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 · Dec 2018
Case ReportsComplete Atrioventricular Block in an Elderly Patient Treated with Low-Dose Lacosamide.
Lacosamide, one of the last antiepileptic drugs marketed, can cause extension of PR interval. Precautions are recommended when used in elderly and with other drugs extending PR interval. ⋯ This dramatic event required a pacemaker implementation. Not being dose-dependent (initiation dosage used), it seemed partially explained by drug-drug interaction with bisoprolol.