The nasal route

Modified from D. F. Egan, Fundamentals of Respiratory Therapy, 3rd edn, Mosby, New York, 1977. 

In vitro analysis of the particle size distribution of aerosols and nebulisers is discussed in Chapter 12. 

Two main classes of medicinal agents are applied by the nasal route  

Intranasal beclometasone dipropionate in a dose as low as 200 / g daily is a useful addition to the therapy of perennial rhinitis. Considerable attention is being paid to the delivery by the 

The air passages through the nasal cavity begin at the nares (nostrils) and terminate at the choanae (posterior nares). Immediately above the nares are the vestibules, lined by skin which bears relatively coarse hairs and sebaceous glands in its lower portion. The hairs curve radially downward providing an 

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Oral administration of arecoline is ineffective for clinical purposes due to first-pass metabolism (Hussain and Mollica 1991). The nasal route is an alternate possibility, with 85% bioavailability compared to intramuscular administration. 

Some effects may be enhanced or reduced as a result of administration via the nasal route. 

Cocaine differs from the other local anesthetics with respect to its cardiovascular effects. Cocaine s blockade of norepinephrine reuptake results in vasoconstriction and hypertension, as well as cardiac arrhythmias. The vasoconstriction produced by cocaine can lead to local ischemia and, in chronic abusers who use the nasal route, ulceration of the mucous membrane and damage to the nasal septum have been reported. The vasoconstrictor properties of cocaine can be used clinically to decrease bleeding from mucosal damage or surgical trauma in the nasopharyneal region. 

Dosages and routes of administration Butorphanol is orally inactive but can be given by the nasal route (Homan 1994). The usual administration is via the intramuscular or intravenous route. The intramuscular doses are 1-4 mg every 3-4 h, the intravenous doses are 0.5-2 mg. Nasal doses are 1mg/spray in each nostril. 

The nasal route of drug delivery is used for the direct administration of medicines to the nose for treatment of local conditions or the systemic delivery of compounds that are not easily delivered by the oral route. It is also suggested that there may be a direct route for drug absorption to the central nervous system (CNS) from the olfactory region of the nose. 

FIGURE 19.3 Drugs for administration via the nasal route have specific formulation requirements which, depending on their ability to overcome physiological barriers, may require an absorptionenhancing strategy. 

The nasal route is generating increasing interest as a route for the administration of local treatments and a cost-effective and patient-friendly alternative to injection for systemic delivery [49]. The special advantages of nasal delivery make it attractive for (i) crisis treatment where rapid onset of action is desirable (e.g., pain, migraine, panic attacks), (ii) systemic delivery of compounds that at present can only be delivered by injection (peptides/pro-proteins/vaccination), and (iii) direct targeting of the CNS (polar drugs for the treatment of CNS disorders). 

Since its discovery, isolation, and purification in the early twentieth century, insulin has been administered to diabetic patients exclusively by injection until the recent introduction of inhaled insulin. Insulin possesses certain physiochemical properties that contribute to its limited absorption from the gastrointestinal tract, and requires subcutaneous injection to achieve clinically relevant bioavailability. With a molecular size of 5.7 kDa, insulin is a moderately sized polypeptide composed of two distinct peptide chains designated the A chain (21 amino acid residues) and the B chain (30 amino acid residues) and joined by two disulfide bonds. Like all polypeptides, insulin is a charged molecule that cannot easily penetrate the phospholipid membrane of the epithelial cells that line the nasal cavity. Furthermore, insulin monomers self-associate into hexameric units with a molecular mass greater than 30 kDa, which can further limit its passive absorption. Despite these constraints, successful delivery of insulin via the nasal route has been reported in humans and animals when an absorption enhancer was added to the formulation. 

The nasal route of drug delivery avoids the liver first-pass effect, but the pseudo-first-pass effect owing to nasal metabolism of drugs is still a concern. Many enzymes such as carboxylesterase, aldehyde dehydrogenase, glutathione transferases, UDP-glucoronyl transferase, epoxide hydrolases, CYP-dependent monoxygenases, exo- and endopeptidases and proteases are present in the nasal mucosa.106 108,110,116 CYP enzymes are present abundantly in the olfactory epithelium.107,110... 

Compare the nasal route with other absorptive sites for chugs in the body... 

Extensive research is currently being carried out in this area and the potential of the nasal route for systemic drag delivery comprises the focus of this chapter. 

As discussed above, the nasal mucosa is highly vascular. This property facilitates its physiological role in heat exchange and also potentially, drug absorption. The rich blood supply means that drags absorbed via the nasal route have a rapid onset of action, which can be exploited for therapeutic gain. 

The nasal route may become a useful alternative to the intestinal route for drag absorption in situations where use of the gastrointestinal route is unfeasible. Examples include ... 

Driving gas for nebulised therapy must be specified in the prescription. If oxygen is needed during nebuliser therapy, nasal cannulae should be used. Care must be taken with the nasal route, as it is difficult to predict the amount of oxygen inspired. 

Drug delivery via the nasal route offers a number of advantages, the most important of which is the possibility of needle-free treatment. It also means that—in addition to the newly developed peptide- and protein-based drugs—this method is also suitable for a wide variety and perhaps most of the drugs that are currently in use. However, it is not only convenience that sets nasal drug delivery apart This method also provides a rapid onset of action and high bioavailability. 

Because of its rich vasculature and highly permeable structure, the nasal route can be used as an alternative to parenteral routes of delivery. It circumvents hepatic... 

In order to understand the delivery and absorption of drugs by the nasal route and appreciate the factors that may affect it, one must begin with a clear picture of the anatomy and physiology of the nose. 

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