Este estudo, tem o objetivo de avaliar a prevalência e tipos de benzodiazepínicos prescritos antes e durante a pandemia da COVID-19, dispensados para atendimento pelo SUS, no Município de São Fidélis, RJ. Os dados coletados se referem ao período de 2019 a 2021, de maneira a atender o estudo proposto. A metodologia foi estudo observacional transversal, utilizando-se pesquisas bibliográfica e documental. A fonte para essa última foram, informações dos bancos de dados da Farmácia Municipal. As informações foram tabuladas e apresentadas em forma de gráficos e comparados os períodos antes e durante a pandemia, sendo considerados os tipos e quantidades de benzodiazepínicos (BDZs) dispensados nesse período. Os resultados poderão contribuir para um diagnóstico a serem utilizadas em futuro(s) estudos e pesquisas, colaborando para a melhoria desse serviço no município em estudo. Constatou-se que os BZDs que apresentaram maior prevalência de dispensação nos anos estudados foram: Alprazolam 1,0 mg e o Clonazepam 2 mg mostrando-se uma maior elevação nos anos de 2020 e 2021 (com pandemia) em relação a 2019 (sem pandemia). Esses dados trazem grande preocupação sobre o uso abusivo e sugerem medidas e planejamento de estratégias para o uso racional dos medicamentos nas Unidades Básicas de Saúde do município de São Fidélis-RJ.

A complicação mais séria da terapia de reposição do fator VIII (FVIII) nos pacientes com Hemofilia A é o desenvolvimento de aloanticorpos ou autoanticorpos inibidores. Os anticorpos inibidores impedem hemostasia efetiva, representando risco real para episódios hemorrágicos de difícil controle. Esta revisão aborda os conceitos pertinentes e cobre os seguintes aspectos farmacogenéticos do desenvolvimento de anticorpos inibidores: tipos de anticorpos, mecanismos de inibição, diagnóstico, fatores genéticos e não-genéticos de risco, alternativas de tratamento e de intervenção.

40Hemophilia A is the most common clotting disorder in humans. It affects one in five 41 thousand live-born children. Mutations in the X-chromosome linked F8 gene lead to the 42 deficiency of circulating factor VIII (FVIII). The defect is characterized by severe 43 bleeding. The standard therapy is to replace the deficient factor intravenously. The main 44 adverse event of the therapy is the development of anti-FVIII inhibitor antibodies that 45 impair coagulation and result in increased complications and risk of death. Several risk 46 factors have been described for the development of inhibitor antibodies, among them 47 age, type of FVIII administered, ethnicity, and variant alleles in immune response 48 genes. Epigenetic risks factors have not yet been explored. This work aimed to evaluate 49 2 the methylation statuses at thirteen CpG sites (5meCpG) in regulatory regions of the 50 IL1B, IL2, IL4, IL6, IL10, TNF, IFNG, CTLA4, CD28, and CST7 immune regulation 51 genes in hemophilia A affected males on replacement therapy who develop or do not 52 develop inhibitor antibodies. At each of the thirteen specific CpG sites, we observed one 53 of three possible statuses: hypermethylated, hypomethylated or intermediate 54 methylated. We found a statistically significant (p = 0.04) decrease in the methylation 55 level at one CpG site in the IL4 intron 1 (CpG-3) in the affected group of patients 56 presenting with anti-FVIII inhibitors as compared with the group of patients without 57 inhibitors. The differential 5meCpG-3 maps within a predicted enhancer region in IL4 58 intron 1 that overlaps DNase I hypersensitive chromatin region of the Th2 IL5, IL13, 59 and IL4 cytokine gene cluster and, therefore, permissive for gene expression. Six-bp 60 upstream of the differentially 5meCpG-3 is the rs2227282 cis expression quantitative 61 trait locus that influences the transcript levels of the PDLIM4, SLC22A4, SLC22A5, 62 RAD50, IL4, KIF3A, SEPT8 genes. We consider the IL4 (CpG-3) site a promising lead 63 epigenetic mark, the potential value of which must be appraised in a larger group of 64 patients. The methodology employed also allowed to evaluate the distribution of the IL6 65 rs35081782 insertion/deletion variant, associated with white blood cell count traits in 66 genome-wide association studies, and which showed no difference in distribution 67 between the groups of patients. 68 69 90 91Risk factors for inhibitor development are classified into non-genetic and genetic. 92Among non-genetic risks, the age at the replacement therapy, the type of hemorrhage 93 and the factor administered have been described (Ragni et al., 2009). Among the genetic 94 risk factors, the most well-described factor is the type of causative mutation. Mutations 95 that associate with a higher risk of developing inhibitors are linked to significant 96 functional alterations or complete absence of FVIII. About 40% of patients with large 97 deletions develop inhibitors, while nonsense mutations account for up to 30% of 98