Potentially inappropriate medication use among institutionalized elderly individuals in southeastern Brazil

In recent decades, the elderly population in Brazil has grown rapidly, as has concern for the health of this population. Institutionalization in nursing homes has appeared as an alternative form of health care for frail elderly that live alone. The present study evaluated the pharmacotherapy and inappropriate drug prescriptions for institutionalized elderly patients living in long-term institutions in southeastern Brazil. This research was conducted at five institutions with a total sample of 151 individuals aged at least 60 years. Databases were used to identify drug interactions, defined daily dose and inappropriate prescriptions. The prevalence of drug intake among the elderly was 95.36%, and there were an average of 3.31 ± 1.80 drug prescriptions per individual. Based on Beers criteria, the prevalence of inappropriate prescriptions was 25.83%. In addition, 70.2% of prescriptions were prescribed at a higher dosage than the defined daily dose (ATC/WHO). Potential drug interactions were identified for 54.11% of prescriptions; 81.42% of these were of moderate severity. The main inappropriate drugs were prescribed for cardiovascular and nervous system problems. Institutionalized elderly individuals presented a high consumption and misuse of medications, requiring professional intervention to monitor prescriptions and improve the quality of service for this population.Nas últimas décadas, o número de idosos no Brasil cresceu rapidamente, bem como, a preocupação com a saúde desta parcela da população. Neste cenário, a institucionalização em casas de repouso aparece como uma alternativa para os cuidados com a saúde dos idosos debilitados ou que vivem sozinhos. O presente estudo avaliou a farmacoterapia e a prescrição inadequada para idosos que residem em instituições de longa permanência no sudeste do Brasil. Esta pesquisa foi realizada em cinco instituições, totalizando uma amostra de 151 indivíduos com idade a partir de 60 anos. O banco de dados foi analisado para identificação de interações medicamentosas, dose diária definida e critérios de Beers. Dentre os indivíduos avaliados, 95,36% consomem algum tipo de medicamento, sendo 3,31 ± 1,80 medicamentos prescritos por indivíduo. Com base nos critérios de Beers, a prevalência de prescrições inapropriadas foi de 25,83%, sendo também encontradas 70,2% das prescrições com doses superiores à dose diária definida (ATC/WHO). Interações medicamentosas potenciais estavam presentes em 54,11% das prescrições, sendo 81,42% com grau moderado de gravidade. Os principais medicamentos inapropriados foram prescritos para problemas cardiovasculares e do sistema nervoso. Os idosos institucionalizados apresentam alto consumo e uso inadequado de medicamentos, sendo necessária a intervenção profissional para monitorar as prescrições médicas e melhorar a qualidade do serviço de distribuição de medicamentos a esta parte da população

Diretriz da Sociedade Brasileira de Cardiologia sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas

This guideline aimed to update the concepts and formulate the standards of conduct and scientific evidence that support them, regarding the diagnosis and treatment of the Cardiomyopathy of Chagas disease, with special emphasis on the rationality base that supported it.  Chagas disease in the 21st century maintains an epidemiological pattern of endemicity in 21 Latin American countries. Researchers and managers from endemic and non-endemic countries point to the need to adopt comprehensive public health policies to effectively control the interhuman transmission of T. cruzi infection, and to obtain an optimized level of care for already infected individuals, focusing on diagnostic and therapeutic opportunistic opportunities.   Pathogenic and pathophysiological mechanisms of the Cardiomyopathy of Chagas disease were revisited after in-depth updating and the notion that necrosis and fibrosis are stimulated by tissue parasitic persistence and adverse immune reaction, as fundamental mechanisms, assisted by autonomic and microvascular disorders, was well established. Some of them have recently formed potential targets of therapies.  The natural history of the acute and chronic phases was reviewed, with enhancement for oral transmission, indeterminate form and chronic syndromes. Recent meta-analyses of observational studies have estimated the risk of evolution from acute and indeterminate forms and mortality after chronic cardiomyopathy. Therapeutic approaches applicable to individuals with Indeterminate form of Chagas disease were specifically addressed. All methods to detect structural and/or functional alterations with various cardiac imaging techniques were also reviewed, with recommendations for use in various clinical scenarios. Mortality risk stratification based on the Rassi score, with recent studies of its application, was complemented by methods that detect myocardial fibrosis.  The current methodology for etiological diagnosis and the consequent implications of trypanonomic treatment deserved a comprehensive and in-depth approach. Also the treatment of patients at risk or with heart failure, arrhythmias and thromboembolic events, based on pharmacological and complementary resources, received special attention. Additional chapters supported the conducts applicable to several special contexts, including t. cruzi/HIV co-infection, risk during surgeries, in pregnant women, in the reactivation of infection after heart transplantation, and others.     Finally, two chapters of great social significance, addressing the structuring of specialized services to care for individuals with the Cardiomyopathy of Chagas disease, and reviewing the concepts of severe heart disease and its medical-labor implications completed this guideline.Esta diretriz teve como objetivo principal atualizar os conceitos e formular as normas de conduta e evidências científicas que as suportam, quanto ao diagnóstico e tratamento da CDC, com especial ênfase na base de racionalidade que a embasou. A DC no século XXI mantém padrão epidemiológico de endemicidade em 21 países da América Latina. Investigadores e gestores de países endêmicos e não endêmicos indigitam a necessidade de se adotarem políticas abrangentes, de saúde pública, para controle eficaz da transmissão inter-humanos da infecção pelo T. cruzi, e obter-se nível otimizado de atendimento aos indivíduos já infectados, com foco em oportunização diagnóstica e terapêutica. Mecanismos patogênicos e fisiopatológicos da CDC foram revisitados após atualização aprofundada e ficou bem consolidada a noção de que necrose e fibrose sejam estimuladas pela persistência parasitária tissular e reação imune adversa, como mecanismos fundamentais, coadjuvados por distúrbios autonômicos e microvasculares. Alguns deles recentemente constituíram alvos potenciais de terapêuticas. A história natural das fases aguda e crônica foi revista, com realce para a transmissão oral, a forma indeterminada e as síndromes crônicas. Metanálises recentes de estudos observacionais estimaram o risco de evolução a partir das formas aguda e indeterminada e de mortalidade após instalação da cardiomiopatia crônica. Condutas terapêuticas aplicáveis aos indivíduos com a FIDC foram abordadas especificamente. Todos os métodos para detectar alterações estruturais e/ou funcionais com variadas técnicas de imageamento cardíaco também foram revisados, com recomendações de uso nos vários cenários clínicos. Estratificação de risco de mortalidade fundamentada no escore de Rassi, com estudos recentes de sua aplicação, foi complementada por métodos que detectam fibrose miocárdica. A metodologia atual para diagnóstico etiológico e as consequentes implicações do tratamento tripanossomicida mereceram enfoque abrangente e aprofundado. Também o tratamento de pacientes em risco ou com insuficiência cardíaca, arritmias e eventos tromboembólicos, baseado em recursos farmacológicos e complementares, recebeu especial atenção. Capítulos suplementares subsidiaram as condutas aplicáveis a diversos contextos especiais, entre eles o da co-infecção por T. cruzi/HIV, risco durante cirurgias, em grávidas, na reativação da infecção após transplante cardíacos, e outros.    Por fim, dois capítulos de grande significado social, abordando a estruturação de serviços especializados para atendimento aos indivíduos com a CDC, e revisando os conceitos de cardiopatia grave e suas implicações médico-trabalhistas completaram esta diretriz.&nbsp

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Efeito neuroprotetor da inibição do transportador de glicina do tipo 1

Exportado OPUSMade available in DSpace on 2019-08-12T00:11:57Z (GMT). No. of bitstreams: 1 tese.pdf: 6565378 bytes, checksum: 92b96fc60f056422f310bf0fa38e0b87 (MD5) Previous issue date: 24A tolerância à isquemia cerebral é um mecanismo de neuroproteção desencadeado por um estímulo pré-condicionante não tóxico que prepara os neurônios contra diversos tipos de danos. Este fenômeno pode ser induzido pela ativação de receptores de NMDA (NMDAR) em neurônios. Estudos recentes têm demonstrado que os inibidores dos transportadores de glicina do tipo 1 (GlyT-1) podem potencializar a neurotransmissão glutamatérgica através de NMDAR, sugerindo uma via alternativa de pré-condicionamento cerebral. Neste trabalho, nós avaliamos o efeito do précondicionamento cerebral utilizando dois tipos de inibidores de GlyT-1 (sarcosina e NFPS) em diferentes modelos de dano cerebral. Na primeira etapa, nós testamos a sarcosina, um bloqueador competitivo de GlyT-1, a qual foi administrada durante sete dias consecutivos antes da indução de modelos de isquemia em ratos. O précondicionamento com sarcosina reduziu a morte celular em fatias de hipocampo submetidas à privação de oxigênio glicose (POG) e preveniu a morte neuronal no modelo de oclusão de quatro vasos (4VO). Durante o período de isquemia, os animais pré-condicionados com sarcosina apresentaram uma redução da liberação de glutamato, da produção de óxido nítrico e de espécies reativa de oxigênio. Estes efeitos estavam associados à redução da expressão de transportadores de glicina (GlyT-1 e GlyT-2), redução da captação de [3H]-glicina e redução do conteúdo de glicina no hipocampo. Além disso, o pré-condicionamento com sarcosina reduziu a expressão da subunidade NR2B de NMDAR, a qual é comumente associada à excitotoxicidade. Na segunda etapa, nós avaliamos o efeito do pré-condicionamento com NFPS, um bloqueador não competitivo de GlyT-1, em camundongos submetidos à um dano excitotóxico induzido pela injeção intrahipocampal de NMDA. O pré-condicionamento com NFPS reduziu o número de neurônios degenerados no hipocampo, sendo este efeito também associado à redução da expressão da subunidade NR2B de NMDAR. Este estudo demonstra que o pré-condicionamento com inibidores de GlyT-1 induz tolerância à isquemia cerebral e resistência à excitotoxicidade, sendo este efeito associado a modulação das vias glicinérgicas hipocampais e com a redução da subunidade NR2B de NMDAR.Brain ischemic tolerance is a protective mechanism achieve by a preconditioning stimulus that prepare the tissue against a harmful insult. This phenomenon can be induced by activation of NMDA receptors (NMDAR) in neurons. Recently, the glycine transporters type 1 (GlyT-1) have been shown to potentiate glutamate neurotransmission through NMDA receptors, suggesting an alternative pathway to induce brain preconditioning. In this study, we evaluated the brain preconditioning induced by two GIyT-1 inhibitors (sarcosine and NFPS) in different models of brain damage. In the first part, we tested sarcosine, a competitive blocker of GlyT-1, which was administered for seven consecutive days before the induction of ischemia models in rats. Sarcosine preconditioning reduced cell death in hippocampal slices submitted to oxygen glucose deprivation (OGD) and four vessels occlusion (4VO) model. During the period of ischemia, the preconditioned animals with sarcosine showed a reduction of glutamate release, the production of nitric oxide and reactive oxygen species. These effects were associated with reduction in glycine transporters expression (GIyT-1 and GlyT-2), reduction of [3H]-glycine uptake and reduction in the glycine level in hippocampus. Interestingly, sarcosine preconditioning reduced expression of NR2Bcontaning NMDAR, which is associated with high susceptibility to excitotoxicity. In the second step, we evaluated the effect of preconditioning with NFPS, a noncompetitive blocker of GIyT-1, in mice submitted to excitotoxic damage induced by intrahippocampal injection of NMDA. NFPS preconditioning generated a neuroprotective effect in hippocampus, being this effect also related to reduction of NR2B-contaning NMDAR. This study demonstrates that brain preconditioning with GlyT-1 inhibitors induces ischemic tolerance and resistance against excitotoxicity, being that neuroprotection related to neuromodulation of glycinergic neurotransmission and reduction of NR2B-contaning NMDAR

Trypan blue exclusion assay by flow cytometry

Submitted by Nuzia Santos ([email protected]) on 2015-01-28T15:27:26Z No. of bitstreams: 1 2014_003.pdf: 1135145 bytes, checksum: dc2e947d746266f16712e0890b86299c (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-01-28T15:27:34Z (GMT) No. of bitstreams: 1 2014_003.pdf: 1135145 bytes, checksum: dc2e947d746266f16712e0890b86299c (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-01-28T15:33:09Z (GMT) No. of bitstreams: 1 2014_003.pdf: 1135145 bytes, checksum: dc2e947d746266f16712e0890b86299c (MD5)Made available in DSpace on 2015-01-28T15:33:09Z (GMT). No. of bitstreams: 1 2014_003.pdf: 1135145 bytes, checksum: dc2e947d746266f16712e0890b86299c (MD5) Previous issue date: 2014Universidade Federal dos Vales do Jequitinhonha e Mucuri. Departamento de Farmácia. Laboratório de Imunologia. Diamantina, MG, Brasil.Universidade Federal dos Vales do Jequitinhonha e Mucuri. Departamento de Farmácia. Laboratório de Imunologia. Diamantina, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Farmacologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Farmacologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Farmacologia. Belo Horizonte, MG, Brasil.Fundação Osvaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração Belo Horizonte, MG, Brasil.Universidade Federal dos Vales do Jequitinhonha e Mucuri. Departamento de Farmácia. Laboratório de Imunologia. Diamantina, MG, Brasil.Universidade Federal dos Vales do Jequitinhonha e Mucuri. Departamento de Farmácia. Laboratório de Imunologia. Diamantina, MG, Brasil.Dye exclusion tests are used to determine the number of live and dead cells. These assays are based on the principle that intact plasma membranes in live cells exclude specific dyes, whereas dead cells do not. Although widely used, the trypan blue (TB) exclusion assay has limitations. The dye can be incorporated by live cells after a short exposure time, and personal reliability, related to the expertise of the analyst, can affect the results. We propose an alternative assay for evaluating cell viability that combines the TB exclusion test and the high sensitivity of the flow cytometry technique. Previous studies have demonstrated the ability of TB to emit fluorescence when complexed with proteins. According to our results, TB/bovine serum albumin and TB/cytoplasmic protein complexes emit fluorescence at 660 nm, which is detectable by flow cytometry using a 650-nm low-pass band filter. TB at 0.002% (w/v) was defined as the optimum concentration for distinguishing unstained living cells from fluorescent dead cells, and fluorescence emission was stable for 30 min after cell treatment. Although previous studies have shown that TB promotes green fluorescence quenching, TB at 0.002% did not interfere with green fluorescence in human live T-cells stained with anti-CD3/fluorescein isothiocyanate (FITC) monoclonal antibody. We observed a high correlation between the percentage of propidium iodide+CD3/FITC+ and TB+CD3/FITC+ cells, as well as similar double-stained cell profiles in flow cytometry dot-plot graphs. Taken together, the results indicate that a TB exclusion assay by flow cytometry can be employed as an alternative tool for quick and reliable cell viability analysis

Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate

Submitted by Nuzia Santos ([email protected]) on 2014-11-28T13:32:48Z No. of bitstreams: 1 Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells.pdf: 952430 bytes, checksum: c80a532f9fefe7ae8cc25e5c90d280ad (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2014-11-28T13:36:12Z (GMT) No. of bitstreams: 1 Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells.pdf: 952430 bytes, checksum: c80a532f9fefe7ae8cc25e5c90d280ad (MD5)Made available in DSpace on 2014-11-28T13:36:12Z (GMT). No. of bitstreams: 1 Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells.pdf: 952430 bytes, checksum: c80a532f9fefe7ae8cc25e5c90d280ad (MD5) Previous issue date: 2011Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilInstitut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, FranceInstitut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, FranceUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilAims: We evaluated biological activity in leukemia cells lines of R and S enantiomers of tert-butyl 4-[(3-nitrophenoxy)-methyl]-2,2-dimethyloxazolidine-3-carboxylate (BNDC). Main methods: Cytotoxic activity was assessed by MTT assay. Flow cytometry assays were used to determined DNA fragmentation (Propidium Iodide-PI staining) and phosphatidylserine exposure (Annexin-V and PI staining). DNA condensation was evaluated by fluorescence microscopy using double-staining in leukemia cells (Hoechst and PI). Caspase activities were measured using Z-VAD-FMK, a non-selective caspase inhibitor, by flow cytometry and Z-DEVD-AMC, a selective caspase-3 substrate, by fluorescence spectrometry. Key findings: Both enantiomers displayed cytotoxic activity against leukemia cell lines (HL60, HL60.Bcl-2, HL60.Bcl-XL and Jurkat) with low toxicity against human peripheral blood mononuclear cell — PBMC based on IC50values. In HL60 cell lines, compounds induce exposure of phosphatidylserine and DNA fragmentation, which could be blocked by pretreatment of cells with Z-VAD-FMK. Confirming this observation, both enantiomers induced caspase-3 activation. Additional analysis revealed an increased percentage of apoptotic cells (defined as those with fragmented nuclei and condensed chromatin) after treatment with compounds. Significance: Taken together, the results indicate that BNDC compounds exhibited cytotoxic and pro-apoptotic activities and have a potential for developing a new class of anticancer drugs

The Role of Astrocytes in the Neurorepair Process

Astrocytes are highly specialized glial cells responsible for trophic and metabolic support of neurons. They are associated to ionic homeostasis, the regulation of cerebral blood flow and metabolism, the modulation of synaptic activity by capturing and recycle of neurotransmitters and maintenance of the blood-brain barrier. During injuries and infections, astrocytes act in cerebral defense through heterogeneous and progressive changes in their gene expression, morphology, proliferative capacity, and function, which is known as reactive astrocytes. Thus, reactive astrocytes release several signaling molecules that modulates and contributes to the defense against injuries and infection in the central nervous system. Therefore, deciphering the complex signaling pathways of reactive astrocytes after brain damage can contribute to the neuroinflammation control and reveal new molecular targets to stimulate neurorepair process. In this review, we present the current knowledge about the role of astrocytes in brain damage and repair, highlighting the cellular and molecular bases involved in synaptogenesis and neurogenesis. In addition, we present new approaches to modulate the astrocytic activity and potentiates the neurorepair process after brain damage.publishe

Potentially inappropriate medication use in a city of Southeast Brazil

Potentially inappropriate medication use by the Diamantina (Minas Gerais State) population was investigated by analyzing medicine consumption, self-medication, polypharmacy and drug interactions of medicines prescribed among those interviewed. Level of knowledge about rational drug use and its relationship to socio-economic variables was also evaluated using a semi-structured questionnaire. This survey was based on stratified sampling of 423 individuals selected randomly. The prevalence of prescription drug consumption was 42.32% (n=179) and cardiovascular drugs were the most prescribed. Drug interactions were found in 45.81% (n=82) of prescriptions and 92.68% (n=76) of these interactions were moderate, with co-administration of cardiovascular drugs occurring in more than half of the cases. The inappropriate use of medication, according to Beers criteria, occurred in 44.73% of prescriptions to the elderly. The prevalence of self-medication was 63.34% (n=268) while 21.99% (n=91) of individuals administered medications to their children without formal prescriptions, where this practice was associated to analgesic/antipyretic consumption. The population showed a high prevalence of inappropriate use of drugs across all strata of society, representing an issue requiring effective actions to promote rational use of medicines.<br>O consumo inapropriado de medicamentos pela população de Diamantina-MG foi investigado através da análise do consumo de medicamentos, automedicação, polifarmácia e interações medicamentosas prescritas aos entrevistados. Também foi avaliado o nível de conhecimento sobre uso racional de medicamentos e sua relação com variáveis sócio-econômicas através de um questionário semi-estruturado. Este estudo transversal foi baseado em amostragem estratificada e contou com a participação de 423 indivíduos selecionados aleatoriamente. A prevalência do consumo de medicamentos prescritos foi de 42,32% (n=179), sendo os medicamentos cardiovasculares os mais prescritos. Entre as prescrições foram encontradas 45,81% (n=82) de interações medicamentosas, sendo 92,68% (n=76) destas interações moderadas e a co-administração de medicamentos cardiovasculares presente em mais da metade dos casos. O uso inadequado de medicamentos, segundo os critérios de Beers, esteve presente em 44,73% das prescrições de idosos. Com relação à automedicação, 63,34% (n=268) dos entrevistados admitem fazer uso de medicamento sem prescrição e 21,99% (n=91) administram medicamentos aos filhos sem prescrição profissional, sendo os analgésicos e antitérmicos os mais comumente administrados em ambas as situações. A população avaliada apresentou alta prevalência de uso inadequado de medicamentos observados em todas as camadas da sociedade, sendo necessário estabelecer medidas eficazes para promoção do uso racional de medicamentos