Inhalation therapy

The respiratory system provides a route of entry into the body for a variety of airborne substances but is also a route of medication. The large contact area of its surfaces extends to more than 30 m. The surfaces have been described as gossamer-thin membranes that separate the lung air from the blood, which courses through some 2000 km of capillaries in the lungs. There is consequently an exquisite degree of intimacy between the lung tissue and blood and the atmospheric environment. The route is thus used for rapid relief of asthmatic conditions, where both local and systemic effects are required, for chronic therapy and for the administration of peptides and proteins. 

Orally administered corticosteroids are effective in the treatment of chronic bronchial asthma. The inhalation route has been widely used in attempts to avoid systemic side-effects, such as adrenal suppression, but evidence suggests that inhaled steroids are absorbed systemically to a significant extent. The respiratory tract epithelium has permeability characteristics similar to those of the classical biological membrane, so lipid-soluble compounds are absorbed more rapidly than lipid-insoluble molecules. Cortisone, hydrocortisone and dexamethasone are absorbed rapidly by a nonsaturable diffusion process from the lung, the half-time of absorption being of the order of 1-1.7 min. Quaternary ammonium compounds, hippurates and mannitol have absorption half-times, in contrast, of between 45 and 70 min. 

Relative to the gastrointestinal mucosa the pulmonary epithelium possesses a high permeability to water soluble molecules, which is an advantage with dmgs such as sodium cromoglicate (IX), a bischromone with two carboxylic acid groups and a pK of approximately 1.9. The dmg is well absorbed from the 

Structure IX Sodium cromoglicate (DSCG sodium cromo-glycate cromolyn sodium) 

Dmgs administered by inhalation are mostly intended to have a direct effect on the lungs. However, the efficiency of inhalation therapy is often not high because of the difficulty in targeting particles to the sites of maximal absorption. Only about 8% of the inhaled dose of sodium cromoglicate administered from a Spinhaler device (see section 9.9.2) reaches the alveoli.  

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Cooper CB, Tashkin DP. Recent developments in inhaled therapy in stable chronic obstructive pulmonary disease. BMJ 2005 330 640-644. 

The answer is c. (Hardman, p 666.) Inhalation therapy minimizes systemic effects of steroids. Of the agents above, beclomethasone is the only one delivered by mete red-dose inhaler (MDl). 

Appropriate situations to consider corticosteroids in COPD include (1) shortterm systemic use for acute exacerbations and (2) inhalation therapy for chronic stable COPD. 

Side effects of inhaled corticosteroids are relatively mild and include hoarseness, sore throat, oral candidiasis, and skin bruising. Severe side effects such as adrenal suppression, osteoporosis, and cataract formation are reported less frequently than with systemic corticosteroids, but clinicians should monitor patients receiving high-dose chronic inhaled therapy. 

HUMIDIFIER INHALATION THERAPY APPAR 50CC HYGROSCOPIC PLASTIC 25S 6515012750093 PG 120.49 ... 

HUMIDIFIER INHALATION THERAPY APPARATUS 300MM RESERVOIR GAP50S 6515010988264 PG 81.86 ... 

Purified water or saline in pretilled nebulizers for use in inhalation therapy Skin protectants (intended for use on intact skin) ... 

Aerosolised medicines have been used for centuries to treat respiratory diseases, with inhalation therapy for the airways focused primarily on the treatment of asthma and chronic obstructive pulmonary disease (COPD). The development of new products for delivery to the lungs for these respiratory diseases includes new steroids and beta agonists plus combination products featuring both agents. New classes of anti-asthma medication are also being developed for inhalation with the aim of delivering them directly to the inflamed airways. 

Anabousi S, Bakowsky U, Schneider M, Huwer H, Lehr CM, Ehrhardt C (2006) In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer. Eur J Pharm Sci 29(5) 367-374... 

The provision of optimal drug action through inhalation therapy (such as inhalants and inhalation aerosols)... 

Dry powder inhalers have initially found their application in inhalation therapy as a CFC-free alternative for the older MDIs. However, nowadays they seem to have a much larger potential [14,53], because of the high lung deposition that can be attained and also because they are suitable for the pulmonary delivery of therapeutic peptides and proteins [2,10,16]. 

Figure 3.4. Relevant variables and interactions in dry powder inhalation therapy.

Elderly Nicotine inhaler therapy appeared to be as effective in elderly patients 60 years of age or older as in younger smokers. 

Accelerated hypertension - Nicotine therapy constitutes a risk factor for development of malignant hypertension in patients with accelerated hypertension. Inhaler therapy should be used with caution in these patients and only when the benefits of including nicotine replacement in a smoking cessation program outweigh the risks. 

Plasma concentrations after aerosol administration are substantially lower than those observed after a comparable IV dose. The extent of pentamidine accumulation and distribution following chronic inhalation therapy are not known. 

Flushing, asthenia, mouth and throat dryness or irritation (with inhalation therapy) Serious Reactions... 

Wall, D.A. and Smith, P.L. (1997). Inhalation therapy for growth hormone deficiency. In ... 

Effects on growth occur early in treatment with sensitive testing methods they can be detected in growing children within a few weeks of starting therapy. The effects can be produced by any route of administration, including even inhalation therapy (at least with dexamethasone) (SEDA-18, 391). Comparisons of attained heights with expected heights in children who have used inhaled or oral... 

Since glucocorticoids reduce the immunological defences of the body to most types of infection, their use in the eyes should be monitored carefully. When longterm use is necessary, even with oral or inhalation therapy, eye examination should be performed every 6 months. The ophthalmological follow-up of patients using topical glucocorticoids should include tonometry at least twice a year, careful slit-lamp examination for... 

When a patient switches from oral or parenteral therapy to inhalation therapy, the systemic effect is reduced, just as if the dose of systemic glucocorticoid is reduced, and precautions should be taken to avoid withdrawal symptoms. 

The concept of the L T ratio in inhalation therapy is a useful one, where L represents the local or lung availability of an inhaled drug and T the total systemic availability. This ratio will be affected by differences in first-pass metabolism. Another important variable that determines the L T ratio is the inhalation device. The L T ratio for budesonide is 0.66-0.85, depending on the method of inhalation (12). 

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