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1.
Rev. bras. med. fam. comunidade ; 17(44): 3019, 20220304.
Article in Portuguese | LILACS, ColecionaSUS | ID: biblio-1380399

ABSTRACT

Introdução: A fumicultura concentra-se sobretudo em áreas rurais do Sul do país. Reconhecidamente, as áreas rurais apresentam disparidades socioeconômicas, desigualdades no acesso geográfico, bem como dificuldade de retenção de profissionais na Atenção Primária à Saúde (APS). Apresentação do caso: Descrevem-se, neste artigo, as intersecções de determinantes socioeconômicos de saúde ao se abordar um paciente masculino, de 57 anos, em uso crônico de benzodiazepínicos para o tratamento de insônia. Ao se aprofundar a anamnese, os determinantes socioeconômicos que levaram ao desenvolvimento da insônia foram identificados como: dificuldades financeiras na produção de tabaco, preocupações excessivas com o trabalho e presença de depressão como comorbidade. Nesse sentido, ser produtor de tabaco e a relação com a empresa podem ser considerados determinantes socioeconômicos da saúde para o desenvolvimento de insônia. Conclusões: No contexto deste caso, a rotatividade de profissionais e a falta de criação de vínculo fez com que o paciente permanecesse cronicamente a tratar a insônia como benzodiazepínico, o que é proscrito. Assim, revelam-se a fragmentação do cuidado e a alta rotatividade de profissionais como determinantes socioeconômicos da saúde.


Introduction: Tobacco production is mainly concentrated in rural areas of the southern region of the country. Rural areas present socioeconomic disparities, inequalities in geographic access, and difficulties in retaining professionals in primary care. Mental health problems, such as insomnia, are common in clinical practice. Case presentation: This article describes the intersections of the social determinants of health when approaching a patient with chronic use of benzodiazepines for treatment of insomnia. By delving deep into anamnesis, the socioeconomic determinants that led to the development of insomnia were identified as: financial trouble with tobacco production, excessive concern about work and presence of depression as comorbidity. Conclusions: In this context, the turnover of health professionals and lack of doctor-patient relationship meant that the patient continued using benzodiazepines, which are not recommended for long-term treatment. Therefore, fragmented care and high professional turnover stand out as socioeconomic determinants of health.


Introducción: La producción de tabaco se concentra principalmente en las zonas rurales del sur del país. Se reconoce que las zonas rurales presentan desigualdades socioeconómicas, desigualdades en el acceso geográfico, así como dificultad para retener profesionales en Atención Primaria de Salud (APS). Los problemas de salud mental como el insomnio son comunes en la práctica clínica. Presentación de caso: Este artículo describe las intersecciones de los determinantes socioeconómicos de la salud al abordar a un paciente uso crónico de benzodiazepinas para el tratamiento del insomnio. Al profundizar la anamnesis, se identificaron los determinantes socioeconómicos que llevaron al desarrollo del insomnio como: dificultades económicas en la producción de tabaco, excesiva preocupación por el trabajo y la presencia de depresión como comorbilidad. En este sentido, ser productor de tabaco y la relación con la empresa pueden considerarse determinantes socioeconómicos de la salud para el desarrollo del insomnio. Conclusiones: En el contexto de este caso, la rotación de profesionales y la falta de vinculación hicieron que el paciente continuara crónicamente tratando el insomnio como una benzodiazepina, lo que no es recomendable. Así, la fragmentación de la atención y la alta rotación profesional se evidencia como un determinante socioeconómico de la salud.


Subject(s)
Humans , Male , Middle Aged , Rural Health , Diazepam/therapeutic use , Social Determinants of Health , Financial Stress/drug therapy , Amitriptyline/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Tobacco , Farmers/psychology
2.
Braz. J. Pharm. Sci. (Online) ; 58: e19702, 2022. tab
Article in English | LILACS | ID: biblio-1394037

ABSTRACT

Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.


Subject(s)
Humans , Male , Female , Adult , Substance-Related Disorders/drug therapy , Alcohol-Related Disorders/drug therapy , Cocaine-Related Disorders/drug therapy , Drug Therapy/instrumentation , Patients/classification , Chlorpromazine/adverse effects , Public Health/instrumentation , Diazepam/adverse effects , Disulfiram/adverse effects , Disulfiram/agonists
3.
Rev. colomb. psiquiatr ; 49(2): 84-95, abr.-jun. 2020. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1115648

ABSTRACT

ABSTRACT Introduction: In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations. Methods: The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4. Results: Case 1 was characterized by a history of high carbamazepine doses (up to 2,000 mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning. The high activity of the CYP3A4 isoenzyme was manifested by fast metabolism for quetiapine and diazepam, which took more than 1 year to normalize after the inducer, phenytoin, was stopped. Case 2 was also very sensitive to CYP3A4 inducers as indicated by very low C/D ratios for carbamazepine, risperidone and paliperidone. The carbamazepine (2,800 mg/day) and risperidone (20 mg/day) dosages for this second patient are the highest doses ever seen for these drugs by the senior author. Risperidone induction appeared to last for many months and metabolism was definitively normal 3 years after stopping carbamazepine. On the other hand, olanzapine C/D ratios were normal for induction. Conclusions: The literature has never described similar cases of very high doses of drugs metabolized by CYP3A4. We speculate that these 2 patients may have unusual genetic profiles at the nuclear receptor levels; these receptors regulate induction of drugs.


RESUMEN Introducción: Durante sus últimos 20 años de práctica, el último autor ha identificado estos 2 infrecuentes casos que necesitaban dosis extremadamente altas de medicaciones metabolizadas por el CYP3A4 para alcanzar y mantener concentraciones séricas terapéuticas. Métodos: La gran capacidad metabólica de estos 2 pacientes se demostró por los bajos cocientes entre concentración y dosis (C/D) de varias medicaciones metabolizadas por el CYP3A4. Resultados: El caso 1 se caracterizaba por una historia de altas dosis de carbamazepina (1.500 mg/día) y la necesidad de tomar 170 mg de diazepam en 2 días para facilitar una limpieza dental. La gran actividad de la isoenzima CYP3A4 se manifestó por una gran capacidad metabólica de quetiapina y diazepam, cuya normalización tardó más de 1 año tras la toma de un inductor, fenitoína. El caso 2 tambien era muy sensible a la inducción, lo cual se demuestra por los bajos cocientes C/D de carbamazepina, risperidona y paliperidona. Las dosis de carbamazepina (2.800 mg/día) y risperidona (20 mg/día) de este segundo paciente son las más altas nunca vistas por el último autor. La inducción de risperidona duró muchos meses y su metabolismo era normal 3 años después de interrumpir la carbamazepina. El cociente C/D de olanzapina era normal para la inducción. Conclusiones: Nunca se habían descrito casos similares de dosis tan altas de medicaciones metabolizadas por el CYP3A4. Se especula con que estos pacientes podrían tener unos perfiles genéticos inusuales en los receptores nucleares que regulan la inducción de medicamentos.


Subject(s)
Humans , Pharmaceutical Preparations , Cytochrome P-450 CYP3A , Cytochrome P-450 CYP3A Inducers , Triacetoneamine-N-Oxyl , Carbamazepine , Receptors, Cytoplasmic and Nuclear , Risperidone , Diazepam , Dosage , Quetiapine Fumarate , Paliperidone Palmitate , Olanzapine , Methods
4.
Int. j. odontostomatol. (Print) ; 14(1): 19-26, mar. 2020. graf
Article in English | LILACS | ID: biblio-1056496

ABSTRACT

ABSTRACT: Anxiety in dental surgery may lead to behavioral and physiological changes for the patient and constitute a frequent challenge for the oral surgeon. The objective of this study was to compare the effect of inhalatory nitrous oxide and oxygen (N2O/O2) with oral diazepam conscious sedation in vital signs of patients undergone third molar extraction. Outpatients who needed removal of partially impacted, bilateral lower third molars, during the period of one year, were included. Each patient underwent conscious sedation with either oral diazepam or inhalatory N2O/O2 on a randomized controlled trial, split-mouth design. Systolic and diastolic blood pressure, heart rate and oxygen blood saturation were the changes measured before, at the beginning and the end of the procedure. Also, surgical procedure duration was recorded. Data from vital signs were submitted to analysis of variance and the duration of the surgery to paired Student's t-test. Twenty-five healthy outpatients (13 women and 12 men) with a mean age of 21.6 years were studied. There was an increase in systolic and diastolic pressure and in heart rate in the beginning; these values decreased and stabilized at the end of the surgical procedure in both treatments (p < 0.001) being lower in N2O/O2 but without difference between treatments. The surgical procedure duration was lower and occurred an expected increase of oximetry under N2O/O2 sedation (p < 0.001). Both treatments were effective for the conscious sedation but N2O/O2 showed better outcomes, mainly in duration of the surgery.


RESUMEN: La ansiedad en la cirugía dentoalveolar puede conducir a alteraciones fisiológicas y de comportamiento en el paciente, constituyendo así un desafío frecuente para el cirujano maxilofacial. El objetivo de este estudio fue comparar el efecto del óxido nitroso inhalatorio con oxígeno (N2O/O2) y la sedación consciente oral con diazepam por médio de los signos vitales de pacientes sometidos a la extracción del tercer molar. Fueron incluídos pacientes ambulatoriales com necesidad de exodoncia de terceros molares inferiores bilaterales, parcialmente impactados, durante el período de un año. Cada paciente fue sometido a sedación consciente con diazepam oral o N2O/O2 por inhalación en un ensayo controlado aleatorio, diseño de boca dividida. La presión arterial sistólica y diastólica, la frecuencia cardíaca y la saturación de oxígeno en la sangre fueron medidos antes, al inicio y al final del procedimiento. Además, se registró la duración del procedimiento quirúrgico. Los datos de los signos vitales fueron enviados para análisis de varianza y la duración de la cirugía para la prueba t de Student pareada. Se estudiaron 25 pacientes ambulatorios sanos (13 mujeres y 12 hombres) con una edad media de 21,6 años. Al início hubo un aumento en la presión sistólica y diastólica y en la frecuencia cardíaca; estos valores disminuyeron y se estabilizaron al final del procedimiento quirúrgico en ambos tratamientos (p <0,001), siendo más bajos en N2O/ O2 pero sin diferencia entre los tratamientos. La duración del procedimiento quirúrgico fue menor y se produjo un aumento esperado de la oximetría bajo sedación con N2O/O2 (p <0,001). Ambos tratamientos fueron efectivos para la sedación consciente, pero el N2O/O2 mostró mejores resultados, principalmente en la duración de la cirugía.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Tooth, Impacted/surgery , Conscious Sedation/methods , Diazepam/adverse effects , Molar, Third/surgery , Nitrous Oxide/adverse effects , Blood Pressure , Brazil , Oximetry/methods , Administration, Oral , Heart Rate , Nitrous Oxide/administration & dosage
5.
Article in English | WPRIM | ID: wpr-787136

ABSTRACT

Regulator of calcineurin 1 (RCAN1) can be induced by an intracellular calcium increase and oxidative stress, which are characteristic features of temporal lobe epilepsy. Thus, we investigated the spatiotemporal expression and cellular localization of RCAN1 protein and mRNA in the mouse hippocampus after pilocarpine-induced status epilepticus (SE). Male C57BL/6 mice were given pilocarpine hydrochloride (280 mg/kg, i.p.) and allowed to develop 2 h of SE. Then the animals were given diazepam (10 mg/kg, i.p.) to stop the seizures and sacrificed at 1, 3, 7, 14, or 28 day after SE. Cresyl violet staining showed that pilocarpine-induced SE resulted in cell death in the CA1 and CA3 subfields of the hippocampus from 3 day after SE. RCAN1 immunoreactivity showed that RCAN1 was mainly expressed in neurons in the shammanipulated hippocampi. At 1 day after SE, RCAN1 expression became detected in hippocampal neuropils. However, RCAN1 signals were markedly enhanced in cells with stellate morphology at 3 and 7 day after SE, which were confirmed to be reactive astrocytes, but not microglia by double immunofluorescence. In addition, real-time reverse transcriptase–polymerase chain reaction showed a significant upregulation of RCAN1 isoform 4 (RCAN1-4) mRNA in the SE-induced hippocampi. Finally, in situ hybridization with immunohistochemistry revealed astrocytic expression of RCAN1-4 after SE. These results demonstrate astrocytic upregulation of RCAN1 and RCAN1-4 in the mouse hippocampus in the acute and subacute phases of epileptogenesis, providing foundational information for the potential role of RCAN1 in reactive astrocytes during epileptogenesis.


Subject(s)
Animals , Astrocytes , Calcineurin , Calcium , Cell Death , Diazepam , Epilepsy , Epilepsy, Temporal Lobe , Fluorescent Antibody Technique , Hippocampus , Humans , Immunohistochemistry , In Situ Hybridization , Male , Mice , Microglia , Neurons , Neuropil , Oxidative Stress , Pilocarpine , RNA, Messenger , Seizures , Status Epilepticus , Up-Regulation , Viola
6.
Braz. J. Pharm. Sci. (Online) ; 56: e18819, 2020. tab, graf
Article in English | LILACS | ID: biblio-1249169

ABSTRACT

The plant world represents an important source of potential therapeutic agents, but concomitant administration of herbal and conventional medications may result in interactions with subsequent beneficial or adverse effects. This study was designed to examine the analgesic effect of thyme tincture and thyme syrup, two commonly used thyme formulations, and their interactions with codeine, paracetamol, pentobarbital and diazepam in mice. The identification and quantification of thymol and carvacrol were carried out by GC/MS and GC/FID. The analgesic activity was studied using a hot plate method. Effects of thyme syrup on diazepam-induced motor coordination impairment in rotarod test and on pentobarbital-induced sleeping time were also determined. Thymol (175.3 µg/mL and 9.73 µg/mL) and carvacrol (10.54 µg/mL and 0.55 µg/mL) concentrations were measured in tincture and syrup, respectively. Thyme syrup and tincture exhibited effective analgesic activity in the hot plate pain model. Pretreatment with thyme formulations reduced analgesic activity of codeine, and potentiated the analgesic activity of paracetamol. Co-administration of thyme formulations has led to potentiation of diazepam and pentobarbital depressive central nervous system effects. Thyme formulations interacted with tested conventional drugs, probably through interference with their metabolic pathways and succeeding altered concentrations and pharmacological effects.


Subject(s)
Animals , Male , Female , Mice , Thymus Plant/drug effects , Drug Interactions , Analgesics/adverse effects , Pentobarbital/adverse effects , Pharmaceutical Preparations , Diazepam/adverse effects , Phytotherapeutic Drugs
7.
Rev. Soc. Bras. Clín. Méd ; 17(4): 180-182, dez 2019.
Article in Portuguese | LILACS | ID: biblio-1284242

ABSTRACT

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso


Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Health Profile , Aged , Cognition/drug effects , Polypharmacy , Middle Aged , Omeprazole/therapeutic use , Brazil/epidemiology , Enalapril/therapeutic use , Comorbidity , Aspirin/therapeutic use , Medical Records/statistics & numerical data , Prevalence , Cross-Sectional Studies , Clonazepam/adverse effects , Age Distribution , Losartan/therapeutic use , Simvastatin/therapeutic use , Diabetes Mellitus/epidemiology , Diazepam/adverse effects , Dyslipidemias/epidemiology , Thiazides/therapeutic use , Inappropriate Prescribing/statistics & numerical data , Zolpidem/adverse effects , Amitriptyline/adverse effects , Hypertension/epidemiology , Hypoglycemic Agents/therapeutic use
8.
Einstein (Säo Paulo) ; 17(3): eAO4521, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011989

ABSTRACT

ABSTRACT Objective: To characterize severe potential drug interactions in maternal intensive care, and to determine their frequency, risk factors and potential risk medications. Methods: An observational and longitudinal study conducted between December 2014 and December 2015 in a maternal intensive care unit. Clinical data were collected and severe potential drug interactions were identified on pregnant inpatients. The drug interactions were classified by type, prevalence and exposure rate. A multivariate logistic regression model was used to identify the severe potential drug interactions and the related drugs (p<0.05). Results: A total of 95.1% of patients were exposed to, at least, one potential drug interaction; in that, 91.7% 33.9% were related to, respectively, moderate and severe potential drug interactions. The patients were exposed, on average, on 69.2% of days they were in the intensive care unit. The main drugs involved in more severe drug interactions were magnesium sulfate, metoclopramide, propranolol and diazepam. Conclusion: The severe potential drug interactions were observed in almost all patients of the study, and, approximately one third of those interactions were related to greater severity and resulted in exposure during long hospital stay. The higher number of prescribed drugs and its previous use of medications at home increase the occurrence of severe potential drug interactions.


RESUMO Objetivo: Caracterizar as interações medicamentosas potenciais graves em terapia intensiva materna, e determinar sua frequência, os fatores e os medicamentos de risco associados à ocorrência dessas interações. Métodos: Estudo observacional e longitudinal executado entre dezembro de 2014 a dezembro de 2015, conduzido em uma unidade de terapia intensiva materna. Foram coletados dados clínicos e identificadas interações medicamentosas potenciais graves de gestantes admitidas. As interações medicamentosas foram caracterizadas quanto ao tipo, à prevalência e à taxa de exposição. Um modelo multivariado de regressão logística foi utilizado para identificação de fatores associados à ocorrência de interações medicamentosas potenciais graves e os medicamentos implicados (p<0,05). Resultados: Um total de 95,1% das pacientes foi exposto a, no mínimo, uma interação medicamentosa potencial, com 91,7% delas envolvidas com interações medicamentosas potenciais moderadas e 33,9% com as interações graves. As pacientes ficaram expostas, em média, em 69,2% dos dias que estiveram sob terapia intensiva. Os principais medicamentos implicados em interações medicamentosas de maior gravidade foram sulfato de magnésio, metoclopramida, propranolol e diazepam. Conclusão: As interações medicamentosas potenciais graves ocorreram na maioria das pacientes avaliadas. Aproximadamente um terço das interações foram graves e levaram à maior exposição por um longo período de internação. Maior número de fármacos prescritos e uso prévio domiciliar de medicamentos elevam a ocorrência de interações medicamentosas potenciais graves.


Subject(s)
Humans , Female , Child , Adolescent , Adult , Young Adult , Risk Assessment/methods , Drug Interactions , Intensive Care Units/statistics & numerical data , Metoclopramide/pharmacology , Propranolol/pharmacology , Severity of Illness Index , Brazil/epidemiology , Pregnancy/drug effects , Logistic Models , Serial Cross-Sectional Studies , Prevalence , Multivariate Analysis , Risk Factors , Diazepam/pharmacology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Hospitalization/statistics & numerical data , Magnesium Sulfate/pharmacology
9.
Rev. cuba. med ; 57(1)ene.-mar. 2018.
Article in Spanish | LILACS, CUMED | ID: biblio-960629

ABSTRACT

El síndrome de la persona rígida es un trastorno neurológico infrecuente y desconcertante, caracterizado por contractura progresiva, rigidez y espasmos dolorosos que afectan la musculatura axial, lo que imposibilita la deambulación del paciente. Se presenta un paciente masculino de 22 años de edad con manifestaciones clínicas y electromiográficas compatibles con esta entidad nosológica. El tratamiento descrito para la enfermedad no produjo mejoría de los síntomas. Con respecto a los casos descritos en la literatura científica, es el primer paciente con diagnóstico de síndrome de la persona rígida que ha recibido una dosis de diazepam de 500 mg diarios por vía oral sin efectos adversos y una dosis en bolo de propofol de 800 mg para lograr la relajación muscular(AU)


Stiff-Man Syndrome is an uncommon and disturbing neurological disorder characterized by progressive contracture, stiffness and painful spasms that affect the axial musculature, making it impossible for the patient to walk around. We present a 22-year-old male patient with clinical and electromyographic manifestations compatible with this nosological disease. The treatment described for the disease did not produce an improvement in symptoms. Regarding the cases described in the scientific literature, this is the first patient diagnosed with Stiff-Man Syndrome who has received a dose of diazepam of 500 mg daily orally without adverse effects and a bolus dose of 800 mg of propofol to achieve muscle relaxation(AU)


Subject(s)
Humans , Male , Adult , Stiff-Person Syndrome/complications , Stiff-Person Syndrome/diagnosis , Stiff-Person Syndrome/drug therapy , Case Reports , Diazepam/therapeutic use
10.
Braz. J. Pharm. Sci. (Online) ; 54(2): e17617, 2018. tab, graf
Article in English | LILACS | ID: biblio-951924

ABSTRACT

ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p < 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p < 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.


Subject(s)
Animals , Male , Female , Rats , Hypoglycemia/chemically induced , Insulin/administration & dosage , Anticonvulsants/adverse effects , Lactic Acid/adverse effects , Diazepam
11.
São Paulo; s.n; s.n; 2018. 117 p. graf, tab, ilus.
Thesis in Portuguese | LILACS | ID: biblio-883276

ABSTRACT

A obesidade está associada a um processo inflamatório crônico de baixa intensidade e representa um dos fatores de risco para o desenvolvimento de uma série de comorbidades. A proteína TSPO está envolvida em inúmeras funções celulares, incluindo biossíntese e transporte de esteróides, transporte de porfirinas, apoptose, biossíntese do heme, processos oxidativos e imunomodulação. Ademais, a presença e a função da proteína TSPO no tecido adiposo e na inflamação ainda não estão bem estabelecidas. Deste modo, o objetivo do presente estudo foi validar a expressão e função do TSPO durante a diferenciação de células 3T3-L1, e investigar se o tratamento de adipócitos 3T3-L1 com diazepam, um benzodiazepínico de ação central (GABAA) e periférica (TSPO), é capaz de modular os efeitos inflamatórios induzidos pela incubação das células 3T3-L1 com TNF-α. Nossos resultados evidenciaram que, em nosso estudo, o tratamento de pré-adipócitos com diazepam não modulou a adipogênese. Entretanto, apesar de o diazepam per se não modular o acúmulo de triacilglicerol e a expressão gênica e protéica de PPAR-γ; em células estimuladas pelo TNF-α, o tratamento com diazepam foi capaz de reverter a diminuição da expressão gênica e protéica de PPAR-γ induzida pelo TNF-α. Ademais, o tratamento dos adipócitos com diazepam foi capaz de modular positivamente a expressão protéica de TSPO, efeito este que não observamos em células tratadas pelo clonazepam, um benzodiazepínico de ação exclusivamente central. Em resumo, os dados obtidos neste estudo, pela primeira vez, demonstram a possível relação entre as vias que controlam a sinalização de TSPO, TNF-α e PPAR-γ. Assim, nos é possível inferir que a ativação de TSPO pelo seu ligante diazepam foi capaz de modular a ativação de NF-kB induzida pelo TNF-α, promovendo, com a diminuição da lipólise e aumento da expressão gênica de TSPO e gênica e protéica de PPAR-γ, o reestabelecimento da homeostase celular, o que aumentaria a sobrevida das células, a atividade mitocondrial, e a atividade adipogênica dos adipócitos


Obesity is associated with a chronic low-grade inflammation and these represents one of the risk factors to development of other non-communicable diseases. TSPO 18 kDa is involved in several cellular functions, including biosynthesis and steroids transport, porphyrin transport, apoptosis, heme biosynthesis, oxidative metabolism and immunomodulation. Furthermore, the TSPO expression and function on adipose tissue and in the chronic low-grade inflammation have not been established. Thus, the aim of present study was to validate the TSPO expression and function on the 3T3-L1 differentiation process and to investigate whether diazepam treatment is able to modulate the TNF-α induced inflammatory effects on 3T3-L1 cells. Our results showed that diazepam treatment of preadipocytes was not able to modulate the adipogenesis. However, although diazepam treatment per se does not modulate the triacylglycerol accumulation and gene and protein expression of PPAR-γ; in TNF-α stimulated adipocytes, the treatment with diazepam was able to modulate the decreased of PPAR-γ gene and protein expression induced by TNF-α. In addition, the diazepam treatment of adipocytes was able to positively modulate the TSPO protein expression, an effect that we did not observe in cells treated with clonazepam, a central benzodiazepine ligand. In summary, the data obtained in this study, for the first time, demonstrate the possible relationship between the pathways that control the TSPO, TNF-α and PPAR-γ signaling. Thus, it is possible that the activation of TSPO by diazepam was able to modulate TNF-α-induced activation of NF-kB, promoting the reduction of lipolysis and increased of TSPO gene expression and PPAR-γ gene and protein expression, reestablishment of cellular homeostasis, which would increase cell survival, mitochondrial activity, and adipogenic activity of adipocytes


Subject(s)
Mice , Adipocytes , 3T3-L1 Cells/classification , Mitochondrial ADP, ATP Translocases , Lymphotoxin-alpha , Diazepam/agonists , Flow Cytometry/methods , Inflammation , Macrophages , Obesity/diagnosis
12.
Rev. ciênc. farm. básica apl ; 3801/01/2017. ilus, tab
Article in English | LILACS | ID: biblio-1100221

ABSTRACT

The use of Psychoactive Substances brings problems in several areas of the subject's life such as: health, psychological and social. It´s necessary evaluate the factors involved in drug use and potential drug interactions (PDI) in adolescents using psychoactive substances. It was a Cross-sectional, analytical and quantitative study. The research was carried out at the Center for Psychosocial Care and other drugs for children and adolescents 24h, with adolescents under 18 years of age, using medication. The data were obtained by reviewing the charts and the potential interactions were evaluated through the database Micromedex® and Medscape®. Of the 159 records used, there were 815 PDI. By gravity were 59.4% moderate, 23.8% secondary, 15.7% severe and 1.1% contraindicated. The drugs that presented the most PDI were Chlorpromazine (32.3%) and Diazepam (19.6%). The factors involved in polypharmacy were total PDI and those involved in the occurrence of total PDI were studying and the quantity diagnostic hypotheses. Due to the high PDI index, the relationship with polypharmacy and a high number of diagnostic hypotheses, it is necessary to increase the attention of health professionals regarding the topic and the development of protocols to support decision making.(AU)


Subject(s)
Humans , Male , Female , Child , Adolescent , Psychotropic Drugs/therapeutic use , Drug Interactions , Chlorpromazine , Adolescent , Diazepam , Drug Therapy, Combination
13.
Braz. j. med. biol. res ; 50(12): e6346, 2017. tab, graf
Article in English | LILACS | ID: biblio-888962

ABSTRACT

This study evaluated the anesthetic potential of thymol and carvacrol, and their influence on acetylcholinesterase (AChE) activity in the muscle and brain of silver catfish (Rhamdia quelen). The AChE activity of S-(+)-linalool was also evaluated. We subsequently assessed the effects of thymol and S-(+)-linalool on the GABAergic system. Fish were exposed to thymol and carvacrol (25, 50, 75, and 100 mg/L) to evaluate time for anesthesia and recovery. Both compounds induced sedation at 25 mg/L and anesthesia with 50-100 mg/L. However, fish exposed to carvacrol presented strong muscle contractions and mortality. AChE activity was increased in the brain of fish at 50 mg/L carvacrol and 100 mg/L thymol, and decreased in the muscle at 100 mg/L carvacrol. S-(+)-linalool did not alter AChE activity. Anesthesia with thymol was reversed by exposure to picrotoxin (GABAA antagonist), similar to the positive control propofol, but was not reversed by flumazenil (antagonist of benzodiazepine binding site), as observed for the positive control diazepam. Picrotoxin did not reverse the effect of S-(+)-linalool. Thymol exposure at 50 mg/L is more suitable than carvacrol for anesthesia in silver catfish, because this concentration did not cause any mortality or interference with AChE activity. Thymol interacted with GABAA receptors, but not with the GABAA/benzodiazepine site. In contrast, S-(+)-linalool did not act in GABAA receptors in silver catfish.


Subject(s)
Animals , Acetylcholinesterase/metabolism , Anesthetics/pharmacology , Catfishes , Monoterpenes/pharmacology , Receptors, GABA-A/metabolism , Thymol/pharmacology , Acetylcholinesterase/physiology , Adjuvants, Anesthesia/pharmacology , Analysis of Variance , Anesthesia/veterinary , Brain/drug effects , Brain/enzymology , Catfishes/metabolism , Diazepam/pharmacology , GABA Antagonists/pharmacology , Muscles/drug effects , Muscles/enzymology , Oils, Volatile/chemistry , Picrotoxin/pharmacology , Receptors, GABA-A/physiology , Reproducibility of Results , Statistics, Nonparametric , Time Factors
14.
Article in English | WPRIM | ID: wpr-11658

ABSTRACT

Neuropathic pain is usually managed pharmacologically, rather than with botulinum toxin type A (BTX-A). However, medications commonly fail to relieve pain effectively or have intolerable side effects. We present the case of a 62-year-old man diagnosed with an intracranial chondrosarcoma, which was removed surgically and treated with radiation therapy. He suffered from neuropathic pain despite combined pharmacological therapy with gabapentin, amitriptyline, tramadol, diazepam, and duloxetine because of adverse effects. BTX-A (100 units) was injected subcutaneously in the most painful area in the posterior left thigh. Immediately after the injection, his pain decreased significantly from 6/10 to 2/10 on a visual analogue scale. Pain relief lasted for 12 weeks. This case report describes intractable neuropathic pain caused by a brain tumor that was treated with subcutaneous BTX-A, which is a useful addition for the management of neuropathic pain related to a brain tumor.


Subject(s)
Amitriptyline , Botulinum Toxins , Botulinum Toxins, Type A , Brain Neoplasms , Brain , Chondrosarcoma , Diazepam , Duloxetine Hydrochloride , Humans , Middle Aged , Neuralgia , Thigh , Tramadol
15.
Article in English | WPRIM | ID: wpr-10723

ABSTRACT

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via γ-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase (GAD(65/67)) and GABA(A) receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through GABA(A)-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.


Subject(s)
Administration, Oral , Animals , Anti-Anxiety Agents , Benzodiazepines , Blotting, Western , China , Diazepam , Eye Movements , Fever , Glutamate Decarboxylase , Japan , Korea , Lung Diseases , Medicine, Traditional , Mice , Mood Disorders , Motor Activity , Neurons , Pentobarbital , Receptors, GABA-A , Rheumatic Diseases , Rodentia , Sinomenium , Sleep Initiation and Maintenance Disorders
16.
Article in English | WPRIM | ID: wpr-12123

ABSTRACT

We developed a simple, sensitive, and effective ultra-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method with an electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) and positive ion modes to determine diazepam concentrations in human plasma using voriconazole as an internal standard (IS). Diazepam and IS were detected at transition 285.2→193.1 and 350.2→127.1, respectively. After liquid-liquid extraction (LLE) using 1.2 ml of ethyl acetate:n-hexane (80:20, v/v), diazepam and IS were eluted on a Phenomenex Cadenza CD-C18 column (150 × 3.0 mm, 3 µm) with an isocratic mobile phase (10 mM ammonium acetate in water:methanol [5:95, v/v]) at a flow rate of 0.4 mL/min. The peak retention time was 2.32 min for diazepam and 2.01 min for IS, respectively. The lower limit of quantitation (LLOQ) was 0.5 ng/mL (S/N > 10) using 50 µL of plasma, and no interferences were observed in chromatograms. Our analytical method was fully validated and successfully applied to a bioequivalence study of two formulations of diazepam in healthy Korean volunteers.


Subject(s)
Ammonium Compounds , Diazepam , Humans , Liquid-Liquid Extraction , Mass Spectrometry , Methods , Plasma , Therapeutic Equivalency , Volunteers , Voriconazole
17.
Int. j. med. surg. sci. (Print) ; 3(4): 991-996, dic. 2016. ilus
Article in Spanish | LILACS | ID: biblio-1095107

ABSTRACT

El diazepam (DZ) es un tranquilizante menor sintético, utilizado en pacientes con trastornos psicológicos y psiquiátricos. Es sedante, miorrelajante, anticonvulsionante y antipsicótico. El DZ atraviesa la barrera placentaria humana y la del ratón. Mujeres jóvenes que son adictas al fármaco, si se embarazan y continúan utilizándolo, sobre todo durante el primer trimestre, exponen a sus hijos a presentar alteraciones psicomotoras. El propósito de este trabajo fue investigar si el DZ administrado durante la gestación,induce alteraciones ultraestructurales del miocardio fetal de ratón. El grupo (DZ) de hembras gestantes deratón de la cepa CD-1 fue tratado con dosis únicas diarias de 1,0 mg/kg/pc/sc del día 6 al 17 y un grupo (C)que recibió solución salina. El día 18 las hembras de ambos grupos se anestesiaron, los fetos se perfundieron por vía intracardiaca con paraformaldehído al 1 % y glutaraldehido al 2,5 %, se les extrajo el corazón, se disecó el atrio, se fijó en OsO4 al 1 % y se incluyó en resina epóxica. Los cortes finos se contrastaron conacetato de uranilo y citrato de plomo y se observaron en un microscopio electrónico de transmisión. En los miocitos de los fetos del grupo DZ las sarcómeras del miocardio compacto tenían menor longitud que las del grupo C. Se observaron zonas con miofibrillas desorganizadas. El retículo sarcoplásmico de algunos miocitos presentaba cisternas distendidas y fragmentadas, mitocondrias alteradas y se observaron abundantes polirribosomas. Los cambios podrían deberse al efecto del DZ sobre la síntesis de actina y miosina pesada y sobre los organelos citoplásmicos, mediados por receptores benzodiazepínicos periféricos presentes en la membrana externa de las mitocondrias y asociados a canales de calcio dependientes de voltaje. Las alteraciones ultraestructurales del miocardio atrial de fetos de ratones expuestos in utero a DZ podrían tener efectos posnatales.


Diazepam (DZ) is a syntheticminor tranquilizer, used in patients with psychologicaland psychiatric disorders. It is a relaxing sedative,anticonvulsant and antipsychotic. DZ crosses thehuman placental barrier in mouse. Young women who are addicted to the drug, if they become pregnantand continue to use it, particularly during the firsttrimester, expose their children to psychomotor disorders. The purpose of this study was to investigate whether DZ administered during pregnancy induces ultrastructural alterations of fetal mouse myocardium.The group (DZ) of pregnant female mice of the CD-1strain was treated with a single daily dose of 1.0 mg/ kg / pc / sc of day 6 to 17 and a group (C) that received saline solution. On day 18 females of bothgroups were anesthetized, the fetuses were perfusedby intracardiac route with 1 % paraformaldehyde and 2.5 % glutaraldehyde, the heart was removed, theatrium was dissected, fixed in 1 % OsO4, it wasimmersed in epoxy resin. The fine sections werecontrasted with uranyl acetate and lead citrate and observed in a transmission electron microscope. Inthe myocytes of the fetuses of the DZ group, the sarcomers of the compact myocardium were shorter than those of the C group. Areas with disorganized myofibrils were observed. The sarcoplasmic reticulumof some myocytes had distended and fragmented 996cisterns, altered mitochondria, and abundant polyribosomes were observed. The changes may bedue to the effect of DZ on the synthesis of actin and heavy myosin and on cytoplasmic organelles mediatedby peripheral benzodiazepine receptors present onthe outer membrane of the mitochondria and associated with voltage-dependent calcium channels.Ultrastructural alterations of the atrial myocardium of fetuses of mice exposed to DZ in utero may have postnatal effects.


Subject(s)
Animals , Pregnancy , Mice , Diazepam/toxicity , Fetal Heart/drug effects , Sarcoplasmic Reticulum/drug effects , Sarcoplasmic Reticulum/ultrastructure , Benzodiazepines/toxicity , Fetal Heart/ultrastructure
18.
Rev. méd. Chile ; 144(4): 434-441, abr. 2016. graf, tab
Article in English | LILACS | ID: lil-787113

ABSTRACT

Background: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. Aim: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. Patients and Methods: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. Results: In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. Conclusions: Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.


Antecedentes: Las benzodiacepinas tienen un efecto broncodilatador directo. La metacolina es un agonista muscarínico que causa bronco constricción. Objetivo: Evaluar el efecto modulador de la inhalación de diazepam sobre la bronco constricción inducida por metacolina. Pacientes y Métodos: Se estudiaron 12 pacientes con asma bien controlada. En el primer día, se determinó la curva dosis respuesta de parámetros de función pulmonar a una dosis progresiva de metacolina. Después de la última dosis, cuando se consiguió un 20% de reducción en la capacidad vital forzada en el primer segundo (FEV1), se midió FEV1 y la capacidad vital (CV) a los 7, 15 y 30 min después de la provocación. En el segundo día los pacientes se inhalaron con diazepam antes de hacer la prueba con metacolina. Resultados: En el primer día, el FEV1 bajo de 2,98 a 1,69 l con 6 mg/ml de metacolina. En el segundo día, la inhalación de diazepam redujo la respuesta a metacolina con una reducción de FEV1 de 2,48 a 2,21 L. Conclusiones: La benzodiacepinas reducen la respuesta de vasoconstricción a metacolina.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Asthma/prevention & control , Bronchoconstriction/drug effects , Bronchoconstrictor Agents/antagonists & inhibitors , Methacholine Chloride/antagonists & inhibitors , Receptors, GABA/therapeutic use , Diazepam/pharmacology , Reference Values , Asthma/physiopathology , Time Factors , Benzodiazepines/therapeutic use , Administration, Inhalation , Bronchial Provocation Tests/methods , Vital Capacity/physiology , Anthropometry , Forced Expiratory Volume/drug effects , Forced Expiratory Volume/physiology , Reproducibility of Results , Dose-Response Relationship, Drug
19.
Rev. méd. (La Paz) ; 22(2): 56-59, 2016. ilus
Article in Spanish | LILACS | ID: biblio-961360

ABSTRACT

El espasmo Hemifacial (EHF) es un trastorno crónico del movimiento caracterizado por la contracción descontrolada, intermitente y espasmódica o tónica de los músculos de una de las hemicaras. La aplicación de toxina botulínica a través de la quimiodenervación produce parálisis muscular temporal y de forma reversible. Se presenta un caso clínico relacionado con EHF y la aplicación terapéutica de toxina botulínica tipo "A" con buenos resultados.


Hemifacial (EHF) spasm is a chronic movement disorder characterized by uncontrolled, intermittent and spasmodic contraction of the muscles or tone of one of the hemicaras. The application of botulinum toxin through chemodenervation produces temporary muscular paralysis and reversibly. a clinical case involving EHF and the therapeutic application of botulinum toxin type "A" with good results is presented.


Subject(s)
Female , Middle Aged , Botulinum Toxins, Type A/therapeutic use , Hemifacial Spasm/prevention & control , Diazepam , Oculomotor Muscles
20.
Natural Product Sciences ; : 263-269, 2016.
Article in English | WPRIM | ID: wpr-146018

ABSTRACT

Rhynchophylline (RP) is a major tetracyclic oxindole alkaloid of Uncariae Ramulus et Uncus which has been used to treat hypertension, seizures, pain and anxiety in the oriental countries. A recent report revealed that RP attenuated ischemia-induced neuronal damage and kainite-induced convulsions in animals. This study was performed to investigate whether RP enhances pentobarbital-induced sleep behaviors and modulates sleep architecture in mice. Locomotor activity was significantly inhibited by RP at 0.25 and 0.5 mg/kg, similar to 2 mg/kg diazepam (a benzodiazepine agonist) in mice. RP shortened sleep latency and increased total sleep time in a dose-dependent manner when administrated with pentobarbital (42 mg/kg, i.p.). RP also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28mg/kg, i.p.). On the other hand, RP (0.25mg/kg, p.o.) itself significantly inhibited sleep-wake cycles, prolonged total sleep time, and rapid eye movement in rats. In addition, RP also increased chloride influx in the primary cultured hypothalamic neuronal cells. In addition, we found that glutamic acid decarboxylase (GAD(65/67)) was activated by RP. In conclusion, RP augments pentobarbital-induced sleeping behaviors, and can be a candidate for treating insomnia.


Subject(s)
Animals , Anxiety , Benzodiazepines , Diazepam , Electroencephalography , Glutamate Decarboxylase , Hand , Hypertension , Mice , Motor Activity , Neurons , Pentobarbital , Rats , Rodentia , Seizures , Sleep Initiation and Maintenance Disorders , Sleep, REM , Uncaria
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