Beclomethasone asthma

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. 

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

Corticosteroids, such as beclomethasone (Beclovent), flu-nisolide (AeroBid), and triamcinolone (Azmacort), are given by inhalation and act to decrease the inflammatory process in the airways of the patient with asthma, hi addition, the corticosteroids increase the sensitivity of the p2-receptors. With increased sensitivity of the ( -receptors, the p2-receptor agonist drugs are more effective... 

R. Clarke, Exacerbation of asthma after nebulized beclomethasone diproprionate, Lancet, 2, 574 (1986). 

T. B. Casale, S. M. Azzum, R. E. Miller, and J. Oren, Demonstration of therapeutic equivalence of generic and innovator beclomethasone in seasonal allergic rhinitis, Ann. allergy Asthma Immunol, 82, 435 (1999). 

Malmstrom K, Rodriguez-Gomez G, Guerra J et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclometha-sone Study Group. Ann Intern Med 1999 130 487-495. 

Williams, B., Noonan, G., Reiss, T. F., et al. (2001) Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older. Clin. Exp. Allergy. 31, 845-854. 

The majority of the marketed products are used for asthma and COPD. Typical agents that are used for these indications are fl2-agonists such as salbutamol (albuterol), Terbutalin or formoterol, corticosteroids such as budesonide, FUxotide or beclomethasone and mast-cell stabilizers such as sodium cromoglycate or nedocromil. 

The corticosteroids are effective in most children and adults with asthma. They are beneficial for the treatment of both acute and chronic aspects of the disease. Inhaled corticosteroids, including triamcinolone ace-tonide (Azmflcort),beclomethasone dipropionate (Beclo-vent, Vancerit), flunisolide AeroBid), and fluticasone (Flovent), are indicated for maintenance treatment of asthma as prophylactic therapy. Inhaled corticosteroids are not effective for relief of acute episodes of severe bronchospasm. Systemic corticosteroids, including prednisone and prednisolone, are used for the short-term treatment of asthma exacerbations that do not respond to (32-adrenoceptor agonists and aerosol corticosteroids. Systemic corticosteroids, along with other treatments, are also used to control status asthmaticus. Because of the side effects produced by systemically administered corticosteroids, they should not be used for maintenance therapy unless all other treatment options have been exhausted. 

Contraindications Hypersensitivity to beclomethasone, acute exacerbation of asthma, status asthmaticus... 

A 22-year-old male with a five-year history of bronchial asthma has developed increased frequency and severity of acute asthmatic attacks. A low dose of which inhaled steroid could be added to his treatment regimen Prednisolone Amcinonide Beclomethasone Cortisone Fluocinolone... 

Beclomethasone dipropionate, and several other glucocorticoids—primarily budesonide and flunisolide and mometasone furoate, administered as aerosols—have been found to be extremely useful in the treatment of asthma (see Chapter 20). 

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 38-year-old woman who had used inhaled beclo-methasone daily (dosage not stated) during the winter for the past 5 years for mild asthma, developed a perioral rash with numerous small pustules and papules. She stopped using beclomethasone and was treated with oral erythromycin and topical tretinoin. Her rash resolved within 4 weeks. One year later, she restarted beclomethasone and her rash reappeared after 2 weeks. There was no recurrence of her perioral dermatitis during subsequent treatment with monthly intramuscular injections of betamethasone. 

The efficacy and safety of fluticasone 750 micrograms/ day and beclomethasone 1500 micrograms/day delivered by a spacer device have been compared in 30 asthmatic children in a 12-week, randomized, double-blind, crossover study (118). All of the children had persistent asthma requiring 1000-2000 micrograms/day of inhaled glucocorticoids before the trial. There was no significant... 

Beclomethasone dipropionate 400 micrograms/day and salmeterol 50 micrograms bd were compared in asthmatic children treated for 12 months. Beclomethasone dipropionate treatment resulted in better overall asthma control. Over 12 months, linear growth was 3.96 cm/year in the children using beclomethasone dipropionate, compared with 5.40 cm/year in those who used salmeterol and 5.04 cm/year in a placebo group (SEDA-22,186). 

Niitsuma T, Okita M, Sakurai K, Morita S, Tsuyuguchi M, Matsumura Y, Hayashi T, Koshishi T, Oka K, Homma M. Adrenal function as assessed by low-dose adrenocortico-tropin hormone test before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate. J Asthma 2003 40 515-22. 

Gregson RK, Rao R, Murrills AJ, Taylor PA, Warner JO. Effect of inhaled corticosteroids on bone mineral density in childhood asthma comparison of fluticasone propionate with beclomethasone dipropionate. Osteoporos Int 1998 8(5) 418-22. 

Fitzgerald D, Van Asperen P, Mellis C, Honner M, Smith L, Ambler G. Fluticasone propionate 750 micro-grams/day versus beclomethasone dipropionate 1500 micrograms/day comparison of efficacy and adrenal function in paediatric asthma. Thorax 1998 53(8) 656-61. 

Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, Kohno S. Oral candidiasis associated with inhaled corticosteroid use comparison of fluticasone and beclomethasone. Ann Allergy Asthma Immunol 2003 90 646-51. 

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