The pharmacovigilance-center FAKOS – Detection of drug induced agranulocytosis, immune thrombocytopenia, hepatitis, pancreatitis, LongQT-Syndrome and Torsade de pointes

2010 ◽  
Vol 72 (08/09) ◽  
Author(s):  
E Bronder ◽  
H Kurtal ◽  
A Klimpel ◽  
F Andersohn ◽  
W Haverkamp ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Torsade De Pointes ◽  
Drug Induced ◽  
Pharmacovigilance Center

scholarly journals Case Report: Oxaliplatin-Induced Immune-Mediated Thrombocytopenia

2018 ◽  
Vol 11 (3) ◽  
pp. 880-882 ◽  
Author(s):  
Elizabeth Pan ◽  
Eric Hsieh ◽  
Caroline Piatek
Keyword(s):  
Case Report ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Immune Thrombocytopenia ◽  
Drug Induced ◽  
Gastrointestinal Malignancies ◽  
Common Cause ◽  
Immune Mediated ◽  
Chemotherapy Agents ◽  
Platinum Derivative

Thrombocytopenia is a frequent complication of cancer may be due to a variety of causes including malignancy itself, acute disease processes, or cancer therapy. Systemic cancer therapy is the most common cause of thrombocytopenia in cancer patients observed nearly two-thirds of patients with solid tumors. Thrombocytopenia with traditional chemotherapy agents is most frequently the result of megakaryocyte cytotoxicity. Oxaliplatin is a platinum derivative commonly used in gastrointestinal malignancies and is associated with drug-induced immune thrombocytopenia.

scholarly journals Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

2013 ◽  
Vol 27 (3) ◽  
pp. 137-145 ◽  
Author(s):  
Donald M. Arnold ◽  
Ishac Nazi ◽  
Theodore E. Warkentin ◽  
James W. Smith ◽  
Lisa J. Toltl ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Drug Induced ◽  
Diagnosis And Management

scholarly journals Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects

2021 ◽  
Author(s):  
Yangyang Lin ◽  
Sam Z. Grinter ◽  
Zhongju Lu ◽  
Xianjin Xu ◽  
Hong Zhan Wang ◽  
...  
Keyword(s):  
Action Potential ◽  
In Silico ◽  
Therapeutic Efficacy ◽  
Torsade De Pointes ◽  
Computational Prediction ◽  
Chemical Library ◽  
Drug Induced ◽  
Voltage Dependent ◽  
Life Threatening ◽  
Approved Drugs

AbstractCardiac arrhythmias are the most common cause of sudden cardiac death worldwide. Lengthening the ventricular action potential duration (APD) either congenitally or via pathologic or pharmacologic means, predisposes to a life-threatening ventricular arrhythmia, Torsade de Pointes. IKs, a slowly activating K+ current plays a role in action potential repolarization. In this study, we screened a chemical library in silico by docking compounds to the voltage sensing domain (VSD) of the IKs channel. Here we show that C28 specifically shifted IKs VSD activation in ventricle to more negative voltages and reversed drug-induced lengthening of APD. At the same dosage, C28 did not cause significant changes of the normal APD in either ventricle or atrium. This study provides evidence in support of a computational prediction of IKs VSD activation as a potential therapeutic approach for all forms of APD prolongation. This outcome could expand the therapeutic efficacy of a myriad of currently approved drugs that may trigger arrhythmias.Significance statementC28, identified by in silico screening, specifically facilitated voltage dependent activation of a cardiac potassium ion channel, IKs. C28 reversed drug-induced prolongation of action potentials, but minimally affected the normal action potential at the same dosage. This outcome supports a computational prediction of modulating IKs activation as a potential therapy for all forms of action potential prolongation, and could expand therapeutic efficacy of many currently approved drugs that may trigger arrhythmias.

scholarly journals Drug-induced QT interval prolongation in cancer patients

2011 ◽  
Vol 4 (4) ◽  
pp. 223
Author(s):  
Torben K. Becker ◽  
Sai-Ching J. Yeung
Keyword(s):  
Cancer Patients ◽  
Qt Interval ◽  
Alkylating Agents ◽  
Torsade De Pointes ◽  
Interval Prolongation ◽  
Drug Induced ◽  
Vascular Disruption ◽  
Qt Interval Prolongation ◽  
Increased Risk ◽  
Multiple Drugs

Cancer patients are at an increased risk for QT interval prolongation and subsequent potentially fatal Torsade de pointes tachycardia due to the multiple drugs used for treatment of malignancies and the associated symptoms and complications. Based on a systematic review of the literature, this article analyzes the risk for prolongation of the QT interval with antineoplastic agents and commonly used concomitant drugs. This includes anthracyclines, fluorouracil, alkylating agents, and new molecularly targeted therapeutics, such as vascular disruption agents. Medications used in the supportive care can also prolong QT intervals, such as methadone, 5-HT3-antagonists and antihistamines, some antibiotics, antifungals, and antivirals. We describe the presumed mechanism of QT interval prolongation, drug-specific considerations, as well as important clinical interactions. Multiple risk factors and drug–drug interactions increase this risk for dangerous arrhythmias. We propose a systematic approach to evaluate cancer patients for the risk of QT interval prolongation and how to prevent adverse effects.

scholarly journals Assessing Drug-Induced Long QT and Proarrhythmic Risk Using Human Stem-Cell-Derived Cardiomyocytes in a Ca2+ Imaging Assay: Evaluation of 28 CiPA Compounds at Three Test Sites

2019 ◽  
Vol 170 (2) ◽  
pp. 345-356 ◽  
Author(s):  
Hua Rong Lu ◽  
Haoyu Zeng ◽  
Ralf Kettenhofen ◽  
Liang Guo ◽  
Ivan Kopljar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Microelectrode Array ◽  
Torsade De Pointes ◽  
Transient Assay ◽  
Potential Drug ◽  
Human Stem Cell ◽  
Long Qt ◽  
Drug Induced ◽  
Vitro Assay

Abstract The goal of this research consortium including Janssen, MSD, Ncardia, FNCR/LBR, and Health and Environmental Sciences Institute (HESI) was to evaluate the utility of an additional in vitro assay technology to detect potential drug-induced long QT and torsade de pointes (TdP) risk by monitoring cytosolic free Ca2+ transients in human stem-cell-derived cardiomyocytes (hSC-CMs). The potential proarrhythmic risks of the 28 comprehensive in vitro proarrhythmia assay (CiPA) drugs linked to low, intermediate, and high clinical TdP risk were evaluated in a blinded manner using Ca2+-sensitive fluorescent dye assay recorded from a kinetic plate reader system (Hamamatsu FDSS/µCell and FDSS7000) in 2D cultures of 2 commercially available hSC-CM lines (Cor.4U and CDI iCell Cardiomyocytes) at 3 different test sites. The Ca2+ transient assay, performed at the 3 sites using the 2 different hSC-CMs lines, correctly detected potential drug-induced QT prolongation among the 28 CiPA drugs and detected cellular arrhythmias-like/early afterdepolarization in 7 of 8 high TdP-risk drugs (87.5%), 6 of 11 intermediate TdP-risk drugs (54.5%), and 0 of 9 low/no TdP-risk drugs (0%). The results were comparable among the 3 sites and from 2 hSC-CM cell lines. The Ca2+ transient assay can serve as a user-friendly and higher throughput alternative to complement the microelectrode array and voltage-sensing optical action potential recording assays used in the HESI-CiPA study for in vitro assessment of drug-induced long QT and TdP risk.

A Comparison of Two Assays for Platelet Antibodies

1979 ◽  
Author(s):  
J.G. Kelton ◽  
A. Giles ◽  
P.B. Neame ◽  
M. Blajchman ◽  
J. Hirah
Keyword(s):  
Multiple Myeloma ◽  
Immune Thrombocytopenia ◽  
Test System ◽  
Healthy Controls ◽  
Fluorescent Assay ◽  
Drug Induced ◽  
Optimal Method ◽  
Platelet Antibodies ◽  
Immune Mediated ◽  
Fluorescence Test

The optimal method for assaying platelet bound antibody is uncertain. We have compared a fluorescent assay (FA) with a (quantitative) antiglobulin consumption assay for platelet associated IgG (PAIgG) in normals and thrombocytopenics with ITP, SLE, non-immune and drug-induced thrombocytopenia. Forty-eight of 49 hospitalized and healthy controls had normal PAIgG levels by the antiglobulin consumption assay (2.6 ± 0.2 fg IgG/platetet, ± SE, normal 0-5 fg) and the FA was negative in 41. The PAIgG level was elevated (20.0 ± 1.9 fq IgG/platdet) in 42 of 45 determinations on ITP patients. The FA was positive in 21. Positivity in the FA test did not relate closely to PAIgG level. The PAlqG was elevated (29.0 - 7.3) in 14 of 15 assays in thrombocytopenic SLE patients. The FA was positive in 3. The PAIgG level was elevated in all 9 patients with drug-induced thrombocytopenia (42.4 ± 23.2) without addition of the drug to the test system. The FA was positive in 5. In 2 of 12 patients with non-immune thrombocytopenia the PAIgG level was slightly elevated (both patients had multiple myeloma) and the FA was positive in 5. The results suggest that the quantitative antiglobulin consumption assay is more sensitive than the fluorescent assay in the diagnosis of immune mediated throinbocytopenia. The significance of the lack of correlation between positivity in the fluorescence test and the PAIgG levels found in patients with ITP is uncertain.

Terfenadine-Induced Torsade de Pointes: Risk Factors and Mechanisms

1997 ◽  
Vol 13 (3) ◽  
pp. 127-132 ◽  
Author(s):  
Thomas Yk Chan
Keyword(s):  
Risk Factors ◽  
Liver Dysfunction ◽  
Qt Interval ◽  
Torsade De Pointes ◽  
Pharmacokinetic Studies ◽  
Drug Induced ◽  
Significant Prolongation ◽  
Concurrent Use ◽  
Cyp3a4 Inhibitors

Objective: To review the risk factors and mechanisms of terfenadine-induced torsade de pointes and to discuss how this adverse reaction might be avoided. Data Sources: Previous reports of terfenadine-induced torsade de pointes and studies of the underlying mechanisms were identified by a MEDLINE search or from the reference lists of pertinent articles. Study Selection and Data Extraction: All relevant articles were included in the review. Pertinent information was selected for discussion. Data Synthesis: Terfenadine is extensively (99%) metabolized by CYP3A4 to an active acid metabolite (terfenadine carboxylate), and with therapeutic dosages, unchanged terfenadine is usually undetectable in plasma. A review of all the reported cases of torsade de pointes indicated that most patients had one or more factors that would be expected to cause excessively high concentrations of unchanged terfenadine, such as overdose; use of supratherapeutic dosages; concurrent use of CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin, and troleandomycin; and liver dysfunction. Many patients had one or more factors known to predispose to drug-induced torsade de pointes (e.g., preexisting prolonged QT interval, ischemic heart disease, hypokalemia). Pharmacokinetic studies in healthy volunteers have shown that ketoconazole, itraconazole, erythromycin, and clarithromycin can alter the metabolism of terfenadine and result in the accumulation of unchanged terfenadine, which is associated with significant prolongation of the QT interval. In vitro studies have shown that the proarrhythmic effects of terfenadine are secondary to the blockade of cardiac potassium channels. Terfenadine carboxylate does not have such an effect. Conclusions: Supratherapeutic dosages of terfenadine should never be used. The concurrent use of CYP3A4 inhibitors should be avoided. Terfenadine should be avoided in patients with liver dysfunction or factors known to predispose to drug-induced torsade de pointes.

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