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    CLINICAL POTENTIAL OF CARIPRAZINE IN THE TREATMENT OF ACUTE MANIA
    (Medicinska Naklada, 2013) Altinbas, Kursat; Guloksuz, Sinan; Oral, Esat Timucin
    Cariprazine (RGH-188, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-aminehydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors antagonist-partial agonist properties. Cariprazine has also moderate affinity for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B receptors with pure antagonism and low affinity for 5-HT2A receptors. Randomized, double blind, placebo controlled, flexible-dose (3-12 mg/day) studies have demonstrated cariprazine is effective in both schizophrenia and acute manic episodes associated with bipolar disorder. The incidence of serious adverse events in cariprazine arm was no different than in placebo arm in these studies. The most common adverse events were extrapyramidal symptoms, headache, akathisia, constipation, nausea, and dyspepsia which can be explained with cariprazine's partial dopamine agonism. Although cariprazine treatment was associated with a higher incidence of treatment-emergent adverse events, particularly akathisia and tremor, common side effects of marketed second generation antipsychotics such as weight gain, metabolic disturbances, prolactin increase or QTc prolongation were not associated with cariprazine, probably due to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. Animal studies show that cariprazine may have additional therapeutic benefit on impaired cognitive functioning with D3 receptor activity, however clinical data is still scarce. The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date.
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    Electrocardiography changes in bipolar patients during long-term lithium monotherapy
    (Elsevier Science Inc, 2014) Altinbas, Kursat; Guloksuz, Sinan; Caglar, Ilker Murat; Caglar, Fatma Nihan Turhan; Kurt, Erhan; Oral, Esat Timucin
    Objective: Cardiovascular side effects of lithium have been reported to occur mainly at higher-than-therapeutic serum levels. We aimed to investigate the impact of the long-term lithium use on electrocardiogram (ECG) parameters in association with the serum levels in patients with bipolar disorder (BD) and in healthy controls (HCs) serving as the reference group. Methods: The study sample consisted of 53 euthymic BD type I patients on lithium monotherapy at therapeutic serum levels (M=0.76, S.D.=0.14, range=0.41-1.09 mmol/l) for at least 12 months and 45 HCs. A 12-lead surface ECG was obtained from all participants at resting state for at least half an hour for 5-min recording. Heart-rate, Pmax, Pmin, QRS interval, QT dispersion, QT dispersion ratio (QTdR) and Tpeak-to-end interval (TpTe) were measured. Results: Regression analyses revealed that QTdR (B=14.17, P=.001), TpTe (B=18.38, P<.001), Pmax (B=17.84, P<.001) and Pmin (B=25.10, P<.001) were increased in BD patients who were on chronic lithium treatment than in HCs after controlling for age, sex and strict Bonferroni correction for multiple testing. There were no associations between serum lithium levels and ECG parameters. Conclusion: Our findings suggest that the use of lithium is associated with both atrial and ventricular electrical instability, even when lithium levels are in the therapeutic range. (C) 2014 Elsevier Inc. All rights reserved.