Corticosteroids and adrenoceptor agonists: the compliments for combination therapy in chronic airways diseases.
The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor agonists is increasingly used as maintenance therapy in patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of inhaled corticosteroids is thought to be mediated through suppression of airway inflammation, while long-acting beta2-adrenoceptor agonists are thought to work by inducing bronchodilation. However, there is emerging data to indicate that these two classes of drugs interact positively with each other, leading to added or perhaps synergistic benefits for patients. Corticosteroids enhance the expression of beta2-adrenoceptor, thus providing protection against desensitization and development of tolerance to beta2-adrenoceptor agonists, which may occur with prolonged use of these medications. Long-acting beta2-adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory effects of corticosteroids by accelerating nuclear translocation of the glucocorticoid receptor complex, and enhancing transcription and expression of steroid-inducible genes in pro-inflammatory cells. In clinical trials, corticosteroids in combination with long-acting beta2-adrenoceptor agonists reduce exacerbation rates, and improve lung function and health status of patients with moderate to severe asthma or COPD beyond that achieved by individual component therapy. Their effects on mortality are unknown. There is a large clinical trial currently underway, which will provide mortality data by the year 2006. On balance, clinical evidence supports the use of combination therapy in moderate to severe asthma and COPD.
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Don D
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James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Room 368A, 1081 Burrard Street, and Department of Medicine (Pulmonary Division), University of British Columbia, Vancouver, B.C., Canada V6Z 1Y6. dsin@mrl.ubc.ca
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D000305:Adrenal Cortex Hormones / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D000420:Albuterol / Q000031:analogs & derivatives / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use; D000730:Androstadienes / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D019819:Budesonide / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D000068759:Formoterol Fumarate; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D000068297:Fluticasone-Salmeterol Drug Combination; D018343:Receptors, Adrenergic, beta-2; D011965:Receptors, Glucocorticoid; D019819:Budesonide; D000420:Albuterol; D000068759:Formoterol Fumarate