Part 1: adverse reactions
1.1 Introduction (QT prolongation)
The toxicity of antipsychotic drugs is considered a good example of specific gender differences in Adverse Drug Reactions (ADRs) in a dose-dependent manner [1]. This adverse effect is induced cardiac arrhythmia known as torsade de pointes (TdP) (delay of cardiac repolarization), are associated with the following drugs such as; chlorpromazine, mesoridazine, pimozide and thioridazone, which increase the risk of QT prolongation. It also has been shown with medications that block cardiac voltage-gated potassium channels, protracting repolarization and the QT interval [22].
The QT prolongation is known to be more frequent in women than men due to the specific regulation of potassium channel expression by sex steroids and estrogen [15]. For example, quinidine is a pharmaceutical agent used for arrhythmia, which produces 44% increases in the slope of the QTc interval, occurring more in females than in males [21]. Recent statistical analyses of drug induced torsade de pointes showed that this type of ADR has occurred more in females - equivalent to two – thirds of all cases [12,5]. Sex-specific differences in QT prolongation might be associated with sex hormones. In general, women have longer QT intervals than men even in the absence of drug therapy (414.5 ± 24.0 vs. 406.8 ± 22.2 mesc …show more content…
In small clinical trials has been done experiment on rabbit hearts, they showed that there are two repolarization K+ currents which were measured after administering a second generation of antipsychotics agents (SGA’s), IKr (rapid delayed rectifier) and IK1 (inward rectifier), and the results suggested that a lower outward current density in Female rabbits cells known as Potassium rectifier channel (Ikr) leading that to decrease the flow of repolarization K+ currents and made the myocardium more
1.1 Introduction (QT prolongation)
The toxicity of antipsychotic drugs is considered a good example of specific gender differences in Adverse Drug Reactions (ADRs) in a dose-dependent manner [1]. This adverse effect is induced cardiac arrhythmia known as torsade de pointes (TdP) (delay of cardiac repolarization), are associated with the following drugs such as; chlorpromazine, mesoridazine, pimozide and thioridazone, which increase the risk of QT prolongation. It also has been shown with medications that block cardiac voltage-gated potassium channels, protracting repolarization and the QT interval [22].
The QT prolongation is known to be more frequent in women than men due to the specific regulation of potassium channel expression by sex steroids and estrogen [15]. For example, quinidine is a pharmaceutical agent used for arrhythmia, which produces 44% increases in the slope of the QTc interval, occurring more in females than in males [21]. Recent statistical analyses of drug induced torsade de pointes showed that this type of ADR has occurred more in females - equivalent to two – thirds of all cases [12,5]. Sex-specific differences in QT prolongation might be associated with sex hormones. In general, women have longer QT intervals than men even in the absence of drug therapy (414.5 ± 24.0 vs. 406.8 ± 22.2 mesc …show more content…
In small clinical trials has been done experiment on rabbit hearts, they showed that there are two repolarization K+ currents which were measured after administering a second generation of antipsychotics agents (SGA’s), IKr (rapid delayed rectifier) and IK1 (inward rectifier), and the results suggested that a lower outward current density in Female rabbits cells known as Potassium rectifier channel (Ikr) leading that to decrease the flow of repolarization K+ currents and made the myocardium more