Administration by Inhalation

Inhalation in the form of an aerosol, a gas, or a mist permits drugs to be applied to the bronchial mucosa and, to a lesser extent, to the alveolar membranes. This route is chosen for drugs intended to affect bronchial smooth muscle or the consistency of bronchial mucus. Furthermore, gaseous or volatile agents can be administered by inhalation with the goal of alveolar absorption and systemic effects (e.g., inhalational anesthetics, p.216). Aerosols are formed when a drug solution or micronized powder is converted into a mist or dust, respectively. 

Drug deposited on the mucous lining of the bronchial epithelium is partly absorbed and partly transported with bronchial mucus toward the larynx. Bronchial mucus travels upward owing to the orally directed un-dulatory beat of the epithelial cilia. Physiologically, this mucociliary transport functions to remove inspired dust particles. Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms 

Even when the swallowed portion of an inhaled drug is absorbed in unchanged form, administration by this route has the advantage that drug concentrations at the bronchi will be higher than in other organs. 

Theef ciency of mucociliary transport depends on the force of kinociliary motion and the viscosity of bronchial mucus. Both factors can be altered pathologically (e.g., by smoker s cough or chronic bronchitis). 

Depth of penetration of inhaled aerosolized drug solution 

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Administration by inhalation has been explored by Brilli [124], mentioned previously for his work with NONOates. Here he uses one of these same NONOates, DMAEP/NO (see Fig. 8.11), in aerosol form. When administered in an aerosolized state, DMAEP/NO again shows selective pulmonary vasodilation in a porcine model. This is achieved without affecting the systemic vascular resistance index (SVRI) or the cardiac index (Cl). Work from the same year by Adrie et al. [125] compared aerosolized DEA/NO with aerosolized SNP and inhaled NO, in sheep. As the NONOate has a short half-life (2.1 min), it was predicted that this would be a selective pulmonary vasodilator. However, compared with inhaled NO this was not observed, though SNP... 

Baldrick P, Bamford DG. A toxicological review of lactose to support clinical administration by inhalation. Food Chem Tox 1997 35 719. 

Most knowledge of the adverse effects of glucocorticoids has been acquired in connection with their use as oral products. However, various other routes of administration have been developed, sometimes specifically in the hope of securing a local therapeutic effect while avoiding systemic adverse reactions. Although experience has shown that the latter cannot be eliminated in this way, they can be diminished in some cases. In other cases, new problems arise. Administration by inhalation is covered in the monograph on inhaled glucocorticoids. 

Bromhexine is taken orally or by aerosol and reduces sputum viscosity as measured ex vivo. Although it is still used empirically by some physicians, there have been no controlled studies showing a significant improvement in clinical status or lung function. Administration by inhalation aerosol or nasal spray produces a local expectorant/ mucolytic effect (1). Inhaled bromhexine (Paxirasol) reduces the amount of sputum, but does not reduce symptoms (SEDA-17, 208). 

If bronchospasm is predominant, then administration by inhalation of a p -selective agonist like albuterol—or intravenous administration of theophylline—may be useful. If cardiovascular collapse is predominant, then vasopressor drugs may be helpful these include a-adrenoceptor agonists such as phenylephrine and P,-adrenoceptor agonists sueh as dobutamine or dopamine. 

Morgan A, Black A, Belcher DR. 1970. The excretion in breath of some aliphatic halogenated hydrocarbons following administration by inhalation. Ann Occup Hyg 13 219-233. 

In the end, let us consider (very hypothetically ) terroristic use of one of the most obvious drugs insulin. It is known that some other routes (e.g., inhalation) of administration for medical purposes have been developed (Mastrandrea, 2010). Therefore, this does not rule out the development of effective administration by inhalation. If suitable stability and aerosolization is achieved, could we realistically conclude that this drug would not... 

Topical application and systemic administration as well as administration by inhalation can lead to atrophy of the skin which may be severe and lead to skin thinning, skin tearing and other dermal effects which may result in increased morbidity and mortality. " The effects are also seen in animal models and hydrocortisone, dexamethasone, betamethasone and triamcinolone have induced dermal atrophy in the rat. ... 

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