Antagonism of long-acting β2-adrenoceptor agonism

被引:16
作者
Lipworth, BJ [1 ]
机构
[1] Univ Dundee, Ninewells Hosp & Med Sch, Dept Clin Pharmacol & Therapeut, Asthma & Allergy Res Grp, Dundee DD1 9SY, Scotland
关键词
asthma; beta(2)-adrenoceptor agonists; formoterol; salmeterol; subsensitivity;
D O I
10.1046/j.1365-2125.2002.01651.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The established place of regular long-acting beta(2) -adrenoceptor agonists at step 3 in asthma management guidelines has evolved as a consequence of evidence showing additive effects of salmeterol and formoterol on exacerbation rates, resulting in a putative inhaled corticosteroid sparing effect. There is however, evidence to show that although long-acting beta(2) -adrenoceptor agonists facilitate using a lower dose of inhaled corticosteroid, this may occur at the expense of suboptimal anti-inflammatory control. This is likely to be the case especially with fixed dose combination inhalers where it is not possible to properly titrate anti-inflammatory therapy with inhaled corticosteroids without also inadvertently overtreating with unnecessarily high doses of long-acting beta(2) -adrenoceptor agonists. Most patients with mild to moderate persistent asthma can be adequately controlled on monotherapy with inhaled corticosteroid in low or medium dosage, which is considerably cheaper than concomitant use of a long-acting beta(2) -adrenoceptor agonist. Subsensitivity to long-acting beta(2) -adrenoceptor agonists is a predictable pharmacological phenomenon which occurs despite concomitant inhaled corticosteroid therapy and occurs more readily for bronchoprotective than bronchodilator effects. Subsensitivity of salbutamol protection against bronchoconstrictor stimuli occurs in patients receiving concomitant long-acting beta(2) -adrenoceptor agonists, which may be due to beta(2) -adrenoceptor down-regulation or prolonged receptor occupancy. Prospective large scale long-term studies are required to further define the clinical relevance of beta(2) -adrenoceptor polymorphisms, to look at clinical control outcomes as well as propensity for subsensitivity. It would therefore make more sense to first of all optimize the dose of anti-inflammatory therapy with inhaled corticosteroid and to then consider adding a long-acting beta(2) -adrenoceptor agonist for patients who are poorly controlled.
引用
收藏
页码:231 / 245
页数:15
相关论文
共 90 条
[1]   Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults [J].
Aziz, I ;
Wilson, AM ;
Lipworth, BJ .
CHEST, 2000, 118 (04) :1049-1058
[2]   In vivo effect of albuterol on methacholine-contracted bronchi in conjunction with salmeterol and formoterol [J].
Aziz, I ;
Lipworth, BJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1999, 103 (05) :816-822
[3]   A bolus of inhaled budesonide rapidly reverses airway subsensitivity and β2-adrenoceptor down-regulation after regular inhaled formoterol [J].
Aziz, I ;
Lipworth, BJ .
CHEST, 1999, 115 (03) :623-628
[4]   Concomitant inhaled corticosteroid resensitises cardiac β2-adrenoceptors in the presence of long-acting β2-agonist therapy [J].
Aziz, I ;
McFarlane, LC ;
Lipworth, BJ .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1998, 54 (05) :377-381
[5]   Subsensitivity to bronchoprotection against adenosine monophosphate challenge following regular once-daily formoterol [J].
Aziz, I ;
Tan, KS ;
Hall, IP ;
Devlin, MM ;
Lipworth, BJ .
EUROPEAN RESPIRATORY JOURNAL, 1998, 12 (03) :580-584
[6]   RAPID ONSET OF TOLERANCE TO THE BRONCHOPROTECTIVE EFFECT OF SALMETEROL [J].
BHAGAT, R ;
KALRA, S ;
SWYSTUN, VA ;
COCKCROFT, DW .
CHEST, 1995, 108 (05) :1235-1239
[7]   Salmeterol tachyphylaxis in steroid treated asthmatic subjects [J].
Booth, H ;
Bish, R ;
Walters, J ;
Whitehead, F ;
Walters, EH .
THORAX, 1996, 51 (11) :1100-1104
[8]   The effect of salmeterol on markers of airway inflammation following segmental allergen challenge [J].
Calhoun, WJ ;
Hinton, KL ;
Kratzenberg, JJ .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2001, 163 (04) :881-886
[9]   REGULAR VS AS-NEEDED INHALED SALBUTAMOL IN ASTHMA CONTROL [J].
CHAPMAN, KR ;
KESTEN, S ;
SZALAI, JP .
LANCET, 1994, 343 (8910) :1379-1382
[10]   LONG-TERM EFFECTS OF A LONG-ACTING BETA-2-ADRENOCEPTOR AGONIST, SALMETEROL, ON AIRWAY HYPERRESPONSIVENESS IN PATIENTS WITH MILD ASTHMA [J].
CHEUNG, D ;
TIMMERS, MC ;
ZWINDERMAN, AH ;
BEL, EH ;
DIJKMAN, JH ;
STERK, PJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (17) :1198-1203