Nasal administration, popularly known assnorting, is aroute of administration in whichdrugs areinsufflated through thenose. It can be a form of eithertopical administration orsystemic 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 asdecongestants for cold and allergy treatment, whose systemic effects are usually minimal. Examples of systemically active drugs available as nasal sprays aremigraine drugs, rescue medications for overdose and seizure emergencies,hormone treatments,nicotine nasal spray, andnasal vaccines such aslive attenuated influenza vaccine.
Anasal septum perforation is a medical condition in which thenasal septum, thebony/cartilaginous wall dividing thenasal cavities, develops a hole or fissure.[1] Nasal administration may cause nasal septum perforation by gradually injuring and ulcerating the epithelium, causing cartilage exposure andnecrosis.[2]
Sharing snorting equipment (nasal spray bottles, straws, banknotes, bullets, etc) has been linked to the transmission ofhepatitis C. In one study, the University of Tennessee Medical Center researchers warned that other blood-borne diseases such asHIV could be transmitted as well.[4]
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 forsmaller 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 thecentral 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, usinginsulin, a largepeptide hormone that acts as a nerve growth factor in the brain.[12]
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]
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 analoguedesmopressin is, for example, available for both nasal and oral administration, for the treatment ofdiabetes insipidus. Thebioavailability 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] Intranasalcalcitonin, calcitonin-salmon, is used to treathypercalcaemia arising out of malignancy,Paget's disease of bone, post menopausal and steroid inducedosteoporosis,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 andcryptorchidism. Other potential drug candidates for nasal administration include anaesthetics, antihistamines (Azelastine),antiemetics (particularly metoclopramide and ondansetron) andsedatives that all benefit from a fast onset of effect.[17] Intranasalmidazolam is found to be highly effective in acute episodes of seizures in children. Recently, the upper part of the nasal cavity, as high as thecribriform 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 PrimaryMeningoencephalitis.[18]
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 includingalcohol withdrawal,anorexia nervosa,PTSD,autism,anxiety disorders, pain sensation andschizophrenia.
List of substances that have higher bioavailability when administered intranasally compared to oral administration.
Insufflation ofcocaine 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]
Among the less invasive routes forketamine, the intranasal route has the highest bioavailability (45–50%).[21][22]
Snuff is a type ofsmokeless tobaccoproduct made from finely ground or pulverizedtobacco leaves.[23] It issnorted or "sniffed" (alternatively sometimes written as "snuffed") into the nasal cavity, deliveringnicotine 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 thehand, held pinched between thumb and index finger, or held by a specially made "snuffing" device.
Snuff trays and tubes similar to those commonly used foryopo were found in the central Peruvian coast dating back to 1200 BC, suggesting that insufflation ofAnadenanthera 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]
There is about 20 mL capacity in the adult humannasal cavity.[26] The major part of the approximately 150 cm2 surface in the human nasal cavity is covered byrespiratory epithelium, across which systemic drug absorption can be achieved. Theolfactory 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 theolfactory 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 theblood–brain barrier (BBB), which is virtually impermeable topassive 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]
Theolfactory 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 thecerebrospinal 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 forParkinson's orAlzheimer's diseases. Studies have been presented showing that direct transfer of drugs is achievable.[28][29]
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