Clinical pharmacology of corticosteroids in bronchial asthma

doi:10.1016/0163-7258(93)90049-J

Pharmacology & Therapeutics

Volume 58, Issue 2, 1993, Pages 173-209

https://doi.org/10.1016/0163-7258(93)90049-J Get rights and content

Abstract

It is now recognised that suppression of the inflammatory cascade should be the cornerstone of management in bronchial asthma. Inhaled corticosteroids are the most effective and widely used form of anti-inflammatory therapy for use in patients with asthma. The limited data available on dose-response relationships for inhaled corticosteroids suggest that a plateau occurs for antiasthmatic efficacy above 1600 μg either for budesonide and beclomethasone dipropionate with no appreciable differences between the two drugs. However, in most cases it should be possible to achieve adequate asthma control with doses of either drug less than 1000 μg with a use of an optimal inhaler device and good compliance. In contrast to topical anti-inflammatory activity in airways, for both local and systemic adverse effects there is a steep dose-response above 1600 μg with budesonide and beclomethasone dipropionate. In comparison with oral prednisolone there is still a better risk-benefit ratio even with higher doses of inhaled corticosteroids. There is evidence to suggest that inhaled budensonide may have a slightly more favourable profile in terms of the ratio of topical to systemic activity, particularly for effects on bone metabolism. A significant degree of adrenal suppression is unlikely at doses less than 1600 μg of budesonide or beclamethasone, although there is a degree of interindividual variability in the dose-response relationship for this effect, as well as for antiasthmatic activity. Thus, doses of inhaled corticosteroid should be titrated on an individual basis in order to achieve adequate disease control. At doses in excess of 800 μg it would seem rational to use a large volume spacer device since this will lessen local adverse effects such as oral candidiasis and dysphonia, as well as reducing systemic absorption and improving lung deposition. Mouth washing may reduce local and systemic adverse effects when using dry powder devices at high doses. Another possible strategy to improve efficacy with higher doses is to increase the dosing frequency from twice to four times daily, although this may at the same time produce an increase in local adverse effects. Fluticasone propionate is a novel inhaled corticosteroid with very high topical anti-inflammatory activity and minimal systemic bioavailability and might, therefore, provide a favourable therapeutic profile at the high end of the dose range. The next decade of research into the clinical pharmacology of inhaled corticosteroids is, therefore, eagerly awaited and will hopefully consolidate improvements in asthma management with this important class of anti-inflammatory drugs.

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Clinical pharmacology of corticosteroids in bronchial asthma

Abstract

Br. J. Dis. Chest.

J. Allergy clin. Immun.

Resp. Med.

Resp. Med.

Resp. Med.

J. Allergy clin. Immun.

Lancet

J. Allergy clin. Immun.

Am. J. Med.

J. Allergy clin. Immun.

Lancet

Am. J. Obstet. Gynec.

Resp. Med.

Lancet

Br. J. Anaesth.

J. Allergy clin. Immun.

J. Allergy clin. Immun.

J. Allergy clin. Immun.

Lancet

Lancet

Am. J. Med.

High dose inhaled budesonide in the treatment of severe steroid-dependent asthmatics: a two year study

Allergy

Bone turnover during high-dose inhaled corticosteroid treatment

Thorax

Steroid aerosols and cataract formation

Br. med. J.

Biotransformation of the topical glucocorticoids budesonide and beclomethasone 17, 21 dipropionate in human liver and lung homogenate

J. Pharm. Pharmac.

The course and outcome of pregnancy in women with bronchial asthma

Acta Allerg.

Growth and childhood asthma

Arch. Dis. Child.

A comparison of the relative safety and efficacy of inhaled fluticasone propionate (F.P.). 1 mg daily and beclomethasone dipropionate (BDP) 2mg daily

Eur. J. Allergy clin. Immun.

New concepts in asthma and the implications for therapy

A self management plan in the treatment of adult asthma

Thorax

Development of posterior subcapsular cataracts in asthmatic children

Pediatrics

Methodological aspects of clinical trials with inhaled corticosteroids: results of two comparisons between two steroid aerosols in patients with asthma

Eur. J. Resp. Dis.

Beclomethasone dipropionate aerosol: haemotologic and immunologic effects

Ann. Allergy

Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma

Allergy

Development of new glucocorticosteroids with a very high ratio between topical and systemic activities

Eur. J. Resp. Dis.

Guidelines for management of asthma in adults: I—chronic persistent asthma

Br. Med. J.

High dose corticosteroids in severe acute asthma

Br. Med. J.

Terbutaline induced desensitization of human lymphocyte beta-2 adrenoceptors. Accelerated restoration of beta-adrenoceptor responses by prednisolone and ketotifen

J. clin. Invest.

Effects of prednisolone and ketotifen on β2-adrenoceptors in asthmatic patients receiving β2-bronchodilators

Eur. J. clin. Pharmac.

Double blind trial comparing two dosage schedules of beclomethasone dipropionate aerosol in the treatment of chronic bronchial asthma

Lancet

Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids?

Thorax

Intranasal fluticasone propionate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in allergic rhinitis

Drugs

Purpura and dermal thinning associated with high-dose inhaled corticosteroids

Br. Med. J.

Long-term effects of a long-acting β2-adrenoceptor agonist, salmeterol in airway hyperresponsiveness in patients with mild asthma

New Engl. J. Med.

Beclomethasone dipropionate by inhalation in the treatment of airways obstruction

Br. J. Dis. Chest

Inhaler therapy

Q. J. Med.

Effect of beclomethasone dipropionate delivered by aerosol in patients with asthma

Lancet

The use of corticosteroids in treatment of acute asthma

Q. J. Med.

Correlation between chemical structure, receptor binding and biological activity of some novel, high active, 16-alpha, 17-alpha-acetal-substituted glucocorticoids

Molec. Pharmac.

Comparison of oral prednisolone and intramuscular depot triamcinolone in patients with chronic severe asthma

Thorax

Effects of prednisolone and ketotifen on β₂-adrenoceptors in asthmatic patients receiving β₂-bronchodilators

Long-term effects of a long-acting β₂-adrenoceptor agonist, salmeterol in airway hyperresponsiveness in patients with mild asthma