Aerosol therapeutic inhalation

Van Helden, H.P., Kuijpers, W.C., Diemel, R.V. (2004). Asthma like symptoms following intratracheal exposure of guinea pigs to sulfur mustard aerosol therapeutic efficacy of exogenous lung surfactant curosurf and salhutamol. Inhal. Toxicol. 16 537 8. 

Akwete, A.L., Gupta, P.K., Eds. Niven, delivery of biotherapeutics by inhalation aerosol. In Inhalation Delivery of Therapeutic Peptides and Proteins, Marcel Dekker, Inc. New York, 1997 151-231. 

The efficacy of a therapeutic inhalation aerosol depends onits ability to penetrate the respiratory tract. This is primarily dependent on the particle size of the particles or droplets. To penetrate to the peripheral (respiratory) airways, aerosols generally require a size less than approximately 5-6 pm, with a size less than 2 pm being optimal for alveolar deposition. " ... 

MMAD is frequently presented as the parameter characterising aerosols from inhalation devices best. This is not true however. To judge the quality of a therapeutic aerosol from a particular type of inhaler, more information is needed. The MMAD does not give any information about the size distribution of the aerosol particles. Substantial mass fractions may be outside the desired size range for adequate deposition of active substance in the target area, even when MMAD looks very favourable. Moreover, MMAD does not give information about the mass fraction of the dose (label claim) that has been delivered within the desired size range. For aU types of inhalers, the delivered fine particle dose (FPD) is much lower than the label claim and this may vary from 10 % to 60 % for DPIs and up to 90 % for... 

Improvements in asthma treatment include the development of more effective, safer formulations of known dmgs. The aerosol adrninistration of P2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reUable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controlled release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilatots do not usually last through an entire night s sleep (26,27). 

The action of epinephrine and related agents forms the basis of therapeutic control of smooth muscle contraction. Breathing disorders, including asthma and various allergies, can result from excessive contraction of bronchial smooth muscle tissue. Treatment with epinephrine, whether by tablets or aerosol inhalation, inhibits MLCK and relaxes bronchial muscle tissue. More specific bronchodilators, such as albuterol (see figure), act more selec-... 

The therapeutic utility of systemically administered ASON had been limited by their short plasma half life (sometimes even less than 3 min). This is due to their sensitivity to nuclease digestion. When the first-generation ASON were chemically modified, e.g., by replacing the oxygen in the phosphodiester bond with sulfur (phosphorothiorate) they obtained an increased stability in biological fluids while their antisense effect has been maintained. First-generation agents can be delivered via intravitreal injection, parenterally, by topical cream, enema, and inhaled aerosol. These antisense... 

Results clearly indicated effects of diesel exhausts from different engine operating conditions on the cells already after 1 h of exposure. However, a 1-h continuous exposure to a therapeutic aerosol is probably of limited clinical relevance. To study the effect of drugs administered by typical pharmaceutical single-dose inhalers (MDI, DPI) effective deposition of one puff within the time of one breathing maneuver ( 5 s) is probably more relevant. 

Adhesive mixtures require large carrier crystals to improve the handhng properties of the powders. Dispersion of the small drng particles over the larger carrier material should assure dose uniformity. However, the small dmg particles shonld be removed from the carrier material dnring inhalation, to render an aerosol clond of respirable particles. If the particles remain on the carrier, month or throat deposition of the drng will occur, which might decrease therapeutic efficacy or cause serious side-effects. 

Aerosol For management of bronchial asthma in adults and children 5 or more years of age, the usual starting dose is two metered sprays inhaled 4 times/day at regular intervals. Do not exceed this dose. Not all patients will respond to the recommended dose, and a lower dose may provide efficacy in younger patients. Advise patients with chronic asthma that the effect of therapy is dependent upon its administration at regular intervals, as directed. Introduce therapy into the patient s therapeutic regimen when the acute episode has been controlled, the airway has been cleared and the patient is able to inhale adequately. 

Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 2003 56(6) 600-12. 

A major breakthrough in asthma therapy was the introduction in the 1970s of aerosol corticosteroids These agents (Table 39.3) maintain much of the impressive therapeutic efficacy of parenteral and oral corticosteroids, but by virtue of their local administration and markedly reduced systemic absorption, they are associated with a greatly reduced incidence and severity of side effects. The success of inhaled steroids has led to a substantial reduction in the use of systemic corticosteroids. Inhaled corticosteroids, along with 2-(tdreno-ceptor agonists, are front-line therapy of chronic asthma. 

Several portable inhalation devices have been developed and are being tested to determine whether they improve protein and peptide delivery via the airways. Aerosolized DNase has been shown in patients with cystic flbrosis to significantly reduce the buildup of mucus in the lung and the incidence of infections. Devices for delivery of therapeutic proteins to deep-lung alveoli to achieve systemic effects are also in development. These products are formulated so that the device aerosolizes the protein in a defined particle size range that cannot be easily achieved by means of conventional metered dose inhalers. 

Wolff, R.K. (1998). Safety of inhaled proteins for therapeutic use. J. Aerosol Medicine-Deposition Clearance and Effects in the Lung, 11, 197-219. 

Dalby RN, Hickey AJ, Tiano SL. Medical devices for the delivery of therapeutic aerosols to the lungs. In Hickey AJ, ed. Inhalation Aerosols. New York, New York Marcel Dekker, Inc., 1996 441 173. 

Edwards DA, Valente AX, Man J, Tsapis N. Recent advances related to the systemic delivery of therapeutic molecules by inhalation. In Hickey A, ed. Pharmaceutical Inhalation Aerosol Technology. 2d ed. New York Marcel Dekker, 2004 541-550. 

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