Reversible Bronchospasm with the Cardio-Selective Beta-Blocker Celiprolol in a Non-Asthmatic Subject

Respiratory Medicine CME (2009) 2, 141e143

CASE REPORT Reversible bronchospasm with the cardio-selective beta-blocker celiprolol in a non-asthmatic subject

Rubab Ahmed, Howard M. Branley*

Department of Respiratory Medicine, The Whittington Hospital NHS Trust, Magdala Avenue, London N19 5NF, UK

Received 5 October 2008; accepted 16 October 2008

KEYWORDS Summary Selective beta blockers; Beta (b)-blockers are widely used in the treatment of cardiovascular disease but are well Celiprolol; recognised for causing bronchoconstriction in asthmatic subjects. The third-generation car-

Bronchoconstriction; dio-selective b-blocker celiprolol is a selective b1-adrenergic blocking agent with b2-agonist Asthma properties and would therefore be a preferred b-blocker if an asthmatic subject required treatment with b-blockers for cardiovascular disease. We present the case of a 79-year-old man with ischaemic heart disease and hypertension but no preceding respiratory disease who developed signiﬁcant bronchoconstriction on celiprolol, which resolved completely on drug cessation alone with no relapse of respiratory symptoms two years after cessation of treatment. ª 2008 Published by Elsevier Ltd.

Introduction relatively cardio-selective but are not cardio-specific. Cel- iprolol additionally possesses vasodilator properties b-blockers are widely used in the treatment of cardiovas- through blockade of vascular alpha-adrenoceptors. Celiprolol has been widely reported as being non-bron- cular disease, including hypertension, angina, myocardial 1,2 b choconstrictive both in subjects with asthma and infarction, arrhythmias and heart failure. -blockers bind 3,4 to b-adrenoceptors, thereby blocking the effects of propranolol-induced bronchoconstriction. epinephrine and norepinephrine. Some b-blockers, not only We report a case of significant bronchospasm in a patient prevent binding of sympathoamines to the b-adrenoceptor taking celiprolol with no previous history of airway disease, but also partially activate the b-adrenoceptor, and are thus which resolved completely on cessation of the drug. said to possess intrinsic sympathomimetic activity (ISA). Early b-blockers are non-selective, in that they block Case report both b-1 (cardiac) and b-2 (bronchial) adrenoceptors and can lead to unwanted b-2-blockade effects such as airflow A 79-year-old man presented with a 3-year history of obstruction. Newer b-blockers such as celiprolol are wheeze, especially at night. There was no dyspnoea or

* Corresponding author. Tel.: þ44 20 7288 5353; fax: þ44 20 7288 5060. E-mail address: [email protected] (H.M. Branley).

1755-0017/$34 ª 2008 Published by Elsevier Ltd. doi:10.1016/j.rmedc.2008.10.019 142 R. Ahmed, H.M. Branley

Figure 1 (a) PEFR diary on celiprolol demonstrating significant (35%) diurnal PEFR variation; (b) PEFR diary off celiprolol demonstrating non-significant (9%) diurnal PEFR variation. cough. He gave up smoking 30 years ago after 15 pack Discussion years’ consumption. He had ischaemic heart disease and hypertension, for which he took celiprolol 200 mg twice b-blocker induced bronchoconstriction in asthma is widely daily and had been for the preceding 10 years. There was reported, even with the cardio-selective b-blocker ateno- no history of atopic disease, no family history of asthma and lol.5e7 However, b-blocker induced bronchoconstriction in he had no occupational exposures. non-asthmatic subjects is exceedingly rarely reported and Physical examination revealed a clear chest with normal then, only with non-cardio-selective agents such as breath sounds and no added sounds. Peak expiratory flow propranolol.8,9 To the best of our knowledge there are no rate (PEFR) 274 L/min. Spirometry did not demonstrate reported cases of celiprolol-induced bronchoconstriction in airflow obstruction with forced expiratory volume in 1 s non-asthmatic subjects. In fact, celiprolol has been (FEV1) 2.04 L, forced vital capacity (FVC) 2.24 L (ratio 91%). widely reported as being non-bronchoconstrictive both Chest X-ray revealed a cardiothoracic ratio of 18/29 cm in subjects with asthma1,2 and propranolol-induced with clear lung fields. bronchoconstriction.3,4 A PEFR diary [Fig. 1(a)], whilst continuing celiprolol, What makes this case even more interesting is that showed a peak of 460 L/min and trough of 300 L/min celiprolol is regarded as providing a greater margin of (diurnal variation 35%). Following this observation, cel- respiratory safety than other cardio-selective b-blockers7 iprolol was stopped and a repeat PEFR diary [Fig. 1(b)] was due to its b2 agonist and intrinsic sympathomimetic activity recorded after cessation of celiprolol for 3 months. This (ISA). showed a peak of 460 L/min and trough of 420 L/min Celiprolol is a third-generation b-adrenoceptor blocker (diurnal variation 9%). Coincident with this improvement in with selective b-1-antagonist, partial b-2-agonist and mild PEFR was complete resolution of all respiratory symptoms. alpha-2-antagonist actions, with less risk of vasoconstric- During a 2-year period of follow-up there was no recurrence tion, bronchoconstriction and myocardial depression due to of any respiratory symptoms. Celiprolol-induced bronchospasm 143 its ISA. Whilst not being previously described as causing The onset of adverse effects from b-blockers is not bronchoconstriction, celiprolol is reported to cause hyper- necessarily temporally related to the initiation of sensitivity pneumonitis with a lymphocytic alveolitis, which treatment. resolves completely on celiprolol cessation.10 When celiprolol is directly compared to another cardio- selective b-blocker (atenolol) in asthmatic subjects, it has Conflict of interest statement been shown that atenolol is associated with bronchoconstriction but that there is no difference in day-to-day Neither author has any conflict of interest in relation to any asthma control, as judged by PEFR diary, inhaler use and aspect of this manuscript. symptom scores.7 Our patient fulfilled the criteria for diagnosing asthma Funding according to the British Thoracic Society/Scottish Inter- collegiate Guidelines Network (BTS/SIGN) British guide- None. line on the management of asthma 2008. There was significant diurnal variation in PEFR clearly demonstrated References whilst taking celiprolol, which completely resolved on cessation of the drug. Follow-up for 2 years of celiprolol failed to demonstrate any recurrence of respiratory 1. Bruschi C, Casali L, Cerveri I, Peona V, Zoia MC. Effects of celiprolol on the bronchial reactivity in asthma. Am J Cardiol symptoms. 1988;61(5):53Ce4. One common feature of most published data involving 2. Dorow P. Celiprolol e review of airways studies. Am J Cardiol b-blocker usage in asthma is the relatively small number of 1988;61(5):23Ce6. patients recruited in each study, emphasising the need for 3. Matthys H, Doshan HD, Ruhle KH, Braig H, Pohl M, Applin WJ, et al. a larger scale study in this area. The bronchosparing effect of celiprolol, a new beta 1- alpha 2-receptor antagonist on pulmonary function of propranolol- e Conclusions sensitive asthmatics. J Clin Pharmacol 1985;25(5):354 9. 4. 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