Noncardioselective Beta-Blocker Use in Patients With Asthma: Are We Vigilant?

TIMOTHY SELF, PharmD—Series Editor—JESSICA L. WALLACE, PharmD,
JUDITH E. SOBERMAN, MD, FACC, JIMMIE MANCELL, MD,
and MAEGAN L. ROGERS, PharmD, BCPS
University of Tennessee Health Science Center, Memphis

Dr Wallace is a PGY2 clinical pharmacy resident at the University of Tennessee Health Science Center and Methodist University Hospital. Dr Soberman is professor of medicine in the division of cardiovascular disease at the University of Tennessee Health Science Center. Dr Mancell practices internal medicine at Methodist Inpatient Physicians, in Memphis, is a hospitalist at Methodist University Hospital, and is assistant professor of medicine–general internal medicine at the University of Tennessee Health Science Center. Dr Rogers is a clinical specialist at Regional Medical Center at Memphis and is assistant professor of clinical pharmacy at University of Tennessee Health Science Center.

Timothy Self, PharmD—Series Editor:Dr Self is professor of clinical pharmacy at the University of Tennessee Health Science Center and Methodist University Hospital in Memphis.

 

Volume 52 - Issue 9 - September 2012

The benefits of cardioselective beta-blocker therapy outweigh the associated risks in patients with nonsevere asthma after myocardial infarction (MI) or for the long-term treatment of heart failure.1-5 We have recently observed both medical residents and attending physicians prescribing noncardioselective beta-blockers to patients with asthma (Table). Consequently, we believe this summary will be a timely reminder to healthcare professionals to be careful to administer cardioselective beta-blockers for appropriate indications in asthma patients and clearly avoid noncardioselective agents.1-5 We did not include chronic obstructive pulmonary disease in our literature search but specifically focused on asthma.

BETA-BLOCKER–INDUCED BRONCHOSPASM

Noncardioselective beta-blockers are well documented to induce bronchospasm in patients with asthma, and this problem has been reviewed extensively.3-5 In some
patients, noncardioselective beta-blockers are associated with severe bronchospasm and death.6-11 A highly relevant clinical point is that even topical ophthalmic nonselective beta-blockers, such as timolol for the treatment of glaucoma, have caused numerous cases of fatal asthma.10,11

Both the formulation and dosage of beta-blockers can have an effect on the airways. Cardioselective agents such as extended-release metoprolol are appropriate for patients with nonsevere asthma who have a history of MI or heart failure. Although metoprolol succinate administered in dosages not exceeding 100 mg daily may usually be well tolerated, the same may not be true with the immediate-release formulation (metoprolol tartrate). In a double-blind, randomized, crossover study of immediate-release metoprolol in 15 patients with asthma, 6 patients were withdrawn prematurely in response to a decrease in forced expiratory volume in 1 second of more than 20% or symptoms occurring after receiving an average tolerated cumulative dose of only 26.8 mg.12

Even with cardioselective beta-blockers, such as extended-release metoprolol or atenolol, the dose should be increased with caution. With higher doses, the cardioselectivity decreases and the risk of bronchospasm increases.5,13-16

Beyond prescribing cardioselective beta-blockers for the compelling indication of heart failure and as post-MI therapy, some researchers have encouraged the prescribing of these agents to patients with hypertension and asthma.2,3 It is logical to question the routine use of cardioselective beta-blockers by patients with both hypertension and asthma, in view of the wide array of medications available to treat hypertension. Salpeter and colleagues3 point out that the long-term safety of cardioselective beta-blockers, especially during acute asthma exacerbations, must be established, particularly in the treatment of hypertension in patients without concomitant heart failure or history of MI. Unfortunately, as previously mentioned, we have recently seen noncardioselective agents prescribed for hypertension in patients with asthma.

DISCUSSION

Clinicians must consider several factors in the benefit-risk equation before prescribing cardioselective beta-blockers to patients with asthma. These factors, which have been recently summarized, include the severity of the asthma and the management plan for optimal long-term asthma control.17 Closer monitoring and attention to the asthma action plan should certainly be necessary for the patient who has well-controlled asthma while receiving cardioselective beta-blocker therapy, but who then has a respiratory viral infection or other unexpected asthma trigger.

Cardioselective beta-blockers should be initiated at low doses and titrated upward as required.18 Epstein18 and Salpeter and colleagues2 point out that the long-term safety of cardioselective beta-blocker therapy (especially during acute asthma exacerbations) must be established. In addition, as asthma continues to be undiagnosed and suboptimally treated,19 some patients may receive beta-blocker (cardioselective or noncardioselective) therapy initiated by a physican who is unaware of the patient’s asthma.

A recent hypothesis suggests the prolonged dosing of beta-blockers may be paradoxically beneficial in asthma, but extensive clinical research will be required to confirm this possible effect.20 

References

1. National Asthma Education and Prevention Program: Expert panel report 3: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute. Published August 2007. NIH publication no. 08-4051. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed June 27, 2012.

2. Salpeter SR, Ormiston TM, Salpeter EE. Cardio-selective beta blockers in patients with reactive airway disease: a meta-analysis. Ann Intern Med. 2002;137(9):715-725.

3. Salpeter S, Ormiston T, Salpeter E. Cardioselective beta blockers for reversible airway  disease. Cochrane Database Syst Rev 2002;(4):CD002992.

4. Chafin CC, Soberman JE, Demirkan K, Self T. Beta-blockers after myocardial infarction: do benefits ever outweigh risks in asthma. Cardiology. 1999;92(2):99-105.

5. Self T, Soberman JE, Bubla JM, Chafin CC. Cardioselective beta-blockers in patients with asthma and concomitant heart failure or history of myocardial infarction: When do benefits outweigh risks? J Asthma. 2003;40(8):839-845.

6. McNeill RS, Ingram CG. Effect of propranolol on ventilatory function. Am J Cardiol. 1966;18(3):473-475.

7. Raine JM, Palazzo MG, Kerr JH, Sleight P. Near fatal bronchospasm after oral  nadolol in a young asthmatic and response to ventilation with halothane. Br Med J (Clin Res Ed). 1981;282(6263):548-549.

8. Williams IP, Millard FJ. Severe asthma after inadvertent ingestion of oxprenolol. Thorax. 1980;35(2):160.

9. Harries AD. Beta-blockade in asthma. Br Med J (Clin Res Ed). 1981;282(6272):1321.

10. Fraunfelder FT, Barker AF. Respiratory effects of timolol. N Engl J Med. 1984;311(22):1441.

11. Odeh M, Oliven A, Bassan H. Timolol eyedrop-induced fatal bronchospasm in an asthmatic patient. J Fam Pract. 1991;32(1):97-98.

12. Wilcox PG, Ahmad D, Darke AC, Parsons J, Carruthers SG. Respiratory and cardiac effects of metoprolol and bevantolol in patients with asthma. Clin Pharmacol Ther.1986;39(1):29-34.

13. Formgren H. The effect of metoprolol and practolol in lung function and blood pressure in hypertensive asthmatics. Br J Clin Pharmacol. 1976;3(6):1007-1014.

14. Lawrence DS, Sahay JN, Chatterjee SS, Cruickshank JM. Asthma and beta-blockers. Eur J Clin Pharmacol. 1982;22(6):501-509.

15. Jackson SH, Beevers DG. Comparison of the effects of single dose atenolol and labetalol on airways obstruction in patients with hypertension and asthma. Br J Clin Pharmacol. 1983;15(5):553-556.

16. van Zyl AI, Jennings AA, Bateman ED, Opie LH. Comparison of respiratory effects of two cardio-selective beta-blockers,celiprolol and atenolol, in asthmatics with mild to moderate hypertension. Chest. 1989;95(1):209-213.

17. Self T, Rogers ML, Mancell J, Soberman JE. Carvedilol therapy after cocaine-induced myocardial infarction in patients with asthma. Am J Med Sci. 2011;342(1):56-61.

18. Epstein PE. Fresh air and beta-blockade. Ann Intern Med. 2002;137(9):766-767.

19. Nolte H, Neeper-Christensen S, Backer V. Unawareness and undertreatment of asthma and allegic rhinitis in a general population. Respir Med. 2006;100(2):354-362.

20. Lipworth BJ, Williamson PA. Think the impossible: beta-blockers for treating asthma. Clin Sci (Lond). 2009;118(2):115-120.