PMC:1088007 / 2444-5554 JSON TXT

Annnotations TAB JSON ListView MergeView

2_test

{"project":"2_test","denotations":[{"id":"15845138-12109926-2777154","span":{"begin":332,"end":333},"obj":"12109926"},{"id":"15845138-15066127-2777155","span":{"begin":1308,"end":1309},"obj":"15066127"},{"id":"15845138-11232751-2777156","span":{"begin":1664,"end":1665},"obj":"11232751"},{"id":"15845138-12534434-2777157","span":{"begin":1937,"end":1938},"obj":"12534434"},{"id":"15845138-10947683-2777157","span":{"begin":1937,"end":1938},"obj":"10947683"},{"id":"15845138-11477329-2777157","span":{"begin":1937,"end":1938},"obj":"11477329"},{"id":"15845138-10832858-2777158","span":{"begin":2198,"end":2200},"obj":"10832858"},{"id":"15845138-12088171-2777159","span":{"begin":2319,"end":2321},"obj":"12088171"},{"id":"15845138-10510461-2777160","span":{"begin":2381,"end":2383},"obj":"10510461"},{"id":"15845138-12839860-2777161","span":{"begin":2598,"end":2600},"obj":"12839860"},{"id":"15845138-12839862-2777162","span":{"begin":2659,"end":2661},"obj":"12839862"},{"id":"15845138-11805215-2777163","span":{"begin":2696,"end":2698},"obj":"11805215"},{"id":"15845138-10744090-2777164","span":{"begin":2809,"end":2811},"obj":"10744090"}],"text":"Background\nThe QTc interval is a heart rate corrected value that measures the time between the onset and the end of electrical ventricular activity. Prolongation of this interval is considered a marker of the arrhythmogenic potential of a drug specifically linked to an increased risk of torsade de pointes ventricular tachycardia [1].\nAccording to a document presented by the Committee for Proprietary Medicinal Products (CPMP) in 1997, normal subjects can be divided into three groups based on QTc interval length. For males, QTc values less than 430 ms are normal, between 431 and 450 ms are borderline and over 450 ms are prolonged. Whereas for females QTc values less than 450 ms are normal, between 451 and 470 ms are borderline and over 470 ms are prolonged [2].\nThis sex difference appears to be androgen driven and not determined by female hormones: at birth, QTc interval measurements are the same for male and female infants. At puberty, the male QTc interval shortens and remains shorter than its female counterpart by about 20 ms until ages 50 to 55 years, coincident with a decline in testosterone levels moreover, baseline QTc interval duration doesn't show significant fluctuations during the menstrual cycle and Hormone Replacement Therapy in postmenopausal age doesn't affect QTc interval [3].\nIn the above mentioned CPMP document it was also suggested that individual changes of QTc length of between 30 and 60 ms from baseline raises concern for the potential risk of drug induced arrhythmias [2].\nAntipsychotics such as thioridazine, ziprasidone, quetiapine, risperidone, olanzapine or haloperidol have been suggested to prolong QTc interval [4-7].\nSome authors reported that antidepressant drugs, including Selective Serotonine Reuptake Inhibitors (SSRI) (fluvoxamine, paroxetine and sertraline), Tricyclic Antidepressants (TCA) (amytriptiline, clomipramine, imipramine), and lithium can also prolong QTc interval [8-10].\nAlmost all drugs causing significant QT prolongation are known to interact with repolarizing potassium channels, particularly with the rapid component of delayed rectifier potassium currents (Ikr), encoded by the human Ether-a-go-go related gene (HERG) [11].\nHowever, TCA agents may affect the QTc interval primarily by their effect on sodium channels during depolarization [12]. Nonetheless TCA can also affect HERG potassium channels [13].\nDrug trapping and structure-function studies suggest that the inner cavity of HERG channels is larger than other voltage-gated potassium channels and is therefore able to accommodate diverse chemical structures [14]. Among those drugs there are also SSRI like fluvoxamine [15], citalopram [16] and fluoxetine [17].\nThe combination of antipsychotic and antidepressant agents seems to have addictive effects on QTc interval [18].\nWe investigated the effects of polypharmacy on QTc in two groups of psychiatric female inpatients. Our null hypothesis was that patients treated with antipsychotics plus antidepressants or lithium would not have a greater QTc prolongation, if any, than patients treated with antipsychotics alone."}

NEUROSES

PMC:1088007 / 2444-5554 JSONTXT

Annnotations TAB JSON ListView MergeView

2_test

NEUROSES

PMC:1088007 / 2444-5554 JSON TXT