Nasal route

Transdermal dmg dehvery is associated with a relatively long time lag before the onset of efficacy, and removal of the system is foUowed by a correspondingly extended fall in plasma concentration, which probably results from formation of a dmg depot in the skin that dissipates slowly. The time lag is approximately 3 to 5 h for many dmgs that have low binding in the skin (49—51), but may be considerably longer. In contrast, plasma dmg levels may be obtained between 2 and 5 min by the oral, buccal, or nasal routes. 

For inhalation or nasal route only. BALT bronchus-associated lymphoid tissues. NALT nasal-associated lymphoid tis-... 

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). 

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... 

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