Asthma therapy

Beta adrenergic agonists also exert bronchodilating effects. These drugs are thus often used in conjunction with theophiline in asthma therapy. A drug that combines both moieties, reproterol (40), has interestingly proved... 

Bronchial Asthma. Table 1 Asthma therapy, according to the German guidelines for asthma and the GINA report 2006 (GINA, http //www.ginasthma.org). FEV1, forced expiratory volume in 1 s... 

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. 

Evaluate current asthma therapy and make changes when necessary. 

Because of the varying presentation of asthma, treatment guidelines for asthma therapy should serve as a guide for therapy with the therapeutic plan individualized for each patient to achieve these goals. 

There are very few studies on asthma therapy for infants. 

The intensity of pharmacologic therapy is based on the severity of the disease, and the least amount of medications necessary to meet the goals of asthma therapy should be used.1,3 Stepwise therapy for the treatment of chronic asthma based on disease severity is shown in Table 11—1. 

Garcia G, Godot V, Humbert M. New chemokine targets for asthma therapy. Cun-Allergy Asthma Rep 2005 5(2) 155-160. 

Holgate ST, Bradding P, Sampson AP. Leukotriene antagonists and synthesis inhibitors new directions in asthma therapy. J Allergy Clin Immunol 1996 98 1-13. 

Underlying the discovery of a selective asthma therapy are numerous advances in analytical and instrumental techniques as well as synthetic methods that allow the construction of complex molecules. Practical catalytic, stereospecific, and organometallic methods that permit a high level of stereochemical control have enabled production at the multiton level of molecules previously inaccessible even at the gram scale. 

Components of the assessment of control include symptoms, nighttime awakenings, interference with normal activities, pulmonary function, quality of life, exacerbations, adherence, treatment-related adverse effects, and satisfaction with care. The categories of well controlled, not well controlled, and very poorly controlled are recommended. Validated questionnaires can be administered regularly, such as the Asthma Therapy Assessment Questionnaire, Asthma Control Questionnaire, and Asthma Control Test. 

Q69 Disadvantages of inhaled steroids in asthma therapy include ... 

A pulmonary anti-allergic for asthma therapy cromoglycic acid 45... 

The initial publication was sharply criticized by other workers [360] who had reached diametrically opposed conclusions from their own studies and these, in turn, were examined and points of difference clarified by the original authors [361 ]. This exchange reveals the clinical evaluation of a new aid to asthma therapy a too complex for easy resolution of differences of approach and view. 

Data from a large, placebo-controlled US study that compared the safety of salmeterol or placebo added to usual asthma therapy showed a small but significant increase in asthma-related deaths in patients receiving salmeterol (13 deaths out of 13,174 patients treated for 28 weeks) vs those on placebo (4 of 13,179). Subgroup analyses suggest the risk may be greater in blacks compared with whites. 

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. 

A number of medications useful in the treatment of asthma are neither strictly bronchodilators nor antiinflammatory agents. They are classified as alternative asthma therapies (Table 39.4). These drugs, used pro-phylactically to decrease the frequency and severity of asthma attacks, are not indicated for monotherapy. They are used along with adrenomimetic bronchodilators, corticosteroids, or both. 

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... 

Dr David Graham from the FDA, speaking to the US senate in 2004, controversially raised concerns (refuted by the respective Pharmaceutical Companies) over the safety of the retinoid, isotretinoin (used in the treatment of cancer), the statin, rosuvastatin (used to lower cholesterol), a long-acting p2-receptor antagonist, salmeterol (used in asthma therapy), and a selective serotonin reuptake inhibitor, paroxetine (used as an antidepressant) (21). 

Bronchodilators Mabuteml is an adrenergic jS-2 agonist. It is more selective and potent than salbutamol, the reference bronchodilator used in asthma therapy (Figure 8.49). 

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... 

A two-part review was published in 2002, addressing the difficulties of assessing the effects of asthma therapy on childhood growth and reviewing the published literature based on the authors recommendations (136,137). In the first part (136), a simple classification system for growth studies was developed ... 

Wong CA, Subakumar G, Casey PM. Effects of asthma and asthma therapies on bone mineral density. Curr Opin Pulm Med 2002 8(l) 39-44. 

Price J, Hindmarsh P, Hughes S, Effthimiou J. Evaluating the effects of asthma therapy on childhood growth principles of study design. Eur Respir J 2002 19(6) 1167-78. 

Zitt MJ. The role of nonsedating antihistamines in asthma therapy. Allergy Asthma Proc. 2003 24 239-252. 

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