Escitalopram co-prescription in anastrozole-treated breast cancer patients.

OBJECTIVE: The purpose of the study was to evaluate the impact of escitalopram co-prescription on plasma anastrozole levels in post-menopausal breast cancer patients. METHODS: A total of 24 post-menopausal operated breast cancer patients co-prescribed with escitalopram and anastrozole were included. Blood samples were collected, before and 1-month after the onset of escitalopram to analyze plasma anastrozole and estradiol levels. RESULTS: No significant difference was noted in basal plasma anastrozole levels with respect to age, body mass index (BMI), tumor stage, previous antineoplastic treatments, concomitant medications, and serum estradiol levels. Overall, 17 patients completed the 1-month escitalopram treatment, while 7 patients discontinued escitalopram within the 1st week of the treatment. Basal anastrozole levels of 24 patients were 26.1±2.4 ng/mL. Among 17 patients who continued 1-month escitalopram treatment was associated with significant increase in plasma anastrozole levels (24.5±2.3 ng/mL to 32.2±3.2 ng/mL, p<0.05). Notably, 1-month escitalopram use was associated with significant increase in plasma anastrozole levels only in the subgroup of obese (BMI >29 kg/m2) patients (23.1±2.8 to 35.9±4.7 ng/mL, p<0.01), while no such interaction was noted among non-obese patients. The estradiol levels of the patients were below ≤10 pg/mL in 75% of patients and no change occurred after escitalopram administration. CONCLUSION: Escitalopram co-prescription resulted in significant increase in plasma anastrozole levels without affecting the serum estradiol levels. Our findings emphasize the need for close monitoring in case of concomitant use of anastrozole and escitalopram, especially in obese patients and the potential role of therapeutic drug monitoring.

Potential drug-drug interactions in a medical intensive care unit of a university hospital.

BACKGROUND/AIM: Drug-drug interactions (DDIs) can impact patient safety. Occurrence of clinically important DDIs is higher for intensive care unit (ICU) patients. This observational study aimed to evaluate the potential DDIs in medical ICU patients of a university hospital. MATERIALS AND METHODS: The Medical Pharmacology Department organized consultation reports for ICU patients in order to detect the DDIs. To focus on clinically important DDIs, interactions in the C, D, or X risk rating categories of the Lexi-Interact online database were analyzed. Frequency and clinical risk rating categories of DDIs were detected. Relationship between number of prescriptions and DDIs were assessed. The most frequent drug/drug groups were identified. RESULTS: Of 101 ICU patients, 45.5% were found to have DDIs. We detected 125 C (72.2%), 37 D (21.4%), and 11 X (6.4%) risk category interactions. A statistically significant increase in the number of DDIs was shown with the number of prescriptions (P = 0.002). The most frequent DDIs were between agents acting on the cardiovascular system and corticosteroids (12.8%). CONCLUSION: Results of this study show that pharmacological consultation plays a critical role in the recognition of DDIs for improvement of medication management and effective therapeutic endpoints without any adverse or toxic reactions.

The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression.

OBJECTIVE: The aim of this study was to investigate the relationship between plasma glutamate, glutamine and gamma-aminobutyric acid (GABA) levels in female patients with major depression treated with S-citalopram or fluoxetine. METHODS: The patients were assigned into S-citalopram (10 mg/day) or fluoxetine (20 mg/day) groups (n = 15 per group). The Hamilton and Beck Depression Inventory Scales were performed on all study participants, and blood samples were collected. The same procedures were repeated 10 days following the onset of therapy. Fifteen female healthy volunteers were also included in the study for the evaluation of normal plasma levels. RESULTS: The plasma GABA levels of the healthy volunteers were higher whereas those for glutamate and glutamine were lower than the day zero samples of the patients. An increase in plasma GABA levels and a decrease in glutamate and glutamine levels were observed on the 10th day of treatment. No difference was detected between the drug treatments. CONCLUSION: Our findings may suggest that GABA, glutamate and glutamine play a role in depression and that plasma GABA may be used as a biomarker for treatment control.

Fluoxetine partly exerts its actions through GABA: a neurochemical evidence.

Fluoxetine, as a serotonin re-uptake inhibitor augments serotonin concentration within the synapse by inhibiting the serotonin transporter. The contribution of amino acids has also been shown in depression. We hypothesized that fluoxetine exerts its actions at least in part by intervening brain signaling operated by amino acid transmitters. Therefore the aim of this study is to supply neurochemical evidence that fluoxetine produces changes in amino acids in cerebrospinal fluid of rats. Sprague-Dawley rats were anesthetized and concentric microdialysis probes were implanted stereotaxically into the right lateral ventricle. Intraperitoneal fluoxetine (2.5 or 5 mg/kg) or physiological saline was administered and the probes were perfused with artificial cerebrospinal fluid at a rate of 1 mul/min. In the chronic fluoxetine group, the rats were treated daily with oral fluoxetine solution or inert syrup for 3 weeks. The microdialysis probes were placed on the 21st day and perfused the next day. Fluoxetine was ineffective in changing the cerebrospinal fluid GABA levels at the dose of 2.5 mg/kg but produced a significant increase in the perfusates following injection of 5 mg/kg of fluoxetine (P < 0.05). Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05). L: -glutamic acid levels were not affected in all groups. These neurochemical findings show that fluoxetine, a selective serotonin re-uptake inhibitor affects brain GABA levels indirectly, and our results suggest that acute or chronic effects may be involved in beneficial and/or adverse effects of the drug.

The effects of ethosuximide on amino acids in genetic absence epilepsy rat model.

Genetic absence epilepsy rats from Strasbourg (GAERS), a selectively inbred strain of Wistar rats, has been validated as an experimental model for human absence epilepsy. In this model, systemic administration of ethosuximide (ETX) was shown to reduce the spike and wave discharges (SWD). In this study, gamma-aminobutyric acid (GABA) and L-glutamic acid levels in response to ETX injections (i.p., 100 mg/kg) were measured in the microdialysis samples collected from the ventrolateral thalamus (VLT) and the primary motor cortex (M1) area of Wistar rats and GAERS by using HPLC with fluorescent detection. Throughout the microdialysis procedure, continuous EEG recording was performed where ETX was shown to suppress the SWD activity. We demonstrated increased basal GABA levels in the M1 and VLT of GAERS, and ETX treatment did not produce any effect on higher GABA levels in the VLT, but suppressed the increased GABA levels significantly in the M1 of GAERS. All these findings denote the importance of corticothalamic circuitry and the role of increased GABA tonus in primary motor cortex and thalamus of GAERS. The primary motor cortex also seems to be involved in the SWD activity and ETX exerts, at least partially, its neurotransmitter effects through it.

5-hydroxytryptamine release in the anterior hypothalamic and the hippocampal areas of cholestatic rats.

Cholestasis contributes to the genesis of fatigue through several mechanisms. Among these mechanisms, affected serotonergic neurotransmission is important in the pathogenesis of central fatigue. Previously, elevated levels of 5-hydroxyindole acetic acid (5-HIAA), the metabolite of 5-hydroxytryptamine (5-HT) and increased 5-HT(2) receptor density were demonstrated in the anterior hypothalamus and in the hippocampus of bile duct resected rats (BDR), respectively. The aim of this paper is to demonstrate evoked 5-HT release in selected brain regions like anterior hypothalamus and hippocampal CA1 regions of cholestatic rats using BDR rats as an experimental model for cholestasis. In this study, we analyzed the K+ evoked 5-HT and its metabolite 5-HIAA levels by using HPLC with electrochemical detection in the microdialysis samples collected from anterior hypothalamic and hippocampal CA1 regions of sham-operated and BDR rats (n = 6). The ratios of [5-HIAA] to [5-HT] following perfusion with 100 mM K+ artificial cerebrospinal fluid was used for the comparison of the evoked release of 5-HT. Locomotor activity was used to assess the signs of cholestasis associated fatigue in the BDR rats. The vertical and horizontal activity counts within 15 min were found to be decreased in the BDR rats compared to sham-operated rats (p < 0.05). Besides, the number of fecal boli (an index of emotionality) was also significantly fewer in the cholestatic rats (p < 0.05). No significant difference between the sham-operated and the BDR rats was detected in the basal 5-HT and 5-HIAA levels of anterior hypothalamus. K+ stimulation yielded a more profound increase in the [5-HIAA]/[5-HT] in the BDR rats (p < 0.05). The basal levels of 5-HT in CA1 region of the BDR rats was found to be lower than that of sham-operated group (p < 0.05), but no significant difference was observed in terms of evoked 5-HT release in both sham-operated and BDR rats. These findings imply the presence of affected serotonergic system in cholestasis.