16 results on '"Ferreira, Maria Augusta Drago"'
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2. Enantioselective analysis of praziquantel and trans-4-hydroxypraziquantel in human plasma by chiral LC–MS/MS: Application to pharmacokinetics
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Lima, Renata Monteiro, Ferreira, Maria Augusta Drago, Ponte, Teresa Maria de Jesus, Marques, Maria Paula, Takayanagui, Osvaldo Massaiti, Garcia, Hector Hugo, Coelho, Eduardo Barbosa, Bonato, Pierina Sueli, and Lanchote, Vera Lucia
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- 2009
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3. Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity
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Lima, Renata Monteiro, Ferreira, Maria Augusta Drago, de Jesus Ponte Carvalho, Teresa Maria, Dumêt Fernandes, Bruno José, Takayanagui, Osvaldo Massaiti, Garcia, Hector Hugo, Coelho, Eduardo Barbosa, and Lanchote, Vera Lucia
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- 2011
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4. Suicide attempts by exposure to toxic agents registered in a Toxicological Information and Assistance Center in Fortaleza, Ceará, Brazil, 2013
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Gondim, Ana Paula Soares, Nogueira, Rachel Rabay, Lima, João Gabriel Barbosa, Lima, Rayra Aguiar Campos, Albuquerque, Polianna Lemos Moura Moreira, Veras, Maria do Socorro Batista, and Ferreira, Maria Augusta Drago
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Centros de Informação ,Polifarmacia ,Salud del Anciano ,Poisoning ,Utilización de Medicamentos ,Estudios Transversales ,Epidemiologia Descritiva ,Epidemiology, Descriptive ,Information Centers ,Envenenamento ,Suicide Attempted ,Tentativa de Suicídio ,Praguicidas ,Pesticides - Abstract
Resumo Objetivo: descrever casos de tentativa de suicídio por exposição a agentes tóxicos registrados pelo Centro de Informação e Assistência Toxicológica em Fortaleza, Ceará, Brasil. Métodos: estudo descritivo com dados secundários sobre casos registrados em 2013. Resultados: foram registrados 410 casos; 56,2% dos indivíduos eram do sexo feminino e 79,7% tinham de 12 a 39 anos de idade; a maioria (86,4%) residia em áreas urbanas e 67,2% em Fortaleza; em 94,9% dos casos o local de exposição foi o domicílio; os agentes tóxicos mais envolvidos nos casos foram praguicidas (42,9%), principalmente agrotóxicos (30,2%), medicamentos (39,5%) e saneantes de uso doméstico (3,4%); das 16 tentativas de suicídio que resultaram em óbito, 15 foram ocasionadas por agrotóxicos. Conclusão: o estudo evidencia que a ingestão de agentes tóxicos, especialmente os agrotóxicos, é um importante método utilizado em tentativas de suicídio, sendo fundamental a integração das ações de promoção e de prevenção nessas ocorrências. Resumen Objetivo: describir los fármacos utilizados y analizar los factores asociados a la polifarmacia en ancianos de Aiquara, Bahía, Brasil. Métodos: se trata de un estudio transversal, censo, realizado en febrero de 2014, a través de entrevistas con formularios estandarizados. Resultados: entre los 272 ancianos entrevistados, 53,3% utilizaban la medicación prescrita y solamente 31,6% al menos un medicamento sin receta médica; la prevalencia de polifarmacia fue 29,0%; los medicamentos cardiovasculares fueron los más utilizados (n=390; 37,6%); en análisis ajustados, los factores asociados a la polifarmacia fueron sexo femenino (OR=2,20 - IC95% 1,11;4,35), seguro de salud privado (OR=2,18 - IC95% 1,05;4,55), haber sido hospitalizados en el último año (OR=2,34 - IC95% 1,1;4,65) y auto-reporte de cuatro o más enfermedades (OR=3,18 - IC95% 1,60;6,29). Conclusión: hubo una alta prevalencia de polifarmacia, asociada al sexo, plan de salud privado, tener cuatro o más enfermedades auto-reportados y haber sido hospitalizado en el último año, con un mayor uso de fármacos cardiovasculares. Abstract Objective: to describe cases of suicide attempts by exposure to toxic agents registered by the Toxicological Information and Assistance Center in Fortaleza, Ceará, Brazil. Methods: this is a descriptive study using secondary data of the cases registered in 2013. Results: 410 cases were registered; 56.2% of the individuals were female and 79.7% were between 12 and 39 years old; most of them (86.4%) lived in urban areas and 67.2%, in Fortaleza; in 94.9% of the cases, the exposure took place in the individual’s own home; the toxic agents most commonly used were pesticides (42.9%), especially for agricultural use (30.2%), medicines (39.5%) and house cleaning products (3.4%); of 16 suicide attempts that resulted in death, 15 were caused by agricultural pesticides. Conclusion: the study shows that the intake of toxic agents, especially of agricultural pesticides, is a common method used in suicide attempts; the integration between actions of promotion and prevention are essential.
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- 2017
5. Intoxication local anaesthetics : intravenous use of lipid emulsion as antidote
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Rodigues Neto, Edilson Martins, Marques, Lidia Audrey Rocha Valadas, Girão Júnior, Francisco Josimar, Ponte, Emerson Dias, Campos, Márcia Oliveira Coelho, Ferreira, Maria Augusta Drago, Lobo, Patrícia Leal Dantas, and Fonteles, Marta Maria França
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Anestésicos ,Toxicologia ,Anesthetics - Abstract
The local anesthetic technique when performed with a quality product results in the abolition of autonom ic and sensory motors functions . The c ardiotoxicity caused by local anesthetics is a hard condition to manage, given traditional therapies, which are quite limited. Thus, it is crucial to evaluate the clinical fea sibility of using Lipid Emulsion (LE) intravenously in the treatment of poisoning by local anesthetics, because this may be a viable therapeutic option as re scue procedure. Currently , in the hypothetical level that the LE acts by three distinct mechanisms of action: Formation of a "Lipid Trap," transport of fatty acids to the mitochondria of the cardiac muscle tissue and a positive inotropic effect in the myocardium. One can derive that its clinical utility in cardiovascular collapse is higher in the first moments of intoxication AL, before installation of the situation of hypoxia and/or metabolic acidosis. In this context the use of LE as therapy for acute intoxication AL appears as a safe and effective alternative, with a very low risk profile and with a g ood degree documented evidence of benefit. Thus, it is important for the surgical team's the knowledge of this therapy in the cardiotoxicity management caused by acute intoxication for AL.
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- 2017
6. Use of lipid emulsion as an antidote in the treatment of intoxication by local anesthetics and other lipophilic drugs
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Santos, Paula Bruna Sousa, Passos, Ana Cláudia de Brito, Rodrigues Neto, Edilson Martins, Monteiro, Mirian Parente, and Ferreira, Maria Augusta Drago
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Anestésicos Locais ,Antídotos ,Toxicologia - Abstract
Local anesthetics are commonly used in surgical procedures, they are able to promote a reversible blockade of nerve conduction, with loss of sensation in circumscribed area of the body without changing the individual's level of consciousness. The aim of this study was to review the literature that can compose the body of evidence on efficacy and safety of Lipid Emulsion (ELI) for use as an antidote in the treatment of intoxication by local anesthetics and other lipofílicos. Trata is a review drugs literature that we used the Fat Emulsions terms Intravenous AND Antidotes for the search in the following databases: Pubmed; Cochrane Library and Trip Database and were raised studies found in these bases until November 2015. The review conducted showed that the use of ELI as an antidote seems to be a possible alternative for the treatment of poisoning caused by local anesthetics and other lipophilic drugs. Recently the ELI have been used also as an antidote against cardiovascular collapse induced by bupivacaine and other local anesthetics lipophilic. Early studies reported more frequently the use of Intralipid®, intravenously, which is sold in formulations containing soybean oil at different concentrations (10, 20 or 30%) in admixture with other lipids and phospholipids. The effects produced by Intralipid® have also been attributed to other lipid emulsions of formulations composed of different extracts of oils. However, current evidence supporting this use are scarce and uncertain, pointing to the need for additional studies. With respect to this fact, recently the American Academy of Clinical Toxicology.
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- 2016
7. The elderly’s health conditions as a risk factor to accidents
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Campos, Márcia Oliveira Coelho, Rodrigues Neto, Edilson Matins, Bezerra, Jani Cleria Pereira, Peixoto, Diana Cláudia Teixeira, Fonteles, Marta Maria de França, and Ferreira, Maria Augusta Drago
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Fatores de Risco ,Idoso ,Propensão a Acidentes - Abstract
To verify the health status in the elderly who have suffered accidents and treated at a reference hosp ital for emergency care of Ceará, Brazil. This is a cross-se ctional, descriptive study, with quantitative appro ach, developed in an emergency hospital in the city of Fortaleza. For the sample, 182 elderly people were selected. T he data were collected using the BOAS Questionnaire as a tool, e xported to the statistical software STATA ® v.12. Most of the elderly are women (67%); aged between 81 and 90 yea rs (37.4%); have incomplete elementary school (53.3 1%); are widowed (48.3%); have a family income of one to two minimum wages (31.3%); are retired (68%); live with one or two people (48.3%). As for the perception of hea lth, they refer to it as good (37%). Among the heal th problems, fall with fracture/injury and chronic diseases were the most frequent (48.3%). They reported having a great vision (39.5%); good hearing (44.8%); teeth in bad conditi on (79.9%), missing the majority (93.7%). About the presence of clinical depression, it was found that the elder ly had no feeling of loneliness (84.7%); they did n ot want to cry (86.2%); did not feel the life was not worth it (96 %). At the end, they said they felt satisfied with life in general (77.2%). the accidents suffered by the elderly are related to individual factors. These factors are re lated to working life and lack of structure of households and commun ities to meet the protection needs of the populatio n that is increasingly aging in an active mode.
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- 2016
8. Metformina: Uma Revisão da Literatura
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Rodrigues Neto, Edilson Martins, Marques, Lidia Audrey Rocha Valadas, Ferreira, Maria Augusta Drago, Lobo, Patricia Leal Dantas, Girão Junior, Francisco Josimar, Camarão, Gisela Costa, and Moraes, Maria Elisabete Amaral de
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Diabetes Mellitus type 2 ,Diabetes mellitus tipo 2 ,Biguanides ,Biguanidas ,Metformina ,Metformin - Abstract
Metformin, commercialized under several trademarks and also as a generic medicine, is an oral anti-diabetic drug, belonging to the biguanide class. It is actually the first choice in the treatment of Type 2 diabetes mellitus (DM2) due to its toxicity and clinical efficaciousness. It extensive use requires a constant discussion on its characteristics and applications. Current paper is a bibliographical review comprising the application of metformin in DM2 treatment as its chemical, physical-chemical, pharmacokinetic, pharmacodynamics properties, its clinical usages, contraindications and side effects. Review occurred in Pubmed, Bireme, Lilacs and SciELO data banks and in research in journals published on the Brazilian Platform in Scientific Information and in books on the subject. Results show that metformin is the best medicine for diabetic patients, with auxiliary therapy for other physiological disorders. A metformina, medicamento comercializado por diversas marcas e também na forma de genérico, é um antidiabético oral pertencente à classe das biguanidas. Devido ao seu perfil de toxicidade e à sua eficácia clínica é a principal escolha no tratamento do diabetes mellitus tipo dois (DM2). Pelo seu grande uso é necessária uma discussão constante a respeito de suas características e aplicações. Objetivou-se realizar uma revisão bibliográfica, na qual serão abordadas a aplicação da metformina no tratamento de DM2 bem como suas propriedades químicas, físico-químicas, farmacocinéticas, farmacodinâmicas, seus usos clínicos, contraindicações e efeitos adversos. Revisão da literatura realizada nos bancos de dados Pubmed, Bireme, Lilacs e Scielo, bem como pesquisa nos periódicos do Portal Brasileiro da Informação Científica e livros sobre o assunto. Pelo exposto percebe-se que a metformina para pacientes diabéticos é considerada um fármaco ideal tendo ainda aplicações na terapêutica adjuvante de outros distúrbios fisiológicos.
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- 2015
9. Tentativas de suicídio por exposição a agentes tóxicos registradas em um Centro de Informação e Assistência Toxicológica em Fortaleza, Ceará, 2013
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Gondim¹, Ana Paula Soares, primary, Nogueira¹, Rachel Rabay, additional, Lima, João Gabriel Barbosa, additional, Lima, Rayra Aguiar Campos, additional, Albuquerque, Polianna Lemos Moura Moreira, additional, Veras, Maria do Socorro Batista, additional, Ferreira, Maria Augusta Drago, additional, Gondim, Ana Paula Soares, additional, and Nogueira, Rachel Rabay, additional
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- 2017
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10. Local anesthetics toxicity in clinical practice
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Rorigues Neto, Edilson Martins, Marques, Lidia Audrey Rocha Valadas, Lotif, Mara Assef Leitão, Lobo, Patrícia Leal Dantas, Martiniano, Carlos Ricardo de Queiroz, and Ferreira, Maria Augusta Drago
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Anestesiologia ,Toxicologia ,Farmacologia Clínica - Abstract
Local anesthetics (LAs) are essential for most invasive procedures. This study aimed to evaluate the various systemic problems due to the indistinct use of LAs. Were used following sources: electronic databases such as PUBMED, MEDLINE, LILACS and BBO, articles in books and periodicals published between the years 2005 to 2012. The descriptors were used: local anesthetics, toxicity, adverse effects and systemic complications. Among the most frequent systemic complications, the effects have been reported in the central nervous system (CNS) and cardiovascular (CVS). Toxic levels of LAs in the CNS is the clinical manifestation of primary generalized tonic-clonic seizures, and result in widespread depression of both systems. CVS-level, the LAs can cause bradycardia and hypotension. Opposing the LAs, sympathomimetic vasoconstictor generate excitatory effects, which intensify in joining the endogenous catecholamines. Can occur even hypersensitivity reactions or hematologic. True anaphylaxis occur mainly in LAs ester type. Furthermore, methylparaben and sodium bisulfite included in the cartridge of LAs are often generated sensitization. The most common hematological abnormality is methemoglobinemia. According to literature, the LAs are safe drugs, but it is necessary expertise in anesthetic technique, dose titration and knowledge about the care needed for their use. Anestésicos locais (ALs) são imprescindíveis a uma gama de procedimentos invasivos. Objetivou-se avaliar os diversos problemas sistêmicos devidos ao uso indistinto de ALs. Foram utilizadas as seguintes fontes: bases de dados eletrônicos tais como PUBMED, MEDLINE, LILACS e BBO, artigos em livros e periódicos, publicados entre os anos de 2005 a 2012. Foram usados os descritores: anestésicos locais, toxicidade, efeitos adversos e complicações sistêmicas. Dentre as complicações sistêmicas mais frequentes, foram relatados os efeitos no Sistema Nervoso Central (SNC) e Cardiovascular (SCV). Em níveis tóxicos de ALs no SNC a manifestação clínica primária é a convulsão tônico-clônica, podendo culminar em depressão generalizada de ambos os sistemas. Em nível de SCV, os ALs podem causar bradicardia e hipotensão arterial. Contrapondo os ALs, os vasoconstritores simpaticomiméticos geram efeitos excitatórios, que se intensificam ao se somar às catecolaminas endógenas. Podem ocorrer ainda reações de hipersensibilidade ou hematológicas. Anafilaxias verdadeiras ocorrem principalmente em ALs do tipo éster. Ademais, o metilparabeno e o bissulfito de sódio, incluídos no tubete de ALs, têm gerado sensibilização frequente. A alteração hematológica mais comum é a metemoglobinemia. Segundo a literatura, os ALs são fármacos seguros, mas é necessária perícia na técnica anestésica, adequação da dose e conhecimento sobre os cuidados necessários à sua utilização. Anestésicos locales (ALs) son esenciales para una amplia gama de procedimientos invasivos. Este estudio tiene como objetivo evaluar los diferentes problemas sistémicos debido al uso de fuerte regalamiento remitido ALs. Se utilizaron las siguientes fuentes: bases de datos electrónicas como PUBMED, MEDLINE, LILACS y BBO, artículos en revistas y libros, publicados entre los años de 2005 a 2012. Los descriptores se emplearon: anestésicos locales, toxicidad, efectos adversos y complicaciones sistémicas. Entre las complicaciones sistémicas más frecuentes, se informó sobre los efectos en el Sistema Nervioso Central (SNC) y cardiovascular (SCV). Los niveles tóxicos de als en el SNC manifestación clínica es la principal crisis convulsivas convulsiones tónico-clónicas generalizadas y pueden culminar en depresión generalizada de ambos sistemas. En el plano de la SCV, el ALS puede causar bradicardia e hipotensión. La contraposición esclerosis lateral amiotrófica, el vasoconstrictor simpaticomiméticos pueden generar efectos excitatorios, intensifican el resumen cuando las catecolaminas endógenas. Pueden producirse reacciones de hipersensibilidad o hematológicas. Pueden sufrir la anafilaxia verdadera ocurre principalmente en la esclerosis lateral amiotrófica tipo éster. Además, metil parabeno y bisulfito de sodio, están incluidos en las copas de la esclerosis lateral amiotrófica, ha generado conciencia frecuentes. La enmienda es el más común que afecta la metahemoglobinemia. De acuerdo con la literatura, la LAs son fármacos seguros, pero es necesaria la experiencia en la técnica anestésica, ajuste de la dosis y el conocimiento sobre los cuidados necesarios para su uso.
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- 2014
11. Metformina: Uma Revisão da Literatura
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Rodrigues Neto, Edilson Martins, primary, Marques, Lidia Audrey Rocha Valadas, additional, Ferreira, Maria Augusta Drago, additional, Lobo, Patricia Leal Dantas, additional, Girão Junior, Francisco Josimar, additional, Camarão, Gisela Costa, additional, and Moraes, Maria Elisabete Amaral de, additional
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- 2015
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12. Estudo de efeitos tóxicos e atividades farmacológicas da fração quinona de Auxemma oncocalyx Taub
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Ferreira, Maria Augusta Drago and Viana , Glauce Socorro de Barros
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Euphorbiaceae ,Plantas Medicinais ,Quinonas - Abstract
Auxemma oncocalyx Taub. belongs to the Boraginaceae family and is native from the northeastem caatings where is know as “pau branco”. The stem bark of the tree is adstringent and popularly used in the treatment of wounds. The objective of the present work was to study toxicological effects and pharmacological activities of the hydrosoluble fraction isolated from the heartwood of A. oncocalyx. This fraction presents around 80 % of oncocalyxone A (quinone fraction). The LD50 of the quinone fraction (QF) in mice determined by the probit method was 182.16 mg/kg, i.p. and above of 500 mg/kg, o.d. The administration of QF for 15 days at the dose of 50 mg/kg, o.d. in rats, did not alter hematological or blood biochemical parameters . The pharmacological activities investigated were antiaggregating platelet, antioxidant, antiaedematogenic and antinociceptive using several experimental models. Results showed that QF presents a potent antiaggregating platelet activity in human platelets in vitro with different agonists (ADP, IC50 = 53.85 pg/ml; thrombin, IC50 = 93.76 pg/ml; collagen, IC50 = 56.57 pg/ml; arachidonic acid, IC50 = 86.07 pg/ml e adrenaline IC50 = 67.93 jig/ml). The activity was potentiated by aspirin (cyclooxynase inhibitor), pentoxifylline (methylxantine derivative and cAMP-dependent phosphodiesterase inhibitor), but not by L-arginine (NO precursor). The antiaggregating activity of QF was also observed in rat platelet in vitro in the presence of the following agonists: ADP and thrombin. However no activity was observed ex vivo. Surprisingly QF decreased bleeding time and contracted vascular smooth muscle (rat aorta). A potent antioxidant activity of QF was detected by inhibition of lipoperoxidation in rat brain homogenates, as determined by the production of substance reactive to the thiobarbituric acid (TBARS, Q1/2 = 1.64 pg/ml) and chemiluminescence (Q1Z2 = 2.06 jag/ml). However QF exerted a week activity on the model of CCl4-induced hepatotoxicity in rats as determined by measurement of ALT, AST activities and TBARS besides histopathological studies. The hepatoprotective effect of QF manifested itself more intensely in the model of prolongation by CCL4 of the barbiturate sleeping time in mice. Antinociceptive and antiedematogenic activities were also observed after QF administration, in the tests of abdominal contortion by acetic acid, formalin and hot-plate in mice (antinociceptive activity) and carrageenan and dextran-induced rat paw edema (antiedematogenic activity). The antinociceptive activity was dose-dependent, predominantly peripheric and independent of the opioid system. Results from the present work show that QF presents antiplatelet, antiinflamatory and antioxidant activities among others and these actions are probably dependent upon free radicais scavenger ability of QF. A espécie Auxemma oncocalyx Taub. pertencente a família Boraginaceae é característica do sertão nordestino onde é conhecida como pau branco. As cascas dessa árvore são adstringentes e popularmente utilizadas no tratamento de cortes e feridas. O objetivo do presente trabalho foi o de estudar efeitos tóxicos e atividades farmacológicas da fração hidrossolúvel obtida do cerne (caule) de A. oncocalyx, constituída em cerca de 80% pela oncocalixona A (fração quinona). A DL50 da fração quinona (FQ) para camundongos, determinada pelo método dos probitos foi de 182,16 mg/kg, i.p. e acima de 500 mg/kg, v.o. A administração de FQ por 15 dias na dose de 50 mg/kg, v.o. a ratos não alterou parâmetros hematológicos ou bioquímicos do sangue. As atividades farmacológicas investigadas foram: antiagregante plaquetária, antioxidante, antiedematogênica e antinociceptiva, utilizando vários modelos experimentais. Os resultados mostraram que FQ apresenta potente atividade antiagregante plaquetária em plaquetas humanas in vitro, frente a diferentes agonistas (ADP, CI50 = 53,85 pg/ml; trombina, CI50 = 93,76 pg/ml; colágeno, CI50 = 56,57 pg/ml; ácido araquidônico, CI50 = 86,07 pg/ml e adrenalina, CI50 = 67,93 pg/ml). Esse efeito foi potencializado pela presença de aspirina (inibidor de ciclooxigenase), e de pentoxifilina (inibidor de fosfodiesterase de AMPc), porém não pela L-arginina (substrato para a síntese de óxido nítrico). O efeito antiagregante plaquetário da FQ foi observado também em plaquetas de rato in vitro, frente aos agonistas: ADP e trombina, porém não ex vivo. Ao contrário do esperado, a FQ diminuiu o tempo de sangramento e contraiu a musculatura lisa vascular (aorta de ratos). Potente atividade antioxidante de FQ foi também detectada através da inibição de lipoperoxidação em homogeneizados de cérebro de ratos in vitro, determinada pela produção de substâncias reativas ao ácido tiobarbitúrico (TBARS, Q1/2 = 1,64 pg/ml) e quimiluminescência (QL = 2,06 pg/ml). Contudo, a FQ exerceu uma fraca ação protetora no modelo de hepatotoxicidade induzida pelo CCI4 em ratos, determinada pelas atividades de ALT e AST, TBARS e observação histopatológica. A ação hepatoprotetora de FQ manifestou-se de forma mais intensa no modelo de prolongamento pelo tetracloreto de carbono (CCI4) do tempo de sono barbitúrico em camundongos. As atividades antinociceptiva e antiinflamatória de FQ foram também observadas nos testes de contorções abdominais pelo ácido acético e formalina em camundongos (atividade antinociceptiva) e de edema de pata induzido pela carragenina e dextrano em ratos (atividade antiedematogênica). A atividade antinociceptiva é dose- dependente, predominante periférica e independente do sistema opióide. Os resultados desse trabalho nos permitiram concluir que FQ apresenta atividades antiagregante plaquetária, antiinflamatória e antioxidante entre outras e provavelmente essas ações dependem pelo menos em parte de sua capacidade sequestradora de radicais livres.
- Published
- 2001
13. ASPECTOS EPIDEMIOLÓGICOS DA INTOXICAÇÃO POR MEDICAMENTOS EM CRIANÇAS E ADOLESCENTES ATENDIDOS NO CENTRO DE ASSISTÊNCIA TOXICOLÓGICA DO ESTADO DO CEARÁ
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Viana Neto, Aloísio Martins, primary, Ferreira, Maria Augusta Drago, additional, Figueiredo, Sandra Maria Franco Belém de, additional, Da Silva, Fabia Maria Barroso, additional, Soares, Ana Cristina Silva, additional, and Gondim, Ana Paula Soares, additional
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- 2012
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14. Antioxidant Effects in the Quinone Fraction from Auxemma oncocalyx TAUB.
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Ferreira, Maria Augusta Drago, primary, Nunes, Osmar Del Rio Holanda, additional, Leal, Luzia Kalyne Almeida Moreira, additional, Pessoa, Otília Deusdenia Loiola, additional, Lemos, Telma Leda Gomes De, additional, and Viana, Glauce Socorro de Barros, additional
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- 2003
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15. Albendazole – praziquantel interaction in healthy volunteers : kinetic disposition, metabolism, and enantioselectiveness
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Lima, Renata Monteiro, Ferreira, Maria Augusta Drago, and Lanchote, Vera Lucia
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Farmacocinética ,Neurocisticercose ,Albendazol - Abstract
The praziquantel (PZQ), a chiral drug available as racemic, and the albendazole (ABZ), a drug biotransformed into active metabolic chiral suphoxide of abendazol (ASOX), have been used in the treatment of human neurocysticercosis. The study covers the examination / search of the kinetic disposition, the metabolism, and the enantioselectiveness in the ABZ-PZQ association in healthy volunteers. The crossed and random study was developed in three phases (n=9), in which some volunteers started by PHASE 1 (400 mg of ABZ), others by PHASE 2 (1500mg of PZQ), and others by PHASE 3 (400 mg of ABZ + 1500mg of PZQ). The period of washout was of a minimum of 15 days (PHASE 1 followed by PHASE 2 and PHASE 1 followed by PHASE 3) or of 7 days (PHASE 2 followed by one of the other Phases). The serial blood samples were collected in a period of 0-48 hours. The ABZ metabolics were analised by HPLC with detection by fluorescence and the PZQ enantiomers and the trans-4-hydroxypraziquantel (4-OHPZQ) were analised by LC-MS-MS. The pharmacokinetic patterns were determined with the help of the WinNonlin program. The test of Wilcoxon (p≤0.05) was used to evaluate the enantiomer ratios of plasma concentrations of ASOX, PZQ and 4-OHPZQ. The data are shown as medians. The kinetic disposition of the PZQ, 4-OHPZQ and ASOX is enantioselective in the monotherapy situation; the ratios of AUC are of 2.97 to (+)-(S)-PZQ / (-)-(R)-PZQ, 0.78 to (+)-(S)-4-OHPZQ / (-)-(R)-4-OHPZQ, and 7.08 to (+)-ASOX / (-)-PZQ. The administration of the PZQ results in the increase of the plasma concentrations of the (+)-ASOX in 264% (AUC 980.42 vs 2591.80ng.h./ml), of the (-)-ASOX in 358% (139.59 vs 500.28ng.h./ml), and of the sulphona of albendazole in 187% (170.85 vs 319.50ng.h./ml), suggesting the PZQ as an inhibiting factor of the intestinal Pgp. The administration of the ABZ does not change/ alter the kinetic disposition of the (+)-(S)-PZQ, and of the metabolic (-)-(R)-4-OHPZQ and (+)-(S)-4-OHPZQ, but it results in the increase of the plasma concentrations of the (-)-(R)-PZQ in 64.77% (AUC 518.02 vs 853.57ng.h./ml ), suggesting enantioselective inhibition of the metabolism of the ASOX. The data allow us to suggest the possibility of increase of therapeutic efficacy in the ABZ-PZQ interaction; although, other studies are necessary to evaluate the safety of the interaction. O praziquantel (PZQ), um fármaco quiral disponível como racemato, e o albendazol (ABZ), um fármaco biotransformado ao metabólito ativo quiral sulfóxido de abendazol (ASOX), tem sido empregados no tratamento da neurocisticercose humana. O estudo abrange a investigação da disposição cinética, metabolismo e enantiosseletividade na associação ABZ - PZQ em voluntários sadios. O estudo cruzado e aleatório foi desenvolvido em três fases (n=9), sendo que alguns voluntários iniciaram pela FASE 1 (400mg de ABZ), outros pela FASE 2 (1500mg de PZQ) e outros pela FASE 3 (400mg de ABZ + 1500mg de PZQ). O período de washout foi de no mínimo 15 dias (FASE 1 seguida da FASE 2 e FASE 1 seguida da FASE 3) ou 7 dias (FASE 2 seguida de uma das outras FASES). As amostras seriadas de sangue foram coletadas no período de 0-48h. Os metabólitos do ABZ foram analisados por HPLC com detecção por fluorescência e os enantiômeros do PZQ e do trans-4-hidroxipraziquantel (4-OHPZQ) foram analisados por LC-MS-MS. Os parâmetros farmacocinéticos foram determinados com auxílio do programa WinNonlin. O teste de Wilcoxon (p≤0.05) foi empregado para avaliar as razões enantioméricas de concentrações plasmáticas do ASOX, PZQ e 4-OHPZQ. Os dados estão expressos como medianas. A disposição cinética do PZQ, 4-OHPZQ e do ASOX é enantiosseletiva na situação de monoterapia; as razões de AUC são de 2,97 para (+)-(S)-PZQ /(-)-(R)-PZQ, 0,78 para (+)-(S)-4OHPZQ /(-)-(R)-4-OHPZQ e 7,08 para (+)-ASOX/(-)-ASOX. A administração de PZQ resulta em aumento das concentrações plasmáticas do (+)-ASOX em 264% (AUC 980,42 vs 2591,80 ng.h/ml), do (-)-ASOX em 358% (139,59 vs 500,28 ng.h./ml) e do sulfona de albendazol em 187% (170,85 vs 319,50ng.h./ml) sugerindo o PZQ como inibidor da Pgp intestinal. A administração de ABZ não altera a disposição cinética do (+)-(S)-PZQ e dos metabólitos (-)-(R)-4-OHPZQ e (+)-(S)-4OHPZQ, mas resulta em aumento das concentrações plasmáticas do (-)-(R)-PZQ em 64,77% (AUC 518,02 vs 853,57ng.h/ml) sugerindo inibição enantiosseletiva do metabolismo do ASOX. Os dados permitem sugerir a possibilidade de aumento da eficácia terapêutica na interação ABZ-PZQ, embora outros estudos sejam necessários para avaliar a segurança da interação.
- Published
- 2008
16. Suicide attempts by exposure to toxic agents registered in a Toxicological Information and Assistance Center in Fortaleza, Ceará, Brazil, 2013.
- Author
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Gondim AP, Nogueira RR, Lima JG, Lima RA, Albuquerque PL, Veras MD, and Ferreira MA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Brazil epidemiology, Child, Female, Humans, Male, Middle Aged, Poison Control Centers, Young Adult, Household Products poisoning, Pesticides poisoning, Poisoning epidemiology, Suicide, Attempted statistics & numerical data
- Abstract
Objective: to describe cases of suicide attempts by exposure to toxic agents registered by the Toxicological Information and Assistance Center in Fortaleza, Ceará, Brazil., Methods: this is a descriptive study using secondary data of the cases registered in 2013., Results: 410 cases were registered; 56.2% of the individuals were female and 79.7% were between 12 and 39 years old; most of them (86.4%) lived in urban areas and 67.2%, in Fortaleza; in 94.9% of the cases, the exposure took place in the individual's own home; the toxic agents most commonly used were pesticides (42.9%), especially for agricultural use (30.2%), medicines (39.5%) and house cleaning products (3.4%); of 16 suicide attempts that resulted in death, 15 were caused by agricultural pesticides., Conclusion: the study shows that the intake of toxic agents, especially of agricultural pesticides, is a common method used in suicide attempts; the integration between actions of promotion and prevention are essential.
- Published
- 2017
- Full Text
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