Beclomethasone dipropionate, asthma

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. 

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... 

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. 

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. 

R. N. Brogden, R. C. Heel, T. M. Speight, and G. S. Avery, Beclomethasone dipropionate. A reappraisal of its pharmacodynamic properties and therapeutic efficacy after a decade of use in asthma and rhinitis, Drugs 28 99 (1984). 

Beclomethasone dipropionate is the 9-chloro-analogue of betamethasone dipropionate. It was developed by Glaxo and introduced in the United States by Schering Corp. for topical use in the treatment of asthma and allergic rhinitis by the inhalation of a freon-propelled aerosol. 

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. 

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. 

In older women with asthma, who have an increased risk of osteoporosis, there was no significant change in bone mineral density after 1 year of treatment with beclomethasone dipropionate 1000 micrograms/day (100). 

Nayak A, Lanier R, Weinstein S, Stampone P, Welch M. Efficacy and safety of beclomethasone dipropionate extrafine aerosol in childhood asthma a 12-week, randomized, double-bUnd, placebo-controlled study. Chest 2002 122(6) 1956-65. 

Seale J, Harrison L 1998 Effect of changing the fine particle mass of inhaled beclomethasone dipropionate on intrapulmonary deposition and pharmacokinetics. Respiratory Medicine 92 9-15 Sears M R 1995 Is the routine use of beta-adrenergic agonists appropriate in asthma treatment American Journal of Respiratory and Critical Care Medicine 151 599-601... 

Corticosteroids — Beclomethasone dipropionate (17) aerosol has been tested extensively clinically. It is used prophylactically (400 fig per day), not therapeutically, in the treatment of chronic asthma, particularly in children.52 An evaluation of the drug has been published.53 One of the most important clinical advantages is that 1 7 effectively can replace oral corticosteroids in steroid-dependent patients and avoid many of the adverse effects of adrenal suppression.52,54 Most patients with impaired adrenal function due to oral corticosteroids show recovery of adrenal function within 6 months.55 The combination of 17 and disodium cromoglycate (DSCG) showed no additive therapeutic effects.5 Flunisolide (18), when administered as a nasal spray for 4 weeks during the hay fever season in 51 patients, showed significant symptomatic improvement with no systemic steroid effects observed.57... 

Beclomethasone dipropionate, Fluticasone propionate Anti-asthma... 

Steroids such as beclomethasone dipropionate, budesonide, triamcinolone acetonide, and flunisolide are active when given topically and can control asthma without causing the systemic effects or adrenal suppression. However, orally administered steroids such as prednisone, prednisolone, or methylprednisolone are still needed by some patients. 

Corticosteroids (Table 11) are synthetic adrenocortical steroids with antiinflammatory actions and effects, and are used in numerous disorders including bronchial asthma. For example, beclomethasone dipropionate (Beclovent, 85 meg 3 to 4 times daily), dexamethasone sodium phosphate (Decadron phosphate), and triamcinolone acetonide (Azmacort), which are not bronchodilators and are not indicated for rapid rehef of acute asthma, are used in bronchospastic states intractable to an adequate trial of conventional therapy. 

CB s asthma is currently being treated with a low-dose of the inhaled corticosteroid beclomethasone dipropionate (QVAR, 40 pg b.i.d.). She is in your pharmacy now with prescriptions for both chronic medications written by her new provider. After taking her medical history and reviewing her psychosocial situation, you recognize that she has many risk factors for near-fatal asthma" and believe she should have ready access to rescue therapy in case she experiences an acute episode of severe bronchoconstriction. Consider the structures of the adrenergic agents drawn below, and prepare to make a therapeutic recommendation to CB s new physician. 

Gross G, Thompson PJ, Chervinsky P, Vanden Burgt J. Hydrofluoroalkane-134a beclomethasone dipropionate, 400pg, is as effective as chlorofluorocarbon be-clomethasone dipropionate, 800 pg, for the treatment of moderate asthma. Chest 1999 115 343-351. 

Davies RJ, Stampone P, O Connor BJ. Hydrofluoroalkane-134a beclomethasone dipropionate extraflne aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose. Respir Med 1998 92(suppl A) 23-31. 

Corticosteroid therapy, oral or parenteral (by inhalation) may offer dramatic relief from asthma when other less dangerous measures have failed. At least one of the inhalant preparations (beclomethasone dipropionate) seems to compete favourably with other anti-asthmatics as far as the risks involved are concerned. Recent data on the corticosteroids in all their forms can be found in Chapter 37. 

Johannessen, H., Halvorsen, F. J. and Komme-dal, T. M. (1975) Beclomethasone dipropionate aerosol in adult steroid independent patients with perennial bronchial asthma. Curr. ther. lies., 18, 559. 

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