Assessment of carbamazepine acute toxicity in the cockle Cerastoderma edule through chemical, physiological and biochemical tools / Avaliação da toxicidade aguda da carbamazepina no berbigão Cerastoderma edule por meio de ferramentas químicas, fisiológicas e bioquímicas

The cockle Cerastoderma edule was exposed to four concentrations (5, 10, 20 and 70 μg L-¹) of carbamazepine (CBZ). This anticonvulsant was found to alter the mussel behavior of by reducing its clearance rate (CR). Analysis of CBZ accumulation in tissues of C. edule was carried out using HPLC-UV after 48 or 96 hours of exposure. In addition, an overproduction of H2O2 by the bivalves was detected following exposure to CBZ but nitrite levels remained unchanged. Moreover, superoxide dismutase and catalase activities showed a significant increase in relation to their contact with CBZ. The activity of the biotransformation enzyme gluthatione-S-transferase did not change during exposure. Malondialdehyde (MDA) levels indicating cellular damage, increased when bivalves were exposed to 20 and 70 μg l-¹ of carbamazepine for 96 h CBZ. The results also indicate that acetylcholinesterase activity (AChE) was inhibited in all CBZ concentrations during the 48 h exposure period. However, during the 96 h exposure period, AChE was only inhibited at the highest concentration. Further studies are needed now for more exploration of the toxicity of CBZ since it could be bioaccumulable throughout the food web and may affect non-target organisms.

O berbigão Cerastoderma edule foi exposto a quatro concentrações (5, 10, 20 e 70 μg L-¹) de carbamazepina (CBZ). Este anticonvulsivante alterou o comportamento do mexilhão, reduzindo sua taxa de depuração (CR). A análise do acúmulo de CBZ nos tecidos de C. edule foi realizada por HPLC-UV após 48 ou 96 horas de exposição. Além disso, uma superprodução de H2O2 pelos bivalves foi detectada após a exposição à CBZ, mas os níveis de nitrito permaneceram inalterados. Além disso, as atividades de superóxido dismutase e catalase apresentaram aumento significativo em relação ao contato com CBZ. A atividade da enzima de biotransformação glutationa-S-transferase não se alterou durante a exposição. Os níveis de malondialdeído (MDA), indicando dano celular, aumentaram quando os bivalves foram expostos a 20 e 70 μg l-1 de carbamazepina por 96 h CBZ. Os resultados também indicam que a atividade da acetilcolinesterase (AChE) foi inibida em todas as concentrações de CBZ durante o período de exposição de 48 horas. No entanto, durante o período de exposição de 96 horas, a AChE foi inibida apenas na concentração mais alta. Mais estudos são necessários agora para uma maior exploração da toxicidade da CBZ, uma vez que pode ser bioacumulável em toda a cadeia alimentar e pode afetar organismos não alvo.

Epilepsia no período gravídico-puerperal / Epilepsy in puerperal-pregnancy period

A epilepsia, doença cerebral caracterizada pela predisposição à geração de crises epilépticas, representa a patologia neurológica grave mais frequente na gravidez. Quando não acompanhada corretamente, possui um acentuado nível de morbimortalidade materno-fetal, sendo especialmente relacionada a riscos de convulsão materna na gestação e malformações fetais. Este artigo discute o acompanhamento da gestante epiléptica, trazendo recomendações de cuidados no período pré-concepcional, manejo durante o pré-natal, condução do trabalho de parto, peculiaridades no puerpério e tratamento de crises convulsivas, quando necessário. Serão abordados tanto aspectos de tratamento farmacológico quanto de monitoramento e orientações gerais, com o objetivo de contribuir para um suporte mais abrangente e adequado a esse grupo mais vulnerável de pacientes sob o cuidado do médico ginecologista-obstetra e neurologista.(AU)

Epilepsy, which is a brain disease defined for a greater predisposition for epileptic crisis, represents the most frequent neurological pathology during pregnancy. Without proper monitoring it is related to high morbidity and mortality to both mother and baby, especially due to the risks of mother seizure during pregnancy and fetus malformation. This article discusses about health care giving and follow-up for the epileptic pregnant women, pointing recommendations for preconception care, prenatal management, labor conduct, peculiarities in puerperium and treatment of convulsive crisis when needed. There will be approached pharmacological and non-pharmacological aspects, such as follow up exams and general orientations, having as a goal to contribute to an more abrangent and proper support of this more vulnerable group of patients under the care responsibility of obstetrician-gynecologist ad neurologist doctors.(AU)

Anatomical, radiological and clinical features of mesial temporal lobe epilepsy: two illustrated cases reports / Aspectos anatômicos, radiológicos e clínicos da epilepsia do lobo temporal mesial: relato ilustrado de dois casos

Mesial temporal lobe epilepsy is the most commom form of focal epilepsy in adults. Its clinical features include focal seizure, dysmnestic symptoms ­ such as déjà vu or jamais vu ­ and autonomic or psychic aura. We reported two cases of mesial temporal lobe epilepsy with similar clinical features, but with entirely different etiologies. Mesial temporal sclerosis contributes up to 70% of all mesial temporal lobe epilepsy cases and MRI usually shows reduced hippocampal volume and increased signal intensity on T2-weighted imaging. Incomplete hippocampal inversion has uncertain relation with epilepsy and is characterized by an atypical verticalized and medially positioned anatomical pattern of the hippocampus and also a deep collateral sulcus.

A epilepsia do lobo temporal mesial é a forma mais comum de epilepsia focal em adultos. Suas características clínicas incluem crises focais, sintomas dismnésicos - como déjà vu ou jamais vu - e aura autonômica ou psíquica. Relatamos dois casos de pacientes com epilepsia do lobo temporal mesial com manifestações clínicas semelhantes, mas com etiologias completamente diferentes. A esclerose mesial temporal contribui com até 70% de todos os casos de epilepsia do lobo temporal mesial e, geralmente, na ressonância magnética, apresenta atrofia do hipocampo e hipersinal na imagem ponderada em T2. A rotação incompleta do hipocampo possui uma relação incerta com a epilepsia e é caracterizada por alteração da estrutura interna do hipocampo, com um sulco colateral verticalizado e profundo.

Pain management in children with erythromelalgia: case report / Tratamento da dor em criança com eritromelalgia: relato de caso

Abstract Erythromelalgia is a neuropathic pain syndrome due to an autosomal dominant gene, characterized by erythema, increased skin temperature and burning pain in hands and feet, whose treatment is often unsatisfactory. In this paper, we report a case of a 9 years old female patient whose first episode of burning pain, erythema and edema of the hands, without triggering factors, had instant relief after immersion in cold water. She presented with systemic arterial hypertension and had seizures. The patient was treated with gabapentin (150 mg.8 h−1) and amitriptyline (12.5 mg) orally, intravenous lidocaine infusion (120 mg), without relieving pain complaints. Due to the lack of response to the proposed treatment, it was decided to gradually reduce these medications and to introduce carbamazepine (200 mg) orally and, after 4 days of treatment, there was complete relief of the manifestations.

Resumo Eritromelalgia é uma síndrome dolorosa neuropática decorrente de gene autossômico dominante, caracterizada por eritema, aumento da temperatura da pele e dor em queimação, em mãos e pés, e o tratamento é muitas vezes insatisfatório. Neste caso, está o relato de uma paciente do sexo feminino, com nove anos e primeiro episódio de dor em queimação, eritema e edema em mãos, sem fatores desencadeantes, com alívio instantâneo após imersão em água fria. Apresentava hipertensão arterial sistêmica e teve crises convulsivas. Foi tratada com gabapentina (150 mg.8 h-1) e amitriptilina (12,5 mg) via oral, lidocaína (120 mg) venosa em infusão, sem alívio das queixas álgicas. Devido à ausência de resposta ao tratamento proposto, decidiu-se redução gradativa dessas medicações e introdução de carbamazepina (200 mg) via oral e após quatro dias de tratamento houve alívio completo das manifestações.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos debido a la carbamazepina: Caso pediátrico / Drug reaction with eosinophilia and systemic symptoms due to carbamazepine: Pediatric case

Entre las reacciones medicamentosas graves en la piel, se encuentran el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y el síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms; DRESS, por sus siglas en inglés), que son poco comunes en la población pediátrica (incidencia: 1/1000-10 000 niños), sin embargo, tienen mal pronóstico. El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos consiste en erupciones cutáneas, alteraciones hematológicas, linfadenopatía y afectación de órganos. Se presenta el caso de un paciente masculino de 12 años que desarrolló esta patología después de iniciar el tratamiento anticonvulsivo con carbamazepina. Se considera que es importante que el personal de la salud tenga conocimiento de esta enfermedad para que sea incluida entre los diagnósticos diferenciales de pacientes con afecciones similares, ya que este síndrome es potencialmente mortal.

Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000-10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine. We consider that it is important to be aware of this disease and to include it among the differential diagnoses in patients with similar conditions because this syndrome is life-threatening.

Polirradiculoneuropatia periférica desmielinizante associada ao uso de carbamazepina em cão: relato de caso / Demyelinating peripheral polyradiculoneuropathy associated with the use of carbamazepine in dog: case report

Diversos fármacos são utilizados no tratamento da epilepsia e, assim como outros medicamentos, podem induzir a ocorrência de efeitos adversos, alguns tão graves que geram a necessidade de descontinuidade e substituição da terapia. A carbamazepina pode levar a alterações nos sistemas cardiovascular, respiratório e neurológico, sendo descritos na literatura casos de indução de miastenia gravis como distúrbio neuromuscular. Este estudo relata o caso de um cão que desenvolveu polirradiculoneuropatia desmielinizante, tendo como provável desencadeante a terapia com carbamazepina. O paciente apresentou tetraplegia, ausência de reflexos espinhais nos quatro membros, fraqueza cervical, diminuição do reflexo palpebral bilateral e esforço respiratório. A eletroneuromiografia demonstrou sinais de desmielinização. Este, portanto, é o primeiro relato de associação entre carbamazepina e polirradiculoneuropatia desmielinizante em cão.(AU)

Different drugs are used in the treatment of epilepsy and, like other drugs, may induce the occurrence of adverse effects, some of them so severe that the drug must be discontinued and replaced. Carbamazepine may lead to changes in the cardiovascular, respiratory, and neurological systems, and cases of induction of myasthenia gravis as a neuromuscular disorder have been described in the literature. This paper reports the case of a dog that developed demyelinating polyradiculoneuropathy, probably triggered by carbamazepine. The patient presented tetraplegia, absence of spinal reflexes in the four limbs, cervical weakness, decreased bilateral eyelid reflex and respiratory effort. Electroneuromyography showed signs of demyelination. This, therefore, is the first report of association between carbamazepine and demyelinating polyradiculoneuropathy in dogs.(AU)

Comparison of analgesic effects of oral carbamezapine with pregablin in idiopathic trigeminal neuralgia

Idiopathic trigeminal neuralgia, a form of neuropathic pain, caused by not well defined etiology, is a formidable therapeutic challenge to clinicians because it does not respond well to traditional drug therapies. Anticonvulsant drugs are regarded as useful treatment for neuropathic pain. Carbamazepine, the first anticonvulsant studied in clinical trials, probably alleviates pain by decreasing conductance in Na[+] channels and inhibiting ectopic discharges. Pregabalin has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain. The role of anticonvulsant drugs in the treatment of Idiopathic trigeminal neuralgia is evolving and has been clearly demonstrated with Pregabalin and carbamazepine. The aim of this study was to investigate comparison of analgesic effects of oral carbamezapine with pregablin in idiopathic trigeminal neuralgia. Interventional study. Oral and Maxillofacial surgery department, LUMHS. Jan 2012 to DEC 2012 . 30 patients with well defined history and diagnostic clinical symptoms of idiopathic trigeminal neuralgia were selected, divided into two groups of 15 individuals with similar gender and age difference. Clinical trial were conducted with group 1 with carbamazepine and group 2 with Pregabalin for 4 weeks. Subjective pain level of both groups was recorded before intervention [pre treatment recording] and after intervention [1[st], 2[nd], 3[rd] and 4[th]] on weekly basis by using 0-10 visual analogue scale [zero represent no pain 10 represent pain that could not be worse]. Following intervention, both groups were evaluated for pain score in 1[st] and 2[nd] week, there was no significant difference observed between the two groups. [P value 0.44 and 0.456], but after 3[rd] and 4[th] weeks it was observed that, there is significant difference, [p value 0.000 and 0.009] on visual analogue scale. It was observed that there was a significant difference between pretreatment and fourth week mean pain score in group 2, [8.9 and 1.07]. Similarly marginally significant difference with [r = .640] was seen in 1[st] week of group 2 receiving Pregablin, the mean value was [2.53, 1.60] respectively. Based on these results that are in line with the recommendations made by other studies, the 1[st] line medical therapy is Carbamazepine but this should be changed to other drug therapy if there is no pain relief or adverse effect

Uso y abuso en la prescripción de la carbamazepina en el Área Sur de Morón / Use and abuse in carbamazepine prescription in the South Area of Morón

Se realizó un estudio cuantitativo, retrospectivo y descriptivo para determinar el uso y abuso de la prescripción de carbamazepina en el Área Sur de Morón, se distribuyeron los pacientes según sexo, edad, criterio de prescripción, precisar dosis indicada, determinar el tiempo de duración de la terapia, describir las interacciones medicamentosas y narrar las reacciones medicamentosas encontradas. Se determinó que el sexo más afectado fue el masculino con un 50,87 por ciento, el grupo de edad más afectado fue el de 25 a 59 con un 54, 31 por ciento, el criterio que prevaleció fue la epilepsia con un total de 70 pacientes y un 60,74 por ciento, la dosis que con mayor frecuencia se usó fue la de 3 tabletas diarias, el tiempo de duración de la terapia por un año fue el más recomendado con un total de 106 pacientes para un 91,38 por ciento, la interacción medicamentosa más frecuente fue con el fenobarbital en un 70,69 por ciento y la reacción medicamentosa más común fue el vértigo para un 14,65 por ciento.

Efficacy, Safety and Tolerability of Trioptal®d: (Oxcarbazepine) in Children and Adolescents with Newly Diagnosed Partial Seizures or Generalized Tonic-Clonic Seizures: Results of a 6 Months, Prospective, Open-Label, Multicentre, Non-Comparative, Observational Post-Marketing Surveillance Study.

Objective: The current study was designed to analyze the extended efficacy and safety of Trioptal® (Oxcarbazepine) in treatment of children and adolescents with newly diagnosed partial seizures or generalized tonicclonic seizures in Indian population. Methods: This was an open-label non-randomized multi-centric observational prospective study (PMS study) across 54 centers in India. Treatment with Trioptal® (Oxcarbazepine) was initiated with a clinically effective dose (8-10 mg/kg/day in children) given in two divided doses as per the prescribing information. The dose was increased depending on the clinical response of the patient. In children, if clinically indicated, the dose was increased by a maximum of 10 mg/kg/day increments at approximately weekly intervals from the starting dose, to a maximum daily dose of 60 mg/kg/day. The efficacy of Trioptal® was assessed primarily by the percentage of seizure-free patients at 24 weeks. Secondary efficacy of the treatment was assessed through: reduction in seizure frequency at 24 weeks and the Global assessment of efficacy by the investigator at 24 weeks. Results: A total of 485 subjects were enrolled in the study. Majority of the subjects (52%) were stabilized at 8-15 mg/kg/day dose of Trioptal® and mean effective dose was 16.1 mg/kg/day (± 7.02). Approximately 70 % of the subjects were seizures free after 24 weeks of Trioptal® treatment and around 88% of the subjects reported the reduction in seizure of more than 50 %. The mean reduction in seizure frequency after 24 weeks of treatment was 82.3%. The overall efficacy with the Trioptal® treatment for 24 weeks was ‘good’ to ‘excellent’ in more than 97% of the subjects as per the assessment by the physician. A total of 59 adverse events were observed in 43 (8.9%) subjects. Headache was the most common adverse event being recorded in 8 subjects, followed by somnolence, nausea, vomiting, skin rash and weight gain. The overall tolerability of Trioptal® as per assessment by the patients was ‘good’ to ‘excellent’ in more than 98% of the subjects. Conclusion: Trioptal® (Oxcarbazepine) treatment is effective, safe and well tolerable in children and adolescents with newly diagnosed partial seizures or generalized tonic-clonic seizures.

[Invitro comparison studying of dissolution profiles for pharmacopoeial and nonpharmacopoeial native anticonvulsants oral solid dosage forms with brand name]

Dissolution is very important parameter in releasing of active pharmaceutical ingredient from dosage form, and this directly correlate with absorption process and consequently with bioavailability of oral dosage forms [tablet]. Oxcarbazepine is an oral anticonvulsant, and in this research we work on Invitro comparison of dissolution protiles for two native oxcarbazepine tablet 300 mg products with the same of patented [trileptal[rigstered]], calculating similarity factor f[2] as the base of comparison, the value of similarity factors were for product-A [f[2]=77.1], for product-B [f[2]=51] appear similarity of dissolution profiles of two previous product with the same of patented

Bioequivalencia de una formulación cubana de carbamazepina con el producto líder / Bioequivalent of a Cuban formula of Carbamazepine with the leader product

Se demostró la intercambiabilidad terapéutica mediante un estudio de bioequivalencia en 25 voluntarios sanos de una formulación cubana de carbamazepina de 200 mg con respecto al producto innovador (Tegretol®), en condiciones de administración a dosis única; el diseño experimental fue cruzado a doble ciegas y aleatorizado; el periodo de lavado fue de 15 días. Las extracciones para la obtención del plasma, se realizaron a las 0; 0,5; 1; 1,5; 2; 3; 4; 6; 8; 10; 12; 16; 20; 24; 48; 72; 96 y 120 h. Para el análisis se empleó un método analítico por cromatografía líquida de alta eficiencia, isocrático en fase reversa con detección ultravioleta. Se estimaron mediante técnicas no compartimentales los parámetros farmacocinéticos (AUC0-t, AUCt-¥, Cmax, Tmax y T1/2) representativos de la biodisponibilidad en magnitud y velocidad. Sobre la base de los resultados estadísticos, ambas formulaciones resultaron bioequivalentes.

It was possible to demonstrate the therapeutic interchange level by means of a bioequivalence study in 25 healthy volunteers of a Cuban formula of Carbamazepine(200 mg) according to the innovative product (Tegretol®) for a administration of unique dose; the experimental design was of crossed, double-blind and random type; washing period was of 15 days. Extractions for plasma obtaining were performed at 0, 0,5, 1, 1,5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 48, 72, 96 and 120 hours. In analysis we used an analytical method by high performance liquid chromatography, isocratic type in reverse phase with UV detection. By means of non-compartment techniques pharmacokinetic parameters (AUC0-t, AUC t-¥, Cmax, Tmax, and T½) were estimated, which are representative of bioavailability in magnitude and speed. On the base of statistical results, both formulae were bioequivalent.

Papel de la monoterapia con nuevos fármacos antiepilépticos en el tratamiento de la epilepsia infantil / Role of monotherapy with new antiepileptic drugs in the treatment of childhood epilepsy

En este trabajo se revisa la información actual sobre el uso de los nuevos fármacos antiepilépticos (FAEs) en monoterapia en niños, resaltando nuestra experiencia personal. Específicamente, se incluyen los siguientes FAEs: lamotrigina (Lamictal®), topiramato (Topamax®), zonisamida (Zonegran®), levetiracetam (Keppra®), y oxcarbacepina (Trileptal®). Todos estos FAEs tienen un amplio espectro de acción en el tratamiento de crisis epilépticas parciales y generalizadas, excepto la oxcarbacepina, que es eficaz exclusivamente en crisis parciales. No está claro si la monoterapia con estos FAEs, en comparación con los FAEs clásicos (fenobarbital, fenitoína, carbamacepina, valproato sódico), proporciona una mayor eficacia y/o causa menos efectos secundarios y, si por lo tanto, mejora significativamente la calidad de vida de los niños con epilepsia. Se necesitan más estudios para poder contestar estas preguntas.

In this paper we review the current information regarding the use of new antiepileptic drugs (AEDs) used as monotherapy in children. We specifically include the following AEDs: lamotrigine (Lamictal®), topiramate (Topamax®), zonisamide (Zonegran®), levetiracetam (Keppra®), and oxcarbazepine (Trileptal®). All of these AEDs have a broad spectrum of action in the treatment of partial and generalized seizures, except Oxcarbazepine, which is effective only in partial seizures. It is unclear whether or not monotherapy with the new AEDs offers higher efficacy and/or lower side effects compared to classic AEDs (phenobarbital, phenytoin, carbamazepine, or valproate) thereby significantly improving the quality of life in children with epilepsy. More studies are needed to answer these questions.

experimental design for finding of minimum dosage of carbamazepine and valproate in preventing of seizure attacks

Previous studies have shown that physicians use high doses of Carbamazepine [CBZ] and Valproate [VPA] to control of epileptic attacks, while these drugs incur of many side effects include of gastrointestinal, hematologic, psychiatric, cardiac and other side effects. The aim of this study was to determine the minimum therapeutic dose with and an acceptable blood level of these drugs. This semi-experimental study was done in 56 epileptic patients in during of one year. At the first demographic data including of age, sex, weight and the period of drug taking was recorded. Then the drug CBZ and VPA were prescribed to adults [more than 12 years old] 9-11 mg/kg and 12-14 mg/kg respectively, and in children [less than 12 years old] 12-14 and 12-15 mg/kg respectively. Serum levels of CBZ and VPA were measured monthly by gas chromatography method that is separation technique, is mostly employed in chemical analysis. The results indicated that serum levels of CBZ and VPA in adult were 7.4 and 74.7 and serum levels of drugs in children were 8.2 and 66.8 respectively. Also patients have not epilepsy attack in during the period of assessment. These findings showed that with a much lower dosage of the drugs, which is suggested in texts can lead to an appropriate blood level of CBZ and VPA for controlling the epileptic seizures

In vitro and in vivo neuromuscular effects of atracurium and rocuronium in rats treated with carbamazepine for seven days / Efeitos neuromusculares in vitro e in vivo do atracúrio e do rocurônio em ratos submetidos a tratamento de sete dias com carbamazepina / Efectos neuromusculares in vitro e in vivo del atracurio y del rocuronio en ratones sometidos a tratamiento de siete días con carbamazepina

JUSTIFICATIVA E OBJETIVOS: Trata-se de um estudo experimental que investigou in vitro e in vivo o bloqueio neuromuscular produzido pelo rocurônio e atracúrio em ratos tratados com carbamazepina e determinou as concentrações de citocromo P450 e b5 redutase em microssomos hepáticos. MÉTODO: Ratos foram tratados por sete dias com carbamazepina (CBZ) - 40 mg.kg-1 pelo método de gavagem e sacrificados no oitavo dia sob anestesia com uretana. As preparações in vitro e in vivo foram montadas de acordo com as técnicas de Bulbring e de Leeuwin e Wolters, respectivamente. As concentrações e doses utilizadas dos bloqueadores nas preparações in vitro e in vivo foram, respectivamente, 20 µg.mL-1 e 0,5 mg.kg-1 para atracúrio (ATC); 4 µg.mL-1 e 0,6 mg.kg-1 para rocurônio (ROC). Cada protocolo teve um n = 5 e as respostas foram observadas por 60 minutos. Os efeitos do ATC e ROC foram avaliados nas preparações de ratos tratados (Cbz t) e comparados com os observados nas de ratos não-tratados (CBZst). As concentrações de citocromo P450 e b5 redutase foram determinadas em microssomos isolados de fígados de ratos tratados (CBZt) e comparadas com as obtidas em ratos não tratados (CBZst). RESULTADOS: A carbamazepina não alterou a amplitude das respostas musculares; in vitro e in vivo, não houve diferença entre o bloqueio neuromuscular produzido pelo atracúrio nas preparações CBZt versus CBZst; o bloqueio neuromuscular produzido pelo rocurônio nas preparações CBZt foi potencializado in vitro. A carbamazepina não alterou as concentrações de citocromo P450 e b5. CONCLUSÕES: O tratamento por sete dias com carbamazepina não influenciou no bloqueio produzido pelo atracúrio, e alterou in vitro os efeitos do rocurônio. O tempo de tratamento não foi suficiente para causar indução enzimática e diminuir a sensibilidade ao rocurônio.

BACKGROUND AND OBJECTIVES: This experimental study investigated the in vitro and in vivo neuromuscular blockade of rocuronium and atracurium in rats treated with carbamazepine and determined the concentration of cytochrome P450 and b5 reductase in hepatic microsomes. METHODS: Rats were treated with carbamazepine (CBZ) - 40 mg.kg-1 by gavage and sacrificed on the eighth day under anesthesia with urethane. In vitro and in vivo preparations followed the techniques of Bulbring and Leeuwin and Wolters, respectively. Concentrations and doses of the neuromuscular blockers used in in vitro and in vivo preparations were, respectively, 20 µg.mL-1 and 0.5 mg.kg-1 for atracurium (ATC); and 4 µg.kg-1 and 0.6 mg.kg-1 for rocuronium (ROC). Each protocol had an n = 5 and the response was observed for 60 minutes. The effects of ATC and ROC were evaluated in the preparations of rats treated with carbamazepine (CBZt) and compared to those of non-treated rats (CBZst). The concentration of cytochrome P450 and b5 reductase were determined in hepatic chromosomes of rats treated with carbamazepine (CBZt) and non-treated rats (CBZst). RESULTS: Carbamazepine did not change the amplitude of neuromuscular response; differences in the neuromuscular blockade produced by atracurium in CBZ1 preparations were not observed, in vitro or in vivo, when compared with CBZst; the neuromuscular blockade produced by rocuronium in CBZt preparations was potentiated in vitro. Carbamazepine did not change the concentrations of cytochrome P450 and b5. CONCLUSIONS: Seven-day treatment with carbamazepine did not change the neuromuscular blockade produce by atracurium, but altered the in vitro effects of rocuronium. The duration of the treatment was not enough to cause enzymatic induction and decrease the sensitivity to rocuronium.

JUSTIFICATIVA Y OBJETIVOS: Se trata de un estudio experimental que investigó in vitro e in vivo el bloqueo neuromuscular producido por el rocuronio y atracurio en ratones tratados con carbamazepina y determinó las concentraciones de citocromo P450 y b5 reductasis en microsomas hepáticos. MÉTODO: Ratones fueron tratados por siete días con carbamazepina (CBZ) - 40 mg.kg-1 a través de una sonda y sacrificados al octavo día bajo anestesia con uretana. Las preparaciones in vitro e in vivo fueron montadas de acuerdo con las técnicas de Bulbring y de Leeuwin y Wolters, respectivamente. Las concentraciones y dosis utilizadas de los bloqueadores en las preparaciones in vitro e in vivo fueron, respectivamente, 20 µg.mL-1 y 0,5 mg.kg-1 para atracurio (ATC); 4 µg.mL-1 y 0,6 mg.kg-1 para rocuronio (ROC). Cada protocolo tuvo un n = 5 y las respuestas fueron observadas por 60 minutos. Los efectos del ATC y ROC fueron evaluados en las preparaciones de ratones tratados (Cbz t) y comparados a los observados en los de ratones no tratados (CBZst). Las concentraciones de citocromo P450 y b5 reductasis fueron determinadas en microsomas aislados de hígados de ratones tratados (CBZt) y comparadas con las obtenidas en ratones no tratados (CBZst) RESULTADOS: La carbamazepina no alteró la amplitud de las respuestas musculares; in vitro y in vivo, no hubo diferencia entre el bloqueo neuromuscular producido por el atracurio en las preparaciones CBZt versus CBZst; el bloqueo neuromuscular producido por el Rocuronio en las preparaciones CBZt fue potenciado in vitro. La carbamazepina no alteró las concentraciones de citocromo P450 y b5. CONCLUSIONES: El tratamiento por siete días con carbamazepina, no influenció en el bloqueo producido por el atracurio, y alteró in vitro los efectos del rocuronio. El tiempo de tratamiento no fue suficiente para causar la inducción enzimática y disminuir la sensibilidad al rocuronio.

The effects of carbamazepine on sperm morphology in wistar rats.

Carbamazepine (5 H-dibenz (b, f) azepine-5-carboxamide), is an antiepileptic drug which is expected to be administered regularly over a substantial part of patients lifetime. As the gender focus in epilepsy the later years has primarily been on women, there certainly is a lack of studies focused on the effects particular to men. The present study was aimed to investigate its effects on germ cell's by employing the sperm morphology assay. Twelve groups of male wistar rats were treated with sterile water 0.5 ml, cyclophosphamide (CP) 20 mg/kg, carbamazepine 9, 18, 36 mg/kg (i.p) and 2% gumacasia 0.25 ml/100 g respectively for 5 consecutive days at intervals of 24 hrs. Following the last exposure, on days 14 and 35 sperm morphology assay was conducted as per the standard procedure. Mann-Whitney 'U' test was used for statistical analysis and the level of significance was P<0.01. Neither carbamazepine nor cyclophosphamide induced formation of abnormally shaped sperms at 14 day time interval. Whereas on day 35, with 18 mg/kg dose level of carbamazepine there was an increase in the number of sperms with heads defects (P<0.01); Whereas in the other two dose levels the number of abnormally shaped sperms had decreased. 2% gumacasia increased the number of sperms with tail defects at day 35. (Mann-Whitney 'U' test). CONCLUSION: Carbamazepine and 2% gumacasia could be germ cell mutagens and could cause infertility on prolonged use therefore further studies with serum drug level estimations are needed.