Existen diferencias farmacocinéticas y tiempos de despertar entre mujeres y hombres con anestesia total intravenosa

Introducción: La anestesia total intravenosa (TIVA) es ampliamente usada y reportada en la literatura como técnica para disminuir la respuesta a la laringoscopia e intubación, en la inducción y mantenimiento de una adecuada anestesia, además de una mejor estabilidad hemodinámica y recuperación pos anestésica; sin embargo no existen un gran número de estudios que comparen el uso de TIVA, determinando si existen diferencias en el perfil farmacocinético según el género del paciente. Objetivo: Describir diferencias farmacocinéticas y de los tiempos de despertar y salida a la unidad de cuidados pos anestésicos (descarga), según el género; en pacientes que reciben TIVA, con remifentanil y propofol, orientado por Stangraf. Metodología: Estudio observacional analítico de corte transversal, en pacientes llevados a cirugía bajo TIVA en el Hospital Occidente de Kennedy en el periodo de junio de 2013 a Enero de 2014.Usando SPSS versión 20 Windows, se analizaron los datos mediante pruebas Kolmogorov-Smirnov y Shapiro-Wilk y U de Mann Withney. Un valor de p menor 0.05 fue aceptado como estadísticamente significativo. Resultados: Se aplicaron pruebas de normalidad y no se encontraron diferencias estadísticamente significativas entre género. El tiempo de despertar fue 9.36 minutos para mujeres y 11.26 minutos para hombres. Los tiempos de descarga fueron 10.71 minutos para mujeres y 12.82 minutos para hombres. Discusión. El tiempo de despertar y descarga no es diferente entre mujeres y hombres en los pacientes analizados. Se requieren estudios adicionales entre grupos poblacionales de diversas condiciones farmacocineticas para corroborar los datos.

Comparación de la anestesia espinal con anestesia general endovenosa para legrado uterino obstétrico

Introducción: La elección de la técnica anestésica para cualquier procedimiento quirúrgico debe estar basada en su seguridad, la rapidez para su aplicación, la recuperación óptima para el paciente y minimización de los efectos secundarios, la anestesia raquídea es una técnica anestésica que puede ser utilizada con buenos resultados clínicos y minimas complicaciones . Materiales y métodos: Se realizó un estudio observacional con recolección prospectiva en mujeres clasificadas como ASA I - II y que posteriormente fueron llevadas a la realización de legrado uterino obstétrico por embarazo no viable durante las primeras 12 semanas de gestación, las técnicas anestésicas fueron anestesia espinal o anestesia general endovenosa dependiendo de la elección hecha por el anestesiólogo previo al procedimiento. Se midieron variables hemodinámicas, control del dolor postoperatorio, tiempo de recuperación y complicaciones perioperatorias con el fin de determinar si se presentaban diferencias significativas entre estas dos técnicas anestésicas. Resultados: Se incluyeron un total de 110 pacientes, 63.6% (n=70) con anestesia general y 36.4% (n40) con anestesia espinal. Ambas poblaciones fueron comparables. Se presentaron menos efectos secundarios con la técnica espinal, hay una diferencia estadísticamente significativa en cuanto al dolor a favor de la anestesia espinal (p0,000) Discusión: La anestesia raquídea es una opción viable, sencilla , fácil y eficaz para la realización de legrados obstétricos, se puede realizar con monitorización básica y las complicaciones son mínimas. Se requieren estudios más amplios para determinar el papel de cual es la mejor técnica. Palabras claves: legrado uterino instrumentado, anestesia espinal, anestesia general endovenosa

A Vancomicina na prática clínica : artigo de revisão

A vancomicina é um antibiótico glicopeptídico activo contra bactérias Gram-positivos. É usada ao nível hospitalar, prinicipalmente para combater infecções por Staphylococcus aureus resistentes à meticilina (SARM). QUando se administra vancomicina, são várias as situações que requerem a monitorização dos seus seus níveis séricos e o ajuste posológico das dores administradas. O presente artigo tem como objectivo rever os principais conceitos farmacodiâmicos e farmacocinéticos relacionados com este fármaco, realçando-se a importância da sua monitorização na prática clínica.

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis

Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of out permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.

Farmacología en la tercera edad: Medicamentos de uso continuo y peligros de la interacción medicamentosa

Introduction: It was observed a considerable growth of elderly people. They are who use more medicines. The physiological changes associated with the age advancing can make pharmacokinetic and pharmacodynamic alterations. The cognitive decline, physical limitations and associate chronic pathology affect the medications appropriately use ability. Aims: Based in a literature review, appoint the main pharmacological groups prescribed to the elderly and the drug-drug interaction risks. Conclusion: The most of elderly use continually at least 3 medicines, the most prescribed are to cardiovascular and psychic diseases treatment.

Orbifloxacin: A Review of Properties, Its Antibacterial Activities, Pharmacokinetic/Pharmacodynamic Characteristics, Therapeutic Use, and Analytical Methods

Orbifloxacin is a third generation of fluoroquinolone that exhibits increased antibacterial activity against the Enterobacteriaceae, gram-negative and gram-positive bacteria, anaerobes, and mycobacteria. This drug was synthesized in 1987 and developed as a veterinary chemotherapeutic to use for livestock and domestic pets. Orbifloxacin is labeled for the treatment of skin, soft tissue, and urinary tract infections in dogs, and skin and soft tissue infections in cats, but in some countries, orbifloxacin has been given for the treatment of gastrointestinal and respiratory infections in cattle and swine and other animals. The in vitro activity and clinical efficacy of orbifloxacin against naturally occurring bacterial infections of the skin, ear, soft tissue, udder, and gastrointestinal and respiratory systems in different animals have been evaluated and good responses have been found. The minimum inhibitory concentration of orbifloxacin has been determined in various different pathogens and the results found in the literature are shown in this work. The pharmacokinetics of orbifloxacin has been evaluated by different routes of administration in goats, horses, pigs, rabbits, dogs, cats, camels, cattle, sheep, and fish. Orbifloxacin exhibits excellent pharmacokinetic parameters that suggest that this drug may have good clinical effects on various bacterial infections in these species. All methods described in the scientific literature for determination of orbifloxacin in different matrices were collected and discussed. © 2013 Copyright Taylor and Francis Group, LLC.

Avaliação do tratamento com cefquinoma associada a curetagem em bovinos acometidos de processos sépticos podais profundos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise qualitativa e quantitativa de cefoxitina sódica em injetáveis: desenvolvimento e validação de métodos analíticos e estudo de estabilidade

Pós-graduação em Ciências Farmacêuticas - FCFAR

Análise químico-farmacêutica e estudo de estabilidade de cefuroxima sódica injetável

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise químico-farmacêutica de preparações injetáveis de Aztreonam

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate

Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery.

Development and validation of a rapid turbidimetric assay to determine the potency of cefuroxime sodium in powder for dissolution for injection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Medicamentos inadequados para idosos na estratégia da saúde da família

The ageing process can change the pharmacodynamics and pharmacokinetics parameters. Therefore, some medications are considered potentially inappropriate (PIM) for the elderly people, since they can increase the likelihood of occurrence of adverse drug events. The objectives are to estimate the frequency of use of PIM in the elderly people, with potentially hazardous drug interactions (PHDI) and to evaluate the impact of pharmaceutical intervention (PI) for the prescription of safer therapeutic alternatives. A cross-sectional study was performed in a Health Family Strategy (region of Araraquara, SP), between January and February/2012. The medical records of patients aged ≥60 years, that use at least one drug, were consulted for identification of PIM, according to the Beers criteria. The MPI identified were classified considering the Anatomical Therapeutic Chemical Classification System (ATC) and the essentiality of the drug (safety, effectiveness, quality and cost parameters) The inclusion criteria were met by 358 elderly, being that 93 of them (26%) had taken at least one PIM. Of the 114 different drugs prescribed for elderly, ten were classified as PIM, of which four of them act on the central nervous system, four on cardiovascular system and two on the digestive tract. Seven MPI are essential medicines, belonging to national list of essential drugs (RENAME-2010). Fourteen drug interactions were identified, of which two are PHDI (fluoxetine/amitriptyline and digoxin/hydrochlorothiazide).After the PI, there was no change in medical prescriptions of patients with PIM use or with DI. Medical prescriptions of elderly attended in the Health Family Strategy show pharmacotherapeutic safety problems, of which may be responsible for health hazardous for this age group. Although the intervention carried out by letter had been ineffective for the adherence of doctors in prescribing safe alternatives, wide dissemination of the lists that contain PIM and PHDI is need, as well as the inclusion of safer equivalents in RENAME, in order to contribute for rational use of drugs.

Enantioselective analysis of unbound tramadol, O-desmethyltramadol and N-desmethyltramadol in plasma by ultrafiltration and LC-MS/MS: Application to clinical pharmacokinetics

This study describes the enantioselective analysis of unbound and total concentrations of tramadol and its main metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2) in human plasma. Sample preparation was preceded by an ultrafiltration step to separate the unbound drug. Both the ultrafiltrate and plasma samples were submitted to liquid/liquid extraction with methyl t-butyl ether. Separation was performed on a Chiralpak (R) AD column and tandem mass spectrometry consisting of an electrospray ionization source, positive ion mode and multiple reaction monitoring was used as the detection system. Linearity was observed in the following ranges: 0.2-600 and 0.5-250 ng/mL for analysis of total and unbound concentrations of the tramadol enantiomers, respectively, and 0.1-300 and 0.25-125 ng/mL for total and unbound concentrations of the M1 and M2 enantiomers, respectively. The lower limits of quantitation were 0.2 and 0.5 ng/mL for analysis of total and unbound concentration of each tramadol enantiomer, respectively, and 0.1 and 0.25 ng/mL for total and unbound concentrations of M1 and M2 enantiomers, respectively. Intra- and interassay reproducibility and inaccuracy did not exceed 15%. Clinical application of the method to patients with neuropathic pain showed plasma accumulation of (+)-tramadol and (+)-M2 after a single oral dose of racemic tramadol. Fractions unbound of tramadol, M1 or M2 were not enantioselective in the patients investigated. (C) 2011 Elsevier B.V. All rights reserved.

Funktionelle Bedeutung von P-Glykoprotein für Wirkungen und Nebenwirkungen von Antipsychotika

Therapeutisches Drug Monitoring (TDM) ist eine Maßnahme, bei der durch Messung der Medikamentenspiegel im Blut die Dosis ermittelt wird, bei der mit höchster Wahrscheinlichkeit mit Therapieansprechen gerechnet werden kann. Dabei wird angenommen, dass die Konzentrationen im Blut mit denen im Wirkkompartiment korrelieren. Für Antipsychotika wurde gezeigt, dass die Konzentrationen im Blut direkt mit denen im Gehirn korrelieren, die Verteilung zwischen den beiden Kompartimenten ist jedoch für die verschiedenen Antipsychotika sehr unterschiedlich. Die Distribution von Arzneistoffen zwischen Blut und Gehirn wird durch Effluxtransporter in der Blut-Hirn-Schranke kontrolliert. Welche Rolle dabei P-Glykoprotein (P-gp) für die Verteilung von atypischen Antipsychotika spielt und wie die Pharmakokinetik und –dynamik durch diesen Transporter beeinflusst werden, sollte in dieser Arbeit untersucht werden. Für die Messung des neu eingeführten Antipsychotikums Aripiprazol, sowie für seinen aktiven Metaboliten Dehydroaripiprazol, wurde eine hochleistungsflüssigchromatographische (HPLC) Methode mit Säulenschaltung und spektrophotometrischer Detektion etabliert. Die Methode wurde für die Messung von Serumproben schizophrener Patienten eingesetzt, um einen therapeutischen Bereich für Aripiprazol zu ermitteln. Aus der Analyse von 523 Patientenproben wurde herausgefunden, dass Aripiprazol-Serumkonzentrationen von 150 bis 300 ng/ml mit gutem klinischen Ansprechen und einem geringen Risiko für Nebenwirkungen einhergingen. Weiterhin wurde festgestellt, dass die Serumspiegel bei gleichzeitiger Gabe von Inhibitoren und Induktoren der Cytochrom P450 (CYP) Isoenzyme CYP2D6 und CYP3A4 erhöht bzw. gesenkt wurden. Am Modell der P-gp Knockout Maus im Vergleich zu FVB Wildtyp Mäusen wurden Konzentrationsverläufe von Antipsychotika nach i.p. Gabe von Amisulprid, Aripiprazol, Dehydroaripiprazol, Clozapin, Desmethylclozapin, Haloperidol, Olanzapin, Quetiapin, Risperidon und 9-Hydroxyrisperidon sowie der Kontrollsubstanz Domperidon im Gehirn und Blut über 24 Stunden mittels HPLC-Methoden gemessen. Welchen Einfluss eine verminderte Expression von P-gp auf die Pharmakodynamik hat, wurde in zwei Verhaltenstests untersucht. Mit Hilfe des Rotarods wurden motorische Effekte der Arzneistoffe erfasst und mittels Radial Arm Water Maze kognitive Fähigkeiten. Risperidon und sein aktiver Metabolit 9-Hydroxyrisperidon waren die stärksten Substrate von P-gp. 10-fach höhere Konzentrationen im Gehirn der P-gp Knockout Mäuse führten zu 10-fach stärkeren Beeinträchtigungen in den pharmakodynamischen Untersuchungen im Vergleich zu Wildtyp Tieren. Amisulprid, Aripiprazol, Dehydroaripiprazol, Desmethylclozapin und Quetiapin konnten ebenfalls als Substrate von P-gp identifiziert werden. Olanzapin, Haloperidol und Clozapin wurden durch P-gp wenig bzw. nicht in ihrer Pharmakokinetik und –dynamik beeinflusst. Da P-gp von Nagern und Menschen nach derzeitiger Kenntnis in ihren Substrateigenschaften weitgehend übereinstimmen, muss bei einer Behandlung von schizophrenen Patienten mit Antipsychotika, die als Substrate von P-gp identifiziert wurden, davon ausgegangen werden, dass eine Veränderung der Expression oder Aktivität von P-gp, genetisch verursacht oder durch Medikamente bedingt, für das Therapieansprechen oder das Auftreten von Nebenwirkungen bedeutsam sind.