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Revisiting interactions between hypoxaemia and β2agonists in asthma
  1. B J LIPWORTH
  1. Asthma and Allergy Research Group
  2. Department of Clinical Pharmacology & Therapeutics
  3. Ninewells Hospital & Medical School
  4. University of Dundee
  5. Dundee DD1 9SY, UK
  6. b.j.lipworth@dundee.ac.uk

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The excessive use of β2 agonists has been associated with increased asthma mortality, although this seems to be due to confounding by disease severity rather than direct drug toxicity.1 ,2 Dose-response studies in stable asthmatics have shown the potential for high doses of salbutamol to produce direct or indirect cardiovascular sequelae mediated by extrapulmonary β2 adrenoceptor stimulation including chronotropic and inotropic activity, peripheral vasodilatation, electrocardiographic changes, as well as hypokalaemia and hypomagnesaemia.3 ,4

The potential for cardiovascular toxicity with high doses of inhaled β2 agonists may be considered in the context of “the seed and the soil”. In terms of the “seed”, there are conflicting reports as to whether a full agonist such as fenoterol produces greater dose related systemic β2 mediated systemic effects than a partial agonist such as salbutamol in asthmatic patients when comparing microgram equivalent doses with the same bronchodilator potency.4-6 In terms of the “soil” for salbutamol mediated adverse effects, concomitant diuretic therapy may augment hypokalaemic and electrocardiographic sequelae, concomitant corticosteroid may sensitise cardiac β2 adrenoceptors, while the elderly exhibit increased chronotropy and peripheral vasodilatation.7-9 Patients with more severe asthma have reduced systemic effects of salbutamol due to reduced lung absorption so they may, in effect, be protecting themselves from adverse effects.10 The lung absorption of salbutamol …

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Footnotes

  • Conflicts of interest: The author has received financial support on a departmental level or for giving occasional postgraduate talks from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Innovata Biomed, Aerogen, and Novartis who all make β2 agonist formulations.