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Qing-Kai-Ling Injection Induces Immediate Hypersensitivity Reaction via the Activation of Anaphylatoxin C3
Conclusion: QKLI-IHR is complement activation-related pseudoallergy, rather than an IgE-mediated allergy. QKLI activates C3 and might consequently provoke mast cells to release histamine, which is a principal effector of its IHR. The pseudoallergic reaction induced by QKLI was attributed to the extract of Isatidis Radix. This study suggests a potential therapeutic strategy for the prophylaxis and treatment of QKLI-IHR.
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Testing the Translational Power of the Zebrafish: An Interspecies Analysis of Responses to Cardiovascular Drugs
The zebrafish is rapidly emerging as a promising alternative in vivo model for the detection of drug-induced cardiovascular effects. Despite its increasing popularity, the ability of this model to inform the drug development process is often limited by the uncertainties around the quantitative relevance of zebrafish responses compared with non-clinical mammalian species and ultimately humans. Here we provide a comparative quantitative analysis of the in vivo cardiovascular responses of zebrafish, rat, dog, and human to three model compounds (propranolol, losartan, and captopril), which act as modulators of two key systems ...
Source: Frontiers in Pharmacology - August 15, 2019 Category: Drugs & Pharmacology Source Type: research

An Exploratory Study in Healthy Male Subjects of the Mechanism of Mirabegron-Induced Cardiovascular Effects.
Abstract To explore the role of β1 -adrenoceptors (ARs) in the heart rate response to the selective β3 -adrenoceptor agonist mirabegron, 12 young male volunteers received single oral doses of the nonselective β1/2 -AR antagonist propranolol (160 mg), the selective β1 -AR antagonist bisoprolol (10 mg), or placebo on days 1 and 5 of each period in a 3-period crossover study. On day 5, dosing was followed by a supratherapeutic dose of mirabegron (200 mg). Vital signs, impedance cardiography, and plasma renin activity were collected. Mirabegron increased heart rate and systolic blood pressure and reduced stroke vo...
Source: The Journal of Clinical Pharmacology - June 15, 2017 Category: Drugs & Pharmacology Authors: van Gelderen M, Stölzel M, Meijer J, Kerbusch V, Collins C, Korstanje C Tags: J Clin Pharmacol Source Type: research

Drug effects on the CVS in conscious rats: separating cardiac output into heart rate and stroke volume using PKPD modelling
Conclusions and ImplicationsA systems pharmacology model characterizing the interrelationship between MAP, CO, HR, SV and TPR was obtained in hypertensive and normotensive rats. This extended model can quantify dynamic changes in the CVS and elucidate the MoA for novel compounds, with one site of action, using only HR and MAP measurements. Whether the model can be applied for compounds with a more complex MoA remains to be established.
Source: British Journal of Pharmacology - September 5, 2014 Category: Drugs & Pharmacology Authors: N Snelder, B A Ploeger, O Luttringer, D F Rigel, F Fu, M Beil, D R Stanski, M Danhof Tags: RESEARCH PAPER Source Type: research

Drug effects on the cardiovascular system in conscious rats – separating cardiac output into heart rate and stroke volume using PKPD modeling
Conclusions and ImplicationsA systems pharmacology model characterizing the interrelationship between MAP, CO, HR, SV and TPR has been obtained in hypertensive and normotensive rats. The extended model can be used to quantify the dynamic changes in the CVS and elucidate the MoA for novel compounds, with one site of action, using HR and MAP measurements only. The question whether the model can also be applied for compounds with a more complex mechanism of action remains to be established.
Source: British Journal of Pharmacology - June 24, 2014 Category: Drugs & Pharmacology Authors: N. Snelder, B.A. Ploeger, O. Luttringer, D.F. Rigel, F. Fu, M. Beil, D.R. Stanski, M. Danhof Tags: Research Paper Source Type: research