Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions

The purpose of this work was to develop and optimize a simple and suitable method to detect the potential inhibitory effect of drugs and medicines on alcohol dehydrogenase (ADH) activity in order to evaluate the possible interactions between medicines and alcohol metabolism. Commonly used medicines that are often involved in court litigations related with driving under the influence of alcohol were selected. Alprazolam, flunitrazepam and tramadol were tested as drugs with no known effect on ADH activity. Cimetidine, reported previously as having inhibitory effect on ADH, and 4-methylpyrazole (4-MP), a well known ADH inhibitor, were tested as positive controls. Apart from 4-MP, tramadol was identified as having the higher inhibitory effect with an IC50 of 44.7 x 10-3 mM, followed by cimetidine (IC50 of 122.9 x 10-3 mM). Alprazolam and flunitrazepam also reduced liver ADH activity but to a smaller extent (inhibition of 11.8 ± 5.0% for alprazolam 1.0 mM and 34.5 ± 7.1% for flunitrazepam 0.04 mM). Apart from cimetidine, this is the first report describing the inhibitory effect of these drugs on ethanol metabolism. The results also show the suitability of the method to screen for inhibitory effect of drugs on ethanol metabolism helping to identify drugs for which further study is justified

The effect of xenobiotics on rat liver alcohol dehydrogenase activity or how medicines can affect the metabolism of alcohol

Comunicação oral sob a forma de painelIt is well documented that serious side effects or toxic interactions may occur after the administration of some drugs and/or medicines with the concurrent use of alcohol (ethanol). Most of these interactions are attributable to pharmacokinetic changes caused by alcohol in the hepatic drug metabolic pathways catalysed by the cytochrome P450 system. What is not so well known is the potential effect of drugs and medicines on the activity of the liver alcohol dehydrogenase (ADH). Liver cytosolic ADH, the major catabolizing enzyme of alcohol, catalyzes the reversible oxidation of ethanol to acetaldehyde with the corresponding reduction of NAD to NADH. The knowledge of ADH-xenobiotics interactions would be very important because if a drug significantly inhibits liver ADH it will prevent ethanol to be eliminated at normal rates and blood alcohol concentration (BAC) would concomitantly increase. In these situations, it should be definitely known by physicians, pharmacists and patients that drugs with that kind of action present an increased risk of slowing alcohol metabolism. This might then result in potentially toxic plasma alcohol concentrations with behavioural impairment and social, legal and forensic implications. In order to evaluate the possible interactions between commonly prescribed medicines and ethanol metabolism, a spectrophotometric method was developed to study the alcohol dehydrogenase activity of rat liver homogenates by monitoring NADH formation at 340 nm in the presence and in the absence of different xenobiotics. Enzyme activity was calculated from the linear increase in A340nm after ethanol addition1 in the presence of tramadol, flunitrazepam, alprazolam and propanonol. 4-Methylpyrazole, a well-known specific inhibitor of ADH, was used as a positive control. Results will be presented that demonstrate the efficiency of the method and the preliminary data of the interaction between ADH and the tested substances.Financial support: i-Med.UL (Research Institute for Medicines and Pharmaceutical Sciences, MedChem Division) and National Institute of Legal Medicine - South Branch, Lisbon, Portugal

Mudanças tecnológicas e seu impacto no processo de trabalho em saúde Technological changes and their impact on the work process in the area of health

Objetiva-se aqui analisar as mudanças contemporâneas no mundo do trabalho e os seus efeitos ou impactos nos processo de trabalho em saúde. Trata-se de uma análise que toma como referencial teórico uma vertente dos estudos do trabalho em saúde desenvolvida no Brasil, no campo da saúde coletiva, que, partindo do pressuposto da consubstancialidade entre trabalho e necessidades sociais, vai aprofundar a investigação dos processos de trabalho e seus elementos constituintes, bem como da dimensão intersubjetiva e ético-moral da produção de serviços de saúde. Considerada, de um lado, a complexidade dos objetos de trabalho em saúde que requerem simultaneamente o aprofundamento vertical do conhecimento especializado e a sua integração e, de outro, a introdução de novos modelos organizacionais/gerenciais e a constante inovação e incorporação tecnológica, observam-se mudanças marcantes nos processo de trabalho, dentre as quais destacam-se: o caráter multiprofissional e interdisciplinar das práticas de saúde, o redimensionamento da autonomia profissional diante da necessidade de recomposição dos trabalhos especializados, e a necessidades de garantir maior e permanente qualificação profissional para o conjunto dos trabalhadores em saúde, tanto na dimensão técnica quanto na ético-política e comunicacional.<br>Our objective here is to analyze the contemporary changes in the world of work and their effect - or their impact - on the work processes in the area of health. The theoretical reference for this analysis is a specific stream of studies on work developed in Brazil in the area of collective health. Starting from the assumption that work and social needs are consubstantial, the analysis deepens the investigation of the work processes and their constitutive elements, as well as of the inter-subjective and ethical-moral dimensions of the production of health services. Having considered, on the one hand, the complexity of the work objects in the area of health - that demand both a vertical increase in specialized knowledge and the horizontal integration of that knowledge - ; and, on the other, the introduction of new organizational/managerial models and the constant presence of technological innovation and incorporation, we observed significant changes in the work processes, including, among others, the multi-professional and interdisciplinary character of health practices, the re-dimensioning of professional autonomy in the face of a need to recompose specialized work, and the need to provide all health workers with better and permanent professional qualifications, both in its technical and in its ethical-political and communicational dimensions