Beta-Blockers in Hypertension

Ram, C. Venkata S.

doi:10.1016/j.amjcard.2010.08.023

Cited by 99 publications

(73 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Initially, 17 b-adrenergic ligands currently used in various clinical indications (Castle et al, 1993;Cruickshank, 1993;Eichhorn and Young, 2001;Javed and Deedwania, 2009;Ram, 2010) and 2 endogenous ligands were selected to assess their functional selectivity toward 4 signaling pathways: cAMP production, calcium mobilization, ERK1/2 activation, and receptor endocytosis (Tables 1 and 2). For reference purposes, the compounds, structures, binding affinities (from published radioligand binding studies), relative efficacies (previously reported for cAMP production), receptor subtype selectivity profile, and clinical uses are 1 Because model parameter redundancy, it is usually not possible to estimate separate t or K A values for full agonists from direct fitting of the operational model to a full agonist concentration-response curve unless additional experimental manipulations are performed to provide information about other model parameters (e.g., receptor alkylation studies to reduce system maximum responsiveness and thus allow estimation of E m ) or parameter values are constrained to prior known values.…”

Section: Resultsmentioning

confidence: 99%

“…As such, we investigated 19 clinically relevant compounds that are used for treating diseases such as asthma, chronic obstructive pulmonary disease, cardiovascular disease, migraine, and glaucoma and determined their signaling efficacy toward four functional outcomes, namely, the cAMP, ERK1/2, and calcium signaling pathways, as well as b 2 AR endocytosis. Importantly, both formal clinical studies and anecdotal observations suggest that some of these compounds may be more efficacious and/or safer than others for certain clinical indications, despite having the same relative efficacy toward the cAMP pathway (Castle et al, 1993;Cruickshank, 1993;Eichhorn and Young, 2001;Javed and Deedwania, 2009;Ram, 2010). Although these differences may be attributed to other properties of the drugs (polypharmacology, pharmacokinetics, etc.…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Quantification of Ligand Bias for Clinically Relevant β₂-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

et al. 2013

View full text Add to dashboard Cite

The concepts of functional selectivity and ligand bias are becoming increasingly appreciated in modern drug discovery programs, necessitating more informed approaches to compound classification and, ultimately, therapeutic candidate selection. Using the b2-adrenergic receptor as a model, we present a proof of concept study that assessed the bias of 19 b-adrenergic ligands, including many clinically used compounds, across four pathways [cAMP production, extracellular signal-regulated kinase 1/2 (ERK1/2) activation, calcium mobilization, and receptor endocytosis] in the same cell background (human embryonic kidney 293S cells). Efficacy-based clustering placed the ligands into five distinct groups with respect to signaling signatures. In some cases, apparent functional selectivity originated from offtarget effects on other endogenously expressed adrenergic receptors, highlighting the importance of thoroughly assessing selectivity of the responses before concluding receptor-specific ligand-biased signaling. Eliminating the nonselective compounds did not change the clustering of the 10 remaining compounds. Some ligands exhibited large differences in potency for the different pathways, suggesting that the nature of the receptoreffector complexes influences the relative affinity of the compounds for specific receptor conformations. Calculation of relative effectiveness (within pathway) and bias factors (between pathways) for each of the compounds, using an operational model of agonism, revealed a global signaling signature for all of the compounds relative to isoproterenol. Most compounds were biased toward ERK1/2 activation over the other pathways, consistent with the notion that many proximal effectors converge on this pathway. Overall, we demonstrate a higher level of ligand texture than previously anticipated, opening perspectives for the establishment of pluridimensional correlations between signaling profiles, drug classification, therapeutic efficacy, and safety.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Quantification of Ligand Bias for Clinically Relevant β₂-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Furthermore, even if the physical therapist screens for the use of these substances, it may be difficult to confirm usage by the patient. These medications can have effects on the cardiovascular system and therefore may alter patient response to exercise and potentially increase the risk of an adverse event [12].…”

Section: Discussionmentioning

confidence: 99%

Clinical decision making regarding the use of vital signs in physical therapy

Thistle¹,

Basskin²,

Shamus³

et al. 2016

Phys Ther Rehabil

View full text Add to dashboard Cite

Background: Vital signs including body temperature, blood pressure, heart rate, respiratory rate, and pulse oximetry are components of the clinical decision making process by physical therapists. Vital signs help to predict physical therapy indications, contraindications and outcomes. Previous studies have shown that physical therapists do not always objectively measure vital signs each visit. Objectives: The purpose of the study was to examine the clinical decision making process involved in the measurement of vital signs by physical therapists. Design: This study was a qualitative design utilizing a questionnaire with three sections including demographic data, clinical decision making questions, and two risk-based scenarios in which participants were asked to indicate whether or not they would assess vital signs. Methods: Seventeen practicing physical therapists were given a questionnaire by phone, email, or in person. Data were recorded, coded, and transcribed. Answers to open ended questions were grouped into themes based on common responses and similar characteristics. Results: The primary factors cited in response to source of reference for cardiovascular risk included clinical experience, education, and patient presentation. The primary factors provided in response to the decision to treat or refer based on abnormal vital signs included patient history, clinical experience, various parameters, and contacting the physician. Conclusion: The variation of factors that influenced the decision making process by the participants may be reflective of the lack of guidelines and the broad understanding of the need and benefit of objectively assessing vital signs.

show abstract

“…37,38 The popularity of b-blockers declined after the publication of meta-analyses concluding that b-blockers (mainly atenolol). The original premise of b-blockers actions, however, has not been challenged.…”

Section: Discussionmentioning

confidence: 99%

Hypertension Therapeutics Update: A Brief Clinical Summary on Azilsartan, Cilnidipine and Nebivolol

Sharma¹

2015

Hypertension Journal

View full text Add to dashboard Cite

Uncontrolled hypertension is the major risk factor for cardio vascular disease. The economic burden of disease is enor mous in developed as well as in developing countries. The epidemiological studies have explained many etiological factors associated with chronic untreated hypertension, which varies according to geography and ethnicity.In last five decades, many classes and types of antihyper tensive drugs have been developed. This pharma cological review provides an update on new molecules belonging to three pharmacological classes of antihypertensives-angiotensin receptor blocker (azilsartan), calcium channel blocker (cilnidipine) and beta blocker (nebivolol) and their clinical implications.

show abstract

Beta-Blockers in Hypertension

Cited by 99 publications

References 50 publications

Quantification of Ligand Bias for Clinically Relevant β₂-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

Quantification of Ligand Bias for Clinically Relevant β₂-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

Clinical decision making regarding the use of vital signs in physical therapy

Hypertension Therapeutics Update: A Brief Clinical Summary on Azilsartan, Cilnidipine and Nebivolol

Contact Info

Product

Resources

About

Beta-Blockers in Hypertension

Cited by 99 publications

References 50 publications

Quantification of Ligand Bias for Clinically Relevant β2-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

Quantification of Ligand Bias for Clinically Relevant β2-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

Clinical decision making regarding the use of vital signs in physical therapy

Hypertension Therapeutics Update: A Brief Clinical Summary on Azilsartan, Cilnidipine and Nebivolol

Contact Info

Product

Resources

About

Quantification of Ligand Bias for Clinically Relevant β₂-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

Quantification of Ligand Bias for Clinically Relevant β₂-Adrenergic Receptor Ligands: Implications for Drug Taxonomy