Autoantibodies with beta-adrenergic activity from chronic chagasic patients induce cardiac arrhythmias and early afterdepolarization in a drug-induced LQT2 rabbit hearts

2017 ◽  
Vol 240 ◽  
pp. 354-359 ◽  
Author(s):  
Marco Antonio Vidal Jiménez ◽  
José H.M. Nascimento ◽  
Gustavo Monnerat ◽  
Leonardo Maciel ◽  
Claudia N. Paiva ◽  
...  
Keyword(s):  
Cardiac Arrhythmias ◽  
Drug Induced ◽  
Beta Adrenergic ◽  
Early Afterdepolarization ◽  
Adrenergic Activity

Enhanced beta-adrenergic-receptor responsiveness in hypoxic neonatal pulmonary circulation

1981 ◽  
Vol 240 (5) ◽  
pp. H697-H703 ◽  
Author(s):  
J. E. Lock ◽  
P. M. Olley ◽  
F. Coceani
Keyword(s):  
Pulmonary Circulation ◽  
Beta Blockade ◽  
Base Line ◽  
Pulmonary Resistance ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Adrenergic Activity ◽  
Alpha Blockade ◽  
Alveolar Hypoxia ◽  
Constrictor Response

The influence of alveolar hypoxia on pulmonary vascular adrenergic receptors was studied in conscious newborn lambs. In control animals, pulmonary vessels were directly constricted by epinephrine and norepinephrine, but were unaffected by isoproterenol. Pulmonary resistance (PVR) was also unaffected by propranolol, thus implying minimal beta-receptor activity under normoxic conditions. Hypoxia raised PVR but also modified the pulmonary vascular responses to catecholamines: isoproterenol became a dilator, whereas the constrictor effects of epinephrine and norepinephrine were abolished. Although beta-blockade did not alter base-line PVR, propranolol increased the constrictor response to hypoxia, implying that hypoxia increases beta-adrenergic activity or reactivity in the pulmonary circulation. Consistent with this hypothesis are the following: 1) in alpha-blocked lambs, epinephrine was without local effects during normoxia, but caused vasodilation during hypoxia; 2) the absent constrictor response to epinephrine during hypoxia is fully restored by propranolol; and 3) although alpha-blockade blunts the hypoxic constrictor response, the full response is restored when beta-blockade is added. These results indicate that the hypoxic constrictor response is partially opposed by increased beta-mediated vasodilation. These enhanced beta-receptor effects are due, at least in part, to increased beta-receptor reactivity of unknown mechanism.

Use of Disproportionality Analysis to Identify Previously Unknown Drug-Associated Causes of Cardiac Arrhythmias Using the Food and Drug Administration Adverse Event Reporting System (FAERS) Database

2021 ◽  
pp. 107424842098408
Author(s):  
Lindsay N. Moreland-Head ◽  
James C. Coons ◽  
Amy L. Seybert ◽  
Matthew P. Gray ◽  
Sandra L. Kane-Gill
Keyword(s):  
Cardiac Arrhythmias ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Potential Drug ◽  
Drug Induced ◽  
Bundle Branch Block ◽  
Search Terms ◽  
Drug Databases ◽  
Safety Consideration

Introduction: Drug-induced QTc-prolongation is a well-known adverse drug reaction (ADR), however there is limited knowledge of other drug-induced arrhythmias. Purpose: The objective of this study is to determine the drugs reported to be associated with arrhythmias other than QTc-prolongation using the FAERS database, possibly identifying potential drug causes that have not been reported previously. Methods: FAERS reports from 2004 quarter 1 through 2019 quarter 1 were combined to create a dataset of approximately 11.6 million reports. Search terms for arrhythmias of interest were selected from the Standardized MedDRA Queries (SMQ) Version 12.0. Frequency of the cardiac arrhythmias were determined for atrial fibrillation, atrioventricular block, bradyarrhythmia, bundle branch block, supraventricular tachycardia, and ventricular fibrillation and linked to the reported causal medications. Reports were further categorized by prior evidence associations using package inserts and established drug databases. A reporting odds ratio (ROR) and confidence interval (CI) were calculated for the ADRs for each drug and each of the 6 cardiac arrhythmias. Results: Of the 11.6 million reports in the FAERS database, 68,989 were specific to cardiac arrhythmias of interest. There were 61 identified medication-reported arrhythmia pairs for the 6 arrhythmia groups with 33 found to have an unknown reported association. Rosiglitazone was the most frequently medication reported across all arrhythmias [ROR 6.02 (CI: 5.82-6.22)]. Other medications with significant findings included: rofecoxib, digoxin, alendronate, lenalidomide, dronedarone, zoledronic acid, adalimumab, dabigatran, and interferon beta-1b. Conclusion: Upon retrospective analysis of the FAERS database, the majority of drug-associated arrhythmias reported were unknown suggesting new potential drug causes. Cardiac arrhythmias other than QTc prolongation are a new area of focus for pharmacovigilance and medication safety. Consideration of future studies should be given to using the FAERS database as a timely pharmacovigilance tool to identify unknown adverse events of medications.

Clinical Import of Beta-Adrenergic Activity in the Proximal Urethra

1980 ◽  
Vol 124 (2) ◽  
pp. 254-255 ◽  
Author(s):  
M.S. Rao ◽  
B.C. Bapna ◽  
P.L. Sharma ◽  
K.S.N. Chary ◽  
S. Vaidyanathan
Keyword(s):  
Beta Adrenergic ◽  
Adrenergic Activity ◽  
Proximal Urethra

Drug-Induced Cardiac Arrhythmias and Sudden Cardiac Death

Iatrogenicity ◽  
2018 ◽  
pp. 62-76
Author(s):  
Aalap Narichania ◽  
Yasuhiro Yokoyama ◽  
Win K. Shen
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Arrhythmias ◽  
Cardiac Death ◽  
Drug Induced

beta-Receptor influence on lung vasoconstrictor responses to hypoxia and humoral agents

1977 ◽  
Vol 43 (4) ◽  
pp. 612-616 ◽  
Author(s):  
R. J. Porcelli ◽  
A. T. Viau ◽  
N. E. Naftchi ◽  
E. H. Bergofsky
Keyword(s):  
Adrenergic Receptor ◽  
Adrenergic System ◽  
Hypercapnic Acidosis ◽  
Pulmonary Tissue ◽  
Beta Adrenergic ◽  
Vascular Responses ◽  
Adenosine Cyclic Monophosphate ◽  
Adrenergic Activity ◽  
Camp Levels

The role of the adrenergic receptor in mediating pulmonary vascular responses to gaseous and humoral agents was investigated by use of epinephrine injections in the perfused feline pulmonary circulation. Alteration of the balance between alpha- and beta-adrenergic activity was quantified by measurement of decreasing vasoconstrictor activity to epinephrine and rising lobar tissue 3′,5′-adenosine cyclic monophosphate (cAMP) levels. The increased beta-adrenergic activity thus generated was associated with marked reductions in the pulmonary vasoconstrictor responses to hypoxia, hypercapnic acidosis, and histamine, but not to serotonin. Repeated pulmonary vasodilations or increases in blood, but not pulmonary tissue, levels of cAMP induced by theophylline doses, which would not necessarily affect the beta-adrenergic activity, did not alter the pulmonary vasoconstrictor responses to hypoxia, hypercapnia, or histamine. These data support the significant role which the adrenergic system plays in mediating pulmonary vasoconstrictor responses to certain specific gaseous and humoral agents, and the specificity with which this mediation occurs serves to link hypoxia and histamine together so that the latter could serve as a mediator of the former.

scholarly journals Transmural and rate-dependent profiling of drug-induced arrhythmogenic risks through in silico simulations of multichannel pharmacology

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ping’an Zhao ◽  
Pan Li
Keyword(s):  
Cardiac Electrophysiology ◽  
Cell Types ◽  
Cell Models ◽  
Insufficient Information ◽  
Drug Induced ◽  
Rate Dependent ◽  
Early Afterdepolarization ◽  
P Cells ◽  
Quantitative Profiling

AbstractIn vitro human ether-à-go-go related gene (hERG) inhibition assay alone might provide insufficient information to discriminate “safe” from “dangerous” drugs. Here, effects of multichannel inhibition on cardiac electrophysiology were investigated using a family of cardiac cell models (Purkinje (P), endocardial (Endo), mid-myocardial (M) and epicardial (Epi)). We found that: (1) QT prolongation alone might not necessarily lead to early afterdepolarization (EAD) events, and it might be insufficient to predict arrhythmogenic liability; (2) the occurrence and onset of EAD events could be a candidate biomarker of drug-induced arrhythmogenicity; (3) M cells are more vulnerable to drug-induced arrhythmias, and can develop early afterdepolarization (EAD) at slower pacing rates; (4) the application of quinidine can cause EADs in all cell types, while INaL is the major depolarizing current during the generation of drug-induced EAD in P cells, ICaL is mostly responsible in other cell types; (5) drug-induced action potential (AP) alternans with beat-to-beat variations occur at high pacing rates in P cells. These results suggested that quantitative profiling of transmural and rate-dependent properties can be essential to evaluate drug-induced arrhythmogenic risks, and may provide mechanistic insights into drug-induced arrhythmias.

Failure of chronic beta-adrenergic blockade to inhibit overfeeding-induced thermogenesis in humans

1989 ◽  
Vol 256 (3) ◽  
pp. R653-R658 ◽  
Author(s):  
S. L. Welle ◽  
K. S. Nair ◽  
R. G. Campbell
Keyword(s):  
Weight Maintenance ◽  
Resting Metabolic Rate ◽  
Control Group ◽  
Adrenergic Blockade ◽  
Beta Adrenergic ◽  
Initial Reduction ◽  
Adrenergic Antagonist ◽  
Adrenergic Activity ◽  
Propranolol Treatment ◽  
Male Subjects

The effect of the beta-adrenergic antagonist propranolol on the increase in resting metabolic rate (RMR) induced by overfeeding was examined to determine whether increased beta-adrenergic activity contributes to this response. Six male subjects who were overfed with carbohydrate (1,600 excess kcal/day) for 10 days without drug treatment (control group) had increases (compared with values after 10 days of weight maintenance) in RMR after 6 days [0.24 +/- 0.06 kcal/min (22%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. Eight male subjects were given a weight-maintenance diet for 10 days with oral propranolol treatment (40-60 mg every 6 h) over the last 7 days of this period. Five of these subjects were then overfed for 10 days, and three remained on the weight-maintenance diet; propranolol treatment continued until the end of the study. Propranolol significantly reduced RMR (mean 9%) before the onset of overfeeding but did not prevent increases in RMR after 6 days [0.18 +/- 0.05 kcal/min (16%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. In the subjects who remained on the weight-maintenance diet throughout the study, there was no reversal of propranolol's initial reduction of RMR that would have falsely elevated the overfeeding effect. These data provide further evidence that the increase in RMR induced by overfeeding in humans is not mediated by increased beta-adrenergic activity.

Human stem cell research for potential drug-induced cardiac arrhythmias and neuronal side effects: Janssen's strategy

2017 ◽  
Vol 280 ◽  
pp. S24
Author(s):  
Hua Rong Lu ◽  
Ivan Kopljar ◽  
Kreir Mohamed ◽  
Ard Teisman ◽  
David J. Gallacher
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Research ◽  
Cardiac Arrhythmias ◽  
Potential Drug ◽  
Human Stem Cell ◽  
Drug Induced
Sign in / Sign up

Export Citation Format

Share Document