Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD

Jabbal, Sunny; Anderson, William J.; Short, Philip; Morrison, Anne; Manoharan, Arvind; Lipworth, Brian J.

doi:10.1093/qjmed/hcx155

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…Pulmonary effects appear to differ among β blockers; non-selective, but not cardioselective, β blockers have been found to reduce forced expiratory volume in 1 second (FEV 1 ) and to increase airway hypersensitiveness in patients with COPD [9]. In a randomized cross-over study [10], bisoprolol is better tolerated than carvedilol on lung function in patients with moderate to severe COPD.…”

Section: Discussionmentioning

confidence: 99%

Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap

Yang

Perng

et al. 2019

Aging

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The appropriate treatment for patients with coexistent chronic obstructive pulmonary disease (COPD) and heart failure (HF) remains unclear. Data from the Taiwan National Health Insurance Research Database was used for this retrospective cohort study. Patients diagnosed with both diseases between 1997 and 2012 were enrolled as the COPD-heart failure overlap cohort. Patients were categorized as non-users and users of specific COPD and HF medications. Medication prescriptions in each 3-month and 1-year period served as time-dependent covariates. The primary endpoint was cumulative survival. The validation study confirmed the accuracy of definitions of COPD (94.0% sensitivity) and HF (96.3% sensitivity). The study included 275,436 patients with COPD-heart failure overlap, with a mean follow-up period of 9.32 years. The COPD-heart failure overlap cohort had more medical service use and higher mortality than did the COPD alone cohort. Use of inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations, long-acting muscarinic antagonist (LAMA), angiotensin receptor blockers (ARBs), β blockers, aldosterone antagonists, and statins reduced mortality risk compared with non-use. Sensitivity and subgroup analyses confirmed the consistency and robustness of results. ICS/LABA combinations, LAMA, ARBs, β blockers, aldosterone antagonists, and statins use was associated with a lower mortality risk in patients with COPD-heart failure overlap.

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Section: Discussionmentioning

confidence: 99%

Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap

Yang

Perng

et al. 2019

Aging

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“…Because of antagonistic actions, this interaction may reduce the benefits of both medications, particularly the bronchodilatory effect of albuterol [ 40 ]. It can be avoided by prescribing cardioselective β-blocker, i.e., bisoprolol which has 14-fold higher affinity for β1 than β2 receptors and is well tolerated in cardiopulmonary patients [ 41 ]. As class D and X pDDIs are associated with adverse outcomes and healthcare providers should be watchful about their incidence, effects and management, we grouped them together and analyzed the data for finding the factors associated with their presence.…”

Section: Discussionmentioning

confidence: 99%

Potential drug–drug interactions in patients with cardiovascular diseases: findings from a prospective observational study

Akbar

Rehman

Khan

et al. 2021

J of Pharm Policy and Pract

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Background Patients with cardiovascular diseases (CVD) are at high risk of experiencing drug–drug interactions (DDIs). The objective of this study was to evaluate the frequency, level and risk factors associated with potential-DDIs (pDDIs) in hospitalized CVD patients at cardiology departments of two tertiary care hospitals in Quetta, Pakistan. Methods In the current prospective observational study, a total of 300 eligible CVD inpatients were evaluated for pDDIs using Lexicomp Interact®. The pDDIs were classified into class A (no known interaction); B (no action needed); C (monitor therapy: it is documented that the benefits of an interaction outweigh the risk, appropriately monitor therapy in order to avoid potential adverse outcomes); D (consider therapy modification: it is documented that proper actions must be taken to reduce the toxicity resulting from an interaction); X (avoid combination: the risk of an interaction outweighs the benefits and are usually contraindicated). Multivariate binary logistic regression analysis was used to find factors associated with the presence of Class-D and/or X pDDIs. A p-value < 0.05 was considered statistically significant. Results With a median of 8.50 pDDIs per patient, all patients (100%) had ≥ 1 pDDIs. Out of total 2787 pDDIs observed, 74.06% (n = 2064) were of moderate and (n = 483) 17.33% of major severity. Class C pDDIs were most common (n = 1971, 70.72%) followed by D (n = 582, 20.88%), B (n = 204, 7.32%) and X (n = 30, 1.08%). Suffering from cardiovascular diseases other than myocardial infarction (OR 0.053, p-value < 0.001) and receiving > 12 drugs (OR 4.187, p-value = 0.009) had statistical significant association with the presence of class D and/or X pDDIs. Conclusion In the current study, pDDIs were highly prevalent. The inclusion of DDI screening tools, availability of clinical pharmacists and paying special attention to the high-risk patients may reduce the frequency of pDDIs at the study sites.

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“…Neither drug can be considered kinetically selective in terms of their measured off‐rates. Other non‐selective β 2 ‐adrenoceptor blockers such as carvedilol appear to be if anything more selective for β 2 ‐adrenoreceptors over β 1 ‐adrenoreceptors with repercussions for patients with underlying respiratory disease 42 , 43 where greater reductions in forced expiratory volume (lung function) have been observed 44 , 45 , 46 (see Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the kinetic selectivity of drugs targeting the β₁‐adrenoceptor

Sykes

Jiménez‐Rosés

Reilly

et al. 2022

Pharmacology Res & Perspec

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In this study, we report the β 1 ‐adrenoceptor binding kinetics of several clinically relevant β 1/2 ‐adrenoceptor (β 1/2 AR) agonists and antagonists. [ 3 H]‐DHA was used to label CHO‐β 1 AR for binding studies. The kinetics of ligand binding was assessed using a competition association binding method. Ligand physicochemical properties, including logD 7.4 and the immobilized artificial membrane partition coefficient ( K IAM ), were assessed using column‐based methods. Protein Data Bank (PDB) structures and hydrophobic and electrostatic surface maps were constructed in PyMOL. We demonstrate that the hydrophobic properties of a molecule directly affect its kinetic association rate ( k on ) and affinity for the β 1 AR. In contrast to our findings at the β 2 ‐adrenoceptor, K IAM , reflecting both hydrophobic and electrostatic interactions of the drug with the charged surface of biological membranes, was no better predictor than simple hydrophobicity measurements such as clogP or logD 7.4 , at predicting association rate. Bisoprolol proved kinetically selective for the β 1 AR subtype, dissociating 50 times slower and partly explaining its higher measured affinity for the β 1 AR. We speculate that the association of positively charged ligands at the β 1 AR is curtailed somewhat by its predominantly neutral/positive charged extracellular surface. Consequently, hydrophobic interactions in the ligand‐binding pocket dominate the kinetics of ligand binding. In comparison at the β 2 AR, a combination of hydrophobicity and negative charge attracts basic, positively charged ligands to the receptor's surface promoting the kinetics of ligand binding. Additionally, we reveal the potential role kinetics plays in the on‐target and off‐target pharmacology of clinically used β‐blockers.

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Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD

Cited by 12 publications

References 29 publications

Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap

Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap

Potential drug–drug interactions in patients with cardiovascular diseases: findings from a prospective observational study

Exploring the kinetic selectivity of drugs targeting the β₁‐adrenoceptor

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Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD

Cited by 12 publications

References 29 publications

Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap

Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap

Potential drug–drug interactions in patients with cardiovascular diseases: findings from a prospective observational study

Exploring the kinetic selectivity of drugs targeting the β1‐adrenoceptor

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Exploring the kinetic selectivity of drugs targeting the β₁‐adrenoceptor