Fármacos antiepiléticos clásicos y de nueva generación: diferencias de sexo en la efectividad / Clasic antiepileptic and new generation antiepileptic drugs: gender differences

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[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: IV. General principles of antiepileptic polytherapy and therapeutic strategies in refractory epilepsy]. / Guía terapéutica en epilepsia de la Sociedad Andaluza de Epilepsia 2005: IV. Principios generales de politerapia antiepiléptica y estrategias terapéuticas en epilepsia refractaria.

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: III. Antiepileptic therapy in special situations]. / Guia terapeutica en epilepsia de la Sociedad Andaluza de Epilepsia 2005: III. Tratamiento antiepileptico en situaciones especiales.

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: II. Chronic therapy with antiepileptic drugs in adults and in children]. / Guia terapéutica en epilepsia de la Sociedad Andaluza de Epilepsia 2005: II. Terapéutica antiepiléptica crónica en el adulto y en el nino.

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Guía terapéutica en epilepsia de la Sociedad Andaluza de Epilepsia 2005: IV. Principios generales de politerapia antiepiléptica y estrategias terapéuticas en epilepsia refractaria / The andalusia epilepsy society´s guide to epilesy therapy 2005: IV general principles of antiepileptic polytherapy and therapeutic strategies in refractory epilepsy

Aims. The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. Development. A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology’s Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies’ criteria for producing Clinical Practice Guidelines. Conclusions. The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care (AU)

Objetivo. Elaborar una guía de práctica clínica basada en la evidencia científica que aborde las cuestiones básicas acerca del tratamiento de la epilepsia. Desarrollo. Un comité de 11 expertos pertenecientes a la Sociedad Andaluza de Epilepsia, en el que se incluían seis neurólogos, tres neuropediatras, un neurocirujano y una farmacóloga, todos con especial dedicación y competencia en epilepsia, realizó una revisión bibliográfica exhaustiva en busca de las evidencias disponibles relacionadas con el tema propuesto. Se utilizaron las siguientes bases de datos: MEDLINE, Cochrane Library y bases de datos de guías de práctica clínica (National Guideline Clearinghouse, National Institute of Clinical Excellence y Guías Clínicas de la Academia Americana de Neurología). La guía se estructuró en siete secciones y se dividió para su publicación en cuatro partes. Se identificaron 187 documentos relevantes, de los que se extrajeron un total de 63 evidencias científicas y 91 recomendaciones terapéuticas, que se tabularon y clasificaron según los criterios de elaboración de Guías de Práctica Clínica de la Federación Europea de Sociedades Neurológicas. Conclusión. Los resultados de esta revisión proveen unas guías de práctica clínica basadas en la evidencia científica útiles, sencillas y aplicables en los diferentes niveles asistenciales (AU)

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: I. Criteria for starting and discontinuing and the pharmacological bases of antiepileptic treatment]. / Guía terapéutica en epilepsia de la Sociedad Andaluza de Epilepsia 2005: I. Criterios de inicio y cese y bases farmacológicas del tratamiento antiepiléptico.

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Guía terapéutica en epilepsia de la Sociedad Andaluza de Epilepsia 2005: I. Criterios de inicio y cese y bases farmacológicas del tratamiento antiepiléptico / The Andalusia epilepsy society’s guide to epilepsy therapy 2005: I. criteria for starting and discontinuing and the pharmacological bases of antiepileptic treatment

Objetivo. Elaborar una guía de práctica clínica basada en la evidencia científica que aborde las cuestiones básicas acerca del tratamiento de la epilepsia. Desarrollo. Un comité de 11 expertos pertenecientes a la Sociedad Andaluza de Epilepsia, en el que se incluían seis neurólogos, tres neuropediatras, un neurocirujano y una farmacóloga, todos con especial dedicación y competencia en epilepsia, realizó una revisión bibliográfica exhaustiva en busca de las evidencias disponibles relacionadas con el tema propuesto. Se utilizaron las siguientes bases de datos: MEDLINE, Cochrane Library y bases de datos de guías de práctica clínica (National Guideline Clearinghouse, National Institute of Clinical Excellence y Guías Clínicas de la Academia Americana de Neurología). La guía se estructuró en siete secciones y se dividió para su publicación en cuatro partes. Se identificaron 187 documentos relevantes de los que se extrajeron un total de 63 evidencias científicas y 91 recomendaciones terapéuticas, que se tabularon y clasificaron según los criterios de elaboración de Guías de Práctica Clínica de la Federación Europea de Sociedades Neurológicas. Conclusión. Los resultados de esta revisión proveen unas guías de práctica clínica basadas en la evidencia científica útiles, sencillas y aplicables en los diferentes niveles asistenciales

Aims. The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. Development. A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology’s Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies’ criteria for producing Clinical Practice Guidelines. Conclusions. The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health careAims. The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. Development. A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology’s Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies’ criteria for producing Clinical Practice Guidelines. Conclusions. The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care

Guía terapéutica en epilepsia de la Sociedad Andaluza de Epilepsia 2005: II. Terapéutica antiepiléptica crónica en el adulto y en el niño / The Andalusia epilepsy society’s guide to epilepsy therapy 2005: II. chronic therapy with antiepileptic drugs in adults and in children

Objetivo. Elaborar una guía de práctica clínica basada en la evidencia científica que aborde las cuestiones básicas acerca del tratamiento de la epilepsia. Desarrollo. Un comité de 11 expertos pertenecientes a la Sociedad Andaluza de Epilepsia, en el que se incluían seis neurólogos, tres neuropediatras, un neurocirujano y una farmacóloga, todos con especial dedicación y competencia en epilepsia, realizó una revisión bibliográfica exhaustiva en busca de las evidencias disponibles relacionadas con el tema propuesto. Se utilizaron las siguientes bases de datos: MEDLINE, Cochrane-Library y bases de datos de guías de práctica clínica (National Guideline Clearinghouse, National Institute of Clinical Excellence y Guías Clínicas de la Academia Americana de Neurología). La guía se estructuró en siete secciones y se dividió para su publicación en cuatro partes. Se identificaron 187 documentos relevantes, de los que se extrajeron un total de 63 evidencias científicas y 91 recomendaciones terapéuticas, que se tabularon clasificándolas según los criterios de elaboración de Guías de Práctica Clínica de la Federación Europea de Sociedades Neurológicas. Conclusión. Los resultados de esta revisión proveen unas guías de práctica clínica basadas en la evidencia científica útiles, sencillas y aplicables en los diferentes niveles asistenciales

Aims. The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. Development. A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology’s Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies’ criteria for producing Clinical Practice Guidelines. Conclusions. The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health careAims. The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. Development. A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology’s Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies’ criteria for producing Clinical Practice Guidelines. Conclusions. The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care

[Lipid peroxidation in adult epileptic patients treated with valproic acid]. / Peroxidación lipídica en pacientes epilépticos adultos tratados con ácido valproico.

INTRODUCTION: Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epileptic patients. OBJECTIVE: To evaluate the susceptibility to plasma lipid peroxidation in samples from epileptic patients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients' sex or the kind of epilepsy suffered. PATIENTS AND METHODS: Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epileptic patients and 4 healthy subjects. RESULTS: After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epileptic women noticeably higher than those of epileptic men. CONCLUSIONS: Plasma from epileptic patients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject's sex, and epilepsy type.

Peroxidación lipídica en pacientes epilépticos adultos tratados con ácido valproico / Lipid peroxidation in adult epileptic patients treated with valproic acid

Introducción. Aunque los radicales libres son mediadores importantes en la regulación de algunos procesos celulares, pueden causar citotoxicidad cuando se producen en exceso o las defensas antioxidantes disminuyen, y se han implicado en la patogenia de numerosas enfermedades. Asimismo, los fármacos, fundamentalmente a través de la producción de metabolitos intermediarios, pueden aumentar el estrés oxidativo; en este sentido, diversos autores han observado alteraciones del metabolismo oxidativo en pacientes epilépticos tratados. Objetivo. Evaluar la susceptibilidad a la peroxidación lipídica en epilépticos adultos tratados con ácido valproico (VPA), y comprobar si ésta guarda relación con la concentración plasmático del fármaco, el sexo del enfermo o el tipo de epilepsia padecido. Pacientes y métodos. Los lípidos peroxidados (LPO) se midieron mediante espectrofluorometría antes y después de la inducción de una reacción oxidativa de tipo Fenton en el plasma de 76 pacientes epilépticos y 48 sujetos sanos. Resultados. La formación de LPO tras la oxidación mostró una relación lineal positiva con las concentraciones plasmáticas de VPA. Asimismo, fue superior en los pacientes con epilepsias parciales que en aquellos con epilepsias generalizadas. Se observó también un efecto significativo del sexo, puesto que los valores de LPO se elevaron más en las mujeres que en los varones epilépticos. Conclusiones. En el plasma de los pacientes tratados con VPA se aprecia una vulnerabilidad al estrés oxidativo directamente proporcional a la concentración plasmática del fármaco, más acentuada en las mujeres que en los hombres. Ésta, por otra parte, parece ser mayor en los pacientes con epilepsias parciales (AU)

Introduction. Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epileptic patients. Objective. To evaluate the susceptibility to plasma lipid peroxidation in samples from epileptic patients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients’ sex or the kind of epilepsy suffered. Patients and methods. Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epileptic patients and 4 healthy subjects. Results. After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epileptic women noticeably higher than those of epileptic men. Conclusions. Plasma from epileptic patients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject’s sex, and epilepsy type (AU)

[Adverse reactions and interactions of antiepileptic drugs in epileptic women]. / Reacciones adversas e interacciones de los fármacos antiepilépticos en la mujer epiléptica.

OBJECTIVE: To review the present knowledge related with gender differences in drug effects, with special emphasis concerning antiepileptic drugs (AEDs). DEVELOPMENT: Women and men differ in their response to drugs and these differences can be sometimes clinically relevant. Adverse drug reactions are noticeably more frequent in women, probably due to a combination of cultural and biological factors. Gender differences related to antiepileptic treatment have been observed concerning alterations in bone mineral density and lipid profile due to several AEDs, lamotrigine induced rash and visual field loss caused by vigabatrin. It is also important to study potential drug interactions between AEDs and contraceptives, as well as hormonal replacement therapy (HRT). At this respect, the influence of AEDs on the pharmacokinetics and efficacy of contraceptives are well known, but no data are available concerning the effect of contraceptives on AEDs pharmacology. Likewise, data relative to the eventual interactions arising between HRT and anticonvulsant are lacking. CONCLUSION: The knowledge about gender differences in the adverse drug reactions and interactions of AEDs is still limited; more information is necessary to optimize anticonvulsant treatment in epileptic women.

Reacciones adversas e interacciones de los fármacos antiepilépticos en la mujer epiléptica / Adverse reactions and interactions of antiepileptic drugs in epileptic women

Objetivo. Revisar los conocimientos actuales sobre las diferencias farmacológicas de género, con especial referencia a los medicamentos antiepilépticos (FAE). Desarrollo. Se sabe que existen diferencias en los efectos de los fármacos entre la mujer y el varón y que, en algunos casos, estas pueden ser clínicamente relevantes. Las reacciones adversas son mucho más frecuentes en la mujer, lo que puede ser debido a diversos factores causales, tanto de tipo sociocultural como biológico. En relación con los FAE se han apreciado diferencias entre la mujer y el varón respecto a la incidencia y trascendencia de diversos tipos de efectos indeseables, tales como las alteraciones de la densidad ósea y las modificaciones del perfil lipídico inducidas por diversos FAE, las reacciones cutáneas de la lamotrigina y la pérdida de campo visual de la vigabatrina. Otra área específica de interés son las interacciones farmacológicas, ya que el uso de anticonceptivos y de tratamiento hormonal sustitutivo puede ser causa de las mismas. A este respecto, se conocen bastante bien las interacciones que los diversos FAE pueden producir sobre la farmacocinética y la eficacia de los anticonceptivos, pero nada se ha investigado en relación a la acción de estos últimos sobre los primeros. Tampoco existen datos sobre la posible interacción existente entre los FAE y los preparados hormonales utilizados para el tratamiento hormonal sustitutivo en la mujer posmenopáusica. Conclusiones. Sólo recientemente han comenzado a estudiarse las diferencias farmacológicas entre ambos sexos; parece necesario continuar obteniendo información que permita optimizar el uso de los FAE en la mujer epiléptica (AU)

Recomendaciones para el diagnóstico y tratamiento de la migraña en Urgencias* / Recomendations for the management of migraine in the Emergency Outpatient Clinic

El diagnóstico de la migraña es clínico y positivo, no de exclusión. Ante un enfermo que cumple los criterios diagnósticos con exploración física general y neurológica normales no es necesario hacer más exploraciones. Se discuten las diferentes posibilidades terapéuticas de la migraña y se concluye que la mayoría de los enfermos pueden ser tratados con antinflamatorios no esteroideos, si la crisis es leve o está en los pródromos, o con triptanes en el resto de los casos. Sumatriptan nasal es una opción excelente en Urgencias por su rapidez de acción, no se modifica con los vómitos y presenta mínimos efectos secundarios (AU)

[GABA-ergic antiepileptic drugs: pharmacological action and spectrum of clinical activity of tiababine]. / Antiepilépticos de acción gabérgica: perfil farmacológico y espectro de actividad clínica de la tiagabina.

INTRODUCTION: GABA is the major inhibitory neurotransmitter in the brain. It is synthesized by the action of glutamic decarboxylase on glutamate and preferently metabolized by the action of GABA transaminase; it experiences neuronal and glial uptake mediated by four types of highly selective transporters. DEVELOPMENT: The hypothesis that abnormalities in GABAergic function can be involved in the physiopathology of epilepsy, specially those of partial origin, is supported by data from proceeding from experimental and human epilepsies, as well as by the fact that agents that inhibit GABAergic function exert a proconvulsant action whereas gabaergic agents frequently act as anticonvulsant. On the last years, therefore, substances with gabaergic activity have been investigated as potential antiepileptic drugs. CONCLUSIONS: Tiagabine, a nipecotic acid derivative, selectively inhibits GABA neuronal and glial uptake by blocking one of its transporters. Its antiepileptic activity has been assessed in different experimental model and it is currently used in the clinical treatment of partial epilepsies.

[Clinical implications of pharmacology and pharmacokinetics of tiagabine]. / Implicaciones clínicas de la farmacología y la farmacocinética de la tiagabina.

Tiagabine is a new antiepileptic drug which acts by blocking neuronal and glial GABA uptake and it is indicated in the treatment of partial epilepsies. Its pharmacokinetics is lineal, being extensively metabolized in the liver by means of CYP3A4 isoenzyme. Plasma elimination half life ranges between 5-8 hours in healthy volunteers, being markedly reduced when the drug is administered concomitantly with enzyme-inducing antinconvulsants. Tiagabine does not induce nor inhibit hepatic enzymes and, consequently, it does not modify the kinetics of simultaneously prescribed antiepileptic drugs. No relevant kinetic differences have been observed between adults and elderly subjects. Renal impairment does not alter the pharmacokinetic profile of tiagabine; hepatic disease, however, significantly reduces tiagabine elimination and lower daily doses of the drug are necessary in these patients. Although tiagabine elimination half life is short, it has been ascertained that therapeutic efficacy is similar when administered in 2 or 4 divided doses. Tiagabine is usually well tolerated; its most frequent side effects include dizziness, asthenia, nervousness, tremor, diarrhea and depressed mood.

[Serum lipids. lipoproteins, and apolipoproteins in adult epileptics treated with carbamazepine, valproic acid, or phenytoin]. / Lípidos, lipoproteínas y apolipoproteínas séricas en epilépticos adultos tratados con carbamacepina, ácido valproico o fenitoína.

INTRODUCTION: It is known that anticonvulsants are able to modify lipid profile; nevertheless the initial studies were performed in patients or polytherapy whereas later investigations were carried out mostly in children. OBJECTIVES: To evaluate serum lipids, lipoproteins and apolipoproteins in adult epileptic patients on monotherapy. MATERIAL AND METHODS: Total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (including the HDL2 and the HDL3 subfractions) and apolipoproteins A1 and B were measured in 120 epileptics patients treated with carbamazepine (n = 42), sodium valproate (n = 38) and phenytoin (n = 40) and compared with the values of 48 healthy subjects. RESULTS: Most of the measured parameters were significantly higher in patients receiving carbamazepine or phenytoin; carbamazepine-treated subjects showed specifically an increase in HDL2 lipoprotein cholesterol, whereas phenytoin-treated subjects showed specifically an increase of triglycerides; all of the observed alterations, save the increase in HDL lipoprotein cholesterol and apolipoprotein A1, were significant in women but not in men. Carbamazepine nor phenytoin related changes showed any correlation with the dose or the plasma levels of the drugs. No relevant modifications of serum lipids were seen in patients who received sodium valproate. CONCLUSIONS: The observed alterations in serum lipids were associated to the use of anticonvulsants with enzyme inducing activity and showed significant differences between both sexes.

[Monitoring of three delayed-release preparations of theophylline in the plasma of children: pharmacokinetic parameters and therapeutic significance]. / Monitorización plasmática de tres preparados de teofilina de liberación retardada en la infancia: parámetros farmacocinéticos e interés terapéutico.

The pharmacokinetic and clinical efficacy of three theophylline slow-release formulations was studied in 29 children suffering chronic bronchial asthma. Theophylline loading dose was of 6 mg/kg; maintenance dose was adjusted according to therapeutic effect and drug plasma concentrations and ranged to 11.1 to 31.3 mg/kg/daily (means = 22.32 +/- 6.6 mg/kg/daily). Peak theophylline plasma levels were 13.38 +/- 4.83 micrograms/ml and through plasma levels were 8.73 +/- 3.78 micrograms/ml. No difference was found among theophylline formulations for clinical response nor kinetic parameters. Drug plasma half-life varied from 2.9 to 18.2 hr (means = 8.85 +/- 3.64 hr). Theophylline total body clearance and apparent volume of distribution exhibited a marked decrease during chronic drug administration in relation to the values observed after intake of the loading dose. Twenty three of the children reached a good degree of control of bronchospasm and did not require any associated medication.