Beta blocker and COPD

• beta blockers are generally contraindicated in chronic obstructive airways disease and asthma
  • note however that there is evidence that cardioselective beta blockers are >20 times more selective for ß1 than ß2 receptors and should carry less risk of bronchoconstriction in reactive airways disease (1)
    
    
    • there is evidence that, in patients with COPD, cardioselective beta blockers do not change FEV1 or increase respiratory symptoms (2)
      
      
    • in a small study on asthmatics, propranolol caused a reduction in lung function, but celiprolol was shown not only to improve spirometry readings, it also inhibits the bronchoconstrictor effects of propranolol (3)
      
      
    • in mice studies, initial therapy with beta blockers increased airway hyperresponsiveness, whereas longer therapy decreased hyperresponsiveness and seemed to have an anti-inflammatory effect (4)
      
      
  • the BNF states '...beta-blockers can precipitate bronchospasm and should therefore usually be avoided in patients with a history of asthma. When there is no suitable alternative, it may be necessary for a patient with well-controlled asthma, or chronic obstructive pulmonary disease (without significant reversible airways obstruction), to receive treatment with a beta-blocker for a co-existing condition (e.g. heart failure or following myocardial infarction). In this situation, a cardioselective beta-blocker should be selected and initiated at a low dose by a specialist; the patient should be closely monitored for adverse effects..."

Notes:

• there are 3 types of beta receptors
  • beta 1-Adrenoceptors
    • situated in the cardiac sarcolemma
      • if activated, they lead to an increase in the rate and force of myocardial contraction (positive inotropic effect) by opening the calcium channels
  • beta 2-Adrenoceptors
    • found mainly in bronchial and vascular smooth muscles
      • if activated, they cause broncho- and vaso-dilatation
        • there are, however, sizable populations of beta 2-Adrenoceptors in the myocardium, of about 20%-25%, which leads to the cardiac effects of any beta2-Adrenoceptors stimulation. There is a relative up-regulation of these receptors to about 50% in heart failure
  • beta 3 Adrenoceptors
    • the role of beta 3-Adrenoceptors in the heart is not yet fully identified and accepted
      
      
• beta-blockers are classified into three generations
  • the first generation agents (such as Propranolol, Sotalol, Timolol, and Nadolol), are nonselective and block beta 1 and beta 2 receptors
    • blocking beta1-receptors affects the heart rate, conduction and contractility, while blocking beta 2-receptors, tends to cause smooth muscle contraction, therefore, bronchospasm in predisposed individuals
      
      
  • second-generation agents or the cardioselective agents (such as Atenolol, Bisoprolol, Celiprolol, and Metoprolol)
    • block beta 1-receptors in low doses but are capable of blocking beta 2-receptors in higher doses
      • selective mode of action makes the use of these agents more suitable in patients with chronic lung disease or those with insulin-requiring diabetes mellitus
      • cardioselectivity varies between agents with the Bisoprolol among the most selective
        
        
  • third generation agents have vasodilatory properties
    • action is either selective (Nebivolol) or nonselective (Carvidolol and Labetolol)
    • vasodilatory properties are mediated either by nitric oxide release as for Nebivolol or Carvidolol or by added alpha-adrenergic blockade as in Labetolol and Carvidolol
    • a third vasodilatory mechanism, as in Pindolol and Acebutolol, acts via beta 2-intrinsic sympathomimetic activity (ISA)
    • these beta-blockers therefore have the capacity to stimulate as well as to block adrenergic receptors and tend to cause less bradycardia than the other beta-blockers and may cause less coldness of the extremities

Contributor: Dr Nick Bradshaw (January 2014)

Reference:

1. Salpeter SR et al. Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis. Ann Intern Med 2002; 137:715-25.
2. Salpeter S et al. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005;(4):CD003566.
3. Pujet JC, et al. Effects of celiprolol, a cardioselective beta-blocker, on respiratory function in asthmatic patients. Eur Respir J. 1992 Feb;5(2):196-200.
4. Callaerts-Vegh Z, Evans KL, Dudekula N, et al. Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma. Proc Natl Acad Sci USA. 2004;101(14):4948-4953.
5. British National Formulary (BNF). Section 2.4 (Accessed January 7th 2014).
6. Int J Chron Obstruct Pulmon Dis. 2007 December; 2(4): 535-540.