Fitovigilância: avaliação das interações e reações adversas de fitoterápicos no mercado / Phytosurveillance: evaluation of interactions and adverse reactions of herbal medicines on the market

Introdução: O uso de plantas medicinais como insumos farmacêuticos ativos vegetais (IFAV), bem como o uso de fitoterápicos e suas associações com outros medicamentos fitoterápicos e os insumos farmacêuticos ativos (IFA) sintéticos, pode resultar em interações que afetem a eficácia e o uso seguro desses. O principal meio de notificações de reação adversa a medicamento (RAM) é a voluntária, o que dificulta a identificação e o monitoramento dessas RAM e retrata a importância da farmacovigilância em nosso país, realçando a necessidade de fortalecimento da cultura de notificação de eventos adversos a medicamentos (EAM). Objetivo: Analisar a ocorrência de RAM relacionada ao uso simultâneo de cinco fitoterápicos a outros sintéticos, descrevendo as possíveis interações IFAV-IFA sintéticos. Método: Foi realizada pesquisa bibliográfica sobre as interações IFAV-IFA sintéticos e suas notificações de RAM pelos principais sistemas de farmacovigilância do mundo. Resultados: Os principais mecanismos de interação entre IFAV-IFA sintéticos envolvem a metabolização pelas enzimas da família CYP450 ou a ação de transportadores de efluxo como a gp-P. Além disso, grande parte dos EAM fitoterápicos podem não estar sendo notificados, gerando possível subnotificação dessas informações no mundo. Conclusões: Sobre RAM contendo IFAV de Ginkgo biloba, Hypericum perforatum, Matricaria recutita, Allium sativum e Zingiber officinale, foram relatados 7.571 no mundo, classificados por continente, no período de 1971 a agosto de 2021, bem como lista de espécies vegetais da lista do Renisus que apresentam efeitos relatados nas enzimas CYP (1A2, 2C9, 2C19, 2D6 e 3A4), níveis de GSH, UGT e atividade da gp-P.

Introduction: The use of medicinal plants as active plant pharmaceutical ingredients (APPIs) as well as the use of herbal medicines and their associations with other herbal medicines and synthetic active pharmaceutical ingredients (API) can result in interactions that affect the efficacy and safe use of these. The main means of reporting adverse drug reactions (ADR) is voluntary, which makes the identification and monitoring of these ADRs difficult and portrays the importance of pharmacovigilance in our country, highlighting the need to strengthen the culture of reporting adverse drug events (ADE). Objective: To analyze the occurrence of ADR related to the simultaneous use of five herbal medicines with other synthetics, describing possible synthetic APPI-API interactions. Method: A literature search was carried out on synthetic APPI-API interactions and their notifications of ADR by the main pharmacovigilance systems in the world. Results: The main interaction mechanisms between synthetic APPI-API involve the metabolism by enzymes of the CYP450 family or the action of efflux transporters such as P-gp. In addition, a large part of phytotherapeutic AEM may not be being notified, generating possible underreporting of this information in the world. Conclusions: On ADR containing APPI from Ginkgo biloba, Hypericum perforatum, Matricaria recutita, Allium sativum and Zingiber officinale, 7,571 were reported worldwide, classified by continent, in the period 1971 to August 2021, as well as the list of plant species on the list of RENISUS that have reported effects on CYP enzymes (1A2, 2C9, 2C19, 2D6 and 3A4), levels of GSH, UGT and P-gp activity.

Inquérito sobre o uso de contenção física em um hospital psiquiátrico de grande porte no Rio de Janeiro / Survey on the use of restraints in a large psychiatric hospital in Rio de Janeiro city

OBJETIVO: Investigar o uso da contenção física em hospital psiquiátrico no Rio de Janeiro. MÉTODOS: Um inquérito foi conduzido em agosto de 2009. As informações - sexo, idade, diagnóstico, ocorrência e duração de contenção física - foram coletadas no prontuário. RESULTADO: A amostra consistiu em 66 pacientes, dos quais 59 por cento eram mulheres, com idade média de 44 anos. Durante o período estudado, 24 por cento dos pacientes foram contidos no leito pelo menos uma vez, mas não é prática corrente o registro detalhado do procedimento. Não ocorreram eventos adversos importantes. Não houve associação entre o uso de contenção e variáveis sociodemográficas e clínicas. CONCLUSÕES: A prática de contenção física parece consistente nas emergências psiquiátricas do Rio de Janeiro: esse mesmo percentual foi observado em estudos conduzidos em três hospitais em outros momentos, 2001 e 2004, e situa-se em uma faixa intermediária em relação aos resultados observados em outros países. Não existem estudos randomizados para se fazer uma avaliação objetiva dos benefícios e riscos dessa prática, mas a segurança e a eficácia dessa intervenção deveriam ser objeto do mesmo escrutínio científico normalmente destinado aos outros tratamentos.

OBJECTIVE: To evaluate the use of restraints in a large psychiatric hospital in Rio de Janeiro city, Brazil. METHODS:A survey was carried on in August 2009. Data on sex, age, diagnostic, use and duration of restraints were collected from patients' notes. RESULT: Sample consisted on 66 patients, 59 percent women, with mean age of 44 years. During the study 24 percent of the patients were restrained at least once, but registering details of the procedure was not usual. There were no important adverse events. No associations were observed between restraints and sociodemographic and clinic variables. CONCLUSIONS: The use of restraints is a consistent practice in Rio de Janeiro's psychiatric hospitals: the same proportion was observed in three hospitals in distinct periods, 2001 and 2004, and this finding is in an intermediate position in relation to other studies results. There are no randomized trials to properly evaluate the benefits and risks of this practice, but the efficacy and safety of this intervention should be subject to the same scientific scrutiny as other treatments.

Nociception and locomotor activity are increased in ketogenic diet fed rats.

Ketogenic diets have been used to treat epilepsy in children for almost 80 years. However, there are only few studies concerning behavioral effects of these diets, besides their efficacy in treating seizure disorders induced by kainic acid or pentylenetetrazol in rats. Here, rats were fed with a ketogenic diet and locomotion, anxiety and nociception were investigated after 10 weeks. Male Wistar rats were weight matched and divided into two groups: control rats, that received regular laboratory ration, and KD rats, that received ketogenic diet (70% fat, 24% protein and no carbohydrate). Behavioral tests were applied after 10-12 weeks of treatment, and included tests to evaluate exploration (habituation to the open field), anxiety (plus-maze), and nociception (tail-flick measurement). Performance of the animals in the open field revealed a significant difference in the number of crossings, suggesting a higher locomotor activity in animals fed with a ketogenic diet. No differences in anxiety were observed, as evaluated by the plus-maze test. Nociception was measured by the latency in the tail-flick test, and ketogenic rats presented a hypernociceptive response. Yet, these animals responded to a stressor with the classic analgesia, similarly to the controls. The response of ketogenic diet fed rats to the stressor, however, was more prolonged. Exposure to a ketogenic diet may induce higher locomotor activity, together with a hypernociceptive state in the animals, possibly as a result of some alteration in the neural systems involved in the modulation of these behaviors.

Ketogenic diet increases glutathione peroxidase activity in rat hippocampus.

Ketogenic diets have been used in the treatment of refractory childhood epilepsy for almost 80 years; however, we know little about the underlying biochemical basis of their action. In this study, we evaluate oxidative stress in different brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to have not been affected by this diet, and cerebellum presented a decrease in antioxidant capacity measured by a luminol oxidation assay without changes in antioxidant enzyme activities--glutathione peroxidase, catalase, and superoxide dismutase. In the hippocampus, however, we observed an increase in antioxidant activity accompanied by an increase of glutathione peroxidase (about 4 times) and no changes in lipoperoxidation levels. We suggest that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders.

A ketogenic diet increases protein phosphorylation in brain slices of rats.

Ketogenic diets have been used to treat seizure disorders of children and recently it was shown to increase the drug-induced seizure threshold in rats. Protein phosphorylation is a major regulatory mechanism of signal transduction that has been implicated in modulating neuronal excitability. We investigated the basal protein phosphorylation in microslices from different brain regions (hippocampus, cerebral cortex and cerebellum) of young rats fed a ketogenic diet, and we evaluated the effect of this diet on weight development and health of these rats based on serum biochemistry. Thirty-day-old rats consumed ad libitum ketogenic (high fat) or control diets for 8 wk. Rats consuming the high fat diet had ketonemia without signs of undernutrition or illness. Microslices were incubated in media containing (32)P-phosphate, and (32)P-phosphoprotein content was analyzed by one- or two-dimensional electrophoresis followed by autoradiography. Basal protein phosphorylation was greater in brain slices from ketogenic rats. Different increments of synapsin I, GAP-43 and GFAP phosphorylation were observed in two-dimensional autoradiography. A ketogenic diet induced metabolic changes affecting the basal status of protein phosphorylation. This change could affect the mechanisms of signal transduction in neural cells involved in the increase in the seizure threshold.