Conservantes em Formulações de Cloreto de Sódio 0,9% para Aplicação Tópica em Pediatria

As formulações de cloreto de sódio 0,9%, são na sua grande maioria utilizadas com bastante frequência sobretudo na população pediátrica. Tanto os cuidadores como os próprios profissionais de saúde as reconhecem e avaliam como um componente essencial para os cuidados de saúde desta população. No entanto, o grave problema destas formulações reside no facto de muitos dos consumidores após a sua utilização apresentarem reacções adversas, que não são justificáveis se apenas da composição da formulação fizerem parte água purificada e cloreto de sódio. Assim deve ser tida em conta a composição de cada apresentação farmacêutica, a fim de se averiguar quanto à presença de conservantes potencialmente perigosos e para deste modo alertar os possíveis consumidores destes produtos. O principal objectivo deste estudo foi a análise e avaliação da rotulagem e folheto de instruções das formulações de cloreto de sódio 0,9% para aplicação tópica em pediatria, a fim de se averiguar a utilização de conservantes na sua formulação e por conseguinte a sua conformidade para comercialização. Com o auxílio de uma check-list, foram avaliadas 34 apresentações de venda livre de formulações de cloreto de sódio 0,9% para aplicação tópica, no período de Janeiro a Março de 2014. Das 34 apresentações farmacêuticas analisadas, apenas uma dasapresentações não se encontrava descrita como dispositivo médico, mas sim como produto cosmético. Contudo quanto à marcação CE de conformidade, esta encontrava-se devidamente aposta em 94% das apresentações. No que às indicações terapêuticas diz respeito e como seria expectável, na sua maioria estas apresentações destinam-se em 51% dos casos para utilização nasal e em 33% dos casos para utilização oftálmica, sendo o modo de apresentação em gotas (88%) o mais encontrado para comercialização. Quanto à utilização de conservantes, constatou-se uma grande omissão e alguma imprecisão quanto às informações contidas na rotulagem e/ou folheto de instruções das formulações analisadas, expondo assim os indivíduos mais susceptíveis e em especial a população pediátrica ao risco de reacções adversas e que por vezes podem ser fatais. Por outro lado também podem ocorrer complicações aquando do uso inadvertido destasformulações com conservantes, por portadores de lentes de contacto ou sem a devida esterilidade para utilização oftálmica. Assim apesar de o soro fisiológico não ser considerado um medicamento, mas sim um dispositivo médico, deve ser contudo utilizado com algumas precauções, sobretudo nesta população pediátrica e sempre que possível aconselhado por um profissional treinado e consciente da problemática que os conservantes usados nestas formulações podem causar quando utilizados indevidamente.

Biomimetic norfloxacin sensors made of molecularly-imprinted materials for potentiometric transduction

A biomimetic sensor for norfloxacin is presented that is based on host-guest interactions and potentiometric transduction. The artificial host was imprinted into polymers made from methacrylic acid and/or 2-vinyl pyridine. The resulting particles were entrapped in a plasticized poly(vinyl chloride) (PVC) matrix. The sensors exhibit near-Nernstian response in steady state evaluations, and detection limits range from 0.40 to 1.0 μg mL−1, respectively, and are independent of pH values at between 2 and 6, and 8 and 11, respectively. Good selectivity was observed over several potential interferents. In flowing media, the sensors exhibit fast response, a sensitivity of 68.2 mV per decade, a linear range from 79 μM to 2.5 mM, a detection limit of 20 μg mL−1, and a stable baseline. The sensors were successfully applied to field monitoring of norfloxacin in fish samples, biological samples, and pharmaceutical products.

The Risks of Self - Medication: Case Report of Familial Misuse of AM3 (Immunoferon®)

Over the last decades extended medical knowledge has been an important health care benefit in terms of disease prevention and management. However, probably with no exception, most pharmaceutical products are not devoid of adverse consequences. Immunomodulators are commonly considered a “benign” drug whose advantages bypass consequences. The immunomodulator AM3 (Immunoferon®) is a clinically used, orally administered compound whose active principle is stabilised in an inorganic matrix of calcium. We report the misuse of AM3 in three members of a family; father and two children. The drug was prescribed to the father who subsequently administered it to the children without seeking medical advice. Two months later, all subjects developed abdominal and/or flank colicky pain. Hypercalciuria was diagnosed in the children with different degrees of severity. It is likely that the calcium content of the inorganic matrix played an important role in the onset of symptoms. No adverse side effects related to the inorganic matrix of calcium of immunoferon® have been documented so far. This family case report calls attention to the risks of self -medication in a susceptible family. Paediatric patients are vulnerable as they rely on adults for the supply of medications. Concerning the use of drugs in family, especially nonprescription drugs, the quality of health care provided to the children depends on the health literacy of their parents.

Prescription patterns of pharmaceuticals

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics

Catastrophic health care expenditures in Portugal between 2000-2010: Assessing impoverishment, determinants and policy implications

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics

Avaluació del risc ambiental de productes farmacèutics en l'àmbit català

S’ha dut a terme una Avaluació del Risc Ambiental dels productes farmacèutics més consumits en l’àmbit català treballant sobre un model de planta de tractament d’aigües residuals determinat. La Concentració ambiental estimada (PEC) pel medi aquàtic s’ha calculat a partir de dades fisicoquímiques dels fàrmacs tenint en compte una sèrie d’hipòtesis i suposicions prèvies. La Concentració estimada de no-efecte (PNEC) s’ha estimat mitjançant dades d’ecotoxicitat extretes de l’ECOSAR. Es considera que hi ha afecció al medi quan la relació PEC/PNEC excedeix d’1; en aquest estudi s’ha obtingut que l’Ibuprofèn, el Diclofenac i l’Atorvastatina superen aquest valor suposant, per tant, un risc per al medi ambient. D’aquesta manera es mostra que l’eliminació dels fàrmacs durant el procés de la depuració de les aigües residuals no resulta totalment eficient.

Methods for detection and confirmation of Hematide?/peginesatide in anti-doping samples.

Since the 1990's, cheating athletes have abused substances to increase their oxygen transport capabilities; among these substances, recombinant EPO is the most well known. Currently, other investigational pharmaceutical products are able to produce an effect similar to EPO but without having chemical structures related to EPO; these are the synthetic erythropoiesis stimulating agents (ESAs). Peginesatide (also known as Hematide?) is being developed by Affymax and Takeda and, if approved by regulatory authorities, could soon be released on the international market. To detect potential athletic abuse of this product and deter athletes who consider cheating, we initiated a collaboration to implement a detection test for anti-doping purposes. Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. It is undetectable using current anti-doping tests due to its lack of sequence homology to EPO. To detect and deter potential abuse of peginesatide, we initiated an industry/antidoping laboratory collaboration to develop and validate screening and confirmation assays so that they would be available before peginesatide reaches the market. We describe a screening ELISA and a confirmation assay consisting of immune-purification followed by separation with SDS-PAGE and revelation with Western double blotting. Both assays can detect 0.5 ng/mL concentrations of peginesatide in blood samples, enabling detection for several days after administration of a physiologically relevant dose. This initial report describes experimental characterization of these assays, including testing with a blinded set of samples from a clinical study conducted in healthy volunteers.

An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune ethiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applyed for dengue fever.

Profiling of counterfeit medicines by vibrational spectroscopy

Counterfeit pharmaceutical products have become a widespread problem in the last decade. Various analytical techniques have been applied to discriminate between genuine and counterfeit products. Among these, Near-infrared (NIR) and Raman spectroscopy provided promising results.The present study offers a methodology allowing to provide more valuable information fororganisations engaged in the fight against counterfeiting of medicines.A database was established by analyzing counterfeits of a particular pharmaceutical product using Near-infrared (NIR) and Raman spectroscopy. Unsupervised chemometric techniques (i.e. principal component analysis - PCA and hierarchical cluster analysis - HCA) were implemented to identify the classes within the datasets. Gas Chromatography coupled to Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used to determine the number of different chemical profiles within the counterfeits. A comparison with the classes established by NIR and Raman spectroscopy allowed to evaluate the discriminating power provided by these techniques. Supervised classifiers (i.e. k-Nearest Neighbors, Partial Least Squares Discriminant Analysis, Probabilistic Neural Networks and Counterpropagation Artificial Neural Networks) were applied on the acquired NIR and Raman spectra and the results were compared to the ones provided by the unsupervised classifiers.The retained strategy for routine applications, founded on the classes identified by NIR and Raman spectroscopy, uses a classification algorithm based on distance measures and Receiver Operating Characteristics (ROC) curves. The model is able to compare the spectrum of a new counterfeit with that of previously analyzed products and to determine if a new specimen belongs to one of the existing classes, consequently allowing to establish a link with other counterfeits of the database.

Sistema de almacén y dispensación robotizada de productos farmacéuticos

Actualmente, las necesidades de mejora en gestión de stocks y la mayor disponibilidad de sistemas automáticos, están haciendo que muchas empresas inviertan en técnicas modernas para almacenamiento y manipulación de productos. Esta inquietud también ha llegado a las farmacias, que de forma lenta pero firme se van apuntando a su robotización. Uno de los principales problemas a los que se enfrentan las farmacias es la pérdida de tiempo en la gestión y búsqueda de medicamentos, provocando situaciones negativas como las esperas, la falta de tiempo para una atención más personalizada y como consecuencia, la pérdida de clientes. Este inconveniente y la necesidad de mejora en la gestión de los stocks han hecho que aparezcan los Sistemas de dispensación automática de productos farmacéuticos. El dispensador automático facilita el trabajo del farmacéutico al automatizar la búsqueda de la medicina requerida, aumentando la dedicación al cliente y reduciendo los tiempos no productivos y las colas. El presente estudio desarrolla un sistema de dispensación automático de fármacos aplicado a farmacias con una rotación de medicamentos media/ baja, valorando tanto su viabilidad técnica como económica. El almacén propuesto es de tipo caótico con sistema de carga, almacenamiento y descarga completamente automáticos. La mayoría de diseños y conceptos expuestos en este trabajo son de desarrollo propio del autor con el único objetivo de la búsqueda de nuevas soluciones para conseguir un sistema de almacenamiento efectivo y de máximo rendimiento.

Betaiinin tuotannon sivujakeiden mikrosuodattaminen teräskeraamisella kalvolla

Betaiini on ammoniumyhdiste, jota käytetään esimerkiksi eläinten rehussa, kosmetiikassa ja lääkkeissä. Danisco Animal Nutrition Finnfeeds Finland Oy:n Naantalin tehdas on maailman johtava betaiinin tuottaja ja raaka-aineena tehtaalla käytetään melassierotuksesta saatavaa betaiinimelassia. Kiteisen betaiinin puhdistusprosessin yhteydessä syntyybetaiinipitoisia sivujakeita, jotka sisältävät huomattavan määrän betaiinia, minkä takia niiden jatkokäsittely on tärkeää. Betaiinin tuotannon sivujakeet ovat erittäin vaikeasti suodattuvia orgaanisia liuoksia, joiden koostumuksia ei täysin tunneta. Tämän työn tarkoituksena oli puhdistaa betaiinin tuotannon sivujakeita mikrosuodattamalla niitä teräskeraamisella kalvolla. Työn kokeellisessa osassa suoritettiin suodatusparametrien eli pH:n, lämpötilan, TMP:n ja betaiiniliuoksen kuiva-ainepitoisuuden optimointi sekä konsentrointikokeita. Mikrosuodatus suoritettiin Graver Technologiesin Scepter-putkimoduulilla, joka toimi ohivirtausperiaatteella ja jonka huokoskoko oli 0,1 ¿m. Scepter-moduuli koostui ruostumattomasta teräksestä sintratuista putkimoduuleista, joissa erottavana kerroksena toimi TiO2. Esikokeiden perusteella todettiin ettei pH:lla ollut suurta vaikutusta suodatukseen. Permeaattivuo kasvoi selvästi lämpötilan ja TMP:nkasvaessa. Vuo taas huononi ja permeaatin sameus lisääntyi selvästi 35 % korkeammissa kuiva-ainepitoisuuksissa. Konsentrointikokeet suoritettiin betaiiniliuoksen refraktrometrisessa kuiva-ainepitoisuudessa, BetRk, 35 %, 80 °C lämpötilassa ja betaiiniliuoksen omassa pH:ssa (pH 8-9,5). Esikokeiden tulosten perusteella konsentrointikokeet suoritettiin TMP:ssa 0,6; 0,8 ja 1,0 bar. Betaiinin tuotannonsivujakeiden konsentrointikokeissa saannoksi saatiin 95 %. Suodatustuloksista havaittiin, että betaiinin tuotannon sivujakeen erä vaikutti voimakkaasti suodatuksen toimivuuteen. Konsentrointikokeissa suodatukset suoritettiin sekäuusilla mikrosuodatusmoduuleilla että vanhalla moduulilla, joka oli jo kulunut.Kulumisen ei kuitenkaan havaittu huonontavan suodatustehokkuutta. Konsentrointikokeiden perusteella voidaan laitteiston pesuväliksi arvioida noin viikko ja pesu tulisi suorittaa sekä emäksisellä että happamalla pesuaineella.

Toxicity assessment of refill liquids for electronic cigarettes.

We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g). Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure.

Determinação espectrofotométrica por injeção em fluxo de paracetamol (acetaminofeno) em formulações farmacêuticas

A flow injection spectrophotometric procedure is proposed for the determination of paracetamol (acetaminophen) in pharmaceutical formulations. Powdered and liquid samples were previously dissolved/diluted in 0.05 mol L-1 hydrochloric acid solution and a volume of 250 µL was injected directly into a carrier stream of this same acid solution, flowing at 2.5 mL min-1. Paracetamol reacts with sodium hypochlorite forming N-acetyl-p-benzoquinoneimine which then reacts with sodium salicylate in sodium hydroxide solution yielding a blue indophenol dye which was measured at 640 nm in the pH range of 9.5-10.0. Paracetamol was determined in pharmaceutical products in the 1.0 to 100.0 mg L-1 (3.3x10-6 a 6.6x10-4 mol L-1) concentration range, with a detection limit of 0.5 mg L-1 (1.6x10-6 mol L-1). The recovery of this analyte in five samples ranged from 98.0 to 103.6 %. The analytical frequency was 80 determinations per hour and the RSDs were less than 1% for paracetamol concentrations of 25.0, 50.0 and 75.0 mg L-1 (n=10). A paired t-test showed that all results obtained for paracetamol in commercial formulations using the proposed flow injection procedure and a spectrophotometric batch procedure agree at the 95% confidence level.

Determinação de paracetamol em produtos farmacêuticos usando um biossensor de pasta de carbono modificado com extrato bruto de abobrinha (Cucurbita pepo)

Crude extracts of several vegetables such as peach (Prunus persica), yam (Alocasia macrorhiza), manioc (Manihot utilissima), artichoke (Cynara scolymus L), sweet potato (Ipomoea batatas (L.) Lam.), turnip (Brassica campestre ssp. rapifera), horseradish (Armoracia rusticana) and zucchini (Cucurbita pepo) were investigated as the source of peroxidase (POD: EC 1.11.1.7). Among those, zucchini (Cucurbita pepo) crude extract was found to be the best one. This enzyme in the presence of hydrogen peroxide catalyses the oxidation of paracetamol to N-acetyl-p-benzoquinoneimine which the electrochemical reduction back to paracetamol was obtained at a peak potential of ¾0.10V. A cyclic voltammetric study was performed by scanning the potential from + 0.5 to ¾ 0.5 V. The recovery of paracetamol from two samples ranged from 97.3 to 106% and a rectilinear calibration curve for paracetamol concentration from 1.2x10-4 to 2.5x10-3 mol L-1 (r=0.9965) were obtained. The detection limit was 6.9x10-5 mol L-1 and the relative standard deviation was less than 1.1% for a solution containing 2.5x10-3 mol L-1 paracetamol and 2.0x10-3 mol L-1 hydrogen peroxide (n=12). The results obtained for paracetamol in pharmaceutical products using the proposed biosensor and Pharmacopoeial procedures are in agreement at the 95% confidence level.

Fluvial biofilms: a pertinent tool to assess β-blockers toxicity

Among increasingly used pharmaceutical products, β-blockers have been commonly reported at low concentrations in rivers and littoral waters of Europe and North America. Little is known about the toxicity of these chemicals in freshwater ecosystems while their presence may lead to chronic pollution. Hence, in this study the acute toxicity of 3 β-blockers: metoprolol, propranolol and atenolol on fluvial biofilms was assessed by using several biomarkers. Some were indicative of potential alterations in biofilm algae (photosynthetic efficiency), and others in biofilm bacteria (peptidase activity, bacterial mortality). Propranolol was the most toxic β-blocker, mostly affecting the algal photosynthetic process. The exposure to 531 μg/L of propranolol caused 85% of inhibition of photosynthesis after 24 h. Metoprolol was particularly toxic for bacteria. Though estimated No-Effect Concentrations (NEC) were similar to environmental concentrations, higher concentrations of the toxic (503 μg/L metoprolol) caused an increase of 50% in bacterial mortality. Atenolol was the least toxic of the three tested β-blockers. Effects superior to 50% were only observed at very high concentration (707 mg/L). Higher toxicity of metoprolol and propranolol might be due to better absorption within biofilms of these two chemicals. Since β-blockers are mainly found in mixtures in rivers, their differential toxicity could have potential relevant consequences on the interactions between algae and bacteria within river biofilms