Probable interaction between trazodone and carbamazepine.

The need to maintain long-term treatment of chronic pathologies makes the appearance of interactions possible when such therapies incorporate other drugs to deal with the aggravation of the same or other intercurrent pathologies. A case is presented in which the addition of trazodone to a chronic treatment with carbamazepine (CBZ) is associated with symptoms typical for intoxication by this antiepileptic, accompanied by a raised serum concentration. When the trazodone was suspended, these symptoms lessened and the concentration of CBZ decreased progressively, suggesting a probable interaction between the 2 drugs.

Medicamentos transdérmicos en neurología / Transdermal drugs in neurology

No disponible

A strategy to improve the detection of drug-induced hepatotoxicity.

AIMS: To report a new strategy for the detection of hepatotoxic adverse drug reactions (ADRs) in hospitalized patients improving the results obtained with other methods. DESIGN: The model is based on the identification of a single alert signal in various target clinical departments over a 12-month period. Each patient was later interviewed following a set protocol. The main results analyzed were the drugs suspected of ADR; causal relationship between suspected drugs and ADRs; ADR severity, and incidence of hepatotoxic ADR/100,000 inhabitants. SUBJECTS: Population served by a university-affiliated urban teaching hospital (519,381 inhabitants). RESULTS: The overall ratio of confirmed/suspected ADRs was high (35/80). The most commonly reported drug was amoxicillin-clavulanic acid (4 cases). With regard to causality, 2 suspected cases were classified as definite and 14 as probable. The distribution according to the severity of hepatotoxicity was 6 severe and 29 mild cases. The incidence of hepatotoxic ADRs/100,000 inhabitants as revealed by our method was much higher versus voluntary report (6.74 and 1.79, respectively). CONCLUSIONS: Our method has proven effective for improving the detection of hepatotoxic ADRs, and may be extended to other types of adverse reactions.

Una estrategia para mejorar la detección de hepatotoxicidad por medicamentos / A strategy to improve the detection of drug-induced hepatotoxicity

Objetivos: comunicar una nueva estrategia para la detecciónde reacciones hepatotóxicas por medicamentos que mejora los resultadosobtenidos con otros métodos utilizados.Diseño: el modelo se basa en la identificación de una señal dealerta simple en los pacientes de varios servicios diana, durante12 meses. Cada paciente fue posteriormente entrevistado siguiendoun protocolo específico. Se analizaron: los fármacos sospechososde producir hepatotoxicidad, la relación de causalidad entre elfármaco sospechoso y la hepatotoxicidad, la gravedad y la incidenciade hepatotoxicidad medicamentosa/100.000 habitantes.Pacientes: la población del área de influencia de nuestro hospital(519.381 habitantes).Resultados: se encontraron 80 sospechas de reacciones hepatotóxicasa medicamentos. La relación de reacciones confirmadas/sospechadas fue de 35/80. El fármaco imputado con mayorfrecuencia fue amoxicilina/clavulánico (4 casos). En relación algrado de imputabilidad, 2 sospechas fueron calificadas como definitivasy 14 como probables. Según la gravedad, se encontraron6 reacciones graves y 29 leves. La incidencia de reacciones hepatotóxicaspor medicamentos/100.000 habitantes (6,74) fue muchomayor que las obtenidas con otros métodos.Conclusiones: la aplicación de este método mejora la detecciónde reacciones hepatotóxicas por medicamentos y podría serempleado en otros tipos de reacciones adversas

Aims: to report a new strategy for the detection of hepatotoxicadverse drug reactions (ADRs) in hospitalized patients improvingthe results obtained with other methods.Design: the model is based on the identification of a singlealert signal in various target clinical departments over a 12-monthperiod. Each patient was later interviewed following a set protocol.The main results analyzed were the drugs suspected of ADR;causal relationship between suspected drugs and ADRs; ADRseverity, and incidence of hepatotoxic ADR/100,000 inhabitants.Subjects: population served by a university-affiliated urbanteaching hospital (519,381 inhabitants).Results: The overall ratio of confirmed/suspected ADRs washigh (35/80). The most commonly reported drug was amoxicillinclavulanicacid (4 cases). With regard to causality, 2 suspected caseswere classified as definite and 14 as probable. The distributionaccording to the severity of hepatotoxicity was 6 severe and 29mild cases. The incidence of hepatotoxic ADRs/100,000 inhabitantsas revealed by our method was much higher versus voluntaryreport (6.74 and 1.79, respectively).Conclusions: our method has proven effective for improvingthe detection of hepatotoxic ADRs, and may be extended to othertypes of adverse reactions

Carta 1. Réplica / Letter 1. Reply

No disponible

[Calculating how long phenytoin intoxication lasts]. / Cálculo de la duración de una intoxicación por fenitoína.

INTRODUCTION: We report a case of intoxication with phenytoin (DPH), in which the actual time required for it to disappear was compared with that estimated using linear regression. CASE REPORT: A 23-year-old female with tonic-clonic seizures, receiving chronic therapy with DPH 300 mg/day. The patient came to hospital because of tremors, balance disorders, vomiting and headaches. Neurologically, she presented horizontal nystagmus in the two extreme gazes, generalised hyperreflexia and ataxic gait. Cranial CAT scan and cerebrospinal fluid were both normal. Serum concentration of DPH was found to be 60.2 mg/L. When DPH concentration is >8-10 mg/L, its rate of elimination diminishes disproportionately and the risk of toxicity increases. Use of mathematical methods makes it possible to calculate the time required for a toxic concentration to come down to therapeutic values. In our patient the DPH took 204 hours to drop below the toxic level (20 mg/L), whereas by using a linear regression with only two different concentrations a figure of 155 hours was obtained. CONCLUSIONS: The method employed here can be useful as a quick, simple and easily applicable way of estimating the time a toxic concentration of DPH takes to return to a normal level.

[Confirmed and suspected digoxin intoxications]. / Intoxicaciones digitálicas sospechadas y corfimadas.

AIMS: To quantify and analyze suspected and actual digoxin intoxications. METHOD: A drug-use study has been carried out of digoxinaemia requests and results in patients treated chronically with digoxin. RESULTS: Digoxin intoxication (presence of symptoms and typical signs) was suspected in 31.3% of the patients. The percentage analytically confirmed intoxications (digoxinaemia >2 ng/mL) was 16.6%. Sex, age, and dosage had no significant effect in the suspicion or confirmation of digoxin intoxication. Hospitalization and the association of hypokalaemic drugs or those increasing digoxinaemia had no effect in the suspicion of digoxin intoxication. In analytically confirmed intoxications, no significant differences were found between suspected and non-suspected cases. CONCLUSIONS: The suspicion of this intoxications is not usually related with digoxin serum levels, and thus, the toxic limit is imprecise.

Análisis clínico de 91 casos de vasculitis de mediano y pequeño vaso en adultos / Clinical analysis of 91 adults with medium and small sized vessel vasculitis

Fundamento: Analizar las diferencias clínicas y biológicas de las vasculitis de mediano y pequeño vaso. Pacientes y métodos: Estudio descriptivo retrospectivo de 91 casos de vasculitis atendidos en nuestro hospital entre enero de 1991 a marzo de 2001. Se describen las características clínicas y analíticas. Resultados: El 57 por ciento eran varones y la edad media fue de 61,9 ñ 18,6 años (mínima de 17 y máxima de 90). Los síntomas y afectación orgánica fueron: púrpura palpable (89 por ciento), fiebre (36 por ciento), astenia (20 por ciento), artromialgias (19 por ciento), afectación renal (18 por ciento), artritis (16 por ciento), dolor abdominal (16 por ciento), neuropatía (8,7 por ciento), afectación pulmonar (6,5 por ciento). El 24 por ciento mostró varios brotes, clínica prolongada o cronificación del proceso. El 42 por ciento mostró afectación de dos o más órganos o sistemas. Los pacientes con vasculitis consideradas pauci-inmunitarias mostraron mayor astenia (p<0,001), afectación renal y pulmonar (p<0,001 y p<0,01; respectivamente), afectación multiorgánica (p<0,001) y mortalidad relacionada con el proceso (p<0,05). No se encontraron diferencias significativas con respecto al resto de la clínica analizada. Conclusiones: Aunque existe un importante solapamiento clínico entre los distintos tipos de vasculitis, la presencia o ausencia de ciertos datos clínicos y biológicos son de ayuda en la diferenciación y caracterización de las distintas entidades (AU)

Objective: To evaluate the clinical and biological differences between medium sized vessel vasculitis and small vessel vasculitis. Patients and methods: descriptive and retrospective study of 91 patients with vasculitis attended in our hospital from January 1991 to mars 2001. We describe the characteristics of clinical and analytic features. Results: 57% were males. The mean age was 61.9±18.6 years (17 to 90 years). The symptoms and affected organs were: palpable purpura (89%), fever (36%), asthenia (20%), arthromyalgias (19%), nephropaty (18%), arthritis (16%), abdominal pain (16%), neuropathy (8,7%), pulmonary involvement (6,5%). 25% had several episodes, lasting clinical, chronic disease. 42% had evidence of two or more involve organs. The patients with pauci-inmune vasculitis presented more asthenia, nephritis, pulmonary involvement, multi-organic involvement and mortality related to the process. We did not found significant differences respect to the others clinical manifestations analysed. Conclusions: There is a substantial overlap among different vasculitis, the presence or absence of some clinical and biological features can help in the differentiation and characterization of the different entitles (AU)

Intoxicaciones digitálicas sospechadas y confirmadas / Confirmed and suspected digoxin intoxications

Objetivos: Cuantificar y analizar loas intoxicaciones digitálicas y sus sospechas. Método: Se ha realizado un estudio de utilización de medicamentos sobre las peticiones de digoxinemia y los resultados obtenidos en pacientes tratados crónicamente con digoxina. Resultados: Se sospechó intoxicación digitálica (presencia de síntomas y signos propios de la misma) en el 31,3 por ciento de los pacientes y se confirmó analíticamente (digoxinemia > 2 ng/mL) en el 16,6 por ciento. El sexo, la edad y la dosis no influyeron significativamente en la sospecha ni en la confirmación de la intoxicación digitálica. Sí influyeron en las sospechas de intoxicación digitálica, la hospitalización y la asociación de fármacos hipokalemiantes o que eleven la digoxinemia. En las intoxicaciones confirmadas analíticamente no se encontraron diferencias significativas entre las sospechadas y las no sospechadas. Conclusiones: La sospecha de esta intoxicación no suele relacionarse con los niveles plasmáticos de digoxina y, por tanto, su límite tóxico es impreciso. (AU)

[Can treatment associated with ticlopidine and nifedipine increase serum levels of phenobarbital?]. / ¿Puede el tratamiento asociado con ticlopidina y nifedipina aumentar los niveles séricos de fenobarbital?

INTRODUCTION: We report a case in which the association between ticlopidine, nifedipine and phenobarbital was linked with a higher than expected phenobarbital concentration in serum, which suggested a possible interaction between these drugs. CASE REPORT: A 67 year old male who received treatment with phenobarbital, digoxin, nifedipine, ticlopidine, paroxetine and clorazepate dipotassium. The first control of the level of phenobarbital in serum was performed without any symptoms or signs of toxicity or ineffectiveness. A phenobarbital concentration in serum of 21.4 mg/L was obtained, with a serum level/dosage ratio of 16.7. DISCUSSION: The serum level/dosage ratio of phenobarbital that was found in this case is almost twice as high as expected. In the absence of other factors that can explain this finding, we believe that two drugs (ticlopidine and nifedipine) may be involved in an interaction with phenobarbital. CONCLUSIONS: The high value of the serum level/dosage ratio that was found makes it advisable to monitor the concentrations of phenobarbital in serum in treatment associated with ticlopidine or nifedipine, especially when adjusting the dosage, beginning or ending treatment with these drugs.

Estudio de utilización de la profilaxis tromboembólica venosa en cirugía de cadera / Study of the use of venous thromboembolic prophylaxis in hip surgery

Objetivo. Cuantificar la profilaxis tromboembólica en la cirugía de cadera y determinar su calidad. Diseño experimental. Estudio retrospectivo de utilización de medicamentos, del tipo indicación-prescripción. Las variables principales fueron: realización o no de tromboprofilaxis, tipo de la misma (fármaco, dosis y tiempo) y cualidad (correcta, incorrecta y dudosa).Resultados. La profilaxis tromboembólica se indicó en el 91,3 por ciento de los pacientes (p < 0,05). Los fármacos utilizados más frecuentemente fueron las heparinas de bajo peso molecular (p < 0,001). La calidad de la profilaxis fue incorrecta en el 63,3 por ciento (p < 0,001), dudosa en el 28,3 por ciento y correcta en el 8,4 por ciento. Conclusiones. Los cirujanos ortopédicos conocen la indicación de tromboprofilaxis en los pacientes operados de cadera y la prescriben, aunque no siguen unánimemente las recomendaciones aceptadas internacionalmente para su realización (AU)

[The role of olanzapine in Parkinsonian dopaminergic psychosis]. / Papel de la olanzapina en la psicosis dopaminérgica parkinsoniana.

INTRODUCTION: The drug induced psychosis (DIP) that appears in Parkinson s disease (PD) is a frequent complication which is difficult to deal with therapeutically. Treatment is based on lowering the amount of antiparkinson drugs or using classical neuroleptics (haloperidol), which in both cases deteriorates motor function. Recently, antipsychotic drugs have appeared which are called atypical (AA) due to their scarce or null motor effects. METHOD: We carried out a review of the research work that has been published in which one of these AA, olanzapine (OLZ), was used to treat the DIP that appears in PD patients. The results obtained show OLZ to be an effective antipsychotic drug. However, the data on its capacity to deteriorate motor function is contradictory and it has not been possible to pinpoint the reasons why this adverse side effect appears in some patients and not in others. The causes that have been suggested, although they do not account for all the cases, are the use of high doses of OLZ and the prior existence of dementia. Moreover, some cases of OLZ induced agranulocytosis have been detected, although it was thought that this side effect within the AA was exclusive to clozapine. CONCLUSION: Although it is effective as an antipsychotic drug, there exists contradictory data about the capacity of OLZ to deteriorate the state of patients suffering from Parkinson s disease, which means that it does not seem to be the first choice drug in the DIP that appears in PD.

Papel de la olanzapina en la psicosis dopaminérgica parkinsoniana / The role of olanzapine in parkinsonian dopaminergic psychosis

Introducción. La psicosis inducida por fármacos (PIF) que aparece en la enfermedad de Parkinson (EP) es una complicación frecuente y de difícil manejo terapeútico. Su tratamiento se basaba en disminuir los fármacos antiparkinsonianos o usar neurolépticos clásicos (haloperidol), lo que empeoraba en ambos casos la función motora. Recientemente, han surgido unos antipsicóticos denominados atípicos (AA) por sus escasos o nulos efectos motores. Desarrollo. Se han revisado los trabajos publicados en los que se emplea uno de estos AA, la olanzapina (OLZ), para tratar la PIF que aparece en la EP. Los resultados obtenidos demuestran que la OLZ es un eficaz antipsicótico. Sin embargo, existen datos contradictorios en cuanto a su capacidad de empeorar la función motora y no se pueden precisar las causas por las que aparece este efecto adverso en algunos pacientes y en otros no. Las causas manejadas, aunque no explican todos los casos, son el empleo de dosis altas de OLZ y la existencia previa de demencia. Por otra parte, se han detectado algunos casos de agranulocitosis inducida por OLZ, aunque se pensaba que este efecto adverso dentro de los AA era exclusivo en la clozapina. Conclusión. Aunque eficaz como antipsicótico, existen datos contradictorios sobre la capacidad de la OLZ de empeorar la clínica parkinsoniana, por lo que no parece que sea el fármaco de elección en la PIF que aparece en la EP (AU)

[Possible gabapentin phenytoin interaction]. / Posible interacción gabapentina fenitoína.

INTRODUCTION: We report a possible case of gabapentin induced phenytoin toxicity. CASE REPORT: White man, 26 years old, chronically treated with phenytoin (for the past 4 years) and gabapentin (for the past 17 months). He was seen after complaining of dysarthria, ataxia and vertigo for the past 3 months, although having noted slight dizziness and a general, though undefined, indisposition from the start of taking gabapentin. The total and free serum levels of phenytoin found were clearly toxic. Gabapentin was discontinued definitively, and phenytoin for the next 7 days. The clinical symptoms had disappeared completely and phenytoin returned to within therapeutic levels. According to the criteria of causation it can be considered a possible adverse reaction caused by phenytoin related to incorporation of gabapentin. The mechanisms of this possible drug interaction are discussed, with emphasis on cytochrome P450 metabolism. CONCLUSION: The present case is a warning of the possible interaction of a drug (gabapentin) not contemplated when starting or when monitoring an antiepileptic treatment.

[Thromboembolism prevention in acute myocardial infarction]. / Profilaxis tromboembólica en infarto agudo de miocardio.

The objectives were to identify risk factors for vein thromboembolic disease (VTD) among patients with acute myocardial infarction (AMI) and to analyse both quantitatively and qualitatively the performed thromboembolic prophylaxis. A cross-sectional study was carried out with all inpatients at the Coronary Unit at our hospital during 1998. The risk factors for thromboembolism included: inmobilization (79.2%), heart failure (33.2%) and age over 70 years (31%). VTD prophylaxis was performed in 86.9% of the time. Non-fractioned heparin (NFH) and low molecular weight heparins (LMWH), mostly nadroparine, were the most commonly used drugs at admission and at discharge, respectively. Overdosage and underdosage for NFH and LMWH, respectively, were observed. That patients received or not VTD prophylaxis was not influenced by thromboembolic risk factors.

Profilaxis tromboembólica en infarto agudo de miocardio / Thromboembolic prophylaxis in acute myocardial infarction

Los objetivos eran identificar los factores de riesgo de enfermedad tromboembólica venosa (ETV) en los pacientes con infarto agudo de miocardio (IAM) y analizar cuantitativa y cualitativamente la profilaxis tromboembólica realizada. Se ha hecho un estudio transversal de todos los pacientes ingresados en la Unidad Coronaria de nuestro hospital durante 1998. Los factores de riesgo tromboembólico han sido: inmovilización (79,2 por ciento), insuficiencia cardíaca (33,2 por ciento) y edad superior a 70 años (31 por ciento). Se hizo profilaxis de ETV en el 86,9 por ciento. La heparina no fraccionada (HNF) fue el fármaco más utilizado durante el ingreso y las heparinas de bajo peso molecular (HBPM) al alta, mayoritariamente nadroparina. Existía sobredosificación para las HNF e infradosificación para las HBPM. Los factores de riesgo tromboembólico no influyeron en que los pacientes recibieran o no profilaxis de ETV (AU)