Trends in nurse-administered procedural sedation and analgesia across cardiac catheterisation laboratories in Australia and New Zealand : results of an electronic survey

Background Knowledge of current trends in nurse-administered procedural sedation and analgesia (PSA) in the cardiac catheterisation laboratory (CCL) may provide important insights into how to improve safety and effectiveness of this practice. Objective To characterise current practice as well as education and competency standards regarding nurse-administered PSA in Australian and New Zealand CCLs. Design A quantitative, cross-sectional, descriptive survey design was used. Methods Data were collected using a web-based questionnaire on practice, educational standards and protocols related to nurse-administered PSA. Descriptive statistics were used to analyse data. Results A sample of 62 nurses, each from a different CCL, completed a questionnaire that focused on PSA practice. Over half of the estimated total number of CCLs in Australia and New Zealand was represented. Nurse-administered PSA was used in 94% (n = 58) of respondents CCLs. All respondents indicated that benzodiazepines, opioids or a combination of both is used for PSA (n = 58). One respondent indicated that propofol was also used. 20% (n = 12) indicated that deep sedation is purposefully induced for defibrillation threshold testing and cardioversion without a second medical practitioner present. Sedation monitoring practices vary considerably between institutions. 31% (n = 18) indicated that comprehensive education about PSA is provided. 45% (n = 26) indicated that nurses who administer PSA should undergo competency assessment. Conclusion By characterising nurse-administered PSA in Australian and New Zealand CCLs, a baseline for future studies has been established. Areas of particular importance to improve include protocols for patient monitoring and comprehensive PSA education for CCL nurses in Australia and New Zealand.

Impact of cognitive behaviour therapy via mail for cessation of benzodiazepine use : a series of case reports

Benzodiazepines are widely prescribed to manage sleep disorders, anxiety and muscular tension. While providing short-term relief, continued use induces tolerance and withdrawal, and in older users, increases the risk of falls. However, long-term prescription remains common, and effective interventions are not widely available. This study developed a self-managed cognitive behaviour therapy package for cessation of benzodiazepine use delivered to participants via mail (M-CBT) and trialled its effectiveness as an adjunct to a general practitioner (GP)-managed dose reduction schedule. In the pilot trial, participants were randomly assigned to GP management with immediate or delayed M-CBT. Significant recruitment and engagement problems were experienced, and only three participants were allocated to each condition. After immediate M-CBT, two participants ceased use, while none receiving delayed treatment reduced daily intake by more than 50%. Across the sample, doses at 12 months remained significantly lower than baseline, and qualitative feedback from participants was positive. While M-CBT may have promise, improved engagement of GPs and participants is needed for this approach to substantially impact on community-wide benzodiazepine use.

Spectrophotometric analysis of phenols, which involves a hemin-graphene hybrid nanoparticles with peroxidase-like activity

Phenols are well known noxious compounds, which are often found in various water sources. A novel analytical method has been researched and developed based on the properties of hemin–graphene hybrid nanosheets (H–GNs). These nanosheets were synthesized using a wet-chemical method, and they have peroxidase-like activity. Also, in the presence of H2O2, the nanosheets are efficient catalysts for the oxidation of the substrate, 4-aminoantipine (4-AP), and the phenols. The products of such an oxidation reaction are the colored quinone-imines (benzodiazepines). Importantly, these products enabled the differentiation of the three common phenols – pyrocatechol, resorcin and hydroquinone, with the use of a novel, spectroscopic method, which was developed for the simultaneous determination of the above three analytes. This spectroscopic method produced linear calibrations for the pyrocatechol (0.4–4.0 mg L−1), resorcin (0.2–2.0 mg L−1) and hydroquinone (0.8–8.0 mg L−1) analytes. In addition, kinetic and spectral data, obtained from the formation of the colored benzodiazepines, were used to establish multi-variate calibrations for the prediction of the three phenol analytes found in various kinds of water; partial least squares (PLS), principal component regression (PCR) and artificial neural network (ANN) models were used and the PLS model performed best.

Thin-Layer Chromatography with Ultraviolet and Mass Spectrometric Detection: From Preparative-Layer to Miniaturized Ultra-Thin-Layer Technique

The present challenge in drug discovery is to synthesize new compounds efficiently in minimal time. The trend is towards carefully designed and well-characterized compound libraries because fast and effective synthesis methods easily produce thousands of new compounds. The need for rapid and reliable analysis methods is increased at the same time. Quality assessment, including the identification and purity tests, is highly important since false (negative or positive) results, for instance in tests of biological activity or determination of early-ADME parameters in vitro (the pharmacokinetic study of drug absorption, distribution, metabolism, and excretion), must be avoided. This thesis summarizes the principles of classical planar chromatographic separation combined with ultraviolet (UV) and mass spectrometric (MS) detection, and introduces powerful, rapid, easy, low-cost, and alternative tools and techniques for qualitative and quantitative analysis of small drug or drug-like molecules. High performance thin-layer chromatography (HPTLC) was introduced and evaluated for fast semi-quantitative assessment of the purity of synthesis target compounds. HPTLC methods were compared with the liquid chromatography (LC) methods. Electrospray ionization mass spectrometry (ESI MS) and atmospheric pressure matrix-assisted laser desorption/ionization MS (AP MALDI MS) were used to identify and confirm the product zones on the plate. AP MALDI MS was rapid, and easy to carry out directly on the plate without scraping. The PLC method was used to isolate target compounds from crude synthesized products and purify them for bioactivity and preliminary ADME tests. Ultra-thin-layer chromatography (UTLC) with AP MALDI MS and desorption electrospray ionization mass spectrometry (DESI MS) was introduced and studied for the first time. Because of the thinner adsorbent layer, the monolithic UTLC plate provided 10 100 times better sensitivity in MALDI analysis than did HPTLC plates. The limits of detection (LODs) down to low picomole range were demonstrated for UTLC AP MALDI and UTLC DESI MS. In a comparison of AP and vacuum MALDI MS detection for UTLC plates, desorption from the irregular surface of the plates with the combination of an external AP MALDI ion source and an ion trap instrument provided clearly less variation in mass accuracy than the vacuum MALDI time-of-flight (TOF) instrument. The performance of the two-dimensional (2D) UTLC separation with AP MALDI MS method was studied for the first time. The influence of the urine matrix on the separation and the repeatability was evaluated with benzodiazepines as model substances in human urine. The applicability of 2D UTLC AP MALDI MS was demonstrated in the detection of metabolites in an authentic urine sample.

Polypharmacy among inpatients aged 70 years or older in Australia

Objectives To investigate medication changes for older patients admitted to hospital and to explore associations between patient characteristics and polypharmacy. Design Prospective cohort study. Participants and setting Patients aged 70 years or older admitted to general medical units of 11 acute care hospitals in two Australian states between July 2005 and May 2010. All patients were assessed using the interRAI assessment system for acute care. Main outcome measures Measures of physical, cognitive and psychosocial functioning; and number of regular prescribed medications categorised into three groups: non-polypharmacy (0–4 drugs), polypharmacy (5–9 drugs) and hyperpolypharmacy (≥ 10 drugs). Results Of 1220 patients who were recruited for the study, medication records at admission were available for 1216. Mean age was 81.3 years (SD, 6.8 years), and 659 patients (54.2%) were women. For the 1187 patients with complete medication records on admission and discharge, there was a small but statistically significant increase in mean number of regular medications per day between admission and discharge (7.1 v 7.6), while the prevalence of medications such as statins (459 [38.7%] v 457 [38.5%] patients), opioid analgesics (155 [13.1%] v 166 [14.0%] patients), antipsychotics (59 [5.0%] v 65 [5.5%] patients) and benzodiazepines (122 [10.3%] v 135 [11.4%] patients) did not change significantly. Being in a higher polypharmacy category was significantly associated with increase in comorbidities (odds ratio [OR], 1.27; 95% CI, 1.20–1.34), presence of pain (OR, 1.31; 1.05–1.64), dyspnoea (OR, 1.64; 1.30–2.07) and dependence in terms of instrumental activities of daily living (OR, 1.70; 1.20–2.41). Hyperpolypharmacy was observed in 290/1216 patients (23.8%) at admission and 336/1187 patients (28.3%) on discharge, and the proportion of preventive medication in the hyperpolypharmacy category at both points in time remained high (1209/3371 [35.9%] at admission v 1508/4117 [36.6%] at discharge). Conclusions Polypharmacy is common among older people admitted to general medical units of Australian hospitals, with no clinically meaningful change to the number or classification (symptom control, prevention or both) of drugs made by treating physicians.

Bentsodiatsepiinien ja amfetamiinijohdannaisten seulonta virtsasta mikropilarisähkösumutusmassaspektrometrian avulla

Väärinkäytettyjen aineiden seulontaan käytetyn menetelmän tulee olla herkkä, selektiivinen, yksinkertainen, nopea ja toistettava. Työn tavoitteena oli kehittää yksinkertainen, mutta herkkä, esikäsittelymenetelmä bentsodiatsepiinien ja amfetamiinijohdannaisten kvalitatiiviseen seulomiseen virtsasta mikropilarisähkösumutussirun (μPESI) avulla, mikä tarjoaisi vaihtoehdon seulonnassa käytetyille immunologisille menetelmille, joiden herkkyys ja selektiivisyys ovat puutteellisia. Tavoitteena oli samalla tarkastella mikropilarisähkösumutussirun toimivuutta biologisten näytteiden analyysissa. Esikäsittely optimoitiin erikseen bentsodiatsepiineille ja amfetamiinijohdannaisille. Käytettyjä esikäsittelymenetelmiä olivat neste-nesteuutto, kiinteäfaasiuutto Oasis HLB-patruunalla ja ZipTip®-pipetinkärjellä sekä laimennus ja suodatus ilman uuttoa. Mittausten perusteella keskityttiin optimoimaan ZipTip®-uuttoa. Optimoinnissa tutkittavia yhdisteitä spiikattiin 0-virtsaan niiden ennaltamääritetyn raja-arvon verran, bentsodiatsepiineja 200 ng/ml ja amfetamiinijohdannaisia 300 ng/ml. Bentsodiatsepiinien kohdalla optimoitiin kutakin uuton vaihetta ja optimoinnin tuloksena näytteen pH säädettiin arvoon 5, faasi kunnostettiin asetonitriililla, tasapainotettiin ja pestiin veden (pH 5) ja asetonitriilin (10 % v/v) seoksella ja eluoitiin asetonitriilin, muurahaishapon ja veden (95:1:4 v/v/v) seoksella. Amfetamiinijohdannaisten uutossa optimoitiin näytteen ja liuottimien pH-arvoja ja tuloksena näytteen pH säädettiin arvoon 10, faasi kunnostettiin veden ja ammoniumvetykarbonaatin(pH 10, 1:1 v/v) seoksella, tasapainotettiin ja pestiin asetonitriilin ja veden (1:5 v/v) seoksella ja eluoitiin metanolilla. Optimoituja uuttoja testattiin Yhtyneet Medix Laboratorioista toimitetuilla autenttisilla virtsanäytteillä ja saatuja tuloksia verrattiin kvantitatiivisen GC/MS-analyysin tuloksiin. Bentsodiatsepiininäytteet hydrolysoitiin ennen uuttoa herkkyyden parantamiseksi. Autenttiset näytteet analysoitiin Q-TOF-laitteella Viikissä. Lisäksi hydrolysoidut bentsodiatsepiininäytteet mitattiin Yhtyneet Medix Laboratorioiden TOF-laitteella. Kehitetty menetelmä vaatii tulosten perusteella lisää optimointia toimiakseen. Ongelmana oli etenkin toistoissa ilmennyt tulosten hajonta. Manuaalista näytteensyöttöä tulisi kehittää toistettavammaksi. Autenttisten bentsodiatsepiininäytteiden analyysissa ongelmana olivat virheelliset negatiiviset tulokset ja amfetamiinijohdannaisten analyysissa virheelliset positiiviset tulokset. Virheellisiä negatiivisia tuloksia selittää menetelmän herkkyyden puute ja virheellisiä positiivisia tuloksia mittalaitteen, sirujen tai liuottimien likaantuminen.

Treatment of illicit opioid and γ-hydroxybutyrate overdose by Helsinki emergency medical services

Aims: To examine the characteristics, incidence, treatment and outcome of presumed opioid, γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL) overdoses involving users of illicit drugs in Helsinki. GHB/GBL were included in this study, despite not being opioids, due to the relative ease with which they can cause potentially fatal respiratory depression. The incidence and time interval of recurrent opioid toxicity after prehospital administration of naloxone, an opioid antagonist, was studied in presumed heroin overdose patients. Naloxone has been reported to have many adverse effects and the effects of naloxone administered during an opioid overdose on the cardiovascular system and catecholamine levels in piglets were studied. Materials and methods: Patients included in these published retrospective studies were from the following time periods: Study I: 1995-2002, II: 1997-2000, III: 1995-2000, V: 2006-2007. Presumed opioid overdose patients were examined in studies I, II and III. GHB/GBL overdoses among injecting drug users was examined in study V. Recurrent opioid toxicity after prehospital naloxone administration in heroin overdose patients was examined in study III. The effects of naloxone (80 μg/kg i.v.) on the cardiovascular system and catecholamine levels administered during morphine overdose (8mg/kg i.v.) and under propofol anesthesia with spontaneous breathing were studied in eight piglets (IV). In this thesis, previously unpublished data on the incidence of opioid overdose between 2001-2007 and comparison of the characteristics of buprenorphine and heroin overdose patients encountered in 1995-2005 are also included. Results: Helsinki Emergency Medical Service (EMS) ambulances were dispatched annually to 34,153- 45,118 calls from 1995 to 2007. Of them, 7-8% were coded as intoxications or overdoses. During this time, 436 patients were treated by the EMS for presumed opioid overdose. The peak incidence of opioid overdoses was in the year 2000 (113 cases), after which they declined to 6-26 cases annually. The annual incidence of buprenorphine related overdoses increased from 4 (4% of opioid overdoses) in the year 2000 to 8 (30% of opioid overdoses) in 2007. The annual number of GHB related overdose patients treated by Helsinki EMS increased from 21 to 73 between 2004-2007. There appeared to be a peak in the incidence of both GHB/GBL and opioid related overdoses on Saturdays. Characteristics of opioid overdose patients The median age of opioid overdose patients was 28 years (22;33, 25- and 75-percentiles), and 84% were male. Buprenorphine overdose patients had more polydrug, such as alcohol and/or benzodiazepines, use in comparison with heroin overdose patients, 70% versus 33%, respectively. Severe respiratory depression was reported less often with buprenorphine overdoses compared to heroin overdoses, in 67.0% versus 85.4%, respectively. Outcome of heroin overdose patients with cardiac arrest Ninety four patients suffered cardiac arrest due to acute drug poisoning/overdose and were thus considered for resuscitation. Resuscitation was attempted in 72 cases. Cardiac arrest was caused by heroin overdose for 19 patients of which three (16%) were discharged alive. Other agents also induced cardiac arrest in 53 patients, of which six (11%) were discharged alive. The arrest was either EMS witnessed or occurring after the emergency call for all survivors of heroin induced cardiac arrest. Characteristics of GHB/GBL overdose patients The records of 100 GHB/GBL related overdose patients from 2006-2007 were retrieved. The median age of GHB/GBL overdose patients encountered on weekend nights was 24 years (22;27, 25- and 75-percentiles) and 49% were male. Polydrug use was reported in 62-80% of the cases. Thirty nine patients were encountered on Friday-Saturday or Saturday-Sunday night between 11 pm-6 am. The remaining sixty one patients were outside this time frame. There was a statistically significant difference between these two groups in history of chronic injecting drug use (33% vs. 59%, respectively, p=0.012). Recurrent heroin toxicity after prehospital naloxone administration Study III included 145 presumed heroin overdose patients. After prehospital care, 84 patients refused further care and were not transported to an Emergency Department (ED). Seventy one (85%) of them were administered naloxone by the EMS. During a 12-h follow up period, none of these patients developed severe recurrent opioid toxicity. The remaining 61 patients were transported to an ED. Prior to transportation, 52 (85%) patients were administered naloxone by the EMS. Fifteen of them were administered naloxone also in the ED and recurrent opioid toxicity was evident either on arrival at the ED or shortly thereafter. Prehospital naloxone was administered either intravenously, intramuscularly (i.m.) or subcutaneously (s.c.). There was a tendency for more frequent recurrent heroin toxicity among the patients with only intravenous administration of prehospital naloxone (13/36) compared with the patients with intramuscular or subcutaneous prehospital naloxone (2/16), p=0.106. The effects of naloxone on the cardiovascular system and catecholamine levels in piglets The administration of morphine to piglets resulted in an obvious respiratory depression, which was reversed by naloxone. Two severely hypoxemic piglets developed cardiac arrest after naloxone administration. In the other six animals, the administration of naloxone did not provoke arrhythmias, cardiac ischemia or visible evidence of pulmonary edema. There was a statistically significant (p=0.012) increase in norepinephrine levels after morphine administration and before naloxone administration: from 1.9 (1.3-2.3) ng/ml at baseline, to 31.7 (8.3-83.0) ng/ml (median, 25 and 75 percentiles parentheses) after morphine administration. After the administration of naloxone, the catecholamine levels continued to increase in only one of the animals. Conclusions: The incidence of buprenorphine related overdoses increased during the study period, but was still lower in comparison to those involving heroin. Injecting drug users have also started to use GHB/GBL. While recreational drug users use GHB/GBL during weekend nights, a GHB/GBL overdose patient encounter during weekdays has a more probable history of injecting drug use. Patients with cardiac arrest after heroin overdose have a poor prognosis. It appears to be safe to leave heroin overdose patients on scene after prehospital treatment with naloxone. Although no statistically significant difference was observed, it seems prudent to administer part of the total naloxone dose s.c. or i.m. to reduce the risk of recurrent respiratory depression. If transported to an ED, an observation period of one to two hours after the last naloxone dose seems adequate. The treating physician must be vigilant, however, due to the high prevalence of polydrug use and high morbidity after non fatal heroin overdose. Furthermore, care should be taken regarding possible chronic disorders and drug rehabilitation should be addressed. In the experimental animal study, two animals developed cardiac arrest after receiving naloxone while in hypoxemia and bradycardia. Further studies are required to assess the effect of naloxone during opioid-induced hypercapnia and hypoxemia in animals addicted to opioids.

Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

Antsietate asaldura orokorraren tratamenduaren hausnarketa eta erizaintzaren esku hartzea : berrikuspen bibliografikoa

Antsietate asaldurak gaixotasun mentalen artean ugarienak dira; hau horrela izanik, Antsietate Asaldura Orokorraren tratamenduak aztertu beharrekoak dira gaur egun. Lehenik eta behin, ikerketa askoren arabera dependentzia, tolerantzia eta bigarren mailako efektu asko ematen baitira epe luzeko antsietatearen aurkako farmakoetan. Bentzodiazepinak eragiten dituzten arazoak direla eta, garrantzitsua da tratamendu psikologikoaren eraginkortasuna aztertzea. Helburua: Tratamendu farmakologiko eta ez-farmakologikoaren eraginkortasunaren hausnarketa egitea eta patologiaren kudeaketan Erizaintzaren funtzioa baloratzea dira. Metodologia: Scopus, Pubmed, Cochrane library, Trip database, Science Direct, Ministerio de Sanidad Servicios Sociales e Igualdad eta Cuiden bezalako datu baseetan azkeneko 10 urteetako bilaketa bibliografikoaz gain, eskuzko bilaketa ere gauzatu da gaztelaniaz zein ingelesez . Emaitzak: Nahiz eta gidek bentzodiazepinen epe laburrerako erabilpena gomendatu, epe luzerako tratamendu moduan erabiltzen dira bigarren mailako efektu ugari eta dependentzia garatuz. Psikoterapiaren eraginkortasuna, farmakoena baino geldoagoa izaten da baina epe luzera iraupen luzeagoa du. Ondorioak: Bentzodiazepinen eraginkortasuna epe laburrean ezin da ukatu, Terapia Kognitibo-Konduktuala hasteko momentuan erabilgarria izanik bere eraginkortasun sintomatologikoagatik. Erizainaren funtzioa baliagarria da asaldura mental honen balorazioan, beharrezko tratamenduak jasotzea ahalbidetuz eta bideraketa on bat eginez.

Uso de antidepressivos e benzodiazepínicos em mulheres atendidas em unidades de saúde da família e sua dimensão psicossocial

Introdução: A preocupação em torno do uso irracional de psicofármacos tem sido observada em diversos países, constituindo-se uma questão importante para a saúde pública mundial. No Brasil, a promoção do uso racional de psicofármacos é um desafio para a atenção primária, sendo importante caracterizar sua dimensão psicossocial. Objetivos. O artigo 1, com características descritivas, tem como objetivo caracterizar o uso de psicofármacos em unidades de saúde da família segundo a presença de transtornos mentais comuns (TMC) e segundo as principais características socioeconômicas e demográficas. O artigo 2, com um caráter analítico, tem como objetivo avaliar o papel da rede social no uso de cada um destes psicofármacos segundo a presença de TMC. Métodos O estudo utiliza um delineamento seccional e abarca a primeira fase de coleta de dados de dois estudos em saúde mental na atenção primária. Esta se deu em 2006/2007 para o estudo 1 (Petrópolis, n= 2.104) e em 2009/2010 para o estudo2 (São Paulo, n =410, Rio de Janeiro, n= 703, Fortaleza , n=149 e Porto Alegre, n= 163 participantes). Ambos os estudos possuem o mesmo formato no que se refere à coleta de dados, seu processamento e revisão, resultando em uma amostra de 3.293 mulheres atendidas em unidades de saúde da família de cinco diferentes cidades do país. Um questionário objetivo com perguntas fechadas foi utilizado para a coleta de informações socioeconômicas e demográficas. O uso de psicofármacos foi avaliado através de uma pergunta aberta baseada no auto-relato do uso de medicamentos. A presença de TMC foi investigada através do General Health Questionnaire, em sua versão reduzida (GHQ-12). O nível de integração social foi aferido através do índice de rede social (IRS), calculado a partir de perguntas sobre rede social acrescentado ao questionário geral. No estudo descritivo (artigo 1), a frequência do uso de antidepressivos e o uso de benzodiazepínicos na população de estudo foram calculadas para cada cidade, tal como a frequência do uso destes psicofármacos entre as pacientes com transtornos mentais comuns. A distribuição do uso de cada um destes psicofármacos segundo as principais características socioeconômicas, demográficas e segundo transtornos mentais comuns foi avaliada através do teste de qui-quadrado de Pearson. No estudo analítico (artigo 2), a associação entre o nível de integração social e o uso exclusivo de cada um dos psicofármacos foi analisada através da regressão logística multivariada, com estratificação segundo a presença de TMC. Resultados: A frequência do uso de psicofármacos foi bastante heterogênea entre as cidades, destacando-se, porém, a importância do uso de benzodiazepínicos frente ao uso de antidepressivos em sua maioria. A proporção do uso de psicofármacos, sobretudo antidepressivos, foi predominantemente baixa entre as pacientes com TMC. Entre elas, o uso de antidepressivos mostrou-se positivamente associado ao isolamento social, enquanto o uso de benzodiazepínicos associou-se negativamente a este. Conclusão: Os resultados colaboram para a caracterização do uso de psicofármacos em unidades de saúde da família e para a discussão acerca de sua racionalidade. Destaca-se a importância de avaliar a dimensão psicossocial que envolve o uso destas substâncias com vistas ao desenvolvimento de estratégias de cuidado mais efetivas

氮杂环化合物的绿色合成研究

氮杂环化合物大多数都是具有生理活性的物质，例如喹喔啉化合物与苯二氮卓类化合物，因此研究氮杂环化合物骨架的构建方法具有一定意义。绿色化学的迅速发展迫切要求化学家发展清洁、经济和环境较友好条件下的有机合成方法。其中，水相反应与绿色固体酸催化剂的使用都是实现绿色有机合成的重要途径，它们非常具有潜力，近些年受到了广泛关注。本论文的主要工作是围绕水相及固体酸催化条件下两类具有生物活性的含氮杂环小分子的合成方法而开展的，具体包括以下内容： 1. 研究和探索出了两类绿色固体酸催化剂蒙脱土（Mont. K-10）和杂多酸(H4SiW12O40), 在水相条件下成功合成出喹喔啉化合物的有效方法。两个催化体系都以无毒无公害的水作反应溶剂，实验条件温和，操作安全简便，反应速度快，底物普适性强，产率高，且产物易分离收集。两类固体酸催化剂，对设备腐蚀性小，可回收循环使用，对环境无公害; 蒙脱土催化大部分底物能得到当量产率的产物，硅钨酸催化催化剂负载量小。 2. 实现了无溶剂条件下，以杂多酸（H3PW12O40）作催化剂，高效合成1,5-苯二氮卓衍生物的合成方法。该催化体系具有以下一些优势：实验条件温和，反应速度较快，底物普适性良好，产物易分离收集，反应过程中没有加入其它有机溶剂，绿色环保。 ‘Green Chemistry’ is currently a major issue of modern chemistry. It is widely acknowledged that there is a growing need for more environmentally acceptable processes in the chemical industry. New green catalysts and green reaction media are the important and efficient strategies in green chemistry. New green catalysts include solid acid catalysts, solid base catalysts, metal catalysts not only possess higher activity and selectivity, but also are easily separated from reaction system. Green reaction media include water, supercritical fluids and ionic liquids can not only substitute traditional toxic and harmed organic solvents, but also improve reaction activity and selectivity. Meanwhile water is a promising green reaction medium for use in modern chemistry because it has a number of advantages such as the cheapest solvent available on earth, being non-hazardous and non-toxic to the environment. Solid acids had also attracted much attention for realizing green chemistry due to their unique acidity, high activity and efficiency as organic catalysts. Nitrogen-containing heterocyclic compounds of different ring sizes such as quinoxaline and benzodiazepine are the important pharmacologically active compounds. Due to the wide biological significance of these compounds, the synthesis of these types of compounds have received a great deal of attention. Despite the large availability of methods to construct nitrogen-containing heterocyclic compounds, there is still a strong need to further explore green methods to efficiently and safely synthesize these compounds. Thus, we aim at developing efficient and green methodology for the synthesis of quinoxaline and benzodiazepine carried out under water condition with solid acid catalysts. The contents of this dissertation are listed as the following: 1. We have developed two catalytic systems for the synthesis quinoxaline via the condensation of an aryl 1,2-diamine with a 1,2-diketone compound in the presence of Mont. K-10 or H4SiW12O40 as a catalyst in water solvent. Both of these two methods can be applied to wide range of substrates, tolerating aryl 1,2-diamine/1,2-diketone with the electron donating/drawing substituent. Operational simplicity, the ambient conditions, use of an economically convenient catalyst, use of water as a desirable solvent, high yields and short reaction times are the key features of these two protocols. 2. We developed a convenient and efficient protocol for the synthesis of a variety of 1,5-benzodiazepines in high yields via condensation of aryl o-phenylenediamine derivatives with a variety of ketones using H3PW12O40 as a green recyclable and heterogeneous catalyst under solvent-free condition. The simple experiment procedure combined with ease of recovery and reuse of this catalyst make this procedure quite simple, more convenient and environmentally benign.

Neonatal exposure to estradiol in female rats influences neuroactive steroid concentrations and behaviour in the adult rat

The gonadal steroids, in particular estradiol, exert an important action during perinatal period in the regulation of sexual dimorphism and neuronal plasticity, and in the growth and development of nervous system. Exposure of the developing female to estrogens during perinatal period may have long-lasting effects that are now regarded as “programming” the female neuroendocrine axis to malfunction in adulthood. The purpose of this study was to describe the effect of a single administration of a low dose (10 μg) of β-estradiol 3-benzoate (EB) to female rats on the day of birth on brain and plasma concentrations of the neuroactive steroid allopregnanolone, general behaviours and behavioral sensitivity to benzodiazepines. Neonatal administration of EB induces a dramatic reduction in the cerebrocortical and plasma levels of allopregnanolone and progesterone that were apparent in both juvenile (21 days) and adult (60 days). In contrast, this treatment did not affect 17β-estradiol levels. Female rats treated with β-estradiol 3-benzoate showed a delay in vaginal opening, aciclicity characterized by prolonged estrus, and ovarian failure. Given that allopregnanolone elicits anxiolytic, antidepressive, anticonvulsant, sedative-hypnotic effects and facilitates social behaviour, we assessed whether this treatment might modify different emotional, cognitive and social behaviours. This treatment did not affect locomotor activity, anxiety- and mood-related behaviours, seizures sensitivity and spatial memory. In contrast, neonatal β-estradiol 3-benzoate-treated rats showed a dominant, but not aggressive, behaviour and an increase in body investigation, especially anogenital investigation, characteristic of male appetitive behaviour. On the contrary, neonatal administration of β-estradiol 3-benzoate to female rats increases sensitivity to the anxiolytic, sedative, and amnesic effects of diazepam in adulthood. These results indicate that the marked and persistent reduction in the cerebrocortical and peripheral concentration of the neuroactive steroid allopregnanolone induced by neonatal treatment with β-estradiol 3-benzoate does not change baseline behaviours in adult rats. On the contrary, the low levels of allopregnanolone seems to be associated to changes in the behavioural sensitivity to the positive allosteric modulator of the GABAA receptor, diazepam. These effects of estradiol suggest that it plays a major role in pharmacological regulation both of GABAergic transmission and of the abundance of endogenous modulators of such transmission during development of the central nervous system.

Sedação Consciente em Medicina Dentária

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

An operant determination of the behavioural mechanism of benzodiazepine enhancement of food intake

Rationale A recent review paper by Cooper (Appetite 44:133–150, 2005) has pointed out that a role for benzodiazepines as appetite stimulants has been largely overlooked. Cooper’s review cited several studies that suggested the putative mechanism of enhancement of food intake after benzodiazepine administration might involve increasing the perceived pleasantness of food (palatability). Objectives The present study examined the behavioral mechanism of increased food intake after benzodiazepine administration. Materials and methods The cyclic-ratio operant schedule has been proposed as a useful behavioral assay for differentiating palatability from regulatory effects on food intake (Ettinger and Staddon, Physiol Behav 29:455–458, 1982 and Behav Neurosci 97:639–653, 1983). The current study employed the cyclic-ratio schedule to determine whether the effects on food intake of chlordiazepoxide (CDP) (5.0 mg/kg), sodium pentobarbital (5.0 mg/kg), and picrotoxin (1.0 mg/kg) were mediated through palatability or regulatory processes. Results The results of this study show that both the benzodiazepine CDP and the barbiturate sodium pentobarbital increased food intake in a manner similar to increasing the palatability of the ingestant, and picrotoxin decreased food intake in a manner similar to decreasing the palatability of the ingestant. Conclusions These results suggest that the food intake enhancement properties of benzodiazepines are mediated through a mechanism affecting perceived palatability.

Effect on prescribing of the limited list in a computerised group practice

The prescribing of drugs in the therapeutic classes that are affected by the government's limited list was investigated in a computerised group practice of just over 3,000 patients. Prescribable drugs in categories that are affected by the list were identified for two consecutive six month periods before and one six month period after the introduction of the list. A significant decrease in the prescribing of cough and cold remedies, vitamins, and antacids occurred after the list was introduced, whereas no change occurred in the prescribing of laxatives, benzodiazepines, or analgesics. The prescribing of iron and penicillin increased significantly after the list was introduced, whereas the use of H2 antagonists and non-steroidal anti-inflammatory drugs showed no significant change.