Asthma glucocorticoids, systemic

Inhaled glucocorticoid preparations, such as be-clomethasone dipropionate and betamethasone valerate, provide an effective alternative to systemic steroids in the treatment of chronic asthma, with lesser side effects than oral or parenteral glucocorticoids (see Chapter 39). In fact, inhaled glucocorticoids have become a mainstay of asthma therapy. Inhalation delivers the agent directly to the target site in relatively low doses, with the potential for more frequent administration. Moreover, inhaled glucocorticoids are metabolized in the lung before they are absorbed, which reduces their systemic effects. However, even modest doses of... 

The first inhaled glucocorticoid, beclomethasone dipropionate, revolutionized asthma therapy, when it was found that topical delivery to the lung resulted in reduced systemic side-effects (adrenal suppression, oseteoporosis and growth inhibition) typically seen with oral steroid treatments. Interestingly, a further reduction in systemic exposure was achieved with the introduction of fluticasone propionate (1). The evolution of this drug stemmed from observations with the steroid 17-carboxylates that showed that these esters were active topically when esterified, while the parent acids were inactive. Thus it was realized that enzymatic hydrolysis of the ester would lead to systemic deactivation. SAR studies led to a series of carbothioates, which were very active in vivo when topically applied to rodents, but were inactive after oral administration. It was shown that fluticasone propionate (1) underwent first pass metabolism in the liver to the corresponding inactive 173-carboxylic acid (la) (Scheme 1). This observation was... 

Other factors that determine the absorbed fraction of inhaled glucocorticoids include the age of the child, as lung deposition of inhaled drugs increases with age (80). Therefore, the minimum effective dose may fall as the child becomes older. Moreover, it is reasonable to hypothesize that systemic absorption will increase once asthma control is established (81). Furthermore, patient adherence and inhaler technique are two factors that can have a large influence on the amount of glucocorticoid inhaled and absorbed. 

Beclomethasone dipropionate and several other glucocorticoids—primarily budesonide and flunisolide and mometasone furoate, administered as aerosols—have been found to be effective in the treatment of asthma (see Chapter 20 Drugs Used in Asthma). The switch from therapy with systemic glucocorticoids to aerosol therapy must be undertaken with caution, since manifestations of glucocorticoid deficiency will appear if adrenal function has been suppressed. In such patients, a slow, graded reduction of systemic therapy and monitoring of endogenous adrenal function should accompany the institution of aerosol administration. 

Inhaled glucocorticoids are the drugs of first choice in patients with moderate to severe asthma who require inhalation of p2-adrener-gic agonists more than once daily (see Figure 22.2). Severe asthma may also require systemic glucocorticoids, usually for short term. Inhaled glucocorticoids often reduce (or eliminate) the need for oral glucocorticoids in patients with severe asthma. To be... 

The correct answer is B. Due to the increased severity of this allergic reaction secondary to re-exposure, the next step in therapy is oral steroids. Prednisone, a glucocorticoid, is commonly used to treat conditions such as skin inflammation, asthma, and arthritis. Prednisone acts by decreasing the production of the mediators of inflammation, thereby resulting in its antiinflammatory action. A is incorrect. Hydrocortisone is a low potency glucocorticoid that is indicated for mild inflammation and irritation of the skin. The child s inflammation is severe enough to require systemic steroid therapy. 

Oral glucocorticoids such as dexamethasone and prednisolone are still used in patients with severe asthma, though these agents are associated with adverse systemic effects such as growth retardation, osteoporosis, and the suppression of hypothalamic-pituitary adrenal function and the immune system. 

Beclomethasone dipropionate is a corticosteroid with mainly glucocorticoid activity that is started to exert a topical effect on the lungs, without significant systemic activity. It is used by inhalation, generally from a metered-dose aerosol, for the prophylaxis of asthma. Inhalation of nebulized beclomethasone dipropionate has also been used in the management of asthma in children. 

In certain therapeutic situations, rapid presystemic elimination may be desirable. An important example is the use of glucocorticoids in the treatment of asthma. Because a significant portion of inhaled drug is swallowed, glucocorticoids with complete presystemic elimination entail only a minimal systemic load for the organism (p.340). The use of acetylsalicylic acid for inhibition of thrombocyte aggregation (see p.155) provides an example of a desirable presystemic conversion. 

---