Inhaled glucocorticoid therapy

A 37-year-old woman who was pregnant developed Churg-Strauss syndrome after withdrawal of her usual high-dose inhaled glucocorticoid therapy (drug not stated) that she had used for 3 years for bronchial asthma (148). 

Intranasal or inhalation glucocorticoid therapy reduces the expression of Th2-related interleukins and increases IFN-y as well as the corresponding receptors [13],... 

Oral glucocorticoids such as dexamethasone and prednisolone are still used in patients with severe asthma, though these agents are associated with adverse systemic effects. Inhaled glucocorticoid therapy was introduced in 1972 with beclomethasone dipropionate, which dramatically reduced systemic effects. Fluticasone propionate (launched in 1993) is very efficiently inactivated in the liver, and exhibits low oral bioavailability, which in turn leads to a further reduction in systemic exposure. 

The addition of cromolyn to inhaled glucocorticoid therapy yields no additional benefit in moderately severe asthma. Nedocromil may allow a reduction of steroids in patients receiving high doses of inhaled steroids. 

In a study, from the same cohort, of the association of prior outpatient inhaled glucocorticoid therapy with mortality in 6353 patients with COPD who were hospitalized because of pneumonia, and of whom 38% were taking inhaled glucocorticoids, overall mortality was 9% at 30 days and 16% at 90 days [3 ]. In regression analyses, outpatient inhaled glucocorticoid therapy was associated with a lower mortality at both 30 days (OR = 0.8 95% Cl =0.7, 0.8) and 90 days (OR = 0.80 95% Cl=0.75, 0.86). 

Bernecker C, West TB, Mansmann G, Scherbaum WA, Wfllenberg HS. HypercortisoUsm caused by ritonavir associated inhibition of CYP 3A4 under inhalative glucocorticoid therapy. 2 case reports and a review of the literature. Exp CUn Endocrinol Diabetes 2012 120(3) 125-7. 

Glucocorticoids are widely used to treat a variety of inflammatory and immune diseases. With the recognition that airway inflammation is present even in patients with mild asthma, treatment with glucocorticoids is now the mainstay of asthma therapy. Consequently, by far the most common use of glucocorticoids today is in the treatment of asthma and inhaled glucocorticoids have now become established as first-line treatment in adults and children with persistent asthma, the commonest chronic airway inflammatory disease. 

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... 

Based on the concept that asthma is an inflammatory disease that leads to airway obstruction, inhaled glucocorticoids are the first-line treatment for moderate to severe asthma. Inhaled preparations are particularly effective when used to prevent recurrent attacks. This therapy is often combined with an inhaled bron-chodUator such as a p-adrenergic agonist. The use of p-adrenergic agonists or theophylline enables use of a lower dose of glucocorticoid, especially in patients relatively resistant to therapy (see Chapter 39). 

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... 

Estimates of the important outcome of bone fracture have shown a small increased risk with inhaled glucocorticoids, but this may well be a feature of the disease rather than the therapy, because comparisons with treatment with bronchodilator drugs show no difference between risk factors in patients taking glucocorticoids or bronchodilators. 

The effect of high-dose inhaled glucocorticoids and anti-resorptive therapy with sodium etidronate has been studied for 18 months in 38 Chinese patients (24 men and 14 premenopausal women aged 30-50 years), of whom 28 were asthmatics who had already been treated for at least 12 months with high-dose inhaled glucocorticoids (beclo-methasone or budesonide over 1.5 mg/day), and 10 healthy controls (129). The patients were randomly... 

Inhaled glucocorticoids are therefore the cornerstone of drug therapy for patients with asthma. Leukotriene inhibitors, beta agonists, and theophylline can be used to supplement glucocorticoids as needed, with the specific drug regimen determined on... 

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