Reacciones adversas a múltiples antibióticos / Adverse drug reactions to multiple antibiotics

Resumen La información sobre reacciones adversas es fundamental para conocer la seguridad real de los medicamentos comercializados. Existen casos de pacientes con síndrome de intolerancia a múl tiples drogas, una entidad poco reportada, la que puede presentarse cuando en un mismo paciente ocurren reacciones adversas a más de dos medicamentos no relacionados farmacológicamente. Se describe el caso de una mujer con diagnóstico de endocarditis por Staphylococcus aureus multisensible, que cursó con reacciones adversas a cinco antibióticos estructuralmente no relacionados y con mecanismos de acción diferentes, en dos internaciones consecutivas. Las reacciones fueron secundarias a cefazolina (tricitopenia), vancomicina (injuria renal), daptomicina (elevación de creatina fosfoquinasa) y linezolid (hepatotoxicidad) en la primera internación, y a cotrimoxazol (plaquetopenia) en la segunda. En todos los casos se observó daño transitorio en diferentes sistemas de órganos. Finalmente, se otorgó alta hospitalaria con clindamicina sin nuevas intercurrencias hasta finalizar tratamiento. Este caso podría corresponder al síndrome antes mencionado o a una entidad aún no caracterizada.

Abstract Adverse reaction reporting is essential to understand the actual safety of marketed medicines. There are cases of patients with multidrug intolerance syndrome, an under-reported entity, which can occur when adverse reactions to more than two pharmacologically unrelated drugs occur in the same patient. We describe the case of a woman diagnosed with multisensitive Staphylococcus aureus endocarditis who experienced adverse reactions to five structurally unrelated antibiotics with different mechanisms of action in two consecutive hospitalisations. The reactions were secondary to cefazolin (tricytopenia), vancomycin (renal injury), daptomycin (elevated creatine phosphokinase) and linezolid (hepatotoxicity) in the first hospitalization, and to cotrimoxazole (thrombocytopenia) in the second. Transient damage to different organ systems was observed in all cases. Finally, hospital discharge was granted with clindamycin without further intercurrences until treatment was completed. This case could cor respond to the aforementioned syndrome or to an as yet uncharacterized entity.

[Adverse drug reactions to multiple antibiotics]. / Reacciones adversas a múltiples antibióticos.

Adverse reaction reporting is essential to understand the actual safety of marketed medicines. There are cases of patients with multidrug intolerance syndrome, an under-reported entity, which can occur when adverse reactions to more than two pharmacologically unrelated drugs occur in the same patient. We describe the case of a woman diagnosed with multisensitive Staphylococcus aureus endocarditis who experienced adverse reactions to five structurally unrelated antibiotics with different mechanisms of action in two consecutive hospitalisations. The reactions were secondary to cefazolin (tricytopenia), vancomycin (renal injury), daptomycin (elevated creatine phosphokinase) and linezolid (hepatotoxicity) in the first hospitalization, and to cotrimoxazole (thrombocytopenia) in the second. Transient damage to different organ systems was observed in all cases. Finally, hospital discharge was granted with clindamycin without further intercurrences until treatment was completed. This case could correspond to the aforementioned syndrome or to an as yet uncharacterized entity.

La información sobre reacciones adversas es fundamental para conocer la seguridad real de los medicamentos comercializados. Existen casos de pacientes con síndrome de intolerancia a múltiples drogas, una entidad poco reportada, la que puede presentarse cuando en un mismo paciente ocurren reacciones adversas a más de dos medicamentos no relacionados farmacológicamente. Se describe el caso de una mujer con diagnóstico de endocarditis por Staphylococcus aureus multisensible, que cursó con reacciones adversas a cinco antibióticos estructuralmente no relacionados y con mecanismos de acción diferentes, en dos internaciones consecutivas. Las reacciones fueron secundarias a cefazolina (tricitopenia), vancomicina (injuria renal), daptomicina (elevación de creatina fosfoquinasa) y linezolid (hepatotoxicidad) en la primera internación, y a cotrimoxazol (plaquetopenia) en la segunda. En todos los casos se observó daño transitorio en diferentes sistemas de órganos. Finalmente, se otorgó alta hospitalaria con clindamicina sin nuevas intercurrencias hasta finalizar tratamiento. Este caso podría corresponder al síndrome antes mencionado o a una entidad aún no caracterizada.

Tromboprofilaxis en COVID-19: ¿Seguimos en la neblina? / Thromboprophylaxis in COVID-19: Still in the fog?

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COVID-19: el turno de los anticoagulantes / No disponible

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Esquizofrenia en niños y adolescentes / Schizophrenia in children and adolescents

La población infantil y adolescente es considerada, junto con los ancianos y embarazadas, vulnerable por representar un sistema fisiológico que dista del adulto promedio para el cual están basadas la mayoría de prácticas terapéuticas. La esquizofrenia tiene una especial importancia en este grupo ya que es considerada una enfermedad del neurodesarrollo. Para poder instaurar un tratamiento adecuado resulta capital conocer los procesos y circuitos neurobilógicos que constituyen la base de la patología. Las hipótesis mejor estudiadas son la dopaminérgica, de la cual deriva el arsenal farmacológico actual, y la hipoglutamatérgica. Esta última invita al desarrollo de nuevas moléculas con potencial antipsicótico pero que no posean blancos terapéuticos dopaminérgicos. Hasta hoy, no existe un fármaco comercializado que actúe sobre las vías glutamatérgicas para tratar la esquizofrenia pero sí existen varios ejemplos en ensayos clínicos de fases I y II. También es necesario establecer las pautas de dosificación para los grupos vulnerables las cuales derivan, en su mayoría, de las establecidas para adultos.

The population of children and adolescents is considered, along with the elderly and pregnant women, vulnerable, for representing a physiological system that is far from the average adult, for whom most therapeutic practices are based on. Schizophrenia has special relevance within this group, since it is considered a neurodevelopmental disorder. In order to establish an adquate treatment, it is key to know the processes and neurobiological circuits which form the basis of this disease. The best studied hypotheses are the dopaminergic hypothesis, from which the current pharmacological studies derive, and the hypoglutamatergic hypothesis. The latter proposes the development of new molecules with antipsychotic potential, which do not have dopaminergic therapeutic targets. Up to now, there is no marketed drug which acts on glutamatergic pathways to treat schizophrenia, although several examples can be found in phase I and II clinical trials. It is also necessary to establish dosing guidelines for vulnerable groups, most of which result from the ones established for adults.

Esquizofrenia en niños y adolescentes / Schizophrenia in children and adolescents

La población infantil y adolescente es considerada, junto con los ancianos y embarazadas, vulnerable por representar un sistema fisiológico que dista del adulto promedio para el cual están basadas la mayoría de prácticas terapéuticas. La esquizofrenia tiene una especial importancia en este grupo ya que es considerada una enfermedad del neurodesarrollo. Para poder instaurar un tratamiento adecuado resulta capital conocer los procesos y circuitos neurobilógicos que constituyen la base de la patología. Las hipótesis mejor estudiadas son la dopaminérgica, de la cual deriva el arsenal farmacológico actual, y la hipoglutamatérgica. Esta última invita al desarrollo de nuevas moléculas con potencial antipsicótico pero que no posean blancos terapéuticos dopaminérgicos. Hasta hoy, no existe un fármaco comercializado que actúe sobre las vías glutamatérgicas para tratar la esquizofrenia pero sí existen varios ejemplos en ensayos clínicos de fases I y II. También es necesario establecer las pautas de dosificación para los grupos vulnerables las cuales derivan, en su mayoría, de las establecidas para adultos. (AU)

The population of children and adolescents is considered, along with the elderly and pregnant women, vulnerable, for representing a physiological system that is far from the average adult, for whom most therapeutic practices are based on. Schizophrenia has special relevance within this group, since it is considered a neurodevelopmental disorder. In order to establish an adquate treatment, it is key to know the processes and neurobiological circuits which form the basis of this disease. The best studied hypotheses are the dopaminergic hypothesis, from which the current pharmacological studies derive, and the hypoglutamatergic hypothesis. The latter proposes the development of new molecules with antipsychotic potential, which do not have dopaminergic therapeutic targets. Up to now, there is no marketed drug which acts on glutamatergic pathways to treat schizophrenia, although several examples can be found in phase I and II clinical trials. It is also necessary to establish dosing guidelines for vulnerable groups, most of which result from the ones established for adults. (AU)

Tratamiento de la esclerosis múltipple: la era del natalizumab / Treatment of Multiple Sclerosis: the era of Natalizumab

La esclerosis múltiple es una enfermedad inflamatoria crónica y autoinmune del sistema nervioso central. Produce un variado abanico de síntomas que suelen llevar a la incapacidad del paciente que la padece. Para su tratamiento se ha empleado una amplia gama de drogas, todas destinadas a contrarrestar la respuesta inflamatoria. Entre ellas se destacan los corticoides, acetato de glatiramer, interferón beta, entre otras. Ninguna de ellas trata la causa primaria de la enfermedad pero pueden aminorar su progresión y retrasar la aparición de nuevos síntomas. Sin embargo, no son capaces de lograr el control de la enfermedad sin que sus efectos adversos o sus pautas y formas de administración se interpongan en la terpéutica. La introducción del natalizumab en el tratmiento de la esclerosis múltiple constituye un avance sin precedentes. Esta droga controla el progreso de la enfermedad como ninguna de sus antecesoras con una muy baja frecuencia de administración y una gran aceptación del tratamiento por parte de los pacientes. Sin embargo, el riesgo de aparición de leucoencefalopatía multifocal progresiva durante el tratamiento con natalizumab hace que su terapéutica requiera un enfoque multidisciplinario de profesionales de la salud

Multple Sclerosis is a chronic, inflammatory and autoimmune disease of the central nervous system. It causes a wide range of symptoms which may lead to the impairment of the patient that suffers from it. Numerous drugs have been used for its treatment to counteract the inflammatory response. Among these drugs are corticosteriods, glatiramer acetate and Interferon beta. Although none of them treat the primary cause of the disease, they may slow down its progression and delay the appearance of new symptoms. In addition, they are not capable of achieving the control of the disease without their adverse effects, guidelines, or ways of administration interposing in the therapeutic treatment. The introduction of natalizumab in the treatment of multiple sclerosis is an unprecedented advance. This drug controls the progression of the disease in a way which none of the former drugs has achieved, with a very low frequency of administration and a high treatment acceptance by the patients. However, the risk of developing progressive multifocal leukoencephalopathy during treatmente with natalizumab makes its therapeutic treatment require a multidisciplinary approach on the part of healthcare professionals

Tratamiento de la esclerosis múltipple: la era del natalizumab / Treatment of Multiple Sclerosis: the era of Natalizumab

La esclerosis múltiple es una enfermedad inflamatoria crónica y autoinmune del sistema nervioso central. Produce un variado abanico de síntomas que suelen llevar a la incapacidad del paciente que la padece. Para su tratamiento se ha empleado una amplia gama de drogas, todas destinadas a contrarrestar la respuesta inflamatoria. Entre ellas se destacan los corticoides, acetato de glatiramer, interferón beta, entre otras. Ninguna de ellas trata la causa primaria de la enfermedad pero pueden aminorar su progresión y retrasar la aparición de nuevos síntomas. Sin embargo, no son capaces de lograr el control de la enfermedad sin que sus efectos adversos o sus pautas y formas de administración se interpongan en la terpéutica. La introducción del natalizumab en el tratmiento de la esclerosis múltiple constituye un avance sin precedentes. Esta droga controla el progreso de la enfermedad como ninguna de sus antecesoras con una muy baja frecuencia de administración y una gran aceptación del tratamiento por parte de los pacientes. Sin embargo, el riesgo de aparición de leucoencefalopatía multifocal progresiva durante el tratamiento con natalizumab hace que su terapéutica requiera un enfoque multidisciplinario de profesionales de la salud (AU)

Multple Sclerosis is a chronic, inflammatory and autoimmune disease of the central nervous system. It causes a wide range of symptoms which may lead to the impairment of the patient that suffers from it. Numerous drugs have been used for its treatment to counteract the inflammatory response. Among these drugs are corticosteriods, glatiramer acetate and Interferon beta. Although none of them treat the primary cause of the disease, they may slow down its progression and delay the appearance of new symptoms. In addition, they are not capable of achieving the control of the disease without their adverse effects, guidelines, or ways of administration interposing in the therapeutic treatment. The introduction of natalizumab in the treatment of multiple sclerosis is an unprecedented advance. This drug controls the progression of the disease in a way which none of the former drugs has achieved, with a very low frequency of administration and a high treatment acceptance by the patients. However, the risk of developing progressive multifocal leukoencephalopathy during treatmente with natalizumab makes its therapeutic treatment require a multidisciplinary approach on the part of healthcare professionals (AU)

The response to postnatal stress: amino acids transporters and PKC activity.

It is well known that animals exposed to stressful stimuli during their early life develop different neurological disorders when they become adults. In this study, we evaluated the effect of acute cold stress on gamma-aminobutyric acid (GABA) and L-Serine (L-Ser) transporters in vitro, using the uptake of [(3)H]-GABA and [(3)H]L-Ser by synaptosomes-enriched fractions isolated from rat cerebral cortex during postnatal development. GABA and L-Ser uptake studies in vitro will be used in this investigation as a colateral evidence of changes in the expression of transporters of GABA and L-Ser. We observed that the maximum velocity (V (max)) in L-Ser and GABA uptake after stress session increased in all stages studied. In contrast, K (m) values of L-Ser uptake enhancent in almost age calculated, excluding at PD21 after cold stress during development, at the same time as K (m) (uptake affinity) values of GABA increased in just about age considered but not at PD5 compared with the control group. Finally we investigated the mechanism by which cells regulate the substrate affinity of L-Ser and GABA transporters. We demonstrated a significantly increase in total PKC activity to PD5 from PD21. Pretreatment with PKC inhibitor: staurosporine (SP) led to a restoration of control uptake in several postnatal-days suggesting a relationship between amino acids system and PKC activation. These findings suggest that a single exposure to postnatal cold stress at different periods after birth modifies both GABA and L-Ser transporters and the related increase in total PKC activity could be intracellular events that participate in neuronal plasticity by early life stress, which could be relevant to function of transporters in the adult rat brain.

Hipótesis epigenética de la esquizofrenia: bases moleculares y modelos experimentales / Epigenetic Hypothesis for Schizophrenia: Molecular bases and Experimental Models

Si bien la predisposición a desarrollar esquizofrenia ha sido, en parte, atribuida a un componente genético, la evidencia experimental de los últimos años sugiere que este trastorno puede ser el resultado de una aberración epigenética. De ahí que a las hipótesis hiperdopaminérgica e hipoglutamatérgica, se le sume la hipótesis epigenética de la esquizofrenia. Esta última propone que la fisiopatología de la enfermedad se sostiene en cambios en la expresión génica por una estructura aberrante de la cromatina, más que por cambios en la secuencia del ADN. De los múltiples blancos moleculares propuestos en la etiología de la enfermedad, cobra particular importancia la enzima ácido glutámico descarboxilasa, encargada de sintetizar el ácido γ - amino butírico (GABA), en especial la isoforma de 67 kDa, y la reelina, cuyos genes codificantes parecen estar hipermetilados en pacientes con esquizofrenia cuando se los compara con individuos sanos. Esto determina un menor nivel de expresión de la enzima y niveles disminuidos de GABA, lo que involucra íntimamente a este neurotransmisor en el desarrollo de la esquizofrenia.

Although the tendency to develop shizophrenia has partly been ascribed to a genetic component, experimental evidence gathered in recent years suggests that this disorder may be the producto of an epigenetic aberration. Hence, the hyperdopaminergic and hupoglutamatergic hypotheses add on the epigenetic hypothesis for shizophrenial. The latter proposes that the physiopathology of schizophrenia stems from changes in the gene expression, into an aberrant structure of the chromatin, rather than from DNA sequence variations. Oif the multiple molecular targets proposed in the etiology of shizophrenia, one which acquires particular significance is the enzyme, glutamic acid decarboxylase, which synthesizes Y-aminobutyric acid (GABA), especially 67-kDa isoform and reelin, whose codifying genes seem to be hypermethylated in patients with schizophrenia, as compared with healthy individuals. This determines a lower level of expression of the enzyme, as well as rduced GABA levels, which evidences the close relationship betweeen this neurotransmissor and the development of schizophrenia.

Hipótesis epigenética de la esquizofrenia: bases moleculares y modelos experimentales / Epigenetic Hypothesis for Schizophrenia: Molecular bases and Experimental Models

Si bien la predisposición a desarrollar esquizofrenia ha sido, en parte, atribuida a un componente genético, la evidencia experimental de los últimos años sugiere que este trastorno puede ser el resultado de una aberración epigenética. De ahí que a las hipótesis hiperdopaminérgica e hipoglutamatérgica, se le sume la hipótesis epigenética de la esquizofrenia. Esta última propone que la fisiopatología de la enfermedad se sostiene en cambios en la expresión génica por una estructura aberrante de la cromatina, más que por cambios en la secuencia del ADN. De los múltiples blancos moleculares propuestos en la etiología de la enfermedad, cobra particular importancia la enzima ácido glutámico descarboxilasa, encargada de sintetizar el ácido γ - amino butírico (GABA), en especial la isoforma de 67 kDa, y la reelina, cuyos genes codificantes parecen estar hipermetilados en pacientes con esquizofrenia cuando se los compara con individuos sanos. Esto determina un menor nivel de expresión de la enzima y niveles disminuidos de GABA, lo que involucra íntimamente a este neurotransmisor en el desarrollo de la esquizofrenia.(AU)

Although the tendency to develop shizophrenia has partly been ascribed to a genetic component, experimental evidence gathered in recent years suggests that this disorder may be the producto of an epigenetic aberration. Hence, the hyperdopaminergic and hupoglutamatergic hypotheses add on the epigenetic hypothesis for shizophrenial. The latter proposes that the physiopathology of schizophrenia stems from changes in the gene expression, into an aberrant structure of the chromatin, rather than from DNA sequence variations. Oif the multiple molecular targets proposed in the etiology of shizophrenia, one which acquires particular significance is the enzyme, glutamic acid decarboxylase, which synthesizes Y-aminobutyric acid (GABA), especially 67-kDa isoform and reelin, whose codifying genes seem to be hypermethylated in patients with schizophrenia, as compared with healthy individuals. This determines a lower level of expression of the enzyme, as well as rduced GABA levels, which evidences the close relationship betweeen this neurotransmissor and the development of schizophrenia.(AU)

L-serine and GABA uptake by synaptosomes during postnatal development of rat.

Postnatal development changes in mechanisms of synaptosomal amino acid transport have been studied in rat cerebral cortex. Specific uptake of radiolabeled L-serine was examined and compared with that of radiolabeled GABA using synaptosomes-enriched fractions freshly prepared from cerebral cortex at different postnatal days from the birth to young adulthood. The preparations were incubated with 10 nM of [3H]L-serine and 10 nM of [3H]-GABA in either the presence or absence of NaCl, KCl or choline chloride, at 2 and 30 degrees C, for different periods up to 30 min. The uptake of [3H]l-serine was temperature dependent in synaptosomal fractions prepared from cerebral cortex of rats in postnatal days 5, 7, 13 and 21, but stronger dependence was observed in adult brain, irrespective of the presence of Na+, K+ or choline ions. At all postnatal ages studied, [3H]-GABA uptake showed a high activity in the presence of Na+ ions and at 30 degrees C. The values of Km were 90-489 microM in L-serine uptake. However, in the uptake of GABA the values of Km were 80-150 microM. The highest values of Vmax were obtained at 5 and 21 postnatal days for both transport systems. These results indicate that the uptake of l-serine and GABA are regulated differentially during postnatal development.