen. The nose. Upper airway physiology and the atmospheric environment , Elsevier Biomedical Press, Amsterdam, 1982.</ref> Therefore, a drug molecule can be transferred quickly across the single epithelial cell layer directly to the systemic blood circulation without first-pass hepatic and intestinal metabolism. The effect is often reached within 5 minutes for [[Small molecule|smaller drug molecules]].<ref>Y.W. Chien, K.S.E. Su, and S.-F. Chang. Nasal systemic drug delivery, Marcel Dekker, Inc., New York, 1989.</ref> Nasal administration can therefore be used as an alternative to oral administration, by crushing or grinding tablets or capsules and snorting or sniffing the resulting powder, providing a rapid onset of effects if a fast effect is desired or if the drug is extensively degraded in the gut or liver.<ref name="Fransén 2008">{{cite thesis |last1=Fransén |first1=Nelly |date=2008 |title=Studies on a Novel Powder Formulation for Nasal Drug Delivery |type=PhD dissertation |publisher=Uppsala University |url=http://urn.kb.se/resolve?urn=urn%3Anbn%3Ase%3Auu%3Adiva-9292 |isbn=978-91-554-7288-7}}</ref>

Large-molecule drugs can also be delivered directly to the brain by the intranasal route, the only practical means of doing so, following the olfactory and trigeminal nerves [[Nasal administration#Olfactory transfer|(see section below)]], for widespread central distribution throughout the [[central nervous system]] with little exposure to the blood.<ref name="Thorne 1995">{{cite journal |last1=Thorne |first1=RG |last2=Emory |first2=ER |last3=Ala |first3=TA |last4=Frey |first4=William II |title=Quantitative analysis of the olfactory pathway for drug delivery to the brain |journal=Brain Research |date=September 18, 1995 |volume=692 |issue=1–2 |pages=278–282 |doi=10.1016/0006-8993(95)00637-6 |pmid=8548316|s2cid=11522233 }}</ref><ref name="Thorne 2004">{{cite journal |last1=Thorne |first1=RG |last2=Pronk |first2=GJ |last3=Padmanabhan |first3=V |last4=Frey |first4=WH II |title=Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration |journal=Neuroscience |date=2004 |volume=127 |issue=2 |pages=481–96 |doi=10.1016/j.neuroscience.2004.05.029 |pmid=15262337|s2cid=40872017 }}</ref><ref name="Björn">{{cite thesis |last=Jansson |first=Björn |date=2004 |title=Models for the Transfer of Drugs from the Nasal Cavity to the Central Nervous System |type=PhD dissertation |publisher=Uppsala University |url=http://urn.kb.se/resolve?urn=urn%3Anbn%3Ase%3Auu%3Adiva-3905 |access-date=18 March 2023 |isbn=91-554-5834-3}}</ref><ref name="Ulrika">{{cite thesis |last=Espefält Westin |first=Ulrika |date=2007 |title=Olfactory Transfer of Analgesic Drugs After Nasal Administration |type=PhD dissertation |publisher=Uppsala University |url=http://urn.kb.se/resolve?urn=urn%3Anbn%3Ase%3Auu%3Adiva-7829 |access-date=18 March 2023 |isbn=978-91-554-6871-2}}</ref> This delivery method to the brain was functionally demonstrated in humans in 2006, using [[insulin]], a large [[peptide]] hormone that acts as a nerve growth factor in the brain.<ref name="Reger 1">{{cite journal |last1=Reger |first1=MA |last2=Watson |first2=GS |last3=Frey |first3=WH II |last4=Baker |first4=LD |last5=Cholerton |first5=B |last6=Keeling |first6=ML |last7=Belongia |first7=DA |last8=Fishel |first8=MA |last9=Plymate |first9=SR |last10=Belongia |first10=GD |last11=Cherrier |first11=MM |last12=Craft |first12=S |title=Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype |journal=Neurobiol Aging |date=March 2006 |volume=27 |issue=3 |pages=451–458 |doi=10.1016/j.neurobiolaging.2005.03.016 |pmid=15964100|s2cid=21158378 }}</ref>

== Limitations ==
Nasal administration is primarily suitable for potent drugs since only a limited volume can be sprayed into the nasal cavity. Drugs for continuous and frequent administration may be less suitable because of the risk of harmful long-term effects on the nasal epithelium.<ref name="Fransén 2008"/> Nasal administration has also been associated with a high variability in the amount of drug absorbed. Upper airway infections may increase the variability as may the extent of sensory irritation of the nasal mucosa, differences in the amount of liquid spray that is swallowed and not kept in the nasal cavity and differences in the spray actuation process.<ref>H. Kublik and M.T. Vidgren. Nasal delivery systems and their effect on deposition and absorption. Adv Drug Deliv Rev. 29:157-177 (1998).</ref> However, the variability in the amount absorbed after nasal administration should be comparable to that after oral administration.<ref>B.A. Coda, A.C. Rudy, S.M. Archer, and D.P. Wermeling. Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg. 97:117-123 (2003).</ref><ref>J. Studd, B. Pornel, I. Marton, J. Bringer, C. Varin, Y. Tsouderos, and C. Christiansen. Efficacy and acceptability of intranasal 17 beta-oestradiol for menopausal symptoms: randomised dose-response study. Aerodiol Study Group. Lancet. 353:1574-1578 (1999).</ref>

== Nasal drugs ==
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. Steroids, and a large number of inhalational anaesthetic agents are being used commonly. The recent developments in intranasal drug delivery systems are prodigious. [[Peptide therapeutics|Peptide drugs]] (hormone treatments) are also available as nasal sprays, in this case to avoid drug degradation after oral administration. The peptide analogue [[desmopressin]] is, for example, available for both nasal and oral administration, for the treatment of [[diabetes insipidus]]. The [[bioavailability]] of the commercial tablet is 0.1% while that of the nasal spray is 3-5% according to the SPC ([[Summary of Product Characteristics]]).<ref>FerringPharmaceuticals. SPC: Minirin nasal spray, Minirin Freeze-dried tablet and Minirin tablet, 2005.</ref> Intranasal [[calcitonin]], calcitonin-salmon, is used to treat [[hypercalcaemia]] arising out of malignancy, [[Paget's disease of bone]], post menopausal and steroid induced [[osteoporosis]], [[Phantom limb|phantom limb pain]] and other metabolic bone abnormalities, available as Rockbone, Fortical and Miacalcin Nasal Spray. [[Gonadotropin-releasing hormone modulator|GnRH analogues]] like nafarelin and busurelin are used for the treatment of anovulatory infertility, [[hypogonadotropic hypogonadism]], [[delayed puberty]] and [[cryptorchidism]]. Other potential drug candidates for nasal administration include anaesthetics, antihistamines (Azelastine), [[antiemetic]]s (particularly metoclopramide and ondansetron) and [[sedative]]s that all benefit from a fast onset of effect.<ref>H.R. Costantino, L. Illum, G. Brandt, P.H. Johnson, and S.C. Quay. Intranasal delivery: physicochemical and therapeutic aspects. Int J Pharm. 337:1-24 (2007).</ref> Intranasal [[midazolam]] is found to be highly effective in acute episodes of seizures in children. Recently, the upper part of the nasal cavity, as high as the [[cribriform plate]], has been proposed for drug delivery to the brain. This "transcribrial route", published first in 2014, was suggested by the author for drugs to be given for Primary [[Meningoencephalitis]].<ref>Baig AM, Khan NA. Novel chemotherapeutic strategies in the management of primary amoebic meningoencephalitis due to Naegleria fowleri.CNS Neurosci Ther. 2014 Mar;20(3):289-90. doi: 10.1111/cns.12225. Epub 2014 Jan 24</ref>

===Medicines===

====Oxytocin====
[[Oxytocin (medicine)|Oxytocin]] (brand name Syntocinon) nasal spray is used to increase duration and strength of contractions during labour. Intranasal oxytocin is also being actively investigated for many psychiatric conditions including [[Alcohol withdrawal syndrome|alcohol withdrawal]], [[anorexia nervosa]], [[Post-traumatic stress disorder|PTSD]], [[autism]], [[anxiety disorder]]s, pain sensation and [[schizophrenia]].

===Recreational drugs/entheogens===

List of substances that have higher bioavailability when administered intranasally compared to oral administration.

====Cocaine====
Insufflation of [[cocaine]] leads to the longest duration of its effects (60–90 minutes).<ref name="Zimmerman2012">{{Cite journal | vauthors = Zimmerman JL | title = Cocaine intoxication | journal = Critical Care Clinics | volume = 28 | issue = 4 | pages = 517–26 | date = October 2012 | pmid = 22998988 | doi = 10.1016/j.ccc.2012.07.003 }}</ref> When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%.<ref>{{Cite web|title=The Dangers Of Snorting Cocaine (Insufflation)|url=https://vertavahealth.com/cocaine/insufflation/|access-date=2022-02-25|website=Vertava Health|language=en-US}}</ref>

====Ketamine====
[[Image:SpiRaL.jpg|thumb|left|[[Ketamine]] prepared in a spiral for "snorting"]]

Among the less invasive routes for [[ketamine]], the intranasal route has the highest bioavailability (45–50%).<ref name="MathewZarate2016">{{cite book | vauthors = Mathew SJ, Zarate Jr CA |title=Ketamine for Treatment-Resistant Depression: The First Decade of Progress |url=https://books.google.com/books?id=QDOgDQAAQBAJ&pg=PA22 |date=25 November 2016 |publisher=Springer |isbn=978-3-319-42925-0 |pages=8–10, 14–22 |url-status=live |archive-url=https://web.archive.org/web/20170908185726/https://books.google.com/books?id=QDOgDQAAQBAJ&pg=PA22 |archive-date=8 September 2017 }}</ref><ref name="pmid23521979">{{cite journal |vauthors=Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, Weatherall A, Paal P |title=Ketamine: use in anesthesia |journal=CNS Neurosci Ther |volume=19 |issue=6 |pages=381–9 |date=June 2013 |pmid=23521979 |pmc=6493613 |doi=10.1111/cns.12072 }}</ref>

====Snuff====
[[Snuff (tobacco)|Snuff]] is a type of [[smokeless tobacco]] [[List of tobacco products|product]] made from finely ground or pulverized [[tobacco]] leaves.<ref name="OSHFT">
The Old Snuff House of Fribourg & Treyer at the Sign of the Rasp & Crown, No.34 James's Haymarket, London, S.W., 1720, 1920. Author: George Evens and Fribourg & Treyer. Publisher: Nabu Press, London, England. Reproduced 5 August 2010, {{ISBN|978-1176904705}}
</ref> It is [[Insufflation (medicine)|snorted]] or "sniffed" (alternatively sometimes written as "snuffed") into the nasal cavity, delivering [[nicotine]] and a flavored scent to the user (especially if flavoring has been blended with the tobacco).<ref name="OSHFT" /> Traditionally, it is sniffed or inhaled lightly after a pinch of snuff is either placed onto the back surface of the [[hand]], held pinched between thumb and index finger, or held by a specially made "snuffing" device.

====Yopo====
[[Snuff tray]]s and tubes similar to those commonly used for [[Anadenanthera peregrina|yopo]] were found in the central Peruvian coast dating back to 1200 BC, suggesting that insufflation of ''Anadenanthera'' beans is a more recent method of use.<ref>{{Cite journal |last1=Pochettino |first1=M. L. |last2=Cortella |first2=A. R. |last3=Ruiz |first3=M. |date=1999-04-01 |title=Hallucinogenic snuff from Northwestern Argentina: Microscopical identification of anadenanthera colubrina var. cebil (fabaceae) in powdered archaeological material |url=https://link.springer.com/article/10.1007/BF02866491 |journal=Economic Botany |language=en |volume=53 |issue=2 |pages=127–132 |doi=10.1007/BF02866491 |bibcode=1999EcBot..53..127P |issn=1874-9364}}</ref> Archaeological evidence of insufflation use within the period 500-1000 AD, in northern Chile, has been reported.<ref>{{cite journal |author1=Juan P. Ogalde |author2=Bernardo T. Arriaza |author3=Elia C. Soto | title = Uso de plantas psicoactivas en el north de Chile: evidencia química del consumo de ayahuasca durante el periodo medio (500-1000 d.C.) | journal = Latin American Antiquity | volume = 21 | issue = 4 | year = 2010 | pages = 441–450 | doi=10.7183/1045-6635.21.4.441|s2cid=163915994 }}</ref>

==Research==

=== Olfactory transfer ===
There is about 20 mL capacity in the adult human [[nasal cavity]].<ref name="Remington">{{cite book|editor1-last=Troy|editor1-first=David|editor2-last=Beringer|editor2-first=Paul|title=Remington: The Science and Practice of Pharmacy|date=2006|publisher=Lippincott Williams & Wilkins|page=752|language=en|chapter=39}}</ref> The major part of the approximately 150 cm<sup>2</sup> surface in the human nasal cavity is covered by [[respiratory epithelium]], across which systemic drug absorption can be achieved. The [[olfaction|olfactory epithelium]] is situated in the upper posterior part and covers approximately 10 cm<sup>2</sup> of the human nasal cavity. The nerve cells of the olfactory epithelium project into the [[olfactory bulb]] of the brain, which provides a direct connection between the brain and the external environment. The transfer of drugs to the brain from the blood circulation is normally hindered by the [[blood–brain barrier]] (BBB), which is virtually impermeable to [[passive transport|passive diffusion]] of all but small, lipophilic substances. However, if drug substances can be transferred along the olfactory nerve cells, they can bypass the BBB and enter the brain directly.<ref name="Björn"/><ref name="Ulrika"/>

The '''olfactory transfer''' of drugs into the brain is thought to occur by either slow transport inside the olfactory nerve cells to the olfactory bulb or by faster transfer along the perineural space surrounding the olfactory nerve cells into the [[cerebrospinal fluid]] surrounding the olfactory bulbs and the brain.<ref>S. Mathison, R. Nagilla, and U.B. Kompella. Nasal route for direct delivery of solutes to the central nervous system: Fact or fiction? J Drug Target. 5:415-441 (1998)</ref><ref name="auto">L. Illum. Is nose-to-brain transport of drugs in man a reality? J Pharm Pharmacol. 56:3-17 (2004).</ref>

Olfactory transfer could theoretically be used to deliver drugs that have a required effect in the central nervous system such as those for [[Parkinson's disease|Parkinson's]] or [[Alzheimer's disease|Alzheimer's]] diseases. Studies have been presented showing that direct transfer of drugs is achievable.<ref name="auto"/><ref>U.E. Westin, E. Bostrom, J. Grasjo, M. Hammarlund-Udenaes, and E. Bjork. Direct nose-to-brain transfer of morphine after nasal administration to rats. Pharm Res. 23:565-572 (2006).</ref>

== References ==
{{Reflist}}

{{Dosage forms}}
{{Nasal preparations}}

{{DEFAULTSORT:Nasal Administration}}
[[Category:Medical treatments]]
[[Category:Dosage forms]]
[[Category:Routes of administration]]

Nasal administration - Revision history

imported>Citation bot: Added work. | Use this bot. Report bugs. | Suggested by CorrectionsJackal | Category:Medical treatments | #UCB_Category 60/239