Chemical Constituents, Anticancer and Anti-Proliferative Potential of Limonium Species: A Systematic Review.

Limonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cells lines (especially hepatocellular carcinoma-HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds.

Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies.

OBJECTIVES: This scoping review aims to present flavonoid compounds' promising effects and possible mechanisms of action on potential therapeutic targets in the SARS-CoV-2 infection process. METHODS: A search of electronic databases such as PubMed and Scopus was carried out to evaluate the performance of substances from the flavonoid class at different stages of SARS-CoV-2 infection. RESULTS: The search strategy yielded 382 articles after the exclusion of duplicates. During the screening process, 265 records were deemed as irrelevant. At the end of the full-text appraisal, 37 studies were considered eligible for data extraction and qualitative synthesis. All the studies used virtual molecular docking models to verify the affinity of compounds from the flavonoid class with crucial proteins in the replication cycle of the SARS-CoV-2 virus (Spike protein, PLpro, 3CLpro/ MPro, RdRP, and inhibition of the host's ACE II receptor). The flavonoids with more targets and lowest binding energies were: orientin, quercetin, epigallocatechin, narcissoside, silymarin, neohesperidin, delphinidin-3,5-diglucoside, and delphinidin-3-sambubioside-5-glucoside. CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.

Cost of Illness in Patients With COVID-19 Admitted in Three Brazilian Public Hospitals.

OBJECTIVES: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives. METHODS: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission. RESULTS: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively. CONCLUSIONS: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.

Bioactive compounds as potential angiotensin-converting enzyme II inhibitors against COVID-19: a scoping review.

OBJECTIVE AND DESIGN: The current study aimed to summarize the evidence of compounds contained in plant species with the ability to block the angiotensin-converting enzyme 2 (ACE-II), through a scoping review. METHODS: PubMed and Scopus electronic databases were used for the systematic search and a manual search was performed RESULTS: Studies included were characterized as in silico. Among the 200 studies retrieved, 139 studies listed after the exclusion of duplicates and 74 were included for the full read. Among them, 32 studies were considered eligible for the qualitative synthesis. The most evaluated class of secondary metabolites was flavonoids with quercetin and curcumin as most actives substances and terpenes (isothymol, limonin, curcumenol, anabsinthin, and artemisinin). Other classes that were also evaluated were alkaloid, saponin, quinone, substances found in essential oils, and primary metabolites as the aminoacid L-tyrosine and the lipidic compound 2-monolinolenin. CONCLUSION: This review suggests the most active substance from each class of metabolites, which presented the strongest affinity to the ACE-II receptor, what contributes as a basis for choosing compounds and directing the further experimental and clinical investigation on the applications these compounds in biotechnological and health processes as in COVID-19 pandemic.

The naturally-derived alkaloids as a potential treatment for COVID-19: A scoping review.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has a high mortality rate and transmissibility. In this context, medicinal plants have attracted attention due to the wide availability and variety of therapeutic compounds, such as alkaloids, a vast class with several proven pharmacological effects, like the antiviral and anti-inflammatory activities. Therefore, this scoping review aimed to summarize the current knowledge of the potential applicability of alkaloids for treating COVID-19. A systematic search was performed on PubMed and Scopus, from database inception to August 2021. Among the 63 eligible studies, 65.07% were in silico model, 20.63% in vitro and 14.28% clinical trials and observational studies. According to the in silico assessments, the alkaloids 10-hydroxyusambarensine, cryptospirolepine, crambescidin 826, deoxynortryptoquivaline, ergotamine, michellamine B, nigellidine, norboldine and quinadoline B showed higher binding energy with more than two target proteins. The remaining studies showed potential use of berberine, cephaeline, emetine, homoharringtonine, lycorine, narciclasine, quinine, papaverine and colchicine. The possible ability of alkaloids to inhibit protein targets and to reduce inflammatory markers show the potential for development of new treatment strategies against COVID-19. However, more high quality analyses/reviews in this field are necessary to firmly establish the effectiveness/safety of the alkaloids here described.

Validation of the Brazilian version of the hepatitis B quality of life evaluation instrument - HBQOL, and its application to patients with chronic hepatitis B in Cascavel - PR

Abstract The objective of this study is to validate the specific questionnaire for Hepatitis B HBQOL (Hepatitis B Quality of Life Instrument, version 1.0) for the Brazilian version, in addition to testing its applicability in patients with hepatitis B under treatment and comparing the quality of life between patients using first-line drugs (tenofovir and entecavir). For the validation, the back-translation technique was used in a sample of 47 patients. Factor analysis was performed between the items in each domain of the questionnaire and the internal consistency was calculated using Cronbach's α coefficient. In assessing the applicability of the validated questionnaire, interviews were carried out with 124 patients. Sociodemographic and treatment data were collected to characterize the sample and perform correlation analyzes. The results demonstrate that the Brazilian version of the questionnaire was successfully validated. In the analysis carried out among the 124 patients, the domains psychological well-being and stigma obtained the highest scores in quality of life and the lowest level of education conferred better results in these two domains. The comparison between tenofovir and entecavir showed no significant difference in patients' quality of life. The use of this validated instrument can make therapeutic decisions more rational

Concepts applied in daily practice in administration of medicines via nasogastric tube by the nursing team / Conceitos aplicados na prática diária na administração de medicamentos via sonda nasoenteral pela equipe de enfermagem

The study aimed to assess the current situation of medication administration via nasogastric tube (VNGT) and identify weaknesses in the process. As a tool, the application of questionnaires to the professionals of the nursing service was used. The questionnaire contained questions and each of them, during the correction, was assigned a specific score. The participant could according to the evaluation system get a grade of 0 to 100 points. Among the participants, 66.7% stated that they had already received some guidance on medication administration via the tube, and after correction and assignment of the notes, the averages obtained were: 47.3 points by the nurses; 38.7 points by nursing technicians; 34.5 points for resident nurses; and 37.0 points by the nursing assistants. The findings of the study indicate that there is a difference between the usual practice and the recommended practice in the literature and the professionals knowledge about administration of medication VNGT is still limited. The insertion of the pharmacist in the multidisciplinary team and disseminating knowledge on incompatibilities, interactions and reactions are of great importance for the improvement of this scenario.

O estudo teve por objetivos avaliar o panorama atual da administração de medicamentos via sonda nasoenteral (VSNE) e identificar as fragilidades nesse processo. Como ferramenta utilizou-se a aplicação de questionários aos profissionais do serviço de enfermagem. O questionário continha questões e a cada uma delas, durante a correção, atribuiu-se uma pontuação específica. O participante poderia de acordo com o sistema de avaliação obter uma nota de 0 a 100 pontos. Dentre os participantes, 66,7% afirmaram já ter recebido alguma orientação sobre a administração de medicamentos, via sonda, e após correção e atribuição das notas, as médias obtidas foram: 47,3 pontos pelos enfermeiros; 38,7 pontos pelos técnicos em enfermagem; 34,5 pontos pelos enfermeiros residentes; e 37,0 pontos pelos auxiliares de enfermagem. Os achados do estudo indicam que existe diferença entre a prática usual com o recomendado na literatura e o conhecimento dos profissionais sobre administração de medicamentos VSNE ainda é limitado. A inserção do farmacêutico na equipe multidisciplinar e disseminação do conhecimento referente às incompatibilidades, interações e reações presentes são de grande importância para a melhoria deste cenário.

Reduction of glycated hemoglobin (HbA1c) and cost analysis of treatment with insulin analogues in the state of Paraná: a retrospective cohort study / Redução de hemoglobina glicada (HbA1c) e análise de custo do tratamento com análogas insulinas no estado do Paraná: estudo de coorte retrospectivo

Objective: Diabetes mellitus (DM) is a serious public health problem in Brazil. The goal of this study was to evaluate the effectiveness of long-acting insulin analogues in controlling glycemia in type 1 DM patients and to analyze the direct costs of the treatment. Methods: A retrospective cohort study was undertaken with data collected from the State Health Secretary's 2nd Regional Health Center from the State of Paraná. After randomization, socio-demographic data, the source of their drug prescriptions, and the pharmacotherapeutic profiles of the drugs were collected, along with clinical outcome information, such as glycated hemoglobin (HbA1c) and fasting plasma glucose levels. The direct costs of treatment with analogue insulin were evaluated based on the drugs and supplies acquisition data from the Center for Drugs, Paraná Cemepar. Results: One hundred and forty-eight type 1 diabetes mellitus patients, older than 18 years of age, were included in the cohort study. The HbA1c reduction after the insulin treatment was 0.36 ± 2.75, and the direct costs to reduce this parameter by 1% over a period of 24 months were U$ 1,806. The estimated costs to reduce HbA1c by 1% are U$ 5,016. Conclusions: In this study, we were able to estimate the public health system costs of using insulin analogues to reduce HbA1c by 1% in patients with type 1 DM. This information will assist clinicians in decision-making regarding insulin treatment.

Objetivo: Diabetes mellitus (DM) é um grave problema de saúde pública no Brasil. O objetivo deste estudo foi avaliar a redução da HbA1c em pacientes usuários de insulinas análogas de longa duração no controle glicêmico de pacientes com DM tipo 1 e avaliar custos diretos do tratamento com insulinas análogas. Métodos: O estudo é uma coorte retrospectiva e análise de custos para o tratamento de DM tipo 1, com pacientes pertencentes a 2a Regional de Saúde do estado do Paraná. Após randomização dos pacientes, foram coletados dados sociodemográficos, origem da prescrição e seu perfil farmacoterapêutico, além dos desfechos clínicos, como hemoglobina glicada (HbA1c) e glicemia em jejum. Foi realizada uma análise dos custos diretos do tratamento com insulinas análogas, e os valores foram obtidos por meio dos dados de compra dos medicamentos e insumos realizados pelo Centro de Medicamentos Básicos do Paraná (Cemepar). Resultados: Foram incluídos 148 pacientes maiores de 18 anos. A variável avaliada foi redução na HbA1c que, entre os pacientes, foi de 0,36 ± 2,75. Os resultados médios dos custos diretos totais do tratamento com DM tipo 1 durante 24 meses foram de R$ 7.224,00, para obter redução em 0,36% dos valores de HbA1c. O custo teórico para a redução em 1% de HbA1c é de R$ 20.064,00. Conclusões: Neste estudo foi possível estimar o custo para o sistema público de saúde, da redução de 1% da HbA1c em pacientes com DM tipo 1 usando insulinas análogas. Essa informação serve de subsídios para gestores e clínicos na tomada de decisão do tratamento com insulinas.

Cost-minimization analysis of oral and intravenous administration of linezolid in a public hospital in southern Brazil / Análise de custo-minimização entre as vias de administração oral e endovenosa de linezolida em um hospital público da região sul do Brasil

Due to the paucity of cost-minimization studies about linezolid, the aim of this study was to estimate the cost differential between intravenous and oral administration. A retrospective cohort study and costminimization analysis was conducted between August 2009 and August 2013 in a public hospital in southern Brazil. Inpatient records were evaluated for 152 patients who received linezolid intravenously or orally. Over two-thirds of the patients (103, 67.8%) received the antibiotic by the intravenous route only (IV group), and the remainder received the antibiotic both routes sequentially (mixed group). In the IV group, 33 patients (31.7%) were eligible to receive the antibiotic orally. The total cost per patient (mean) after changing from intravenous to oral administration was significantly lower than the real cost paid per patient (mean) (p<0.001). The cost savings associated with switching to oral linezolid administration would be US$14,328.32 over four years. Pharmacoeconomic analyses of linezolid therapy can inform hospitals' decisions about the rational use of therapeutics and economic resources.

Devido à escassez de estudos de custo-minimização a cerca da linezolida, o objetivo deste estudo foi estimar a diferença de custo entre a administração intravenosa e oral desse antibiótico. Um estudo de coorte retrospectiva e uma análise de custo-minimização foram realizados entre agosto de 2009 e agosto de 2013, em um hospital público do sul do Brasil. Foram avaliados os prontuários médicos de 152 pacientes que receberam linezolida por via intravenosa e / ou oralmente. Mais de dois terços dos pacientes (103, 67.8%) receberam o medicamento exclusivamente por via intravenosa (grupo IV), e o restante (grupo misto) recebeu o antibacteriano por via intravenosa e por via oral sequencialmente. No grupo IV, 33 pacientes (31.7%) eram elegíveis para receber o antibiótico por via oral. O custo médio total por paciente após a troca hipotética da via de administração intravenosa para oral foi significativamente mais baixo do que o custo médio real pago por cada tratamento com linezolida (p <0.001). A economia de custos associados com a mudança para a administração oral de linezolida seria de US $ 14,328.32 ao longo de quatro anos. A análise farmacoeconômica da terapia com linezolida pode orientar as decisões dos hospitais quanto ao uso racional de terapêuticas e de recursos econômicos.

Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

All patients with Diabetes Mellitus (DM) receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily) and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%). Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety. Our results indicate that long- and short-acting insulin analogues offer few clinical advantages over conventional human insulin.

Todos os pacientes com Diabetes Mellitus (DM) tipo 1 recebem insulina. Neste estudo, avaliaram-se eficácia, segurança e tolerabilidade de insulinas humanas e análogas. Realizou-se uma revisão sistemática e meta-análise, de acordo com o preconizado pela Colaboração Cochrane. Na ausência de estudos clínicos comparando insulinas entre si, realizaram-se meta-análises de comparações indiretas a fim de estabelecer diferenças entre tratamentos ativos. Incluíram-se estudos de 1995 a 2010. Resultados de HbA1c, episódios de hipoglicemia e hipoglicemia noturna foram extraídos e analisados. Após leitura de resumos e, posteriormente, de artigos na íntegra, selecionaram-se 35 ensaios clínicos randomizados, totalizando 4206 pacientes utilizando insulina análoga de longa duração e 5733 pacientes insulina análoga de curta duração. Os resultados não demonstraram diferença estatisticamente significativa para redução de HbA1c entre glargina e detemir (uma vez ao dia) comparados a NPH. No entanto, insulina detemir utilizada duas vezes ao dia reduz a HbA1c (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%). Comparações diretas e indiretas indicam que não existem diferenças significativas na médica de redução de HbA1c, independente da posologia de detemir, sendo estes resultados de eficácia e segurança consistentes. Os resultados indicam que insulinas análogas de longa ou curta duração apresentam pequenas vantagens, quando comparadas às insulinas tradicionais. Ademais, não existem diferenças entre eficácia e segurança quando comparamos insulinas análogas entre si.

Efficacy of topical antifungal drugs in different dermatomycoses: a systematic review with meta-analysis.

OBJECTIVE: To evaluate and compare the efficacy of topical antifungal drugs applied to the treatment of each dermatomycosis. METHODS: A systematic review of randomized clinical trials, published in Portuguese, Spanish and English until July 2010, which compared the use of azole and allylamine antifungal drugs among themselves and with placebo in the treatment of cutaneous candidiasis and T. versicolor, T. pedis, T. cruris and T. corporis was performed. The efficacy outcomes evaluated were mycological cure at the end of treatment and sustained cure. RESULTS: Of the 4,424 studies initially identified, 49 met the selection criteria and were included in the meta-analyses. The grouped efficacy data evidenced the superiority of antifungal drugs compared to placebo, regardless of the dermatomycosis under evaluation, with odds ratio values ranging from 2.05 (95% CI 1.18-3.54) to 67.53 (95% CI 11.43-398.86). Allylamines were better than azoles only for the outcome sustained cure (OR 0.52 [95% CI 0.31-0.89]). CONCLUSION: There is consistent evidence of the superiority of antifungal drugs over the use of placebo, and placebo-controlled studies are no longer justifiable. Allylamines maintain the mycological cure for longer periods compared to azole drugs. Given the significant cost difference among the classes, pharmacoeconomic analyses should be performed.

Eficácia de antifúngicos tópicos em diferentes dermatomicoses: uma revisão sistemática com metanálise / Efficacy of topical antifungal drugs in different dermatomycoses: a systematic review with meta-analysis

OBJETIVO: Avaliar e comparar a eficácia dos antifúngicos tópicos empregados no tratamento de cada dermatomicose. MÉTODOS: Foi desenvolvida uma revisão sistemática de ensaios clínicos randomizados, publicados em português, espanhol ou inglês até julho de 2010, que comparassem o uso de antifúngicos azólicos e alilamínicos entre si ou com placebo, no tratamento de candidíase cutânea, e das tineas versicolor, pedis, cruris e corporis. Os desfechos de eficácia avaliados foram cura micológica ao final do tratamento e cura sustentada. RESULTADOS: Dos 4.424 estudos inicialmente identificados, 49 alcançaram os critérios de seleção, sendo incluídos nas metanálises. Os dados agrupados de eficácia demonstraram superioridade dos antifúngicos frente a placebo, independente da dermatomicose avaliada, com valores de odds ratio (OR) variando de 2,05 (IC 95% 1,18-3,54) a 67,53 (IC 95% 11,43-398,86). Alilaminas foram superiores aos azólicos apenas para o desfecho cura sustentada (OR 0,52 [IC 95% 0,31-0,89]). CONCLUSÃO: Há evidência consistente da superioridade dos antifúngicos com relação ao uso de placebo, não sendo mais justificável a realização de estudos controlados por placebo. Alilaminas mantêm a cura micológica por períodos mais extensos que fármacos azólicos. Dada a significativa diferença de custo entre as classes, recomenda-se a realização de análises farmacoeconômicas.

OBJECTIVE: To evaluate and compare the efficacy of topical antifungal drugs applied to the treatment of each dermatomycosis. METHODS: A systematic review of randomized clinical trials, published in Portuguese, Spanish and English until July 2010, which compared the use of azole and allylamine antifungal drugs among themselves and with placebo in the treatment of cutaneous candidiasis and T. versicolor, T. pedis, T. cruris and T. corporis was performed. The efficacy outcomes evaluated were mycological cure at the end of treatment and sustained cure. RESULTS: Of the 4,424 studies initially identified, 49 met the selection criteria and were included in the meta-analyses. The grouped efficacy data evidenced the superiority of antifungal drugs compared to placebo, regardless of the dermatomycosis under evaluation, with odds ratio values ranging from 2.05 (95% CI 1.18-3.54) to 67.53 (95% CI 11.43-398.86). Allylamines were better than azoles only for the outcome sustained cure (OR 0.52 [95% CI 0.31-0.89]). CONCLUSION: There is consistent evidence of the superiority of antifungal drugs over the use of placebo, and placebo-controlled studies are no longer justifiable. Allylamines maintain the mycological cure for longer periods compared to azole drugs. Given the significant cost difference among the classes, pharmacoeconomic analyses should be performed.

Revisiting the efficacy of long-acting insulin analogues on adults with type 1 diabetes using mixed-treatment comparisons.

AIM: To perform a network meta-analysis between long-acting insulin analogues (glargine and detemir) and Neutral Protamine Hagedorn (NPH) insulin on adults with type 1 diabetes. METHODS: A systematic review of the literature was conducted according to the Cochrane Collaboration guidelines. The search for randomized controlled trials was performed in process databases, conferences and "gray literature" by 1995. RESULTS: We found 1051 citations comparing glargine or detemir with human insulin and 187 comparing long-acting insulin analogues. Data on Glycated Hemoglobin (HbA1c), hypoglycemia episodes, nocturnal hypoglycemia and withdrawal were meta-analyzed. After review, 8 studies comparing glargine and 9 comparing detemir with NPH and 2 comparing glargine with detemir were considered relevant. Were included 1508 patients that received glargine, 2698 detemir and 2654 NPH insulin. Efficacy data showed no significant differences in HbA1c change between glargine or detemir (once daily) and NPH insulin. Twice-daily regimen of detemir caused a difference in HbA1c that favored detemir (-0.14% [95% CI -0.21 to -0.08]). Direct comparisons showed no significant differences between glargine and detemir in safety or HbA1c mean change. CONCLUSION: The long-acting insulin analogues offer little to no clinical advantages over NPH insulin, and there is no significant difference in the efficacy and safety.

Frequency of potential interactions between drugs in medical prescriptions in a city in southern Brazil.

CONTEXT AND OBJECTIVE: Drug interactions form part of current clinical practice and they affect between 3 and 5% of polypharmacy patients. The aim of this study was to identify the frequency of potential drug-drug interactions in prescriptions for adult and elderly patients. TYPE OF STUDY AND SETTING: Cross-sectional pharmacoepidemiological survey in the Parque Verde housing project, municipality of Cascavel, Paraná, Brazil, between December 2006 and February 2007. METHODS: Stratified cluster sampling, proportional to the total number of homes in the housing project, was used. The sample consisted of 95 homes and 96 male or female patients aged 19 or over, with medical prescriptions for at least two pharmaceutical drugs. Interactions were identified using DrugDigest, Medscape and Micromedex softwares. RESULTS: Most of the patients were female (69.8%), married (59.4%) and in the age group of 60 years or over (56.3%), with an income less than or equal to three minimum monthly salaries (81.3%) and less than eight years of schooling (69.8%); 90.6% of the patients were living with another person. The total number of pharmaceutical drugs was 406 (average of 4.2 medications per patient). The drugs most prescribed were antihypertensives (47.5%). The frequency of drug interactions was 66.6%. Among the 154 potential drug interactions, 4.6% were classified as major, 65.6% as moderate and 20.1% as minor. CONCLUSION: The high frequency of drug prescriptions with a potential for differentiated interactions indicates a situation that has so far been little explored, albeit a reality in household surveys.

Antioxidant capacity of extracts and isolated compounds from Stryphnodendron obovatum Benth / Capacidade antioxidante de extratos e compostos isolados de Stryphnodendron obovatum Benth

The extract from stem bark of Stryphnodendron obovatum Benth. was chromatographed on a Sephadex® LH-20 column, and yielded nine compounds: gallic acid (GA), p-hydroxybenzoic acid (PHB), gallocatechin (GC), epigallocatechin (EPG), 4'-O-methylgallocatechin (MGC), epigallocatechin-(4β→8)-epigallocatechin (EPEP), epigallocatechin-(4β→8)-gallocatechin (EPGC), robinetinidol-(4α→8)-gallocatechin (ROGC) and robinetinidol-(4β→8)-epigallocatechin (ROEP). Evaluation of the antioxidant capacity in vitro by the methods of DPPH free radical (IC50; μg/mL) and reduction of the phosphomolybdenum complex (RAC) gave the following results, respectively: crude extract 4.52 and 0.8242; ethyl-acetate fraction 4.04 and 0.9537; aqueous fraction 5.58 and 0.9275. The crude extract and ethyl-acetate fraction were shown to possess an antioxidant capacity comparable to that of vitamin C (4.93 and 1.0). The values obtained by the DPPH free-radical method for the isolated compounds were IC50 (μM): GA=8.89; PHB=10.12; GC=16.46; EPG=13.20; MGC=21.00; EPEP=6.89; EPGC=4.91; ROGC=7.78 and ROEP=6.20. Vitamin C and trolox showed 30.11 and 30.10, respectively. Dimers showed greater activity in scavenging free radicals, possibly related to the number of hydroxyls. However, compounds without a hydroxyl at position 5 of the A-ring (5-deoxy-proanthocyanidins) did not change the antioxidant activity of the DPPH free radical, as evaluated here for the first time. Among the monomers, there appeared to be a direct relationship in scavenging of free radicals because of the stereochemistry of the compounds. The presence of a methyl radical on the B-ring significantly reduced the scavenging of free radicals of gallocatechin. All compounds showed greater scavenging of radicals than vitamin C and trolox, and these two compounds showed no significant difference from each other.

O extrato das cascas de Stryphnodendron obovatum submetido à cromatografia em coluna, Sephadex® LH-20, forneceu nove substâncias: ácido gálico (GA), ácido p-hidróxibenzóico (PHB), galocatequina (GC), epigalocatequina (EPG), 4'-O-metilgalocatequina (MGC), epigalocatequina-(4β→8)-epigalocatequina (EPEP), epigalocatequina-(4β→8)-galocatequina (EPGC), robinetinidol-(4α→8)-galocatequina (ROGC) e robinetinidol-(4β→8)-epigalocatequina (ROEP). A capacidade antioxidante in vitro pelos métodos do radical livre DPPH (IC50; μg/mL) e do complexo fosfomolibdênio (CAR) apresentou os seguintes resultados, respectivamente: extrato bruto 4,52 e 0,8242; fração acetato de etila 4,04 e 0,9537 e fração aquosa 5,58 e 0,9275 demonstrando possuírem capacidade antioxidante quando comparados com vitamina C 4,93 e 1,0. Os valores obtidos pelo método do radical livre DPPH com as substâncias isoladas foram: IC50 (μM): GA=8,89; PHB=10,12; GC=16,46; EPG=13,20; MGC=21,00; EPEP=6,89; EPGC=4,91; ROGC=7,78 e ROEP=6,20. Vitamina C e trolox mostraram valores de 30,11 e 30,10, respectivamente. Os dímeros mostraram maior atividade no sequestro de radicais livres, possivelmente relacionada com o número de hidroxilas. No entanto, substâncias com ausência de hidroxila na posição 5 do anel A (5-desoxi-proantocianidinas) não alteraram o poder antioxidante frente ao radical livre DPPH, tendo sido avaliadas aqui pela primeira vez. Entre os monômeros, parece haver uma relação direta com a estereoquímica. A presença de um radical metila no anel B reduziu significativamente a atividade da galocatequina. Todas as substâncias isoladas mostraram maior atividade do que a vitamina C e trolox, e estes não mostraram diferença significativa entre si.

Frequency of potential interactions between drugs in medical prescriptions in a city in southern Brazil / Frequência de potenciais interações entre drogas nas prescrições médicas em uma cidade do Sul do Brasil

CONTEXT AND OBJECTIVE: Drug interactions form part of current clinical practice and they affect between 3 and 5 percent of polypharmacy patients. The aim of this study was to identify the frequency of potential drug-drug interactions in prescriptions for adult and elderly patients. TYPE OF STUDY AND SETTING: Cross-sectional pharmacoepidemiological survey in the Parque Verde housing project, municipality of Cascavel, Paraná, Brazil, between December 2006 and February 2007. METHODS: Stratified cluster sampling, proportional to the total number of homes in the housing project, was used. The sample consisted of 95 homes and 96 male or female patients aged 19 or over, with medical prescriptions for at least two pharmaceutical drugs. Interactions were identified using DrugDigest, Medscape and Micromedex softwares. RESULTS: Most of the patients were female (69.8 percent), married (59.4 percent) and in the age group of 60 years or over (56.3 percent), with an income less than or equal to three minimum monthly salaries (81.3 percent) and less than eight years of schooling (69.8 percent); 90.6 percent of the patients were living with another person. The total number of pharmaceutical drugs was 406 (average of 4.2 medications per patient). The drugs most prescribed were antihypertensives (47.5 percent). The frequency of drug interactions was 66.6 percent. Among the 154 potential drug interactions, 4.6 percent were classified as major, 65.6 percent as moderate and 20.1 percent as minor. CONCLUSION: The high frequency of drug prescriptions with a potential for differentiated interactions indicates a situation that has so far been little explored, albeit a reality in household surveys.

CONTEXTO E OBJETIVO: As interações medicamentosas fazem parte da prática corrente na clínica médica e a sua incidência oscila entre 3 por cento e 5 por cento nos pacientes fazendo uso da polifarmácia. O objetivo do estudo foi identificar a frequência de interações droga-droga potenciais em prescrições de pacientes adultos e idosos. TIPO DE ESTUDO E LOCAL: Inquérito farmacoepidemiológico de corte transversal, realizado de 12/2006 a 02/2007 no conjunto habitacional Parque Verde, Cascavel, Paraná, Brasil. MÉTODO: A amostra foi por conglomerado e estratificada, proporcional ao total de residências no conjunto habitacional, constituída de 95 residências, com 96 pacientes de 19 anos ou mais, sexo feminino e masculino, com prescrição de no mínimo duas especialidades farmacêuticas. As interações foram identificadas de acordo com os softwares DrugDigest, Medscape, Micromedex. RESULTADOS: A maioria dos pacientes pertencia ao gênero feminino (69,8 por cento), em situação conjugal casada (59,4 por cento), com renda menor ou igual a três salários mínimos (81,3 por cento), faixa etária 60 anos ou mais (56,3 por cento) e 8 anos ou menos de estudo (69,8 por cento) com 90,6 por cento dos pacientes moravam com mais outra pessoa. O total de especialidades farmacêuticas foi de 406, correspondendo a uma média de 4,2 medicamentos por paciente. Os fármacos mais prescritos foram os anti-hipertensivos (47,5 por cento). A frequência de interações medicamentosas foi de 66,6 por cento. Dentre as 154 interações medicamentosas potenciais, 4,6 por cento foram classificadas como maior e 65,6 por cento como moderada e 20,1 por cento como menor. CONCLUSÃO: A alta frequência de prescrições de drogas com potencial de interações diferenciado indica uma situação ainda pouco explorada, mas real em pesquisa domiciliar.

Determinação quantitativa de taninos em três espécies de stryphnodendron por cromatografia líquida de alta eficiência / Quantitative determination of tannins in three species of stryphnodendron by high performance liquid chromatography

Um método de separação e quantificação por cromatografia líquida de alta eficiência (CLAE) em fase reversa foi desenvolvido usando água (0,05 por cento de TFA):acetonitrila (0,05 por cento de TFA) como fase móvel, em sistema gradiente para a análise dos flavan-3-óis presentes em extrato semipurificado das cascas de Stryphnodendron adstringens, Stryphnodendron polyphyllum e Stryphnodendron obovatum. A CLAE foi realizada com a fração acetato de etila (FAE) sendo submetida à extração em fase sólida (cartucho C18-E) com metanol:água (2:8), filtrada por membrana de porosidade 0,5 μm; a pré-coluna e coluna empregadas foram Phenomenex® Gemini C-18 (5 μm), com esta última mantida a 30 ºC, com vazão de 0,8 mL/min e detecção a 210 nm. Utilizaram-se soluções dos padrões de ácido gálico e galocatequina para a obtenção da curva analítica. O método proposto foi validado de acordo com a resolução RE nº 899/2003 da ANVISA. A análise quantitativa da FAE das três espécies mostrou que existe similaridade no teor de galocatequina. S. adstringens possui ácido gálico em uma proporção superior a 60 por cento em relação às outras duas espécies. A metodologia desenvolvida mostrou-se viável à aplicação em plantas ricas em taninos, como nos casos de S. adstringens, S. polyphyllum e S. obovatum.

A method of separation and quantification by reverse-phase high-performance liquid chromatography (HPLC) was developed, using water (0.05 percent TFA):acetonitrile (0.05 percent TFA) as the mobile phase in a gradient system. Flavan-3-ols present in a semipurified extract from the stem bark of Stryphnodendron adstringens, Stryphnodendron polyphyllum and Stryphnodendron obovatum were analyzed. The HPLC was performed with the ethyl-acetate fraction (EAF) using a solid-phase extraction on cartridges C18-E with methanol:water (2:8), filtered through a membrane of 0.5 μm pore size; the column was Phenomenex® Gemini C-18 (5 μm) at 30 ºC, with a flow rate of 0.8 mL/min. The analysis was done at 210 nm. Gallic acid and gallocatechin solutions were used as calibration standards. The proposed method was validated by resolution RE No. 899/2003 of the National Health Surveillance Agency. Quantitative analysis of the EAF showed high contents of flavan-3-ols in the stem bark of all three species. This study demonstrated that it is possible to determine the concentration of individual substances in tannin-rich plants. The system developed can be used as a chromatographic profile for the semipurified fraction of S. adstringens, S. polyphyllum, and S. obovatum.

Inquérito farmacoepidemiológico de pacientes de meia idade e idosos em três comunidades de Cascavel, PR - Brasil: verificação evolutiva do conhecimento terapêutico / Pharmacoepidemiological survey of middle-age and elderly patients in three communities of Cascavel, PR - Brazil: progressive verification of their therapeutic knowledge

O objetivo da pesquisa foi identificar variáveis relacionadas ao conhecimento da terapêutica nos períodos pré e pós-intervenção e características sócio-demográficas de 80 pacientes de meia idade e idosos (45 anos ou mais) em três comunidades paroquiais de Cascavel-PR. Desenvolveu-se um inquérito farmacoepidemiológico, seguido de estudo prospectivo no período de novembro de 2003 a dezembro de 2004, e os dados foram coletados em formulário semi-estruturado. Houve predominância para o sexo feminino (82,5 por cento), idade média de 67,3 anos, escolaridade de menos de oito anos de estudo (75,0 por cento), maioria casado (57,5 por cento), morando apenas o casal (63,7 por cento), renda de 1 a 3 salários (80 por cento), número médio de medicamentos prescritos na fase pré (4,3) e na pós-intervenção (3,5). A classe de fármacos mais prescrita foi para o sistema cardiovascular (48,2 por cento). As variáveis, leitura da bula e freqüência, conhecimento sobre o medicamento, esquecimento da dose prescrita, satisfação com o medicamento e importância das informações, embora apresentassem diferenças na freqüência relativa do período pré-intervenção para o pós-intervenção, não sustentaram diferença estatisticamente significativa. Apesar desse resultado, é preciso considerar que a diferença quanto ao grau de evolução dos resultados apresentam relevância clinica, pendendo favoravelmente a relação benefício/risco.

Variables on therapeutic knowledge in pre- and post-intervention periods and the social and demographic characteristics of 80 middle-aged and elderly (45 years or more) patients in three parish communities in Cascavel, PR - Brazil are provided. A pharmacoepidemiological survey was developed; a prospective study between November 2003 and December 2004 was undertaken; data were collected in a semi-structured form. Females (82.5 percent) were predominant; average age 67.3 years old; schooling less than 8 years; most of them married (57.5 percent); only the couple inhabits the house (63.7 percent); income 1 to 3 salaries (80 percent); mean numbers of prescribed medicines pre- and post-intervention were 4.3 and 3.5, respectively. Medicine for the cardiovascular system (48.2 percent) was the most described (48.2 percent). Variables - reading information on drug and its frequency, knowledge on the medicine used and importance of information - were statistically non-significant, although difference in relative frequency from the pre- to the post-intervention period existed. Nevertheless, difference with regard to degree of progress in results shows clinical relevance with a favorable trend towards the benefit/risk ratio.

Detecção de risco de interações entre fármacos antidepressivos e associados prescritos a pacientes adultos / Interaction risk detection between antidepressant and associated drugs prescribed for adult patients

CONTEXTO: O uso de fármacos combinados para o tratamento de patologias diversas em psiquiatria tem aumentado progressivamente. Os antidepressivos estão envolvidos em diversas interações farmacológicas clinicamente importantes. OBJETIVO: Detectar risco de interações entre fármacos antidepressivos e associados prescritos a pacientes adultos. MÉTODOS: Pesquisa retrospectiva e descritiva foi desenvolvida em uma farmácia magistral da cidade de Cascavel, Paraná. Os dados foram coletados de 151 receituários médicos de pacientes adultos (19 anos ou mais), envolvendo fármacos antidepressivos e associados entre outubro e novembro de 2005. O estudo limitou-se às variáveis registradas no receituário médico (sexo, idade, fármaco antidepressivo e associado prescrito). RESULTADOS: A categoria de 31 a 40 anos de idade foi a mais freqüente (32,46 por cento) e o sexo foi o feminino (64,90 por cento). Os fármacos antidepressivos tricíclicos (ADT) e associados apresentaram um total de oito episódios de interações relativos ao grau de severidade, sendo quatro de grau moderado e quatro menor. Em relação aos fármacos antidepressivos inibidores seletivos da recaptura de serotonina (ISRS) e associados, o risco de ocorrência foi de 16 casos; quatro de severidade menor, dez moderada e dois maior. CONCLUSÃO: Os dados mostram que os pacientes com prescrição de fármacos ISRS e associados possuíam mais risco de interações de maior severidade, totalizando o dobro de interações em relação aos ADTs.

BACKGROUND: The combination of drugs for the treatment of psychiatric disorders has become a relatively frequent practice. The antidepressants are involved in several clinically important pharmacological interactions. OBJECTIVES: To detect the risk of interactions between antidepressants and associated drugs prescribed for adults patients. METHODS: Data on 151 medical prescriptions of antidepressants and other psychiatric drugs were retrospectively assessed at a teaching pharmacy in the city of Cascavel (state of Parana, Brazil), between October and November 2005. Only prescriptions provided for adults patients (19 years and older) were analyzed. RESULTS: Prescriptions were most frequently provided for female patients (64.9 percent), and for patients in the 31 to 40 year-old age group (32.5 percent). Considering prescription information only, we identified a clinically relevant risk of drug-drug interactions in eight prescriptions of tricyclic antidepressants (TADs) and associated drugs; the putative consequence of such pharmacological interaction was considered moderately relevant in four of these. The co-prescription of selective serotonin reuptake inhibitors (SSRIs) with other related drugs bearing a putative risk of interaction was observed in 16 cases, two of which involved a significant risk, ten a moderate risk, and four a minor risk of clinically relevant consequences. DISCUSSION: We provide evidence that the risk of pharmacological interactions may be often overlooked in the prescription of antidepressants (TAD and SSRIs) and related drugs in this clinical setting.