Nasal administration

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A medical professional applies nose drops. Instilling nasal medication.jpg
A medical professional applies nose drops.

Nasal administration, popularly known as snorting, is a route of administration in which drugs are 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 decongestants for cold and allergy treatment, whose systemic effects are usually minimal. Examples of systemically active drugs available as nasal sprays are migraine drugs, rescue medications for overdose and seizure emergencies, hormone treatments, nicotine nasal spray, and nasal vaccines such as live attenuated influenza vaccine.

Contents

Risks

Nasal septum perforation

Nasal septum perforation caused from cocaine abuse. Cocaine nose.jpg
Nasal septum perforation caused from cocaine abuse.

A nasal septum perforation is a medical condition in which the nasal septum, the bony/cartilaginous wall dividing the nasal cavities, develops a hole or fissure. [1] Nasal administration may cause nasal septum perforation by gradually injuring and ulcerating the epithelium, causing cartilage exposure and necrosis. [2]

Risk factors for shared drug paraphernalia

Lines of cocaine prepared for snorting. Contaminated currency such as banknotes might serve as a fomite of diseases like hepatitis C Cocaine lines 2.jpg
Lines of cocaine prepared for snorting. Contaminated currency such as banknotes might serve as a fomite of diseases like hepatitis C

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. [4]

Advantages

The nasal cavity is covered by a thin mucosa which is well vascularised. [5] 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 smaller drug molecules. [6] 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. [7]

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 (see section below), for widespread central distribution throughout the central nervous system with little exposure to the blood. [8] [9] [10] [11] 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. [12]

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. [7] 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. [13] However, the variability in the amount absorbed after nasal administration should be comparable to that after oral administration. [14] [15]

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 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). [16] 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 pain and other metabolic bone abnormalities, available as Rockbone, Fortical and Miacalcin Nasal Spray. 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), antiemetics (particularly metoclopramide and ondansetron) and sedatives that all benefit from a fast onset of effect. [17] 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. [18]

Medicines

Oxytocin

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, anorexia nervosa, PTSD, autism, anxiety disorders, 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). [19] When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%. [20]

Ketamine

Ketamine prepared in a spiral for "snorting". a common technique for self-administration of some recreational drugs. SpiRaL.jpg
Ketamine prepared in a spiral for "snorting". a common technique for self-administration of some recreational drugs.

Among the less invasive routes for ketamine, the intranasal route has the highest bioavailability (45–50%). [21] [22]

Snuff

Snuff is a type of smokeless tobacco product made from finely ground or pulverized tobacco leaves. [23] It is 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). [23] 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 trays and tubes similar to those commonly used for 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. [24] Archaeological evidence of insufflation use within the period 500-1000 AD, in northern Chile, has been reported. [25]

Research

Olfactory transfer

There is about 20 mL capacity in the adult human nasal cavity. [26] The major part of the approximately 150 cm2 surface in the human nasal cavity is covered by respiratory epithelium, across which systemic drug absorption can be achieved. The olfactory epithelium is situated in the upper posterior part and covers approximately 10 cm2 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 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. [10] [11]

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. [27] [28]

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 or Alzheimer's diseases. Studies have been presented showing that direct transfer of drugs is achievable. [28] [29]

Related Research Articles

<span class="mw-page-title-main">Central nervous system</span> Brain and spinal cord

The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric and triploblastic animals—that is, all multicellular animals except sponges and diploblasts. It is a structure composed of nervous tissue positioned along the rostral to caudal axis of the body and may have an enlarged section at the rostral end which is a brain. Only arthropods, cephalopods and vertebrates have a true brain, though precursor structures exist in onychophorans, gastropods and lancelets.

<span class="mw-page-title-main">Anosmia</span> Inability to smell

Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells.

<span class="mw-page-title-main">Olfactory nerve</span> Cranial nerve I, for smelling

The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to the sense of smell.

<span class="mw-page-title-main">Route of administration</span> Path by which a drug, fluid, poison, or other substance is taken into the body

In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body.

<span class="mw-page-title-main">Nasal cavity</span> Large, air-filled space above and behind the nose in the middle of the face

The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nasal cavity is the uppermost part of the respiratory system and provides the nasal passage for inhaled air from the nostrils to the nasopharynx and rest of the respiratory tract.

<span class="mw-page-title-main">Nasal concha</span> Piece of bone in the breathing passage of humans and other animals

In anatomy, a nasal concha, also called a nasal turbinate or turbinal, is a long, narrow, curled shelf of bone that protrudes into the breathing passage of the nose in humans and various other animals. The conchae are shaped like an elongated seashell, which gave them their name. A concha is any of the scrolled spongy bones of the nasal passages in vertebrates.

<span class="mw-page-title-main">Olfactory epithelium</span> Specialised epithelial tissue in the nasal cavity that detects odours

The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is involved in smell. In humans, it measures 5 cm2 (0.78 sq in) and lies on the roof of the nasal cavity about 7 cm (2.8 in) above and behind the nostrils. The olfactory epithelium is the part of the olfactory system directly responsible for detecting odors.

<span class="mw-page-title-main">Nasal spray</span> Spray that delivers medications locally in the nasal cavities or systemically

Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for systemic therapy because it provides an agreeable alternative to injection or pills. Substances can be assimilated extremely quickly and directly through the nose. Many pharmaceutical drugs exist as nasal sprays for systemic administration. Other applications include hormone replacement therapy, treatment of Alzheimer's disease and Parkinson's disease. Nasal sprays are seen as a more efficient way of transporting drugs with potential use in crossing the blood–brain barrier.

<span class="mw-page-title-main">Nasal septum perforation</span> Medical condition

A nasal septum perforation is a medical condition in which the nasal septum, the bony/cartilaginous wall dividing the nasal cavities, develops a hole or fissure.

<span class="mw-page-title-main">Cribriform plate</span> Part of the ethmoid bone in the skull

In mammalian anatomy, the cribriform plate, horizontal lamina or lamina cribrosa is part of the ethmoid bone. It is received into the ethmoidal notch of the frontal bone and roofs in the nasal cavities. It supports the olfactory bulb, and is perforated by olfactory foramina for the passage of the olfactory nerves to the roof of the nasal cavity to convey smell to the brain. The foramina at the medial part of the groove allow the passage of the nerves to the upper part of the nasal septum while the foramina at the lateral part transmit the nerves to the superior nasal concha.

<span class="mw-page-title-main">Flunisolide</span> Chemical compound

Flunisolide is a corticosteroid often prescribed as a treatment for allergic rhinitis. Intranasal corticosteroids are the most effective medication for controlling symptoms.

<span class="mw-page-title-main">Azelastine</span> Chemical compound

Azelastine, sold under the brand name Astelin among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis. Other uses may include asthma and skin rashes for which it is taken by mouth. Onset of effects is within minutes when used in the eyes and within an hour when used in the nose. Effects last for up to 12 hours.

Phantosmia, also called an olfactory hallucination or a phantom odor, is smelling an odor that is not actually there. This hallucination is intrinsically suspicious as the formal evaluation and detection of relatively low levels of odour particles is itself a very tricky task in air epistemology. It can occur in one nostril or both. Unpleasant phantosmia, cacosmia, is more common and is often described as smelling something that is burned, foul, spoiled, or rotten. Experiencing occasional phantom smells is normal and usually goes away on its own in time. When hallucinations of this type do not seem to go away or when they keep coming back, it can be very upsetting and can disrupt an individual's quality of life.

Chronic atrophic rhinitis, or simply atrophic rhinitis, is a chronic inflammation of the nose characterised by atrophy of nasal mucosa, including the glands, turbinate bones and the nerve elements supplying the nose. Chronic atrophic rhinitis may be primary and secondary. Special forms of chronic atrophic rhinitis are rhinitis sicca anterior and ozaena. It can also be described as the empty nose syndrome.

<span class="mw-page-title-main">Human nose</span> Feature of the human face

The human nose is the first organ of the respiratory system. It is also the principal organ in the olfactory system. The shape of the nose is determined by the nasal bones and the nasal cartilages, including the nasal septum, which separates the nostrils and divides the nasal cavity into two.

<span class="mw-page-title-main">Esketamine</span> Medication

Esketamine, sold under the brand names Spravato and Ketanest among others, is the S(+) enantiomer of ketamine. It is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. Esketamine is the active enantiomer of ketamine in terms of NMDA receptor antagonism and is more potent than racemic ketamine.

<span class="mw-page-title-main">Insufflation (medicine)</span> Act of blowing something (such as a gas, powder, or vapor) into a body cavity

Insufflation is the act of blowing something into a body cavity. Insufflation has many medical uses, most notably as a route of administration for various drugs.

A nasal vaccine is a vaccine administered through the nose that stimulates an immune response without an injection. It induces immunity through the inner surface of the nose, a surface that naturally comes in contact with many airborne microbes. Nasal vaccines are emerging as an alternative to injectable vaccines because they do not use needles and can be introduced through the mucosal route. Nasal vaccines can be delivered through nasal sprays to prevent respiratory infections, such as influenza.

Intranasal drug delivery occurs when particles are inhaled into the nasal cavity and transported directly into the nervous system. Though pharmaceuticals can be injected into the nose, some concerns include injuries, infection, and safe disposal. Studies demonstrate improved patient compliance with inhalation. Treating brain diseases has been a challenge due to the blood brain barrier. Previous studies evaluated the efficacy of delivery therapeutics through intranasal route for brain diseases and mental health conditions. Intranasal administration is a potential route associated with high drug transfer from nose to brain and drug bioavailability.

Cocaine-Induced Midline Destructive Lesions (CIMDL) is the progressive destruction of nasal architecture with the erosion of the palate, nasal conchae, and ethmoid sinuses associated with prolonged insufflation, colloquially 'snorting', of Cocaine. The condition begins with erosion of mucusal lining and progress with damage to nasal cartilaginous and bony structures.

References

  1. ↑ Downs, Brian W.; Sauder, Haley M. (2023), "Septal Perforation", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30725893 , retrieved 2023-10-17
  2. ↑ Brake, Daniela A.; Hamilton, Grant S.; Bansberg, Stephen F. (2023-12-01). "Nasal Septal Perforation Due to Desmopressin Nasal Spray Use". Ear, Nose & Throat Journal. 102 (12): NP621 –NP624. doi: 10.1177/01455613211026425 . ISSN   0145-5613.
  3. ↑ Laureen Veevers (1 October 2006). "'Shared banknote' health warning to cocaine users". The Observer. Retrieved 2008-07-26.
  4. ↑ Sharing Drug "Snorting Straws" Spreads Hepatitis C, 2016
  5. ↑ D.F. Proctor and I. Andersen. The nose. Upper airway physiology and the atmospheric environment , Elsevier Biomedical Press, Amsterdam, 1982.
  6. ↑ Y.W. Chien, K.S.E. Su, and S.-F. Chang. Nasal systemic drug delivery, Marcel Dekker, Inc., New York, 1989.
  7. 1 2 Fransén, Nelly (2008). Studies on a Novel Powder Formulation for Nasal Drug Delivery (PhD dissertation). Uppsala University. ISBN   978-91-554-7288-7.
  8. ↑ Thorne, RG; Emory, ER; Ala, TA; Frey, William II (September 18, 1995). "Quantitative analysis of the olfactory pathway for drug delivery to the brain". Brain Research. 692 (1–2): 278–282. doi:10.1016/0006-8993(95)00637-6. PMID   8548316. S2CID   11522233.
  9. ↑ Thorne, RG; Pronk, GJ; Padmanabhan, V; Frey, WH II (2004). "Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration". Neuroscience. 127 (2): 481–96. doi:10.1016/j.neuroscience.2004.05.029. PMID   15262337. S2CID   40872017.
  10. 1 2 Jansson, Björn (2004). Models for the Transfer of Drugs from the Nasal Cavity to the Central Nervous System (PhD dissertation). Uppsala University. ISBN   91-554-5834-3 . Retrieved 18 March 2023.
  11. 1 2 Espefält Westin, Ulrika (2007). Olfactory Transfer of Analgesic Drugs After Nasal Administration (PhD dissertation). Uppsala University. ISBN   978-91-554-6871-2 . Retrieved 18 March 2023.
  12. ↑ Reger, MA; Watson, GS; Frey, WH II; Baker, LD; Cholerton, B; Keeling, ML; Belongia, DA; Fishel, MA; Plymate, SR; Belongia, GD; Cherrier, MM; Craft, S (March 2006). "Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype". Neurobiol Aging. 27 (3): 451–458. doi:10.1016/j.neurobiolaging.2005.03.016. PMID   15964100. S2CID   21158378.
  13. ↑ H. Kublik and M.T. Vidgren. Nasal delivery systems and their effect on deposition and absorption. Adv Drug Deliv Rev. 29:157-177 (1998).
  14. ↑ 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).
  15. ↑ 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).
  16. ↑ FerringPharmaceuticals. SPC: Minirin nasal spray, Minirin Freeze-dried tablet and Minirin tablet, 2005.
  17. ↑ 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).
  18. ↑ 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
  19. ↑ Zimmerman JL (October 2012). "Cocaine intoxication". Critical Care Clinics. 28 (4): 517–26. doi:10.1016/j.ccc.2012.07.003. PMID   22998988.
  20. ↑ "The Dangers Of Snorting Cocaine (Insufflation)". Vertava Health. Retrieved 2022-02-25.
  21. ↑ Mathew SJ, Zarate Jr CA (25 November 2016). Ketamine for Treatment-Resistant Depression: The First Decade of Progress. Springer. pp. 8–10, 14–22. ISBN   978-3-319-42925-0. Archived from the original on 8 September 2017.
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  23. 1 2 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
  24. ↑ Pochettino, M. L.; Cortella, A. R.; Ruiz, M. (1999-04-01). "Hallucinogenic snuff from Northwestern Argentina: Microscopical identification of anadenanthera colubrina var. cebil (fabaceae) in powdered archaeological material". Economic Botany. 53 (2): 127–132. doi:10.1007/BF02866491. ISSN   1874-9364.
  25. ↑ Juan P. Ogalde; Bernardo T. Arriaza; Elia C. Soto (2010). "Uso de plantas psicoactivas en el north de Chile: evidencia química del consumo de ayahuasca durante el periodo medio (500-1000 d.C.)". Latin American Antiquity. 21 (4): 441–450. doi:10.7183/1045-6635.21.4.441. S2CID   163915994.
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  28. 1 2 L. Illum. Is nose-to-brain transport of drugs in man a reality? J Pharm Pharmacol. 56:3-17 (2004).
  29. ↑ 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).
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