Cardiovascular toxicology
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Cardiovascular toxicology · Dec 2018
ReviewPoly(ADP-ribose) Polymerase (PARP) and PARP Inhibitors: Mechanisms of Action and Role in Cardiovascular Disorders.
Poly(ADP-ribosyl)ation is an immediate cellular repair response to DNA damage and is catalyzed primarily by poly(ADP-ribose)polymerase-1 (PARP1), which is the most abundant of the 18 different PARP isoforms and accounts for more than 90% of the catalytic activity of PARP in the cell nucleus. Upon detection of a DNA strand break, PARP1 binds to the DNA, cleaves nicotinamide adenine dinucleotide between nicotinamide and ribose and then modifies the DNA nuclear acceptor proteins by formation of a bond between the protein and the ADP-ribose residue. This generates ribosyl-ribosyl linkages that act as a signal for other DNA-repairing enzymes and DNA base repair. ⋯ In this manner, PARP inhibition partially restores the myocardial concentrations of NAD+, limits ventricular remodeling and fibrosis, and prevents significant decreases in myocardial contractility. Based primarily on investigations in preclinical models of atherosclerosis, myocardial infarction, and heart failure, PARP inhibition appears to be beneficial in limiting or inhibiting cardiovascular dysfunction. These studies indicate that investigations of acute and chronic PARP inhibition are warranted in patients with atherosclerotic coronary artery disease.
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Cardiovascular toxicology · Oct 2017
Review Case ReportsTreatment of Amlodipine Intoxication with Intravenous Lipid Emulsion Therapy: A Case Report and Review of the Literature.
We report the case of a 25-year-old female presenting to the emergency department after committing suicide by ingesting 100 mg amlodipine. The patient was initially treated with intravenous fluids, calcium gluconate, catecholamines and glucagone without effect. The clinical condition of the patient improved quickly and dramatically on the 20th minute of intravenous lipid emulsion (ILE) therapy. ⋯ Among these, lipid emulsion therapy has risen over the last decade as a salvation in cases which do not respond to other treatments. However, given the paucity of data, there are conflicting recommendations about the indications, dose and timing of ILE in the literature. In the light of this case report, we review the literature and discuss whether ILE therapy can find itself a place among first-line therapy recommendations.
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Cardiovascular toxicology · Oct 2015
Review Case ReportsEvolving Electrocardiographic Changes in Lamotrigine Overdose: A Case Report and Literature Review.
Lamotrigine overdose usually follows a benign pattern, and the majority of cases reported involve a co-ingestant. Prior reports have suggested the possible use of intravenous lipid emulsion in cases of severe sodium channel blockade. We describe the electrocardiographic changes in a massive lamotrigine overdose treated with intravenous lipid emulsion. ⋯ Cardiac intraventricular conduction could be delayed in cases of lamotrigine overdose resulting in QRS and QTc prolongation and R waves >3 mm in leads I and aVR. A potential role for intravenous lipid emulsion therapy has been described in patients with toxic levels of lamotrigine and electrocardiographic changes refractory to the treatment with sodium bicarbonate. Intravenous lipid emulsion has been successfully used in the treatment of lamotrigine cardiac toxicity.
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Cardiovascular toxicology · Jun 2012
ReviewTimely recognition of cardiovascular toxicity by anticancer agents: a common objective of the pharmacologist, oncologist and cardiologist.
Both conventional and new anticancer drugs can frequently cause adverse cardiovascular effects, which can span from subclinical abnormalities to serious life-threatening and sometimes fatal events. This review examines the principal basic and clinical elements that may be of profit to identify, prevent and treat such toxicities. ⋯ The aspect of anticancer drug cardiotoxicity seems to be somehow underestimated, mainly due to inadequate reporting of adverse reactions from oncology drugs in the post-marketing setting. Thus, the implementation of pharmacovigilance is indispensable to rapidly and fully assess the safety of newer agents in real-life patients.
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Cardiovascular toxicology · Jan 2007
ReviewAnthracycline cardiotoxicity in long-term survivors of childhood cancer.
Anthracycline chemotherapy is a widely-used and effective treatment for a wide spectrum of childhood cancers. Its use is limited by associated progressive and clinically significant cardiotoxic effects. Onset can be acute, early, or late. ⋯ Dexrazoxane prior to anthracycline chemotherapy has been shown to significantly lower rates of elevated serum cardiac troponin levels, a marker of myocyte injury, indicating a cardioprotective effect. Pilot studies indicate that exercise interventions may also be beneficial in long-term survivors with cardiac damage. Support and study of this population to decrease the morbidity and morality associated with anthracycline-induced cardiotoxicity is indicated in a time sensitive fashion.