Estudio comparativo de la calidad biofarmacéutica de Alprazolam 0, 5 mg comercializadas en el mercado peruano / Comparative study of the biopharmaceutical quality of Alprazolam 0. 5 mg commercialized in the Peruvian market

El Alprazolam pertenece a las benzodiazepinas. Sus efectos se atribuyen a que actúa sobre receptores de membrana específicos, lo cual facilita la acción inhibitoria presináptica y postsináptica del ácido γ-aminobutírico (GABA), especialmente en la formación reticular ascendente. Se utiliza para el tratamiento de los estados de ansiedad, crisis de angustia, ataques de pánico y estrés intenso. Este estudio se realizó para analizar los parámetros comparativos de control de calidad in vitro mediante la evaluación de la variación de peso, friabilidad, dureza, tiempo de desintegración, perfil y eficiencia de disolución entre el medicamento innovador (Xanax®) y multifuentes que son comercializados en el mercado peruano. Para realizarlo, se seleccionaron tabletas de Alprazolam 0,5 mg multifuente de diferentes laboratorios comparándolos con el medicamento innovador y se evaluaron las características fisicoquímicas y biofarmacéuticas. Los ensayos farmacopeicos se evaluaron según lo establecido en la USP 42. Los resultados de las pruebas fisicoquímicas indicaron que las muestras analizadas no tenían diferencia significativa y estaban dentro de lo establecido en la farmacopea, así mismo el perfil y eficiencia de disolución permitieron establecer que el comportamiento biofarmacéutico de las mismas era muy similar para ambos tipos de molécula. Se estableció que las tabletas multifuentes de Alprazolam 0,5 mg de esta investigación son bioequivalentes con el innovador, por lo que permite proponer a la comunidad científica la determinación de la equivalencia biofarmacéutica como elemento de apoyo en la toma de decisiones de compra en el servicio farmacéutico

Alprazolam belongs to benzodiazepines. Its effects are attributed to the fact that it acts on specific membrane receptors, which facilitates the presynaptic and postsynaptic inhibitory action of γ-aminobutyric acid (GABA), especially in the ascending reticular formation. It is used to treat anxiety states, panic attacks, and intense stress. This study was carried out to analyze comparative parameters of in vitro quality control by evaluating the variation in weight, friability, hardness, disintegration time, profile and dissolution efficiency between the innovative drug (Xanax®) and multi-sources tablets that are marketed in the Peruvian market. To perform this, Alprazolam 0.5 mg multi-source tablets were selected from different laboratories comparing them with the innovative medicine and the physicochemical and biopharmaceutical characteristics were evaluated. Pharmacopoeial trials were evaluated as established in USP 42. The results of physicochemical tests indicated that analyzed samples did not have a significant difference and were within the established in the pharmacopoeia, as well as the profile and dissolution efficiency allowed to establish that their biopharmaceutical behavior was very similar for both types of molecules. It was established that Alprazolam 0.5 mg multi-source tablets from this research are bioequivalent with innovator, which makes it possible to propose to scientific community determination of biopharmaceutical equivalency as a support element in decision-making process for purchasing services pharmacist

Galphimine-B Standardized Extract versus Alprazolam in Patients with Generalized Anxiety Disorder: A Ten-Week, Double-Blind, Randomized Clinical Trial.

Galphimine-B (G-B), a compound isolated from Galphimia glauca, has been shown to possess important anxiolytic activity. In this study, we evaluated the effectiveness and tolerability of a G-B standardized extract (experimental treatment) that was administered daily for 10 weeks in patients with moderate or severe Generalized Anxiety Disorder (GAD). Alprazolam was used as control treatment and administered under the same conditions. A total of 167 patients were included. At the start of the study, the severe anxiety condition prevailed, with an average on the Hamilton Anxiety Scale of 35.1 ± 8.8 and 35.8 ± 8.1 points in the control and experimental groups, respectively. After the 10 weeks of administration, the average was reduced in the control group to 4.6 ± 6.5 points and in the experimental group to 3.5 ± 5.5 points. Therapeutic success in the control group was 85.7% and in the experimental group, 92.0%. A high proportion of patients (22.2%) treated with Alprazolam manifested daytime sleepiness, while in the group treated with the G-B standardized extract, daytime sleepiness was found in 4.7%. In conclusion, a G-B standardized extract demonstrated therapeutic effectiveness in patients with GAD, without exhibiting significant difference with Alprazolam, but showing fewer cases of daytime sleepiness. The trial was registered at http://clinicaltrials.gov by identifier: NCT03702803.

Impact of alprazolam in allostatic load and neurocognition of patients with anxiety disorders and chronic stress (GEMA): observational study protocol.

INTRODUCTION: The allostatic load model explains the additive effects of multiple biological processes that accelerate pathophysiology related to stress, particularly in the central nervous system. Stress-related mental conditions such as anxiety disorders and neuroticism (a well-known stress vulnerability factor), have been linked to disturbances of hypothalamo-pituitary-adrenal with cognitive implications. Nevertheless, there are controversial results in the literature and there is a need to determine the impact of the psychopharmacological treatment on allostatic load parameters and in cognitive functions. Gador study of Estres Modulation by Alprazolam, aims to determine the impact of medication on neurobiochemical variables related to chronic stress, metabolic syndrome, neurocognition and quality of life in patients with anxiety, allostatic load and neuroticism. METHODS/ANALYSIS: In this observational prospective phase IV study, highly sympthomatic patients with anxiety disorders (six or more points in the Hamilton-A scale), neuroticism (more than 18 points in the Neo five personality factor inventory (NEO-FFI) scale), an allostatic load (three positive clinical or biochemical items at Crimmins and Seeman criteria) will be included. Clinical variables of anxiety, neuroticism, allostatic load, neurobiochemical studies, neurocognition and quality of life will be determined prior and periodically (1, 2, 4, 8, and 12 weeks) after treatment (on demand of alprazolam from 0.75 mg/day to 3.0 mg/day). A sample of n=55/182 patients will be considered enough to detect variables higher than 25% (pretreatment vs post-treatment or significant correlations) with a 1-ß power of 0-80. t Test and/or non-parametric test, and Pearson's test for correlation analysis will be determined. ETHICS AND DISSEMINATION: This study protocol was approved by an Independent Ethics Committee of FEFyM (Foundation for Pharmacological Studies and Drugs, Buenos Aires) and by regulatory authorities of Argentina (ANMAT, Dossier # 61 409-8 of 20 April 2009), following the law of Habeas Data and psychotherapeutic drug control. TRIAL REGISTRATION NUMBER: GEMA 20811.

Efficacy of alprazolam sublingual tablets in the treatment of the acute phase of panic disorders.

BACKGROUND: Panic disorder affects 2-5% of the general population. In Argentina, one million people would be affected with a 91% rate of psychiatric comorbidity. AIM; To compare efficacy parameters between sublingual (ALP-SL) and conventional (ALP-CT) tablets of alprazolam in the treatment of acute phase of panic disorder with and without agoraphobia. SUBJECTS AND METHODS: A comparative, multicenter (6 sites), double blind, randomized study was carried out. A total of 190 outpatients with (n=117) and without (n=73) agoraphobia were treated with ALP-SL or ALP-CT for 12 weeks. Outcome was assessed with the Clinical Global Impressions (CGI-S/CGI-I), Hamilton Rating Scale for Anxiety (HAM-A), Arizona Sexual Experiences Scale (ASEX), Patient Global Impression (PGI), Psychological General Well-Being Index (PGWBI), Panic Disorder Severity Scale (PDSS) also by the number of panic attacks and extension and intensity of panic attacks and anticipatory anxiety. RESULTS. Both treatments resulted in statistically significant clinical improvement in all measures. ASEX presented no changes during the study. The average dose of alprazolam for 12 weeks was 1.36 ± 0.70 mg/day (1.39 ± 0.77 ALP-CT and 1.33 ± 0.64 ALP-SL). With ALP-SL, panic attacks were shorter (p < 0.05) with shorter extension (p=0.16) and intensity of anticipatory anxiety (p=0.14). The treatment was well tolerated, there being no differences between both groups. CONCLUSIONS: Alprazolam has been demonstrated to have efficacy, safety and good tolerability in the treatment of the acute phase of panic disorder, the sublingual tablets showing some comparative advantages.

Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines.

Previous reports from our laboratory described the sedative activity of hesperidin (hesperetin-7-rhamnoglucoside). This property is greatly increased when the glycoside is injected jointly with diazepam and this interaction has been shown to be synergistic. In the present work the generality of the synergistic phenomenon is proved, since potentiation also occurs with several other benzodiazepines, namely alprazolam, bromazepam, midazolam and flunitrazepam. In order to advance in the study of the mechanism of action of hesperidin, the possible participation of several brain receptors, which are implicated in the control of numerous behavioral and physiological functions, was explored by investigating the effects of a variety of their antagonists on hesperidin actions. The results showed that the 5-HT2 receptor and the alpha1-adrenoceptor seem unlikely to be involved in the behavioral effects of hesperidin. Naltrexone, a nonselective antagonist of opioid receptors, totally blocked hesperidin effects on locomotion, and partially antagonized hesperidin-induced decreased exploration in the hole board test. Nor-binaltorphimine, a selective kappa opioid receptor antagonist, was able to partially block hesperidin effects on locomotor activity. Furthermore, hesperidin-induced antinociception was partially blocked by naltrexone, and potentiated by co-administration with alprazolam. Hence, the participation of the opioid system in the sedative, antinociceptive and potentianting effects of hesperidin with benzodiazepines in mice is highly probable. Our results suggest a possible beneficial use of the association of hesperidin with benzodiazepines, not only to improve human sedative therapy, but also in the management of pain.

Peridural torácica para revascularización miocárdica en paciente despierto / Thoracic epidural anesthesia for myocardial revascularization in awake patient

Antecedentes: La tendencia actual en la cirugía coronaria es mejorar el confort del paciente, disminuir la tasa de complicaciones y lograr una rápida recuperación, para lo cual se recurre a distintas técnicas tendientes a disminuir el trauma de la cirugía y de la anestesia. La peridural torácica, como complemento de la anestesia general, disminuye el estrés perioperatorio, tiene efectos hemodinámicos beneficiosos para el paciente con coronariopatía, reduce las complicaciones y controla eficazmente el dolor perioperatorio. Realizar esta cirugía sin anestesia general permitiría una recuperación más rápida del paciente -con menor estadía en la unidad de cuidados intensivos-, precoz ingesta de líquidos, movilización y alta, ya que se aprovecharían los beneficios de la anestesia peridural y se evitarían los efectos colaterales de las drogas anestésicas y de la ventilación mecánica. Objetivo: Valorar la factibilidad de realizar esta técnica, la rapidez de la recuperación y el confort del paciente en una cirugía de bypass coronario sin circulación extracorpórea (CEC) por miniesternotomía bajo anestesia peridural. Resultado: El paciente toleró el procedimiento, no presentó dolor, se mostró muy conforme con la anestesia, se sentó e ingirió líquidos inmediatamente finalizada la cirugía y fue dado de alta 48 horas después, sin que se hayan presentado complicaciones. Conclusiones: Nuestra primera experiencia con este método fue bien tolerada por el paciente, con una rápida y confortable recuperación. (AU)

Administración sublingual de alprazolam. Estudio farmacocinético. Resultados preliminares / Pharmacokinetics of sublingual-administered alprazolam

En 23 voluntarios sanos de entre 21 y 50 años, se estudió la farmacocinética de alprazola, tras la administración de una dosis única (0,5 mg) de un comprimido diseñado para uso sublingual...La utilización de una forma farmacéutica que brinde una rápida absorción del ansiolítico puede ser útil para quienes presenten crisis aguda de ansiedad y requieran un rápido comienzo de acción y efecto de la medicación

Alprazolam en el dolor crónico como equivalente depresivo-ansioso / Alprazolam in chronic pain as a deppresive-anxious equivalent

Diez pacientes con dolor crónico severo, sin evidencia aparente de patología orgánica fueron valorados en un estudio abierto con duración de siete semanas. Después de la primera semana con placebo, los pacientes fueron sometidos a manejo con medicación activa (alprazolam) realizándose evaluación semanal de los siguientes parámetros: escala visual análoga (EVA), récord de síntomas principales, escala de ansiedad de Hamilton (EAH), escala de depresión de Hamilton (EDH), escala de impresión global tanto del paciente como del médico, así como signos vitales. Al final del protocolo nueve pacientes fueron evaluables. Un análisis individual mostró respuestas favorables en la EVA, en EAH y en EDH. La dosis promedio efectiva del alprazolam fue de 2.5mg./día. Los efectos colaterales más frecuentes fueron somnolencia y resequedad de boca. Hubo 3 casos de hipotensión sostenida que determinaron la salida del estudio de esos pacientes

Nuevas Benzodiazepinas / New Benzodiazepines

En el último decenio han aparecido en nuestro mercado cuatro benzodiazepinas, ellas podrían representar avances sutiles pero importantes en el tratamiento de los desórdenes de ansiedad y del insomnio. En este trabajo se revisa brevemente la farmacología, la farmacocinética y las características clínicas de este grupo para facilitar su mejor manejo por el médico. Además, se presenta someramente algunas perspectivas futuras.