Safety Assessment of Potentially Inappropriate Medications (PIM) use in Older People and the Factors Associated with Hospital Admission

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da alteração dos níveis de ansiedade no desempenho de ratos em uma tarefa de discriminação apetitiva

The plus-maze discriminative avoidance paradigm has been used to study the relationship between aversive memory and anxiety. The present study aims to verify if the elevated plus-maze can provide information about appetitive memory and anxiety, through a task motivated by food reward. Animals were allowed to explore an elevated plus-maze and received reinforcement in one of the enclosed arms. In a test session performed 24h later, in the absence of reward, rats showed preference for the previously rewarded enclosed arm over the neutral enclosed arm. The administration of diazepam and pentylenetetrazole before training induced, respectively, anxiolytic and anxiogenic effects (as evaluated by open-arm exploration). Both drugs induced amnestic effects, i.e., lack of preference for the rewarded arm in the test session. The results suggest that appetitive memory can be influenced by anxiety levels as well. The plus-maze appetitive discrimination task seems to be a useful model to investigate the relationship between memory and anxiety

O Tratamento com a fluoxetina (mas não com outros farmacos antidepressivo e ansioíiticos) reverte o déficit de memória aversiva causado por estresse agudo de contenção em camundongos

The physiologist H. Selye defined stress as the nonspecific response of the body to any factors that endanger homeostasis (balance of internal environment) of the individual. These factors, agents stressors, are able to activate the Hypothalamic-Pituitary-Adrenal (HPA) axis, thus resulting in the physiological responses to stress by the release of glucocorticoids that leads to psychophysiological changes, including effects on cognitive functions such as learning and memory. When this axis is acutely stimulated occurs a repertoire of behavioral and physiological changes can be adaptive to the individual. Notwithstanding, when the HPA axis is chronically stimulated, changes may favor the development of, such as anxiety disorders. Some drugs used in the clinic for the treatment of anxiety disorders these can exert effects on cognitive function, on the HPA axis and on the anxiety. In this context, the aim of our study was to investigate the effects of administration i.p. acute of diazepam (DZP, 2 mg/kg), buspirone (BUS, 3 mg/kg), mirtazapine (MIR, 10 mg/kg) and fluoxetine (FLU, 10 mg/kg) in male mice submitted to acute restraint stress, and evaluated using plus-maze discriminative avoidance task (PMDAT), which simultaneously evaluates parameters such as learning, memory and anxiety. Our results demonstrated that (1) the administration of DZP and BUS, but not FLU, promoted anxiolytic effects in animals; (2) administration mirtazapine caused sedative effect to animals; (3) in the training session, the animals treated with BUS, MIR and FLU learned the task, on the other hand DZP group showed impairment in learning; (4) in the test session, animals treated with DZP, BUS, and MIR showed deficits in relation to discrimination between the enclosed arms, aversive versus non-aversive arm, demonstrating an impairment in memory, however, animals treated with FLU showed no interference in the retrieval of this memory; (5) acute stress did not interfere in locomotor activity, anxiety, or learning on the learning task, but induced impairment in retrieval memory, and the group treated with FLU did not demonstrated this deficit of memory . These results suggest that acute administration of drugs with anxiolytic and antidepressant activity does not interfere with the learning process this aversive task, but impair its retrieval, as well as the acute restraint stress. However, the antidepressant fluoxetine was able to reverse memory deficits promoted by acute stress, which may suggest that modulation, even acutely serotonergic neurotransmission, by selectively inhibiting the reuptake of this neurotransmitter, interferes on the process of retrieval of an aversive memory

Evaluation of Hemodynamic, Metabolic, and Electrolytic Changes After Graft Reperfusion in a Porcine Model of Intestinal Transplantation

Background. We sought to establish an anesthetic protocol to evaluate the hemodynamic, metabolic, and electrolytic changes after graft reperfusion in pigs undergoing orthotopic intestinal transplant (ITX).Methods. Fifteen pigs were distributed into two groups: GI (n = 6), without immunosuppression, and GII (n = 9), immunosuppressed before surgery with tacrolimus (0.3 mg/kg). The animals were premedicated at 1 hour before surgery with IM acepromazine (0.1 mg/kg), morphine (0.4 mg/kg), ketamine (10 mg/kg), and atropine (0.044 mg/kg IM). Anesthesia induction used equal proportions of diazepam and ketamine (0.1-0.15 mL/kg/IV) and for maintenance in IV infusion of xylazine (1 mg/mL), ketamine (2 mg/mL), and guaiacol glyceryl ether 5% (50 mg/mL), diluted in 250 mL of 5% glucose solution. In addition, recipient pigs were treated with isofluorane inhalation. Heart rate (HR), systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressure, pulse oximetry, respiratory frequency (f), capnography, body temperature (T), blood gas analysis (pH, PaCO(2), PaO(2), base excess, BE; HCO(3)(-), SatO(2)), serum potassium (K), calcium (Ca), sodium, hematocrit (Hct), and glucose (Glu) were measured at four times; MO: after incision (basal value); M1: 10 minutes before reperfusion; and M2 and M3: 10 and 20 minutes after graft reperfusion.Results. All groups behaved in a similar pattern. There was significant hypotension after graft reperfusion in GI and GII (M2 = 56.2 +/- 6.4 and M3 = 57.2 +/- 8.3 mm Hg and M2 = 65.7 +/- 10.2 and M3 = 67.8 +/- 16.8 mm Hg, respectively), accompanied by elevated HR. The ETCO(2) was elevated at M2 (42 mm Hg) and M3 (40 mm Hg). Metabolic acidosis was observed after reperfusion, with significant increase in K levels.Conclusion. The anesthetic protocol for donors and recipients was safe to perform the procedure, allowing control of hemodynamic and metabolic changes after reperfusion without differences regarding immunosuppression.

The GABAergic system contributes to the anxiolytic-like effect of essential oil from Cymbopogon citratus (lemongrass)

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

Herniorrafia inguinal em crianças: valor da anestesia local associada

OBJETIVO: Descrever uma técnica de anestesia local no tratamento de hérnias inguinais em crianças. MÉTODO: Foram operadas 48 crianças com hérnias inguinais sob anestesia local na Santa Casa de Misericórdia de Cerqueira César, SP, sendo 34 do sexo masculino e 14 do sexo feminino, com idades entre 3 meses e 12 anos. Apenas quatro crianças tinham hérnia bilateral. A anestesia local foi realizada com lidocaína a 1% na dose de 5 mg/kg de peso através do bloqueio dos nervos abdominogenitais próximos à espinha ilíaca ântero-superior, à altura do anel inguinal externo e na pele ao redor da incisão. A sedação foi feita com cetamina na dose de 1 a 2 mg/kg e diazepam 0,2 a 0,4 mg/kg de peso. RESULTADOS: Todas as cirurgias puderam ser realizadas com tranqüilidade com este método, com exceção de uma criança em que o bloqueio não foi efetivo e a anestesia complementada com inalação de halogenado, sob máscara. Como complicações pós-operatórias, ocorreram três hematomas, sendo um de parede e dois em bolsa escrotal, todos com boa evolução. CONCLUSÕES: O uso da anestesia local associada à sedação é procedimento simples e seguro para realizar herniorrafias inguinais em crianças.

Experiência clínica com o uso de sedativos em terapia intensiva: estudo retrospectivo

JUSTIFICATIVA E OBJETIVOS: Dentre as indicações mais freqüentes de sedação em pacientes internados em Unidades de Terapia Intensiva (UTI) estão a instituição e a manutenção de ventilação artificial, a ansiedade e procedimentos desconfortáveis ou dolorosos. O objetivo deste estudo retrospectivo foi verificar as indicações e as técnicas mais comuns de sedação em pacientes graves internados na Unidade de Terapia Intensiva Cirúrgica da Escola Paulista de Medicina (EPM/UNIFESP) durante um período de 11 meses. MÉTODO: Após terem sido excluídos os pacientes que permaneceram na UTI menos de 24 horas ou estavam sem exames indispensáveis para o cálculo do índice de gravidade (APACHE II), a amostra ficou reduzida a 307 pacientes. Foram analisadas as técnicas mais utilizadas, as indicações de sedação e a associação de bloqueadores neuromusculares. RESULTADOS: A sedação foi administrada em 37,4% dos pacientes. Entre as indicações de sedação estão os distúrbios de natureza psiquiátrica, como delírio, agitação, medo e ansiedade. Estas corresponderam a 25,77% de todas as indicações. A maioria dos pacientes ventilados artificialmente também necessita de sedativos. Instalação e manutenção de ventilação mecânica corresponderam à maioria das indicações, em torno de 57,73% dentre os pacientes sedados. Procedimentos como intubação traqueal e broncoscopia tiveram 11,34% das indicações e controle do metabolismo (coma barbitúrico e tétano), 5,15%. As técnicas mais comumente utilizadas incluíram opióides isolados ou associados a benzodiazepínicos. Neste estudo, o fentanil foi utilizado em 58% das técnicas, isoladamente, e em 21,64% associado ao midazolam. Haloperidol, diazepam, propofol e tiopental somaram 19,5%. Bloqueadores neuromusculares foram utilizados em 22,7% dos casos em pacientes ventilados artificialmente. CONCLUSÕES: A sedação é recurso terapêutico freqüente em Terapia Intensiva, comumente utilizada para facilitar a ventilação artificial e tratar os problemas de natureza psiquiátrica. Fentanil, isoladamente ou em associação com midazolam, foi o agente mais utilizado.

Psicologia e odontopediatria: a contribuição da análise funcional do comportamento

Objetivando analisar funcionalmente a atuação do odontopediatra, procedeu-se ao atendimento odontológico de 3 crianças não-colaboradoras, utilizando ansiolítico ou placebo. As sessões foram filmadas e registrou-se os eventos clínicos e comportamentais dos participantes, em intervalos de 15 segundos. Os resultados revelaram que a colaboração das crianças pode ser considerada condição estabelecedora para os comportamentos da profissional. O ansiolítico não demonstrou efeitos sobre o comportamento dos pacientes. Direção, categoria comportamental predominantemente utilizada pela dentista, revelou-se eficaz na evocação de respostas de colaboração para 2 pacientes. Os dados expressam a contribuição da análise funcional do comportamento ao estudo da interação profissional-paciente em odontopediatria.

Handling of female pacas (Agouti paca, Linnaeus, 1766) for ultrasound pregnancy detection

A paca é um roedor sul-americano cujo manejo, tranqüilização ou anestesia oferece um grande campo de pesquisa devido aos poucos artigos existentes. Doze pacas fêmeas adultas foram utilizadas, mantidas separadas em seis baias, sendo capturadas com um puçá de polipropileno e levadas a uma sala na qual se realizava a tricotomia abdominal. Após, os animais eram colocados em uma gaiola de ferro de compressão lateral. A sessão de ultra-sonografia era realizada em modo B com um transdutor setorial eletrônico de 5,0 e 7,5 MHz. Para a diminuição do estresse causado pelos procedimentos, a tranqüilização das fêmeas era realizada com diazepam e maleato de midazolam por via oral. Ambos demonstraram-se efetivos na tranqüilização das pacas previamente e durante as sessões, sendo que o maleato de midazolam proporcionou um melhor manejo dos animais.

Use of the elevated T-maze to study anxiety in mice

We have recently suggested that the elevated T-maze (ETM) is not a useful test to study different types of anxiety in mice if a procedure similar to that originally validated for rats is employed. The present study investigated whether procedural (five exposures in the enclosed arm instead of three as originally described for rats) and structural (transparent walls instead of opaque walls) changes to the ETM leads to consistent inhibitory avoidance acquisition (IAA) and low escape latencies in mice. Results showed that five exposures to the ETM provoked consistent IAA, an effect that was independent of the ETM used. However, the ETM with transparent walls (ETMt) seemed to be more suitable for the study of conditioned anxiety (i.e. IAA) and unconditioned fear (escape) in mice, since IAA (low baseline latency with a gradual increase over subsequent exposures) and escape (low latency) profiles rendered it sensitive to the effects of anxiolytic and anxiogenic drugs. In addition to evaluation of drug effects on IAA and escape, the number of line crossings in the apparatus were used to control for locomotor changes. Results showed that whereas diazepam (1.0-2.0 mg/kg) and flumazenil (10-30 mg/kg) impaired IAA, FG 7142 (10-30 mg/kg) did not provoke any behavioral change. Significantly, none of these benzodiazepine (BDZ) receptor ligands modified escape latencies. The 5-HT1A partial receptor agonist buspirone (1.0-2.0 mg/kg) and the 5-HT releaser fenfluramine (0.15-0.30 mg/kg) impaired IAA and facilitated escape, while the full 5-HT1A receptor agonist, 8-OH-DPAT (0.05-0.1 mg/kg) and the 5-HT2B/2C receptor antagonist, SER 082 (0.5-2.0 mg/kg) failed to modify either response. mCPP (0.5-2.0 mg/kg), a 5-HT2B/2C receptor agonist, facilitated IAA but did not alter escape latency. Neither antidepressant utilized in the current study, imipramine (1.0-5.0 mg/kg) and moclobemide (3.0-10 mg/kg) affected IAA or escape performance in mice. The well-known anxiogenic drugs yohimbine (2.0-8.0 mg/kg) and caffeine (10-30 mg/kg) did not selectively affect IAA, although caffeine did impair escape latencies. Present results suggest the ETMt is useful for the study of conditioned anxiety in mice. However, upon proximal threats (e.g. open arm exposure), mice do not exhibit escape behavior as an immediate defensive strategy, suggesting that latency to leave open arm is not a useful parameter to evaluate unconditioned fear in this species. (C) 2003 Elsevier B.V. All rights reserved.

Gabaergic-benzodiazepine system is involved in the crotoxin-induced anxiogenic effect

The behavioral effects of crotoxin (CTX), the major component of Crotalus durissus terrificus venom, were studied in rats submitted to the open field, holeboard, and social interaction tests. CTX (100, 250, and 500 mu g/kg, IP) was administered 2 h before the tests. In the open field, CTX reduced ambulation (250 mu g/kg) and rearing (250 and 500 mu g/kg) and increased grooming (100 and 250 mu g/kg) and freezing (250 mu g/kg). In the holeboard and social interaction, all the CTX doses evaluated decreased, respectively, head dip and head dipping, and social interaction time. The CTX-induced behavioral alterations could be attributed to its neuromuscular transmission blockade, but this possibility was ruled out because CTX (250 and 500 mu g/kg, IP, 2 h before the rotarod test) was unable to modify the rotarod performance of rats. The involvement of the benzodiazepine receptor in the CTX-induced behavioral alterations was investigated through the pretreatment (30 min before the tests, IP) of the animals with diazepam (1.2 mg/kg), or flumazenil (4 and 10 mg/kg). Both diazepam and flumazenil antagonized the CTX induced behavioral alterations in the open field, holeboard, and social interaction tests. This study demonstrated that: (1) CTX is an anxiogenic compound; and (2) the gabaergic-benzodiazepine system may play a role in the CTX-induced anxiogenic effect. (C) 1999 Elsevier B.V.

Evaluation of the isoflurane-sparing effects of lidocaine and fentanyl during surgery in dogs

Objective-To evaluate the isoflurane-sparing effects of lidocaine and fentanyl administered by constant rate infusion (CRI) during surgery in dogs.Design-Randomized prospective study.Animals-24 female dogs undergoing unilateral mastectomy because of mammary neoplasia.Procedures-After premedication with acepromazine and morphine and anesthetic induction with ketamine and diazepam, anesthesia in dogs (n = 8/group) was maintained with isoflurane combined with either saline (0.9% NaCl) solution (control), liclocaine (1.5 mg/kg [0.68 mg/lb], IV bolus, followed by 250 mu g/kg/min [113 mu g/lb/min], CRI), or fentanyl (5 mu g/kg [2.27 mu g/lb], IV bolus, followed by 0.5 mu g/kg/min [0.23 mu g/lb/min], CRI). Positive-pressure ventilation was used to maintain eucapnia. An anesthetist unaware of treatment, endtidal isoflurane (ETiso) concentration, and vaporizer concentrations adjusted a nonprecision vaporizer to maintain surgical depth of anesthesia. Cardiopulmonary variables and ETiso values were monitored before and after beginning surgery.Results-Heart rate was lower in the fentanyl group. Mean arterial pressure did not differ among groups after surgery commenced. In the control group, mean +/- SD ETiso values ranged from 1.16 +/- 0.35% to 1.94 +/- 0.96%. Fentanyl significantly reduced isoflurane requirements during surgical stimulation by 54% to 66%, whereas the reduction in ETiso concentration (34% to 44%) observed in the lidocaine group was not significant.Conclusions and Clinical Relevance-Administration of fentanyl resulted in greater isoflurane sparing effect than did liclocaine. However, it appeared that the low heart rate induced by fentanyl may partially offset the improvement in mean arterial pressure that would be expected with reduced isoflurane requirements.

Crotoxin-induced behavioral effects in rats

Crotoxin is the major component of Crotalus durissus terrificus venom. In view of the presence of high-affinity specific binding sites for crotoxin in the brain, the objective of this work was to investigate whether crotoxin induces behavioral effects in the open-field and hole-board tests. Adult male Wistar rats (180-220 g) treated with crotoxin, 100, 250 and 500 mu g/kg, ip, administered 2 h before the test, presented statistically significant behavioral alterations (ANOVA for one-way classification complemented with Dunnet test, P<0.05). In the open-field test, 250 and 500 mu g/kg of crotoxin increased freezing (from 3.22 sec to 10.75 sec and 11.2 sec) and grooming (from 13.44 sec to 22.75 sec and 21.22 sec) and decreased ambulation (from 64.8 to 39.38 and 45.8). The dose of 500 mu g/kg also decreased rearing (from 24.9 to 17.5). In the hole-board test, 500 mu g/kg of crotoxin decreased head-dip count (from 6.33 to 4.00). All the crotoxin-induced behavioral effects were antagonized by an anxiolytic dose of diazepam (1.5 mg/kg, ip, 30 min before the tests). These results show that crotoxin reduced open-field activity and exploratory behavior as well. We suggest that these effects express an increased emotional state induced by this toxin.

High intensity social conflict in the Swiss albino mouse induces analgesia modulated by 5-HT1A receptors

Social conflict between mice produces analgesia in the attacked mouse. Both the magnitude and type (opioid or nonopioid) of this analgesia have been related to attack intensity and strain of mouse. In the present study low intensity social conflict (7 bites) did not produce analgesia, whereas high intensity - 30 and 60 bites interactions produced, respectively, short-lasting (5 min) and very short-lasting (1 min) analgesia in Swiss albino mice, when compared with nonaggressive interaction (0 bite). The 30 bites aggressive interaction induced analgesia (AIIA) was not affected by IP injection of either naloxone (5.0 and 7.5 mg/kg) or diazepam (0.5, 1.0, 2.0 and 4.0 mg/kg). However, this attack-induced analgesia was reduced after IP administration of the 5-HT1A agonists, gepirone (0.3 and 3.0 mg/kg) and BAY R 1531 (0.01 mg/kg). These results indicate that the analgesia induced by 30 bites social conflict in Swiss albino mice does not involve opioid and GABA-benzodiazepine (GABA-BZD) mechanisms. In addition, they suggest that high-intensity social conflict activates serotonergic pain modulatory systems that act through 5-HT1A receptors. Copyright (C) 1997 Elsevier B.V.