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      Comprehensive review of cardiovascular toxicity of drugs and related agents

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          Abstract

          Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta‐blockers, calcium channel blockers, female hormones, nonsteroidal anti‐inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.

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          hERG potassium channels and cardiac arrhythmia.

          hERG potassium channels are essential for normal electrical activity in the heart. Inherited mutations in the HERG gene cause long QT syndrome, a disorder that predisposes individuals to life-threatening arrhythmias. Arrhythmia can also be induced by a blockage of hERG channels by a surprisingly diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials. Insights gained from the crystal structures of other potassium channels have helped our understanding of the block of hERG channels and the mechanisms of gating.
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            The epidemiology of venous thromboembolism

            Venous thromboembolism (VTE) is categorized by the U.S. Surgeon General as a major public health problem. VTE is relatively common and associated with reduced survival and substantial health-care costs, and recurs frequently. VTE is a complex (multifactorial) disease, involving interactions between acquired or inherited predispositions to thrombosis and VTE risk factors, including increasing patient age and obesity, hospitalization for surgery or acute illness, nursing-home confinement, active cancer, trauma or fracture, immobility or leg paresis, superficial vein thrombosis, and, in women, pregnancy and puerperium, oral contraception, and hormone therapy. Although independent VTE risk factors and predictors of VTE recurrence have been identified, and effective primary and secondary prophylaxis is available, the occurrence of VTE seems to be relatively constant, or even increasing.
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              The serotonin syndrome.

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                Author and article information

                Contributors
                mladenkap@faf.cuni.cz
                sterbam@lfhk.cuni.cz
                Journal
                Med Res Rev
                Med Res Rev
                10.1002/(ISSN)1098-1128
                MED
                Medicinal Research Reviews
                John Wiley and Sons Inc. (Hoboken )
                0198-6325
                1098-1128
                05 January 2018
                July 2018
                : 38
                : 4 ( doiID: 10.1002/med.2018.38.issue-4 )
                : 1332-1403
                Affiliations
                [ 1 ] Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové Charles University Hradec Králové Czech Republic
                [ 2 ] Department of Radiology and Toxicology, Faculty of Health and Social Studies University of South Bohemia České Budějovice Czech Republic
                [ 3 ] Biomedical Research Centre University Hospital Hradec Kralove Czech Republic
                [ 4 ] UCIBIO, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy University of Porto Porto Portugal
                [ 5 ] Oncogynaecologic Center, Department of Gynecology and Obstetrics University Hospital Ostrava Czech Republic
                [ 6 ] Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy in Hradec Králové Charles University Hradec Králové Czech Republic
                [ 7 ] Department of Pharmacology Louisiana State University Health Sciences Center New Orleans LA USA
                [ 8 ] Department of Pharmacology, Faculty of Medicine in Hradec Králové Charles University Hradec Králové Czech Republic
                Author notes
                [*] [* ] Correspondence

                Přemysl Mladěnka, Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.

                Email: mladenkap@ 123456faf.cuni.cz

                Martin Štěrba, Department of Pharmacology, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03. Email: sterbam@ 123456lfhk.cuni.cz

                Author information
                http://orcid.org/0000-0002-6076-6900
                http://orcid.org/0000-0001-6740-9685
                http://orcid.org/0000-0002-0471-2756
                http://orcid.org/0000-0003-1382-5119
                http://orcid.org/0000-0002-0728-4646
                http://orcid.org/0000-0001-5460-8044
                http://orcid.org/0000-0003-0145-7697
                Article
                MED21476
                10.1002/med.21476
                6033155
                29315692
                4894f2a4-0e3c-4c7a-898b-1fcfd307888d
                © 2018 The Authors Medicinal Research Reviews Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 08 August 2017
                : 20 October 2017
                : 16 November 2017
                Page count
                Figures: 14, Tables: 9, Pages: 72, Words: 38420
                Funding
                Funded by: Charles University
                Award ID: Research Projects Progres Q40 and Progres Q42
                Award ID: UNCE 204019/304019/2012
                Funded by: ERASMUS+
                Award ID: 2015‐1‐ES01‐KA203‐015957
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                med21476
                July 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.3 mode:remove_FC converted:05.07.2018

                dysrhythmia,heart failure,hypertension,myocardial infarction,stroke

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