Comparative assessment of some benzodiazepine drugs based on Density Functional Theory, molecular docking, and ADMET studies

Benzodiazepines are widely used to treat anxiety, insomnia, agitation, seizures, and muscle spasms. It works through the GABAA receptors to promote sleep by inhibiting brainstem monoaminergic arousal pathways. It is safe and effective for short-term use, and arises some crucial side effects based on dose and physical condition. In this investigation, physicochemical properties, molecular docking, and ADMET properties have been studied. Density functional theory with B3LYP/6-311G+(d,p) level of theory was set for geometry optimization and elucidate their thermodynamic, orbital, dipole moment, and electrostatic potential properties. Molecular docking and interaction calculations have performed against human GABAA receptor protein (PDB ID: 4COF) to search the binding affinity and effective interactions of drugs with the receptor protein. ADMET prediction has performed to investigate their absorption, metabolism, and toxic properties. Thermochemical data suggest the thermal stability; the docking result predicts effecting bindings and ADMET calculation disclose non-carcinogenic and relatively harmless phenomena for oral administration of all drugs.

Impacto da automedicação de fármacos benzodiazepínicos / Impact of self-medication of benzodiazepine drugs

A automedicação é o ato que consiste no paciente fazer uso dos fármacos por conta própria sem uma devida prescrição médica, e que nos últimos anos vem se tornando um sério problema de saúde pública. Os psicotrópicos são substancias usadas há milênios e possuem ação hipnóticas, sedativas, ansiolíticas e antidepressivas. Como substancias psicotrópicas constam os fármacos ansiolíticos, dentre os quais, os benzodiazepínicos (BZD). Porém, por se tratarem de fármacos que atuam no SNC seu uso continuo pode acarretar dependência e tolerância. O objetivo do presente trabalho é fazer a revisão da literatura, sobre o tema impacto da automedicação de fármacos benzodiazepínicos. A metodologia utilizada foi a revisão da literatura integrativa, tendo como descritores as seguintes palavras, saber “automedicação”, “psicotrópicos”, “ansiolíticos” e “efeitos tóxicos”. O período de estudo foi 2011 a 2021, o qual as informações foram coletadas nas bibliotecas on lines. Os resultados achados na revisão resultaram em 3 publicações na base de dados Pubmed, 3 na base Scielo e 3 na Google acadêmico. Concluímos que, a automedicação pode trazer consequências serias a saúde dos indivíduos, e que é um problema sério de saúde pública onde ouve uma prevalência significativa nos últimos anos, fatores que contribuem para isto estão os grandes números de medicamentos produzidos pela indústria farmacêutica, influencia por familiares e a própria cultura, entretanto a automedicação produz sérios riscos à saúde podendo gerar intoxicações, os psicotrópicos tem sido objetos de estudo devido ao grande número de prescrições, não são fármacos de primeira linha no tratamento de transtornos de humor e ansiedade, seus efeitos graves são: alterações psicomotoras, dependência e tolerância podendo levar ao abuso do uso, mulheres e idosos são os grupos que mais fazem uso desses fármacos.

Benzodiazepines: Drugs with Chemical Skeletons Suitable for the Preparation of Metallacycles with Potential Pharmacological Activity

The synthesis of organometallic compounds with potential pharmacological activity has attracted the attention of many research groups, aiming to take advantage of aspects that the presence of the metal-carbon bond can bring to the design of new pharmaceutical drugs. In this context, we have gathered studies reported in the literature in which psychoactive benzodiazepine drugs were used as ligands in the preparation of organometallic and metal complexes and provide details on some of their biological effects. We also highlight that most commonly known benzodiazepine-based drugs display molecular features that allow the preparation of metallacycles via C-H activation. These organometallic compounds merit further attention regarding their potential biological effects, not only in terms of psychoactive drugs but also in the search for drug replacements, for example, for cancer treatments.

Analysis of Benzodiazepines Utilization Other than Mental Disorder at District Sukkur Pakistan

The main objective of this research was to evaluate the prescribing ratio of benzodiazepines in the patients suffering from a disease other than a mental disorder. A prospective cross-sectional study was conducted at 24 different community pharmacies and medical stores of District Sukkur. Participants with age more than 18 years and using Benzodiazepines were included in this study. Average age of the Participants, who were participated, was 38 ± 20 years. From the 177 study subjects who visited the community pharmacies or medical stores for the purchase of benzodiazepines 104 were male and remaining 73 were female. From 177 patients 132 were married and remaining 45 were unmarried or widow. It was concluded that the consumption of benzodiazepine drugs is terrifyingly very high, especially as a self-medication without any prescription.

Deprescribing benzodiazepines: Do Brazilian package inserts address this issue?

OBJECTIVE: To analyze the presence and quality of content on drug deprescribing in Brazilian package inserts for benzodiazepine drugs. METHODS: Documentary study where we analyzed data on deprescribing extracted from electronic package inserts of drugs containing benzodiazepines; these documents were available at the Brazilian Health Surveillance Agency website. Our search was performed independently by 2 researchers who used the following keywords: “deprescription,” “withdrawal,” and “tapering.” The deprescribing plan, when presented by the package insert, was compared to deprescribing protocols for benzodiazepines found in the literature. Moreover, we assessed the presence of guidance on the maximum length of treatment and risks of long-term use. RESULTS: We found 12 package inserts for benzodiazepines and 100% of them suggested gradual withdrawal; only 1 (8.33%) suggested a systematized deprescribing plan. One document (8.33%) did not offer guidance on maximum treatment duration. Eleven (91.67%) had the information on long-term use possibly causing dependence or tolerance, and 1 (8.33%) did not describe the risks of continuous use. CONCLUSIONS: It is known that benzodiazepines should be withdrawn in a gradual and schematized manner, but package inserts do not currently bring this information in detail. It is of utmost importance that health professionals be educated on their conduct, hence the necessity for updating medication package inserts.