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Allelic Variants in Long-QT Disease Genes in Patients With Drug-Associated Torsades de Pointes
TLDR
DNA variants in the coding regions of congenital long-QT disease genes predisposing to aLQTS can be identified in ≈10% to 15% of affected subjects, predominantly in genes encoding ancillary subunits. Expand
Droperidol Lengthens Cardiac Repolarization due to Block of the Rapid Component of the Delayed Rectifier Potassium Current
TLDR
The effects of droperidol on cardiac repolarization are characterized and a major time‐dependent outward potassium current involved in cardiacRepolarization (IKr) is evaluated. Expand
Block of the rapid component of the delayed rectifier potassium current by the prokinetic agent cisapride underlies drug-related lengthening of the QT interval.
TLDR
Block of I(Kr) gives an explanation to lengthening of cardiac repolarization observed in isolated guinea pig hearts, and is likely to underlie prolongation of the QT interval observed in patients receiving clinically recommended doses of cisapride. Expand
Thioridazine lengthens repolarization of cardiac ventricular myocytes by blocking the delayed rectifier potassium current.
TLDR
Patch-clamp experiments demonstrated that THIO decreases the time-dependent outward K+ current elicited by short depolarizations in a concentration-dependent manner, which may provide an explanation of Q-T prolongation observed in some patients treated with THIO. Expand
Unusual Effects of a QT-Prolonging Drug, Arsenic Trioxide, on Cardiac Potassium Currents
TLDR
It is inferred that variability in the extent of QT interval prolongation and onset of ventricular arrhythmias during arsenic therapy represents competing effects to block and activate multiple repolarizing potassium currents. Expand
In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists.
TLDR
It is demonstrated that classic histamine H1 receptor antagonists, available in over-the-counter preparations, inhibit CYP2D6 in vitro, suggesting that, under specific circumstances, clinically relevant interactions between classic antihistamines and CYP 2D6 substrates might occur. Expand
Risperidone Prolongs Cardiac Repolarization by Blocking the Rapid Component of the Delayed Rectifier Potassium Current
TLDR
Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs at clinically relevant concentrations, and these actions likely enhance risk for ris peridone-related QT prolongation and proarrHythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs). Expand
Human cardiac potassium channel DNA polymorphism modulates access to drug-binding site and causes drug resistance.
TLDR
Assessing drug sensitivity of I(Kur) generated in vitro in CHO and HEK cells by channels predicted to exhibit or lack this C-terminal alpha-helix found that this secondary structure in the KCNA5 C terminus does not alter baseline currents but renders the channel drug resistant. Expand
Modulation of CYP3a expression and activity in mice models of type 1 and type 2 diabetes
TLDR
The results suggest that these two distinct diseases may have the same modulating effect on the regulation of CYP3a, ultimately leading to variability in drug response, ranging from lack of effect to life‐threatening toxicity. Expand
Decreased CYP3A Expression and Activity in Guinea Pig Models of Diet-Induced Metabolic Syndrome: Is Fatty Liver Infiltration Involved?
TLDR
Diet-induced metabolic syndrome decreases CYP3A expression/activity in guinea pigs, which may ultimately lead to variability in drug response, ranging from lack of effect to life-threatening toxicity. Expand
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