RESUMEN
Zolpidem is a non-benzodiazepine hypnotic drug that works as a positive modulator of Gamma-Amino Butyric Acid-A (GABA-A) receptors, with high selectivity for α1 subunits. Given this selective binding, the drug has a strong hypnotic activity. Social isolation during the SARS-CoV-2 pandemic has contributed to increased rates of anxiety, depression, and insomnia. As a result, studies have pointed to a possible increase in the indiscriminate use of drugs with sedative effects, such as Zolpidem, during the pandemic. The aim of this work was to present prospective evidence that warns of the possibility of the abusive use of Zolpidem even after the pandemic. High rates of addiction to this drug have been reported around the world after the emergence of the coronavirus. Data from the National Survey on Drug Use and Health and from Medicaid support the continuing growth in prescription and indiscriminate use of Zolpidem during the pandemic and afterward. Therefore, there is enough evidence to support the indiscriminate use of this drug since the beginning of the pandemic. Rates of indiscriminate use of sedatives may continue to increase in the post-pandemic period, especially if strict control measures are not taken by health authorities.
RESUMEN
RESUMEN El tratamiento de la catatonía considera habitualmente el uso de benzodiacepinas y, de fallar estas, se procede a la terapia electroconvulsiva. Sin embargo, las hipotéticas vías neurobiológicas implicadas en la catatonía postulan un efecto benéfico de fármacos gabaérgicos y bloqueadores de glutamato. Se presenta el caso clínico de una paciente mujer de 45 años de edad, con diagnóstico de esquizofrenia paranoide, que desarrolló un cuadro de estupor catatónico (sin respuesta a las benzodiacepinas) y varias complicaciones médicas; sin embargo, el cuadro mejoró rápidamente con la combinación de zolpidem, memantina y aripiprazol. De este modo, se registró un desenlace no logrado con la terapia estándar de benzodiacepinas. Se concluye que la combinación de medicamentos gabaérgicos y bloqueadores de glutamato puede ser utilizada beneficiosamente en casos de estupor catatónico que no logran responder al manejo usual con benzodiacepinas.
ABSTRACT Objective: The treatment of catatonia usually involves the use of benzodiazepines and, if these fail, electroconvulsive therapy is applied. Nevertheless, hypothetical neurobiological pathways involved in catatonia postulate beneficial effects of GABAergic drugs and glutamate blockers. Clinical case: A 45-year-old female patient, diagnosed with paranoid schizophrenia who developed a catatonic stupor (with no response to benzodiazepines) and various medical complications; however, the condition improved rapidly with the combination of zolpidem, memantine and aripiprazole. Result: A favorable outcome was obtained in this case, not achieved with the previous use of standard benzodiazepine therapy. Conclusions: The combination of GABAergic drugs and glutamate blockers can be beneficially implemented in cases of catatonic stupor that fail to respond to the usual management with benzodiazepines.
RESUMEN
Dysregulation of GABAergic neurotransmission has long been implicated in several psychiatric disorders, including schizophrenia, depression, and anxiety disorders. Alpha 5 subunit-containing GABAA receptors (α5-GABAAR), which are expressed mainly by pyramidal neurons in the hippocampus, have been proposed as a potential target to treat these psychiatric disorders. Here, we evaluated the effects produced by GL-II-73 and SH-053-2'F-R-CH3 (1, 5, and 10 mg/kg), two positive allosteric modulators of α5-GABAAR in behavioral tests sensitive to drugs with anxiolytic, antidepressant, and antipsychotic properties in male and female C57BL/6 mice. In both males and females, GL-II-73 produced an anxiolytic-like effect in the elevated plus-maze (EPM) and novelty-suppressed feeding and a rapid and sustained antidepressant-like effect in the forced swim test. GL-II-73 also induced antipsychotic-like effects in males indicated by attenuating MK-801-induced hyperlocomotion and prepulse inhibition (PPI) disruption. However, GL-II-73 per se increased locomotor activity and impaired fear memory extinction in males and females and PPI in males. On the other hand, SH-053-2'F-R-CH3 induced anxiolytic-like effects in the EPM and facilitated fear memory extinction in males. Contrary to GL-II-73, SH-053-2'F-R-CH3 attenuated MK-801-induced hyperlocomotion and PPI disruption in females but not in males. Neither of these drugs induced rewarding effects or impaired motor coordination. These findings suggest that GL-II-73 and SH-053-2'F-R-CH3 cause distinct sex-dependent behavioral responses and support continued preclinical research on the potential of positive allosteric modulators of α5-GABAAR for the treatment of psychiatric disorders.
Asunto(s)
Ansiolíticos , Antipsicóticos , Animales , Ansiolíticos/farmacología , Benzodiazepinas/farmacología , Maleato de Dizocilpina , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de GABA-A , Ácido gamma-AminobutíricoRESUMEN
Mesial temporal lobe epilepsy with hippocampal sclerosis is the most frequent form of focal epilepsy in adults, and it is often refractory to drug treatment. Regardless of the efforts on developing new antiepileptic drugs for refractory cases, studies suggest a need for better understanding the molecular bases of epilepsy. The microRNAs have been progressively investigated as potential targets for both epilepsy mechanisms elucidation and treatment. Therefore, the goal of this study was to evaluate the differential expression of miR-219, miR-181b, and miR-195, previously described as regulators of the excitatory neurotransmitter receptors NMDA-R1 and AMPA-GluR2 and inhibitory neurotransmitter GABAA (α2, ß3, and γ2 subunits) in the amygdala and hippocampus of patients with mesial temporal lobe epilepsy. Based on genes and miRNAs' quantitative Polymerase Chain Reaction (qPCR) from 18 patients with epilepsy, our results showed an inverse relationship between miR-219 and NMDA-NR1 expression in both the amygdala and hippocampus in comparison to their expression in controls. NR1 and GluR2 were upregulated in the amygdala of epileptic patients. Low miR-195 expression was observed in the amygdala of patients with epilepsy. Our findings indicate that miR-219 has a possible regulatory role in excitatory neurotransmission in patients with epilepsy, contributing to the new avenue of miRNA biology in drug-resistant epilepsy, reserving huge potential for future applications and clinical interventions in conjunction with existing therapies.
Asunto(s)
Epilepsia del Lóbulo Temporal/metabolismo , MicroARNs/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Amígdala del Cerebelo/metabolismo , Epilepsia del Lóbulo Temporal/genética , Regulación de la Expresión Génica/genética , Hipocampo/metabolismo , Humanos , Regulación hacia ArribaRESUMEN
BACKGROUND: Decreased short-interval intracortical inhibition (SICI) to transcranial magnetic stimulation (TMS) of the primary motor cortex was described in subjects with restless legs syndrome/Willis-Ekbom disease (RLS/WED). It remained to be determined whether the magnitude of SICI decrease would be similar across levels of RLS/WED severity. Moreover, it was unknown whether, in addition to decreases in SICI, changes in cortical thickness or area could be detected in subjects with RLS/WED compared to controls. The objective of this study was to compare SICI, cortical thickness, and cortical area in subjects with idiopathic mild to moderate RLS/WED, severe to very severe RLS/WED, and controls. METHODS: The severity of RLS/WED was assessed by the International Restless Legs Syndrome Severity Scale (IRLSS). SICI and 3T magnetic resonance imaging (MRI) data of subjects with RLS/WED and controls were compared. A receiver operating characteristic curve for SICI was designed for discrimination of participants with RLS/WED from controls. Cortical thickness and area were assessed by automated surface-based analysis. RESULTS: SICI was significantly reduced in patients with mild to moderate and severe to very severe RLS/WED, compared to controls (one-way analysis of variance: F = 9.62, p < 0.001). Receiver operating characteristic curve analysis predicted RLS/WED when SICI was above 35% (area under the curve = 0.79, 95% CI 0.67-0.91, p < 0.001). Analyses of the whole brain and of regions of interest did not reveal differences in gray matter thickness or area between controls and subjects with RLS/WED. CONCLUSION: SICI is an accurate cortical biomarker that can support the diagnosis of RLS/WED even in subjects with mild symptoms, but cortical thickness and area were not useful for discriminating subjects with this condition from controls.
Asunto(s)
Encéfalo/diagnóstico por imagen , Corteza Motora/diagnóstico por imagen , Síndrome de las Piernas Inquietas/terapia , Estimulación Magnética Transcraneal/efectos adversos , Adulto , Encéfalo/fisiopatología , Brasil/epidemiología , Estudios de Casos y Controles , Excitabilidad Cortical , Potenciales Evocados Motores , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiopatología , Calidad de Vida , Receptores de GABA-A/fisiología , Síndrome de las Piernas Inquietas/diagnóstico , Síndrome de las Piernas Inquietas/fisiopatología , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estimulación Magnética Transcraneal/métodosRESUMEN
The role of spinal α5 subunit-containing GABAA (α5-GABAA) receptors in chronic pain is controversial. The purpose of this study was to investigate the participation of spinal α5-GABAA receptors in the reserpine-induced pain model. Reserpine administration induced tactile allodynia and muscle hyperalgesia in female and male rats. Intrathecal injection of L-655,708 and TB 21007 (7 days after the last reserpine injection) decreased tactile allodynia and, at a lesser extent, muscle hyperalgesia in female rats. The effects of these drugs produced a lower antiallodynic and antihyperalgesic effect in male than in female rats. Contrariwise, these drugs produced tactile allodynia and muscle hyperalgesia in naïve rats and these effects were lower in naïve male than female rats. Intrathecal L-838,417 prevented or reversed L-655,708-induced antiallodynia in reserpine-treated female rats. Repeated treatment with α5-GABAA receptor small interfering RNA (siRNA), but not scramble siRNA, reduced reserpine-induced allodynia in female rats. Accordingly, α5-GABAA receptor siRNA induced nociceptive hypersensitivity in naïve female rats. Reserpine enhanced α5-GABAA receptors expression in spinal cord and dorsal root ganglia (DRG), while it increased CD11b (OX-42) and glial fibrillary acidic protein (GFAP) fluorescence intensity in the lumbar spinal cord. In contrast, reserpine diminished K+-Cl- co-transporter 2 (KCC2) protein in the lumbar spinal cord. Data suggest that spinal α5-GABAA receptors play a sex-dependent proallodynic effect in reserpine-treated rats. In contrast, these receptors have a sex-dependent antiallodynic role in naïve rats.
Asunto(s)
Fibromialgia/complicaciones , Dolor/complicaciones , Dolor/tratamiento farmacológico , Receptores de GABA-A/metabolismo , Reserpina/farmacología , Animales , Astrocitos/efectos de los fármacos , Astrocitos/patología , Femenino , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Masculino , Microglía/efectos de los fármacos , Microglía/patología , Dolor/inducido químicamente , Dolor/patología , Ratas , Ratas Wistar , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Simportadores/metabolismo , Cotransportadores de K ClRESUMEN
Nitric oxide (NO) is involved in synaptic plasticity in the hippocampus through different presynaptic and postsynaptic mechanisms that include the modulation of the GABAergic neurotransmission. Inhibitory synapses on hippocampal pyramidal neurons are known to possess the molecular machinery for retrograde NO-signaling, but the modulation of GABAARs function by NO in these neurons and the mechanisms of action involved have not been fully characterized. Here we show that suppression of the endogenous NO generation by the nitric oxide synthase (NOS) inhibitor L-NAME produces significant and reversible increases in the magnitude of both tonic and phasic GABAergic currents in CA1 hippocampal pyramidal neurons. GABA-evoked chloride currents were measured in the presence or absence of L-NAME using whole-cell patch-clamp recordings in acute hippocampal slices from young adult mice. Enhancement of the tonic GABA responses induced by L-NAME was insensitive to TTX and decreased by co-incubation with the NO donor DEA/NO. Applications of DEA/NO alone did not produce significant effects on tonic GABA responses. L-NAME treatment also increased the amplitude of phasic GABAergic currents evoked by GABA-puffs. Our results indicate that the extent of tonic and phasic inhibition mediated by GABAA receptors in CA1 hippocampal pyramidal neurons is affected by endogenous NO production.
Asunto(s)
Región CA1 Hipocampal/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Células Piramidales/efectos de los fármacos , Ácido gamma-Aminobutírico/fisiología , Animales , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/fisiología , Ratones Endogámicos BALB C , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/biosíntesis , Células Piramidales/fisiología , Receptores de GABA-A/fisiología , Transmisión SinápticaRESUMEN
Introdução: O ecocardiograma transesofágico é atualmente uma das principais ferramentas no diagnóstico de diversas alterações cardíacas. Para uma maior segurança e conforto na sua realização, o exame tem sido realizado sob sedação consciente moderada, sendo os benzodiazepínicos os agentes de escolha. Nessa classe de medicamentos, o midazolam é o mais utilizado, todavia não está isento de possíveis complicações relacionadas ao seu uso, como hipóxia, hipotensão, entre outras. Sabemos que grau de sedação é dose-dependente, portanto, quanto menor a dose utilizada, será menor o risco de complicações do procedimento.Objetivo: Verificar o impacto do uso do fentanil na administração endovenosa de midazolam, no intuito de avaliar eficiência de protocolo de sedação de pacientes submetidos a ecocardiograma transesofágico, utilizando ambos os medicamentos. Metodologia: : Estudamos 201 pacientes (idade média de 51,5 anos, 115 homens) submetidos a ecocardiograma transesofágico, com sedação por via endovenosa divididos em dois grupos: Grupo A (n = 89), seguindo protocolo definido com uso de fentanil associado ao midazolam; e Grupo B (n = 112), sem o emprego de fentanil. Comparou-se então a dosagem de midazolam administrada em ambos os grupos. Monitorização adequada dos sinais vitais foi realizada durante todo o procedimento. Resultados: A dose média de midazolam utilizada foide 2,6 ± 1,4 mg no Grupo A e de 4,0 ± 2,7 mg no Grupo B (p < 0,01). A dose de fentanil empregada foi de 66,2 ± 24,8 mcg. Não houve diferença significativa entre idade (p = 0,08) e gênero (p > 0,1) nos grupos estudados. Conclusão: O uso de fentanil na sedação para realização de ecocardiograma transesofágico associado à administração de midazolam permite a administração de uma dose menor desse benzodiazepínico.
Introduction: Transesophageal echocardiography is currently one of the main tools in the diagnosis of various cardiac abnormalities. For greater safety and comfort, the test has been performed under moderate conscious sedation and benzodiazepines were the agents of choice. In this class of drugs, midazolam is the most commonly used, however it is not free of potential complications related to its use, such as hypoxia, hypotension, among others. We know that sedation level is dose-dependent. Therefore, the lower the dose, the lower the risk of complications from the procedure.Objective: To check the impact of fentanyl in the intravenous administration of midazolam in order to assess the sedation protocol efficiency on patients undergoing transesophageal echocardiography using both drugs.Methodology: We have studied 201 patients (mean age 51.5 years, 115 men) who underwent transesophageal echocardiography with intravenous sedation divided into two groups: Group A (n = 89), following the protocol with fentanyl associated with midazolam; and Group B (n = 112) without the use of fentanyl. The dose of midazolam administered in both groups was then compared. Proper monitoring of vital signs was performed throughout the procedure.Results: The mean dose of midazolam used was 2.6 ± 1.4 mg in Group A and 4.0 ± 2.7 mg in Group B (p < 0.01). The dose of fentanyl used was 66.2 ± 24.8 mcg. There was no significant difference between age (p = 0.08) and gender (p > 0.1) in the groups studied. Conclusion: The use of fentanyl in sedation for transesophageal echocardiography associated with administration of midazolam allows the administration of a lower dose of this benzodiazepine.
Introducción: El ecocardiograma transesofágico es actualmente una de las principales herramientas en el diagnóstico de diversas alteraciones cardíacas. Para una mayor seguridad y confort en su realización, el examen ha sido realizado bajo sedación conciente moderada, siendo los benzodiazepínicos los agentes de elección. En esa clase de medicamentos, el midazolam es el más utilizado, sin embargo no está exento de posibles complicaciones relacionadas a su uso, como hipoxia, hipotensión, entre otras. Sabemos que grado de sedación es dosis-dependiente, por lo tanto, cuanto menor es la dosis utilizada, será menor el riesgo de complicaciones del procedimiento.Objetivo: Verificar el impacto del uso del fentanil en la administración endovenosa de midazolam, con el propósito de evaluar eficiencia de protocolo de sedación de pacientes sometidos a ecocardiograma transesofágico, utilizando ambos medicamentos.Metodología: Estudiamos 201 pacientes (edad media de 51,5 anos, 115 hombres) sometidos a ecocardiograma transesofágico, con sedación por vía endovenosa divididos en dos grupos: Grupo A (n = 89), siguiendo protocolo definido con uso de fentanil asociado al midazolam; y Grupo B (n = 112), sin el empleo de fentanil. Se comparó entonces el dosaje de midazolam administrada en ambos grupos. Monitoreo adecuado de los signos vitales fue realizada durante todo el procedimiento. Resultados: La dosis media de midazolam utilizada fue de 2,6 ± 1,4 mg en el Grupo A y de 4,0 ± 2,7 mg en el Grupo B (p < 0,01). La dosis de fentanil empleada fue de 66,2 ± 24,8 mcg. No hubo diferencia significativa entre edad (p = 0,08) y género (p > 0,1) en los grupos estudiados. Conclusión: El uso de fentanil en la sedación para realización de ecocardiograma transesofágico asociado a la administración de midazolam permite la administración de una dosis menor de ese benzodiazepínico
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Ecocardiografía Transesofágica/efectos adversos , Ecocardiografía Transesofágica/métodos , Fentanilo/efectos adversos , Midazolam/efectos adversos , Receptores de GABA-A , Índice de Masa CorporalRESUMEN
Persistent activation of GABAA receptors triggers compensatory changes in receptor function that are relevant to physiological, pathological and pharmacological conditions. Chronic treatment of cultured neurons with GABA for 48h has been shown to produce a down-regulation of receptor number and an uncoupling of GABA/benzodiazepine site interactions with a half-time of 24-25h. Down-regulation is the result of a transcriptional repression of GABAA receptor subunit genes and depends on activation of L-type voltage-gated calcium channels. The mechanism of this uncoupling is currently unknown. We have previously demonstrated that a single brief exposure of rat primary neocortical cultures to GABA for 5-10min (t½=3min) initiates a process that results in uncoupling hours later (t½=12h) without a change in receptor number. Uncoupling is contingent upon GABAA receptor activation and independent of voltage-gated calcium influx. This process is accompanied by a selective decrease in subunit mRNA levels. Here, we report that the brief GABA exposure induces a decrease in the percentage of α3-containing receptors, a receptor subtype that exhibits a high degree of coupling between GABA and benzodiazepine binding sites. Initiation of GABA-induced uncoupling is prevented by co-incubation of GABA with high concentrations of sucrose suggesting that it is dependent on a receptor internalization step. Moreover, results from immunocytochemical and biochemical experiments indicate that GABA exposure causes an increase in GABAA receptor endocytosis. Together, these data suggest that the uncoupling mechanism involves an initial increase in receptor internalization followed by activation of a signaling cascade that leads to selective changes in receptor subunit levels. These changes might result in the assembly of receptors with altered subunit compositions that display a lower degree of coupling between GABA and benzodiazepine sites. Uncoupling might represent a homeostatic mechanism that negatively regulates GABAergic transmission under physiological conditions in which synaptic GABAA receptors are transiently activated for several minutes.
Asunto(s)
Benzodiazepinas/farmacología , Neuronas/efectos de los fármacos , Receptores de GABA-A/química , Receptores de GABA-A/metabolismo , Ácido gamma-Aminobutírico/farmacología , Animales , Benzodiazepinas/metabolismo , Sitios de Unión/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Embrión de Mamíferos , Flunitrazepam/farmacocinética , Antagonistas del GABA/farmacología , Moduladores del GABA/farmacocinética , Regulación de la Expresión Génica/efectos de los fármacos , Picrotoxina/farmacología , Unión Proteica/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de GABA-A/genética , Factores de Tiempo , Tritio/farmacocinéticaRESUMEN
The periaqueductal gray matter (PAG) consists in a brainstem structure rich in 5-hydroxytryptamine (5-HT) inputs related to the modulation of pain. The involvement of each of the serotonergic receptor subtypes found in PAG columns, such as the dorsomedial (dmPAG) and the ventrolateral (vlPAG) columns, regarding post-ictal antinociception have not been elucidated. The present work investigated the participation of the dmPAG and vlPAG columns in seizure-induced antinociception. Specifically, we studied the involvement of serotonergic neurotransmission in these columns on antinociceptive responses that follow tonic-clonic epileptic reactions induced by pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl(-) influx antagonist. Microinjections of cobalt chloride (1.0 mM CoCl2 /0.2 µL) into the dmPAG and vlPAG caused an intermittent local synaptic inhibition and decreased post-ictal antinociception that had been recorded at various time points after seizures. Pretreatments of the dmPAG or the vlPAG columns with the nonselective serotonergic receptors antagonist methysergide (5.0 µg/0.2 µL) or intramesencephalic microinjections of ketanserin (5.0 µg/0.2 µL), a serotonergic antagonist with more affinity to 5-HT2A/2C receptors, decreased tonic-clonic seizure-induced antinociception. Both dmPAG and vlPAG treatment with either the 5-HT2A receptor selective antagonist R-96544 (10 nM/0.2 µL), or the 5-HT2C receptors selective antagonist RS-102221 (0.15 µg/0.2 µL) also decrease post-ictal antinociception. These findings suggest that serotonergic neurotransmission, which recruits both 5-HT2A and 5-HT2C serotonergic receptors in dmPAG and vlPAG columns, plays a critical role in the elaboration of post-ictal antinociception.
Asunto(s)
Nocicepción , Sustancia Gris Periacueductal/metabolismo , Receptor de Serotonina 5-HT2A/metabolismo , Receptor de Serotonina 5-HT2C/metabolismo , Animales , Masculino , Especificidad de Órganos , Sustancia Gris Periacueductal/fisiología , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Convulsiones/fisiopatología , Neuronas Serotoninérgicas/metabolismo , Neuronas Serotoninérgicas/fisiología , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Transmisión SinápticaRESUMEN
GABAA receptors (GABAAR) mediate inhibitory neurotransmission in the human brain. Neurons modify subunit expression, cellular distribution and function of GABAAR in response to different stimuli, a process named plasticity. Human lymphocytes have a functional neuronal-like GABAergic system with GABAAR acting as inhibitors of proliferation. We here explore if receptor plasticity occurs in lymphocytes. To this end, we analyzed human T lymphocyte Jurkat cells exposed to different physiological stimuli shown to mediate plasticity in neurons: GABA, progesterone and insulin. The exposure to 100 µM GABA differently affected the expression of GABAAR subunits measured at both the mRNA and protein level, showing an increase of α1, ß3, and γ2 subunits but no changes in δ subunit. Exposure of Jurkat cells to different stimuli produced different changes in subunit expression: 0.1 µM progesterone decreased δ and 0.5 µM insulin increased ß3 subunits. To identify the mechanisms underlying plasticity, we evaluated the Akt pathway, which is involved in the phosphorylation of ß subunits and receptor translocation to the membrane. A significant increase of phosphorylated Akt and on the expression of ß3 subunit in membrane occurred in cells exposed 15 h to GABA. To determine if plastic changes are translated into functional changes, we performed whole cell recordings. After 15 h GABA-exposure, a significantly higher percentage of cells responded to GABA application when compared to 0 and 40 h exposure, thus indicating that the detected plastic changes may have a role in GABA-modulated lymphocyte function. Our results reveal that lymphocyte GABAAR are modified by different stimuli similarly and by similar mechanisms to those in neurons. This property is of significance for the development of future therapies involving pharmacological modulation of the immune response.
Asunto(s)
Plasticidad Neuronal/fisiología , Receptores de GABA-A/fisiología , Humanos , Insulina/farmacología , Células Jurkat , Plasticidad Neuronal/efectos de los fármacos , Fosforilación , Progesterona/farmacología , Subunidades de Proteína/biosíntesis , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Receptores de GABA-A/biosíntesis , Receptores de GABA-A/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
This study aimed to determine the consumption of benzodiazepines without prescription among first-year students from a nursing school of a public University in Ecuador. This is a descriptive, transversal and explanatory study with a quantitative approach. A questionnaire was used for data collection. The population studied was of 181 students. The results showed that 10.5 percent of the students had consumed benzodiazepine without prescription once in their lives. Of these, 6.1 percent consumed benzodiazepine in the last year, and 3.9 percent are currently consuming it. The diazepam was the most consumed BZD without prescription and pharmacies, were the place of higher access. The main reasons for the benzodiazepine consumption were: insomnia, anxiety, stress, depression, family and economical problems. The use of benzodiazepines with non-medicinal purposes is related to problems such as memory loss, retirement syndrome and sedation. When benzodiazepines are consumed jointly with alcohol or other drugs they can lead to coma or death. This study shows the serious consequences benzodiazepines cause when used by nursing students in Ecuador.
La finalidad de este estudio fue determinar el consumo de benzodiacepinas sin prescripción en estudiantes del primer año de enfermería de una universidad pública de Ecuador. Se trata de un estudio transversal, descriptivo y exploratorio, con aproximación cuantitativa. Un cuestionario fue usado para la recolecta de los datos. La población estudiada fue compuesta por 181 estudiantes. Los resultados muestran que el 10,5 por ciento de los estudiantes consumió benzodiacepinas sin prescripción médica alguna vez en la vida. Del total, el 6,1 por ciento consumió en el último año y el 3,9 por ciento usan actualmente. El Diazepan fue la BZD más usada sin prescripción médica, siendo la farmacia el local de mayor acceso. Entre los principales motivos para el consumo de benzodiacepinas se encuentran: insomnio, ansiedad, estrés, depresión y problemas familiares o económicos. El uso de benzodiacepinas con propósitos no-medicinales está relacionado a problemas de pérdida de la memoria, síndrome de abstinencia y sedación. Cuando son combinados con alcohol u otras drogas, pueden llevar a la coma y a la muerte. Este estudio muestra las graves consecuencias que las benzodiacepinas pueden ocasionar cuando utilizados por estudiantes de enfermería en Ecuador.
O objetivo deste estudo foi determinar o consumo de benzodiazepinos sem prescrição em estudantes do primeiro ano de enfermagem de uma universidade pública do Equador. Trata-se de um estudo transversal, descritivo e exploratório, com abordagem quantitativa. Um questionário foi usado para coleta dos dados. A população estudada foi composta por 181 estudantes. Os resultados mostram que 10,5 por cento dos estudantes consumiram benzodiazepinos sem prescrição médica alguma vez na vida. Do total, 6,1 por cento consumiram no último ano e 3,9 por cento usam atualmente. O Diazepan foi a BZD mais usada sem prescrição médica, sendo a farmácia, o local de maior acesso. Entre os principais motivos para o consumo de benzodiazepinos encontram-se: insônia, ansiedade, estresse, depressão e problemas familiares ou econômicos. O uso de benzodiazepinos com propósitos não-medicinais está relacionado a problemas de perda da memória, síndrome de abstinência e sedação. Quando são combinados com álcool ou outras drogas, podem levar ao coma e à morte. Este estudo mostra as graves conseqüências que os benzodiazepinos podem ocasionar quando utilizados por estudantes de enfermagem no Equador.