Bakgrund: Paracetamol, även känt som acetaminophen, är ett populärt receptbelagt och receptfritt analgetisk och antipyretiskt läkemedel. Paracetamol anses vara säkert läkemedel, även under graviditeten, så länge man inte överskrider de rekommenderade doserna. Syfte: Syftet med litteraturstudien är att utvärdera rekommendationerna kring det receptfria läkemedlet paracetamol för gravida kvinnor och ifall det kan användas under graviditet utan någon ökad risk för fosterskador.Metod: Metoden som användes är en litteraturöversikt och en artikelsökning gjordes i databasen PubMed. Antalet artiklar som granskades är 15.Resultat: Resultatet visade samband där exponering för paracetamol under graviditet i mer än 28 dagar var förknippad med externaliserande beteendeproblem eller dåliga kommunikationsfärdigheter hos barn från tre år. De externaliserande beteendeproblemen är förknippade med försämrad motorik, negativt uppvisade emotioner, hyperaktivitet, inlärning och uppmärksamhetsproblem. Barn födda av mödrar som exponerats för paracetamol mer än en trimester har högre risk att få HKD-diagnos eller ADHD-medicin förskrivet. Även ökade risker för ADHD visades hos barn vars moder tagit paracetamol under andra/tredje trimestern. In vivo studier som mätte neuronala aminosyraproteiner i råtthjärnan resulterade i att råttor som utsatts för paracetamol under hjärnans utveckling visade försämrad kognitiv flexibilitet. Minskad emotionalitet, ökad responsivitet i dopaminerga systemet och ökning av dopaminnivåer går att sammankoppla med en förändring i neuroutveckling för autism samt ADHD.Slutsats: Läkemedelsintag för en gravid kvinna spelar en viktig roll vid vilken stadie av graviditeten som det administreras då fostret utvecklas på olika sätt under trimestrarna. Detta är viktigt att tas i beaktning när man studerar utvecklingstoxikologiska effekter. I denna uppsats beskrivs kopplingar mellan paracetamolexponering in utero och effekter på neurokognitiv utveckling som ses i skolåldern i form av autism, ADHD och långsammare språkutveckling. Statliga myndigheter bör därför skriva om sina rekommendationer vad gäller exponering för paracetamol för gravida kvinnor och uppmana till försiktighetsåtgärder.

Excerpt: In their recent study [ 1 ], Lavesson et al. concluded, “In febrile parturients, neither maternal nor fetal temperatures dropped after paracetamol, but paracetamol halted an increasing trend and stabilized the fetal temperature. The effect of paracetamol on maternal temperature was inconclusive”. This conclusion, however, is not supported by the data in the study, in that the calculation of case and control temperature differences demonstrates clear fetal and maternal temperature decreases after paracetamol.

Yes / The design of a melt synthesis of the first air-stable formulation of the metastable form III of paracetamol is derived from thermo-spectroscopic and thermo-diffraction experiments. Melt crystallisation in the presence of β-1,4-saccharides produces form III selectively and the excipients appear to act as stabilising ‘active’ templates of the metastable polymorph. / This article is part of themed collection: Pharmaceutical Solids.

Made available in DSpace on 2017-07-24T19:37:55Z (GMT). No. of bitstreams: 1 Silvane Machado.pdf: 3592159 bytes, checksum: eb40ce07788b3e465452f6695e411555 (MD5) Previous issue date: 2016-08-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In this work the ruthenium arene complex of general formula [Ru(6-p-cymene)(ampy)Cl]+ (Ru-ampy) containing the 2-aminomethylpiridine ligand was obtained from the cleavage of the chloride bridges of the [Ru(6-p-cimeno)(-Cl)Cl]2 complex. The structure of the Ru-ampy was elucidated by X-ray diffraction, which was compared to the optimized structure DFT theoretical level and there was distinct values of length of Ru-N bond, proving that Ru is coordinated to the ampy ligand by atom of nitrogen N-pyridine ring as the amine nitrogen atom. Experimental electronic spectra, and the theoretical spectra obtained by TDDFT method performed in various solvents showed a small displacement of the bands due to the solvation caused by the nature of the solvent to the complex. From the composition analysis of the orbital, bands observed at 320 and 450 nm were attributed to metal charge transfer transitions to the ligand. In the vibrational spectra observed a shift of the bands of ampy and arene ligands for smaller wavenumber values when they are coordinated to pyridine complex, which results corroborated with the NMR 1H results where there was an increase in shielding of the hydrogen of the p-cymene of the complex Ru-ampy compared with the proton of the precursor. In the electrochemical behavior of Ru-ampy obtained by cyclic voltammetry in CH3CN it was found that a chemical step occurs with the arene labilization and replacement of the solvent after the oxidation of [Ru(6-p-cimeno)(ampy)Cl]+ to [Ru(6-p-cimeno)(ampy)Cl]2+ at 1.5 V, forming the species [Ru(CH3CN)3(ampy)Cl]2+. In order to explore the electrochemical potentiality of Ru-ampy, this was used as a ceramic carbon electrode modifier (CCE-Ru). The cyclic voltammogram of CCE-Ru in Britton-Robinson buffer (pH 7.0) showed only an almost reversible process with oxidation and reduction peaks at 0.39 and 0.35 V vs. Ag/AgCl, respectively, characterized by diffusion process on the electrode surface. With instrumental parameters square wave voltammetry (SWV) optimized (f = 20 s-1, a = 80 mV, ΔEs= 1 mV) analytical curves were constructed in the presence of paracetamol in the concentration intervals 1.99x10-6 - 3.10 x10-5 mol L-1 (R = 0.997), the values detection limit and quantification limit obtained, 1.94 x 10-6 and 5.83 x 10-7mol L-1 respectively are similar to electrodes reported in literature. The proposed method was successfully applied to determination of paracetamol in commercial pharmaceutical formulations (tablets and oral solution), the obtained results are in good agreement with the standard UV-Vis method at a 95% confidence level. / Neste trabalho o complexo de rutênio-areno coordenado ao ligante 2-aminomeltipiridina de fórmula [Ru(6-p-cimeno)(ampy)Cl]PF6 (Ru-ampy) foi obtido a partir da clivagem das pontes do clorido do complexo binuclear [Ru(6-p-cimeno)(-Cl)Cl]2. A estrutura do Ru-ampy foi elucidada por técnica de difração de raios X e comparada à estrutura otimizada em nível da teoria DFT. A combinação dsses resultados comprova a coordenação do ampy ao Ru pelo átomo de nitrogênio do anel N-piridínico e amínico. Os espectros eletrônicos experimentais e teóricos obtidos por método TDDFT, realizados em diferentes solventes, apresentaram um deslocamento das bandas devido à solvatação causada pela natureza do solvente ao complexo. A partir da análise de composição dos orbitais, as bandas observadas foram atribuídas à transição intraligante e transferência de carga do metal para o ligante. Nos espectros vibracionais constatou-se um deslocamento das bandas do ligante ampy e areno deslocam para menores valores de número de onda em relação aos ligantes coordenados. Este resultado corrobora com o aumento da blindagem dos átomo de hidrogênio do 6-p-cimeno em comparação com os prótons do complexo precursor observado por RMN de 1H. No estudo eletroquímico do Ru-ampy obtido por voltametria cíclica em CH3CN constatou-se que uma etapa química ocorre com a labilização do areno e substituição do solvente após a oxidação do [Ru(6-p-cimeno)(ampy)Cl]+ a [Ru(6-p-cimeno)(ampy)Cl]2+ em 1,57 V, formando a espécie [Ru(CH3CN)3(ampy)Cl]2+. O Ru-ampy foi utilizado como modificador de eletrodo de carbono cerâmico (ECC-Ru) a fim de explorar sua potencialidade eletrocatalítica na determinação de paracetamol em tampão Britton–Robinson (pH 7,0). O ECC-Ru apresentou um processo quase-reversível com picos de oxidação e redução em 0,39 e 0,35 V vs. Ag/AgCl, respectivamente, caracterizados por processo difusional na superfície do eletrodo. Os parâmetros instrumentais da voltametria de onda quadrada (VOQ) foram otimizados (f = 20 s-1, a = 80 mV, ΔEs= 1 mV) e as curvas analíticas construídas na presença de paracetamol no intervalo de 1,99x10-6 a 3,10 x10-5 mol L-1 (R=0,997) apresentaram valores de limites de detecção e de quantificação de 5,83 x 10-7 mol L-1 e 1,94 x 10-6mol L-1, respectivamente. O ECC-Ru foi aplicado para determinação de paracetamol em diferentes amostras (comprimido e solução oral) por VOQ e quando comparados aos resultados obtidos pelo método farmacopeico (UV-Vis) não apresentam diferença significativa em um nível de confiança de 95%.

Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2016-03-02T18:00:57Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) PDF - Fernando José de Lima Ramos Júnior.pdf: 2646257 bytes, checksum: 25207836f72f1b5c76c742f3bdf45cad (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2016-06-13T20:35:23Z (GMT) No. of bitstreams: 2 PDF - Fernando José de Lima Ramos Júnior.pdf: 2646257 bytes, checksum: 25207836f72f1b5c76c742f3bdf45cad (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-06-13T20:38:12Z (GMT). No. of bitstreams: 2 PDF - Fernando José de Lima Ramos Júnior.pdf: 2646257 bytes, checksum: 25207836f72f1b5c76c742f3bdf45cad (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-02-18 / In the last years occurred a significant increase in the use of analgesics, for example, those that contain acetaminophen as the active pharmaceutical ingredient, being essential for the pharmaceutical industry and the supervisory organs a rigorous control in the production of these medicines. Thus, it becomes necessary the improvement of techniques with the application of reliable analytical methodologies, which are, preferably, quick and low cost, as, for example, the Near Infrared (NIR) Spectroscopy and the Differential Scanning Calorimetry (DSC). Though, even being techniques with extensive analytical power, its use is hampered in samples such as medicines, because results are presented in a complex way for direct interpretation, making the use of chemometric methods necessary. In this context, the objective of this study was to analyze by differential scanning calorimetry and by near infrared spectroscopy, combined with multivariate chemometric techniques, medicines containing acetaminophen and caffeine. So, three brands of medicines were analyzed by DSC and two classes of medicines by NIR. Having the DSC curves obtained in nitrogen atmosphere (50 mL min -1 ), in the temperature range from 92.00 to 190.00 °C, with heating rate of 10 ° C min -1 and preprocessed with the technique Standard Normal Variate (SNV), and the NIR spectra obtained in the interval from 1950 to 2500 nm and preprocessed employing the first derivative, with the filter Savitzky-Golay, second order polynomial and window of 19 points. Posteriorly, it was performed the analgesics classification using the models Linear Discriminant Analysis (LDA) with Successive Projection Algorithm (SPA) and with Genetic Algorithm (GA-LDA) as variable selection techniques, and the K-Nearest Neighbor (KNN), in addition, the DSC curves data were also submitted to Principal Components Analysis (PCA). It was observed for the data obtained by DSC, that the PCA separated the brand M3 of M1 and M2; SPA-LDA and GA-LDA presented a success rate of 94.74 % for the training set and 90,00 % for the test set and the KNN method classified the samples with 100 % of success. On the other hand, for those obtained by NIR, in the SPA-LDA model the success rate was 97.77 % and 84.44 %, in the GA-LDA 96.66 % and 93.33 %, and in the KNN method 100 % and 80 %, for training set and test set, respectively. Thereby, the analysis of the obtained results showed that DSC and NIR techniques aggregate to chemometric methods are efficient alternatives to the use of High Performance Liquid Chromatography (HPLC), with the advantage of achieving results quickly, low cost and without generating pollutant residues, making feasible the use of these techniques to streamline the quality control in pharmaceutical industries, as well as, to assist the surveillance authorities in the rapid detection of medicines adulteration. / Nos últimos anos ocorreu um aumento significativo no uso de analgésicos, por exemplo, aqueles que contêm o paracetamol como ingrediente ativo farmacêutico, sendo indispensável para a indústria farmacêutica e os órgãos de fiscalização um rigoroso controle na produção desses medicamentos. Para tanto, faz-se necessário o aprimoramento das técnicas com aplicação de metodologias analíticas confiáveis, que sejam, de preferência, rápidas e de baixo custo, como, por exemplo, a Espectroscopia no Infravermelho Próximo (NIR) e a Calorimetria Exploratória Diferencial (DSC). Entretanto, mesmo essas técnicas possuindo amplo poder analítico, sua utilização é dificultada em amostras como medicamentos, pois os resultados apresentam-se complexos à interpretação direta, fazendo-se necessário o uso de métodos quimiométricos. Nesse contexto, o objetivo desse trabalho foi analisar por calorimetria exploratória diferencial e por espectroscopia no infravermelho próximo, associadas a técnicas quimiométricas multivariadas, medicamentos a base de paracetamol e cafeína. Por isso, analisaram-se três marcas de medicamentos por DSC e duas classes de medicamentos por NIR. Tendo as curvas de DSC obtidas em atmosfera de nitrogênio (50 mL min -1 ), na faixa de temperatura de 92,00 a 190,00 ºC, com razão de aquecimento de 10 ºC min -1 e pré-processadas com a técnica de Padrão Normal de Variação (SNV), e os espectros NIR obtidos num intervalo de 1.950 a 2.500 nm e pré-processados empregando-se a primeira derivada, com o filtro de Savitzky-Golay, polinômio de segunda ordem e janela de 19 pontos. Posteriormente, realizou-se a classificação dos analgésicos pelos modelos Análise Discriminante Linear (LDA) com Algoritmo das Projeções Sucessivas (SPA-LDA) e com Algoritmo Genético (GA-LDA) como técnicas de seleção de variáveis, e com o K-ésimo Vizinho Mais Próximo (KNN), além desses, os dados das curvas DSC também foram submetidos a Análise de Componentes Principais (PCA). Observou-se para os dados obtidos por DSC, que a PCA separou a marca M3 de M1 e M2; o SPA-LDA e GA-LDA apresentaram índice de acerto de 94,74 % para o conjunto de treinamento e 90,00 % para o conjunto de teste e o método KNN classificou as amostras com 100 % de sucesso. Por outro lado, para aqueles obtidos por NIR, no modelo SPA-LDA a taxa de acerto foi 97,77 % e 84,44 %; no GA-LDA 96,66 % e 93,33 %; e no método KNN 100 e 80 %, para o conjunto de treinamento e o de teste, respectivamente. Desse modo, a análise dos resultados obtidos permitiu inferir que as técnicas DSC e NIR associadas a métodos quimiométricos são alternativas eficientes ao uso da Cromatografia Líquida de Alta Eficiência (CLAE), com a vantagem de alcançarem resultados com rapidez, baixo custo e sem geração de resíduos poluentes, o que torna viável a utilização dessas técnicas para agilizar o controle da qualidade nas indústrias farmacêuticas, bem como, para auxiliar os órgãos de fiscalização na detecção rápida de adulterações em medicamentos.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Acute liver failure (ALF) induced by acetaminophen (APAP) is a complex process associated with glutathione (GSH) depletion, energetics metabolism changes and mitochondrial dysfunction, resulting in the impairment of maintenance of tissue normal function. On this matter, organoselenium compounds, such as diphenyl diselenide (PhSe)2, have been highlighted in the last years due to the antioxidant properties and the hepatoprotective effects, however, the (PhSe)2 hepatoprotection mechanism remains unclear. So, this work was aimed to deepen into understanding of the effects of (PhSe)2 on the mitochondrial dysfunction as well as the signaling pathway during the ALF induced by APAP. Firstly, it was performed a comparative study between the organoselenium compound and the classical antidote (N-acetylcysteine, NAC) in the liver homogenate. (PhSe)2 presented similar results to the NAC reducing the oxidative damage markers, maintaining the GSH levels and enhancing the survival after the APAP overdose. The treatment with (PhSe)2 reduced plasmatic levels of transaminases (aspartate and alanine aminotransferase) and the morphological/histological changes. In addition, (PhSe)2 was able to reduce significantly the oxidative damage such as lipid peroxidation, reactive oxygen and nitrogen species generation, mitochondrial protein carbonylation and mitochondrial viability after ALF induced by APAP. In this context, the levels of non enzymatic antioxidants, such as GSH, and enzymatic antioxidants, such as catalase, Mn superoxide dismutase, glutathione peroxidase and glutathione reductase remained to the control levels. In general, the results noticed in this work the probably (PhSe)2 mechanism is closely related with the maintenance of antioxidant defense system and inhibition of mitochondrial transition permeability (MPT) indicated by reduction of mitochondrial swelling, activity preservation of respiratory complexes I, II and ATPase, and maintenance of H+ gradient with the mitochondrial membrane potential (Δψm) generation. It was observed that (PhSe)2 was able to limit the impairment of mitochondrial bioenergetics function with the normalization of oxidative phosphorilation (OXPHOS) and activation of heat shock protein pathway through the enhance of HSP70 levels, which in turn, modulates the MPT protecting the mitochondrial viability. (PhSe)2 treatment was able to maintain the appropriated levels of cytokines associated with the liver recovery, such as tumoral necrosis factor alfa (TNF-α), interleukin 6 (IL-6) and nuclear factor kappa B (NF-κB). Moreover, the integrity of cellular bioenergetic function could be associated with the increase of peroxisome proliferator-activated receptor-γ coactivator (PGC-1α), helping to restore the nuclear respiratory factor 1 (NRF1) levels associated with the mitochondrial biogenesis. Finally, (PhSe)2 could be a useful therapeutic alternative that would contribute to the liver recovery, controlling the quality of mitochondrial function and maintaining homeostasis and cellular health. / A insuficiência hepática aguda (IHA) induzida por paracetamol (APAP) é um processo complexo que envolve depleção de glutationa (GSH), mudanças no metabolismo energético e disfunção mitocondrial, o que resulta na incapacidade de manter o funcionamento adequado do órgão. Neste contexto, a utilização de compostos orgânicos de selênio como o difenil disseleneto (PhSe)2 tem se destacado nos últimos anos, devido as propriedades antioxidantes e efeitos hepatoprotetores, no entanto, o mecanismo pelo qual (PhSe)2 age não está totalmente esclarecido. Assim, este estudo busca aprofundar nossos conhecimentos sobre as ações do (PhSe)2 na disfunção mitocondrial assim como a sinalização intracelular durante a IHA induzida por APAP. Para tanto, estabelecemos primeiramente um parâmetro comparativo entre o composto orgânico de selênio e o antídoto clássico (N-acetil cisteina, NAC), em homogenato. O (PhSe)2 foi tão efetivo quanto NAC reduzindo os marcadores de dano oxidativo, auxiliado na manutenção dos níveis de GSH e aumentando o tempo de sobrevivência após a intoxicação por APAP. O tratamento com (PhSe)2 reduziu alterações morfológica, minimizou o dano quando analisamos histologicamente o tecido hepático e determinou uma redução nos níveis plasmáticos dos indicadores de dano hepatocelular (AST e ALT). Além disso, o (PhSe)2 foi eficaz na redução significativa do dano oxidativo ao limitar a peroxidação lipídica, formação de espécies reativas de oxigênio e nitrogênio, carbonilação de proteínas mitocondriais e viabilidade mitocondrial após a IHA induzida por APAP. Neste contexto, os níveis de antioxidantes não enzimáticos, tais como GSH, e enzimáticos, tais como as enzimas catalase, manganês superoxido dismutase, glutationa peroxidase e glutationa redutase, também foram mantidos semelhantes ao grupo controle. Em geral os resultados observados neste estudo indicam que um importante mecanismo pelo qual o (PhSe)2 exerce os seus efeitos terapêuticos está relacionado a manutenção da atividade do sistema de defesa antioxidante e inibição da transição de permeabilidade mitocondrial (MPT) indicados pela redução do inchaço mitocondrial, preservação da atividade dos complexos respiratórios I, II e ATPase, e manutenção do gradiente de H+ com a formação do potencial de membrana mitocondrial (Δψm). Também observamos que o (PhSe)2 limita a perda do funcionamento bioenergético mitocondrial com a manutenção dos níveis adequados de fosforilação oxidativa (OXPHOS) e ativa a via das proteínas do choque térmico aumentando a expressão de HSP70, a qual apresenta um efeito modulador importante sobre a MPT preservando a viabilidade mitocondrial. O tratamento com (PhSe)2 foi efetivo em preservar níveis apropriados de citocinas envolvidas na recuperação do tecido hepático, tais como fator de necrose tumoral alfa (TNF- α), interleucina 6 (IL-6) e fator nuclear kappa B (NF-κB). Além disso, a manutenção bioenergética celular poderia estar associada com os elevados níveis transcricionais do receptor gama ativado por proliferador de peroxissoma (PGC-1α) que auxilia a restaurar os níveis de fator nuclear respiratório 1 (NRF1) os quais estão envolvidos no processo de biogênese mitocondrial. Por fim, o (PhSe)2 poderia ser uma importante alternativa terapêutica a qual auxiliaria na recuperação do fígado, controle de qualidade mitocondrial e manutenção da homeostase e saúde celular.

1 ABSTRACT Background The annual drug overdose rates have been increasing exponentially since the 90's worldwide. Toxicological information centre (TIC) represents a valuable source of information for evaluating the trends in the drug poisonings in Czech Republic. Aim of the study The purpose was to analyze the number and trends in the calls concerning poisonings due to central nervous system (CNS) affecting drugs, identify the reasons of medication errors caused by laymen, frequency and consequences of these errors across all age groups and also to analyze the numbers, causes, symptoms and severity of the paracetamol intoxications. Methods During the reference period the data from the enquiries were extracted from the TIC electronic database, discharge reports from the hospital were studied or phone call follow-ups with the patients were carried out to be able to evaluate the outcome of the poisonings. Results In the years 1997-2002 the number of calls caused by poisoning with tricyclic antidepressants and barbiturates decreased (by 366.7 % and 340,0 %, respectively) whereas the calls due to selective serotonin reuptake inhibitors and benzodiazepines overdose increased (by 1347.4 % and 359.8 %). The 0-5 years old children are at the highest risk of experiencing medication errors or accidental poisonings...

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-12-19T13:49:30Z No. of bitstreams: 1 carinadealmeidabastos.pdf: 468720 bytes, checksum: 78859652a23edd11dab2d4bd91534807 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-12-19T14:28:19Z (GMT) No. of bitstreams: 1 carinadealmeidabastos.pdf: 468720 bytes, checksum: 78859652a23edd11dab2d4bd91534807 (MD5) / Made available in DSpace on 2016-12-19T14:28:19Z (GMT). No. of bitstreams: 1 carinadealmeidabastos.pdf: 468720 bytes, checksum: 78859652a23edd11dab2d4bd91534807 (MD5) Previous issue date: 2008-08-01 / Uma metodologia alternativa por cromatografia líquida em fase reversa por pareamento iônico para a análise simultânea de paracetamol e cloridrato de fenilefrina (associação 1) e paracetamol e maleato de carbinoxamina (associação 2) em comprimidos foi proposta. Fase móvel consistindo de 60% de metanol e 40% de solução aquosa de fosfato de potássio monobásico anidro (62,46 mM) adicionada com 0,5 mL de trietilamina, 0,25 g de lauril sulfato de sódio e 1 mL de ácido fosfórico foi usada, com volume de injeção de 50 µL, fluxo da fase móvel de 1,0 mL/min, coluna cromatográfica C18 de dimensões 300 x 3,9 mm e tamanho das partículas de 5 µm mantida a 27°C, detector UV em 220 e 300 nm, e tempo de análise de 6 min. O método proposto para a análise dos comprimidos foi aplicado na análise de medicamentos na forma farmacêutica de solução oral, que contém os três fármacos em associação. Devido à presença de interferentes nestas formulações, o método foi então reotimizado e nova fase móvel consistindo de 480 mL de acetonitrila, 3520 mL de heptanossulfonato de sódio 0,005 M em água, e 4 mL de ácido fosfórico foi usada, com volume de injeção de 100 µL e fluxo de 2,0 mL/min. Os parâmetros avaliados na validação analítica para as associações 1 e 2 foram: seletividade, linearidade, repetibilidade, precisão intermediária, limite de detecção, limite de quantificação, exatidão e robustez. Devido à simplicidade, seletividade, precisão, exatidão e rapidez, a metodologia é uma alternativa interessante para assegurar a qualidade dessas drogas na indústria farmacêutica. / An alternative methodology by ion-pair reversed phase liquid chromatography for simultaneous analysis of acetaminophen and phenylephrine hydrochloride (association 1) and acetaminophen and carbinoxamine maleate (association 2) in tablets was proposed. Mobile phase consisting of 60% methanol and 40% potassium monobasic phosphate aqueous solution (62.46 mM) added with 0.5 mL trietilamine, 0.25 g sodium lauryl sulfate and 1 mL of phosphoric acid was used, with injection volume of 50 µL, mobile phase flow of 1.0 mL/min, chromatographic column C18 of dimensions 300 x 3.9 mm and particle size of 5 µm maintained at 27°C, UV detection at 220 and 300 nm, within 6 min. The proposed method for the analysis of tablets was applied in the analysis of drugs in the pharmaceutical form of oral solution, which contains the three drugs in combination. Due to the presence of interfering in these formulations, the method was again optimized and new mobile phase consisting of 400 mL of acetonitrile, 3520 mL of sodium heptane sulfonate 0.005 M in water, and 4 mL of phosphoric acid was used, with injection volume of 100 µL and flow of 1.0 mL/min. The analytical validation parameters evaluated for association 1 and 2 were: selectivity, linearity, repeatability, intermediate precision, limit of detection, limit of quantification, accuracy and robustness. Due to its simplicity, selectivity, precision, accuracy and rapidity, the methodology can be an interesting alternative for quality assurance in the pharmaceutical industry of these drugs.

Contexte : Il y a très peu de données sur l’utilisation et la sécurité CV du paracétamol et des AINS à faible dose en l’automédication. Objectifs : établir les caractéristiques des utilisateurs, évaluer et comparer le risque de syndrome coronarien aigu (SCA), associé au paracétamol (P) et à l'ibuprofène à dose antalgique (IDA). Méthodes : Études d'utilisation, études de cohorte auto-contrôlées (self-controlled cohort - SCC), étude de cohorte appariée sur le score de propension et étude cas-témoin nichée (CTN) ont été réalisé dans l’Echantillon Généraliste Bénéficiaires (EGB) en incluant les épisodes de traitement d’IDA et de P chez les adultes entre 2009 et 2014. Des risques de SCA ont été estimés par les rapports de taux d'événement (RTE) ou les hazard ratios (HRs) avec l’IC à 95%. Résultats : L’utilisation d’OSI et de P concerne surtout des jeunes pour des courtes durées de traitement. Les études SCC ont inclu 316265 et 1025877 épisodes d’IDA et P respectivement chez 168407 et 342494 utilisateurs. Chez les utilisateurs d'aspirine à faible dose (AFD) (3,5% et 5,3% des épisodes d’IDA et de P), le risque de SCA a augmenté après la dispensation d’IDA (RTE 1,52 [1.07 à 2.16]) mais diminué après la dispensation de P (HR 0,39 [0,32 à 0,47]). Chez les non-utilisateurs d’AFD (96,5% d’IDA et 94,7% de P), le risque de SCA n’a augmenté qu’après P (1,32 [1,16 à 1,49]). Dans l'étude de cohorte appariée (age moyen 45 ans), il n'y avait pas de différence entre le P et l’IDA sur la durée totale du suivi (HR 0,97 [0,71 à 1,32]), en dépit d'une augmentation plus élevée avec l’IDA dans les 2 premières semaines (1,75 [1,08 à 2,82]). Dans l'étude CTN (age moyen 67), le risque n’a augmenté qu’avec P, pas avec l’IDA (P : 1,36 [1,23 à 1,50]; IDA : 1,16 [0,78 à 1,72]). 11. Conclusion : Le risque de SCA associé à l’IDA ou au P varie en fonction du statut d’utilisation d’AFD et de l'âge. Pour l’IDA, le risque n'a augmenté que chez les utilisateurs d’AFD. Au contraire, pour P, le risque a augmenté seulement chez les non-utilisateurs d’AFD. Chez les jeunes non-utilisateurs d’AFD, il n'y avait pas de différence entre l’IDA et le P (étude de cohorte apparié). Chez les patients âgés (étude CTN), P semble être associé à un risque plus élevé. / Background : There is little data about the CV safety of Paracetamol (P) and OTC NSAIDs. Objectives : Describe usage patterns, to evaluate and compare the risk of acute coronary syndrome (ACS) associated with P and OTC-Strength ibuprofen (OSI). Methods : Drug utilisation, self-controlled cohort (SCC), propensity score- (PS) matched cohort, nested case-control (NCC) studies were conducted in the Echantillon Généraliste Bénéficiaires (EGB). Studies included P and OSI treatment episodes in adults in 2009-2014. Risks were quantified by event rate ratios (ERRs) or hazard ratio (HRs) with 95% CI. Results : Use of OSI and P concerning mostly young persons for short durations. The SCC studies included 316265 OSI and 1025877 P episodes in 168407 and 342494 users. In low-dose aspirin (LDA) users (3.5% OSI and 5% P episodes), ACS risk increased after OSI dispensing (ERR 1.52 [1.07-2.16]) but decreased after P (HR 0.39 [0.32-0.47]). In LDA nonusers, ACS risk increased after P (1.32 [1.16-1.49]), but not after OSI (1.22 [0.63-2.36]). In the PS-matched study (mean age 45), there was no difference between P and OSI over the total follow-up (HR 0.97 [0.71-1.32]), despite a higher increase with OSI in the first 2 weeks (1.75 [1.08-2.82]). In the NCC study (mean age 67), the risk increased with P but not with OSI (P: 1.36 [1.23-1.50]; OSI: 1.16 [0.78-1.72]). Conclusion : ACS risk associated with OSI or P vary according to LDA use and age. For OSI, ACS risk increased only in LDA users. Conversely, for P, ACS risk increased only in LDA nonusers. In young LDA 9 nonusers, there was no difference between OSI and P (PS-matched study). In older patients (NCC study), P appeared to be associated with a higher risk.

Self-medication impacts both negatively and positively the health of people, which has become evident during the COVID-19 pandemic. The study aimed to assess the prevalence of self-medicated drugs used for respiratory symptoms, as COVID-19 preventive, for its symptoms or once tested positive. To determine the perception of symptom relief and demographic variables that promote self-medication in Peru. We performed a cross-sectional, analytical, multicenter study in 3792 study respondents on the use, the reason for use, and perception of relief after the use of six drugs during the quarantine period. An online questionnaire was developed, pretested and submitted to the general public. Multivariable logistic regression was used to ascertain factors that influence an individual's desire to self-medicate, associations were considered significant at p < 0.05 and using region (coast, mountain and jungle) as cluster group. The majority of respondents self-medicated with acetaminophen for respiratory symptoms and mainly because they had a cold or flu. It was observed that all the surveyed drugs (acetaminophen, ibuprofen, azithromycin, penicillin, antiretrovirals and hydroxychloroquine) were consumed for various symptoms including: fever, fatigue, cough, sneezing, muscle pain, nasal congestion, sore throat, headache and breathing difficulty. Over 90% of respondents perceived relief of at least one symptom. Multivariable logistic regression showed that older people have a higher frequency of antiretroviral self-medication, respondents who currently have a job had a higher frequency of penicillin self-medication, and that respondents from the Andes consumed less acetaminophen, while the ones from the rainforest consumed it more. There were significant percentages of self-medication, including drugs without sufficient scientific evidence. Age, region where one lived and job status were variables associated with self-medication frequency. Continuous awareness and sensitization about the risks of self-medication are warranted. / Revisión por pares