Inhaled glucocorticoids asthma

Severe, life-threatening asthma attacks inhaled p2-agonists ineffective Oxygen Glucocorticoids oral or i.v. 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

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... 

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. 

An 18-year-old woman with childhood asthma, using inhaled glucocorticoids and zafirlukast, developed Churg-Strauss syndrome 10 days after starting to use rokitamycin (12). 

Mild intermittent asthma needs a routine glucocorticoid inhaler and a sustained-relief theophylline. 

The risk of pneumonia in patients with asthma using inhaled glucocorticoids has been evaluated in a meta-analysis of trials of budesonide in asthma [6 ]. The primary data set consisted of 26 double-blind, placebo-controlled trials that lasted at least 3 months (n = 9067 for budesonide and 5926 for the comparator) sponsored by AstraZeneca. In a secondary data set 60 double-blind trials that lasted at least 3 months, but lacked placebo control were evaluated (n = 33496 for budesonide and 2773 for fluticasone propionate). In the primary data set, the occurrence of pneumonia-related adverse events was 0.5% (10/1000 patient-years) for... 

Asthma attacks less than twice a week FEV1 >80% Rapid-acting inhaled p2-agonist Low dose inhaled glucocorticoid or cromone (children)... 

Asthma attacks more than twice a week FEV1 60-80% daily use of bronchodilators. Rapid-acting inhaled p2-agonist Inhaled glucocorticoid... 

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... 

Local adverse effects are common in patients with asthma who use inhaled glucocorticoids, as suggested by a survey of the prevalence of throat and voice symptoms in patients with asthma using glucocorticoids by metered-dose pressurized aerosol (SEDA-20, 369 35). 

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