Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

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.

Effects of Oral Diazepam or Inhalatory Nitrous OxideOxygen for Conscious Sedation During Third Molar Surgery: A Randomized Controled Trial, Split Mouth Design / Efectos del Diazepam Oral o la Inhalación de Óxido Nitroso-Oxígeno para la Sedación Consciente Durante la Cirugía del Tercer Molar: Un Ensayo Controlado Aleatorio, Diseño de Boca Dividida

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.

Antinociceptive activity of Thyme (Thymus vulgaris L. ) and interactions with neurotropics and analgesics

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.

Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

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

[Intravenous sedation in dental surgery, midazolam versus diazepam]

A study on intravenous sedation in dental surgery was conducted comparing diazepam with midazolam. One hundred and twenty patients, aged between 12 and 50 years, ASA grade I or II divided randomly into two groups. A total of 80 patients received diazepam 0.03 mg/kg with fentanyl 0.7 microg/kg [Group-A], and 40 patients received midazolam 0.03 mg/kg with fentanyl 0.7 microg/kg [group-B]. In both groups, the dental surgeon gave 1.5-3 ml xylocaine 0.5% with adrenaline 1:200.000 to perform the nerve block to the upper or lower jaw as needed. No premedication was given. Perioperative cardiovascular effects, anterograde amnesia, respiration, oxygen saturation, patient satisfaction and adverse venous sequelae were investigated. Blood pressure was reduced in both groups; the reduction was less than 30 mmHg, the difference was not significant. In diazepam group [A], 30% were able to remember the events, 25% suffered painful injection, 10% suffered redness and swelling at site of injection. In midazolam group [B], 10% were able to remember the events, no patient suffered redness and swelling at site of injection or painful injection, the difference was statistically significant for these adverse effects. Both drugs gave safe and acceptable sedation. Midazolam was superior to diazepam, had better amnesic effects, more patient satisfaction with no incidence of venous sequelae

Uso crônico de diazepam em idosos atendidos na rede pública em Tatuí-SP / Long-term use of diazepam in elderly patients treated by the public health system in Tatuí (SP, Brazil)

Propôs-se caracterizar o perfil de utilização do diazepam na população idosa (60 anos ou mais) usuária crônica, atendida no serviço de atenção primária de Tatuí-SP e estabelecer uma relação entre uso crônico, efeitos adversos, dependência e as recomendações preconizadas na literatura científica. Desenvolveu-se um estudo observacional, transversal, através de entrevistas semiestruturadas aplicadas em 70 idosos. Trata-se de uma amostra não probabilística, por tipicidade, de caráter voluntário. A amostra selecionada era composta por: 77,1% mulheres e 22,9% homens, sendo, 37,1% casados, 44,2% viúvos, 92,8% de baixa escolaridade, 94,2% aposentados e 91,4% portadores de doenças crônicas. O diagnóstico referido, que justificou a prescrição inicial em dose de 10mg/dia foi a ansiedade e a insônia (92,8%). Em 90% dos pacientes a orientação médica foi seguida, sem interrupção, por um tempo mediano de 60 meses com um mínimo de seis e máximo de 360 meses. Os possíveis efeitos adversos foram: tontura, dores articulares, angústia e depressão. Aqueles que tentaram não utilizar o medicamento (97,14%) relataram insônia, ansiedade e irritabilidade. Os dados deste estudo, sugerem que a dose padronizada pela rede pública de 10mg e o tempo de utilização não propicia uma prática consistente de elevação do bem estar desses usuários, visto que a maioria relatou efeitos adversos e síndrome de abstinência na ausência do medicamento; tornando-se conveniente uma cuidadosa monitorização clínica e uma orientação quanto à redução gradativa da dose.

Effect of diazepam on prevention of recurrences of febrile seizures

The objective of this study was to evaluate the efficacy of intermittent oral diazepam for reducing the recurrence of febrile seizures.Prince Rushed military hospital north of Jordan. Prospective controlled study of 280 patients, who were admitted to pediatric ward with first febrile seizures and were r and omized into two groups, one group received short-term prophylaxis for 12 months with oral diazepam 2.5Mg for children less than 7Kg, 5Mg for children weighing 7-15Kg and 10mg diazepam for children weighing more than 15kg and then continued after the temperature >38.5c, the control group received no prophylaxis Short-term diazepam prophylaxis reduces the recurrence rate of febrile seizures to one fifth that is from 43% to 8.2 [p<0.003] when the first febrile seizures are simple and to one-fourth that from 62% to 16% when the first febrile seizures are complex, with mild side effects of diazepam. Short-term prophylaxis with oral diazepam is effective in prevention of recurrence of febrile seizures, with mild side effects

Doenças de Dupuytren e de Ledderhose associadas ao uso crônico de anticonvulsivantes: relato de caso / Dupuytren's and Ledderhose's diseases associated with chronic use of anticonvulsants: case report

Relatamos o caso de um paciente que após uso crônico de anticonvulsivantes, sem epilepsia definida, desenvolveu contraturas das aponeuroses palmar (doença de Dupuytren) e plantar (doença de Ledderhose). Discutimos as principais dessas complicações, os fatores predisponentes e sua estreita relação com o uso de anticonvulsivantes, particularmente de fenobarbital.

Influence of vigabatrin behaviour in rats upon diazepam withdrawal

Frequent administration of diazepam has been reported to induce physical dependence and tolerance in animals and humans. Using an elevated plus-maze model of anxiety, we investigated whether vigabtrin reduces some of withdrawal symptoms of diazepam. Vigabatrin is irreversible inhibitor of the enzyme GABA-transaminase, which induces several increases in brain GABA levels. Previously, treatment of rats with vigabatrin for 14 days was found to produce an anxiolytiiclike effect without a changes in the general locomotor activity. In this study, rats were chronically treated with either diazepam at a dose of 10mg/kg/day, i.p. or vigabatrin at a dose of 200mg/kg/day, i.p. alone or in combination at a dose of 10mg/kg/day diazepam+200mg/kg/day for ivgabatrin for 14 days to examine their effects. The general locomotor activity of the rats did not alter in both groups of tolerance and dependence in comparison with control rats. An increases of horizontal activity of diazepam-dependent rats after 48 hrs of the last injections was observed without a changes in the vertical activity. In the dependence group, the anxiolytic effect of chronic treatment with diazepema was found to persist 48 hrs after last injection. However, the combined treatment of diazepam wth vigabatrin completely abolished the anxiolytic effect of diazepam [10mg/kg]. In the tolerance groups, the effect of 1.5mg/kg diazepam in chronically diazepam-treated rats was significantly lower than that of the control and chronically diazepam and vigabtrin-treated rats, with no difference between control group and combined treatment group. Forty-eight hours after the last injection, the concentration of GABA in the frontal cortex was significantly higher in the chronically treated was with vigabatrin than the other groups. A significantly decrease in the striatal GABA levels was found in acutely and chronically diazepam-treated rats. These findings may suggest that vigabatrin protects rats from development of some of withdrawal symptoms of benzodiazepines

Estudo clínico dos efeitos do diazepam e da dexametasona, associados à bupivacaína a 0,5 por cento, sobre a pressäo arterial e a freqüência cardíaca / Clinic study of the diazepam and dexamethasone effects associated with bupivacaine 0, 5 per cent upon blood pressure and heart rate

Este trabalho teve por objetivo avaliar os efeitos do diazepam e da dexametasona, associados à bupivacaína, sobre os valores de pressäo arterial sangüínea (PA) e freqüência cardíaca (FC), em pacientes submetidos a exodontia de terceiros molares mandibulares inclusos. As avaliaçöes da PA e da FC foram realizadas em cinco tempos distintos. Os resultados mostraram que os valores médios da pressäo arterial sangüínea (sistólica ediastólica) e da freqüência cardíaca situaram-se dentro da faixa de normalidade biológica, durante todo o período experimental

Effect of diazepam sedation on arterial oxygen saturation during esophagogastroduodenoscopy: a placebo-controlled study.

OBJECTIVE: To determine the effect of sedation using diazepam on hemoglobin oxygen saturation (SpO2) in patients undergoing esophagogastroduodenoscopy (EGD). METHOD: 100 consecutive patients scheduled for EGD were randomly allocated to receive 0.03 mL/Kg of either diazepam (5 mg/mL solution) or normal saline intravenously after topical oropharyngeal anesthesia immediately before the procedure. SpO2 was continuously monitored throughout the procedure by an anesthetist who was unaware of the drug received. RESULTS: Fall in SpO2 exceeding 4% was noted in 78% of patients in the diazepam group and in 38% of patients in the placebo group (p < 0.001). Fall in SpO2 to suboptimal level (89%) was seen in 20% of patients in the diazepam group and in 10% patients in the placebo group (p < 0.001). The duration of suboptimal SpO2 was similar (means +/- SD being 2.47 +/- 0.10 min in diazepam group and 2.86 +/- 0.32 min in placebo group). CONCLUSION: Intravenous diazepam administration before EGD produces a significant fall in SpO2 during the procedure, and so should be avoided; continuous monitoring of SpO2 should be done during EGD.

Efectos de la administración prenatal del diazepam en estructuras craneofaciales de ratones Balb/C / Effects of prenatal administration of diazepam on craniofacial structures of Balb/C mice

Una dosis oral de 3 mg/kg diaria de diazepam (DZ) fue administrada a ratones Balb/C durante su gestación. Esta dosis causó una dependencia y sedación hasta de 4 horas. Las crías de estos ratones fueron sacrificadas en los días 1, 3, 7, 14, 21 y 28 postnatales y fueron examinados de anormalidades físicas. Los cráneos y las mandíbulas fueron disecados y pesados para analizarlas estadísticamente. Los ratones del grupo tratado con DZ mostraron un peso menor durante el período de gestación, en comparación con el grupo control. El peso de las mandíbulas y cráneos del grupo DZ también mostró un peso menor en los días 14, 21 y 28 postnatales. La aparición de un tumor en el cráneo fue un hallazgo clínico de esta investigación

Effects of nitroxazepine on diastolic blood pressure in mild hypertensive patients--a short term clinical study.

In a double blind short term clinical study, nitroxazepine has been found to be superior over placebo in reducing the diastolic blood pressure in mild hypertensive patients. In short term open clinical trial design nitroxazepine (25 mg PO, HS) has been found to be superior and better tolerated than diazepam (5 mg PO, HS). In open clinical trial design, nitroxazepine (25 mg PO, HS) reduced the diastolic blood pressure to the target level (100 mm Hg and less) effectively controlling the uncontrolled hypertensive patients receiving maintenance dose of beta blockers. There was no such beneficial effect in patients receiving maintenance doses of other antihypertensive drugs (pilot study). Adverse drug reactions like disturbed sleep in one, uneasiness in 3, palpitation in one and dryness of mouth in one patient have been observed.

Reversal of diazepam withdrawal induced hyperactivity in mice by BR 16-A (Mentat), a herbal preparation.

Abrupt cessation of chronic treatment of diazepam (20 mg/kg/day for 21 days) produced withdrawal reactions. BR 16-A, a multicomponent herbal preparation shown to reverse the withdrawal reactions to opiates was studied against diazepam induced withdrawal reactions in mice. Acute dose of diazepam (20 mg/kg) produced a decrease in the ambulatory and total activity. However, chronic administration for 21 days produced tolerance and no significant change in the ambulatory and total activity. On abrupt termination of diazepam treatment after 21 days, the animals showed anxiety and excitement as there was an increase in ambulatory and total activity. The withdrawal excitement was highest at 72 hr of the last dose of diazepam. Concomittant administration of BR 16-A (100 and 500 mg/kg) reversed the acute effect of diazepam in a dose dependent manner. Similarly, chronic administration of BR 16-A (100 and 500 mg/kg/day for 21 days) with diazepam (20 mg/kg/day for 21 days) also reversed the withdrawal induced hyperambulation and total activity. Chronic administration of BR 16-A per se had no significant effect on the ambulatory and total activity, however, in acute doses, BR 16-A (100 and 500 mg/kg) produced a dose dependent increase in the ambulatory and total activity. BR 16-A with its CNS profile of activity could be a useful preparation in the management of substances of abuse.

A prescriçäo por médicos brasileiros de fórmulas magistrais para emagrecer: uma duvidosa prática para a saúde dos pacientes / The prescription by Brazilian medicins of magistral formulas to reduce weight: a doubtful practice for the health of patients

Consultas pagas foram feitas a pesquisadores (simulando ser pacientes) que procuraram 71 médicos em Säo Paulo e 36 em Recife, visando obter uma receita para emagrecer. Em 90,5 por cento das consultas de Säo Paulo e em 58,7 por cento das de Recife aos "pacientes" foram receitadas fórmulas magistrais, sendo ainda que em 9,5 por cento das de Säo Paulo e 37,9 por cento das de Recife foram prescritos produtos comerciais acabados. Nas fórmulas magistrais de 4 a 6 drogas (53,9 por cento das receitas de Säo Paulo e 27,5 por cento em Recife) mas houve prescriçöes contendo até 17 componentes. Os agentes anorexígenos mais prescritos foram o fenproporex (58,7 por cento em Säo Paulo e 47,2 por cento em Recife) e a anfepramona ou dietilpropiona (46,0 por cento em Sä Paulo e 37,4 por cento em Recife) mas mazindol, d,1-fenifluramina e d-fenfluramina foram também receitados. Sem exceçäo as fórmulas magistrais continham também benzodiazepínicos, sendo o diazepam (28,6 por cento em Sä Paulo e 27,5 por cento em Recife) e o clordiazepóxido (25,4 por cento em Säo Paulo e 21,9 por cento em Recife) os preferidos pelos médicos prescritores de fórmulas magistrais. Agentes diuréticos, tiroidianos, com açäo sobre o aparelho gastrointestinal plantas e substâncias várias completavam a receita. Notou-se também que em 19,0 por cento das receitas de Säo Paulo e em 6,9 por cento das de Recife havia prescriçäo de duas substâncias anorexígenas e que as doses prescritas chegavam até cinco vezes a posologia recomendada internacionalmente. A maior parte dos médicos näo advertiu os pesquisadores sobre as possíveis reaçöes adversas produzidas pelas substâncias anorexígenas e benxodiazepínicas, inclusive o perigo de dependência. Conclui-se que a prática de receitar fórmulas magistrais e medicamentos acabados à base de drogas anorexígenas e benzodiazepínicas é antes um risco do que benefício para a saúde

Efectividad del fenobarbital, diazepam y antipirético para prevenir recurrencias en niños con una primera convulsión febril

El propósito de este estudio fue comparar la efectividad de estos tres tipos de tratamiento para prevenir las recurrencias de las convulsiones febriles durante el primer año posterior a la primera convulsión febril. Se trata de un trabajo prospectivo, tipo ensayo clínico controlado, abierto, no aleatorio. Se incluyeron finalmente 87 niños que consultaron al servicio de urgencias del Hospital Militar Central, por presentar una primera convulsión febril durante el período comprendido entre marzo de 1990 a junio de 1992. Los tres grupos de tratamiento se recomendaron así: fenobarbital como profilaxis continua 5 mg/Kg/día; diazepam 0,5 mg/Kg sublingual o rectal cada 12 horas en caso de presentar fiebre y acetaminofen 10 mg/Kg cada seis horas también en caso de fiebre. Presentaron recurrencias 2/29 pacientes tratados con diazepam, 9/28 niños tratados con fenobarbital y 12/30 casos que recibieron acetaminofen. Encontrándose una diferencia estadísticamente significativa (p<0.025) a favor del tratamiento con diazepam. En este trabajo no se encontró ninguna justificación para continuar recomendando la administración continua de fenobarbital en niños sanos con convulsiones febriles.

Reversión de la sedación por aminofilina en pacientes que recibieron diazepan, fentanil y tiopental

La aminofilina, un antagonista no específico de las benzodiazepinas, fue evaluada para determinar su acción en la reversión de la sedacción de pacientes sometidos a legrados uterinos o braquiterapia intrauterina bajo anestesia general. Veintiocho pacientes recibieron Fentanil 3ug.kg-1, Diazepán 0.2 mg.kg-1 y Tiopental 4mg.kg-1, y fueron ventiladas con Oxido Nitroso- Oxígeno (66/33 por ciento). Después del procedimiento quirúrgico, cada paciente recibió en forma randomizada y doble ciego, ®droga activa¼ (aminofilina 4 mg.kg-1n=14) o ®placebo¼ (solución Salina isotónica; n = 14). Ambos grupos fueron similares en sus variables demográficas y no se detectaron diferencias en las determinaciones de presión arterial, frecuencia cardíaca y frecuencia respiratoria después de la administración de aminofilina. La recuperación fue bien tolerada y significativamente más rápida en el grupo aminofilina (30.9 min+DS4.91) que en el grupo control (39.0 min. + DS 8.06) (p<0.01). Los niveles de sedación revirtieron antes que en el grupo control <0.05), pero esta deferencia desaparecio 30 minutos después de finalizado el procedimiento anestésico quirúrgico. Se infiere que en las pacientes que recibieron fentanil, diazepán y tiopental, la aminofilina acelera el despertar, probablemente debido al bloqueo de los receptores de adenosina