Corticosteroids, inhalation devices

Frost GD, Penrose A, HaU J, MacKenzie DI. Asthma-related prescribing patterns with four different corticosteroid inhaler devices. Respir Med 1998 92 1352-1358. 

The spacer mask can be alarming to young babies and generally a positive smiling parent can cuddle the baby and allay fears. Stroke the baby s cheek with the mask prior to use so that the baby becomes familiar with the device. Often the spacer and mask can be used successfully when the baby is asleep. It is important that if a corticosteroid inhaler is used, the area of the child s face covered by the mask is wiped after use. 

The replacement of systemic corticosteroid therapy and its attendant side effects in asthmatic and allergy patients with locally acting corticosteroids by way of aerosol inhalation devices is a gratifying success story. Even though dexamethasone phosphate was initially used for brief periods, the development of systemic effects such as adrenal suppression offered no advantage over oral therapy. Beclomethasone diproprionate showed itself to be hundreds of times more potent, and it produced no systemic symptoms even even on prolonged use with 400 pg daily doses. Some systemic symptoms developed at three to four times higher doses. 

Because all inhaled corticosteroids are equally effective if given in equipotent doses, product selection should be individualized based on the available dosage form, delivery device, and patient preference. In infants, administration may require the use of a nebulizer or spacer/holding chamber with a facemask. Caregivers should use a soft, damp cloth to wipe the face of infants receiving an inhaled corticosteroid via a facemask to prevent topical candidiasis.18... 

The most common adverse effects from inhaled corticosteroids include oropharyngeal candidiasis and hoarse voice. These can be minimized by rinsing the mouth after use and by using a spacer device with metered-dose inhalers. Increased bruising and decreased bone density have also been reported the clinical importance of these effects remains uncertain.1,2,19... 

Systemic toxicity of inhaled corticosteroids is minimal with low to moderate inhaled doses, but the risk of systemic effects increases with high doses. Local adverse effects include dose-dependent oropharyngeal candidiasis and dys-phonia, which can be reduced by the use of a spacer device. The ability of spacer devices to enhance lung delivery is inconsistent and should not be relied on. 

The first commercially available DPI system appeared on the market in 1949, developed and marketed by Abbott under the name Aerohaler. Like all early pulmonary drug-delivery devices, it delivered small-molecule compoimds (bronchodilators or inhaled corticosteroids) to the airways (not necessarily the deep limg) for the treatment of asthma or chronic obstructive pulmonary disease. Table 6 lists some of the early DPI systems used for asthma and COPD the energy somces in these devices were mechanical and patient inspiration. 

Shaw RJ. Inhaled corticosteroids for adult asthma impact of formulation and delivery device on relative pharmacokinetics, efficacy and safety. Respir Med 1999 93 149-60. 

Dubus JC, Marguet C, Deschildre A, Mely L, Le Roux P, Brouard J, Huiart L. Reseau de Recherche Clinique en Pneumonologie Pediatrique. Local side-effects of inhaled corticosteroids in asthmatic children influence of drug, dose, age, and device. Allergy 2001 56(10) 944-8. 

Wilson A, Demsey O, Couties W, Sims E, Lipworth B. Importance of drug-device interaction in determining systemic effects of inhaled corticosteroids. Lancet 1999 353 2128. 

The first metered dose inhaler, Medihaler Epi was introduced in 1956 by Riker Laboratories (3M Pharmaceuticals) for the management of asthma and COPD. The delivery device has been well accepted since that time, as evidenced by the annual production of over a half-billion units (McDonald and Martin, 2000). Since the introduction of the MDI, (3-adrenergic agonists, anticholinergics, corticosteroids, and cromolyn compounds have been the staple of management for the commonly occurring lung diseases, asthma and COPD. 

The ICSs beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide that are currently available for use are compared and listed in Table 26-12. The ICSs have pharmacokinetic differences that result in different topical/ systemic activity. Most evidence is consistent with log-linear dose-response curves for both indirect and direct responses. The log-linear nature of the dose-response curve for corticosteroid activity raises the issue of how much of a difference in dose (or lung delivery) or potency is detectable. The dose-response curves for the ICSs are relatively flat primarily because all the measures used to assess efficacy (lung function, BHR, symptoms, and as-needed short-acting inhaled /32-agonist use) are downstream events from the anti-inflammatory activity. In general, it takes a fourfold difference in potency or dose to detect clinically significant differences. The table of comparative doses (see Table 26-12) is based on extensive comparative clinical trials. Clinical comparative doses take into consideration potency differences as well as lung delivery differences from the various devices. 

Waies D, Makker H, Kane J, et ai. Systemic bioavaiiabiiity and potency of high-dose inhaled corticosteroids a comparison of four inhaier devices and three drugs in healthy adult volunteers. Chest 1999 115 1278-1284. 

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