Figures
- FIGURE 1
Pictorial representation of β-adrenoceptor activity in the presence of background catecholamines, β-agonists and β-blockers. ISA: intrinsic sympathomimetic activity.
- FIGURE 2
PRISMA flow diagram of articles considered in the literature review.
Tables
- TABLE 1
Commonly used β-blockers and their relative β-adrenoceptor selectivity and partial agonist and inverse agonist properties
Cardioselective β1-blockers (relative selectivity of β1 versus β2) Nonselective β-blockers (relative selectivity of β1 versus β2) Partial agonist/ISA Acebutolol (2.4#)
Practolol (>14.1#)Labetalol (2.5#)
Alprenolol (16.2#)Inverse agonist Metoprolol (2.3#, 6.0¶)
Atenolol (4.7#, 5.7¶)
Bisoprolol (13.5#, 19.6¶)
Nebivolol (40.6¶)Carvedilol (4.5#)
Propranolol (8.3#)
Sotalol (12.0#)
Nadolol (23.4#)
Timolol (25.7#)A relative selectivity ratio of 1 demonstrated equal activity at both β1- and β2-adrenoceptors. ISA: intrinsic sympathomimetic activity. #: according to Baker [26] using cell lines expressing human adrenoceptors; ¶: according to Ladage et al. [49] in their review figure.
- TABLE 2
Summary studies included in review
Type of study Publications found in the search and considered in the review Meta-analysis or systematic review 4 (3 meta-analyses, 1 systematic review) Randomised controlled trial 53 (765 participants in total of which 682 people with asthma and 83 with reversible airways disease) Non-randomised trial 31 (106 915 participants in total of which 63 763 were asthma alone, 43 152 were asthma or COPD) Literature review 12 (9 asthma, 1 obstructive lung disease, 1 reversible airways disease and 1 on adverse reactions to β-blockers) Other 27 (8 case reports, 7 murine models, 7 guinea pig models, 4 opinion articles, 1 questionnaire) Studies that could be allocated to two categories are included in the highest tier (for example, meta-analysis above non-randomised trial).
- TABLE 3
Summary of VigiBase total and fatal reports for cardioselective β1-blockers with asthma or bronchospasm as reported suspected adverse reactions from start to December 2019
Cardioselective β1-blockers Reactions coded as asthma Reactions coded as bronchospasm Total Of which were fatal Total Of which were fatal Metoprolol 286 4 322 6 Atenolol 141 1 385 3 Bisoprolol 95 0 108 1 Nebivolol 29 0 32 0 Betaxolol 18 0 86 0 Acebutolol 5 1 30 0 Celiprolol 6 0 41 1 Landiolol 1 0 0 0 Esmolol 1 0 11 1 Esatenolol 1 0 0 0 - TABLE 4
VigiBase data: clinical details of all five reported fatalities with cardioselective β1-blocker use in patients with an adverse drug reaction of asthma or bronchospasm who had evidence of pre-existing asthma
Report Year Cardioselective β1-blockers Reported adverse drug reactions Name Dose Duration Indication 1 1985 Metoprolol Not stated 1.1 years Not stated Asthma (general anaesthetic medications listed) 2 2017 Metoprolol 100 mg by mouth once daily Not stated Hypertension Asthma, sepsis, pneumonia, emphysema, decreased immune response, renal cancer 3 2018 Acebutolol 600 mg by mouth once daily Not stated Not stated Asthma, acute MI, cardiogenic shock, metastatic renal cancer 4 2009 Atenolol 50 mg once daily Not stated Not stated Bronchospasm, acute MI, cardiac failure, aspiration, sudden cardiac death 5 2019 Atenolol Not stated 11 years Hypertension Asthma, viral pneumonia (immunosuppressant medicines listed) MI: myocardial infarction.
Supplementary Material
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Supplementary material 00801-2020.SUPPLEMENT
