Possible Genetic Determinants of Response to Phenytoin in a Group of Colombian Patients With Epilepsy.

BACKGROUND: Epilepsy is a serious health problem worldwide. Despite the introduction of new antiepileptic drugs (AEDs) almost 30% of these patients have drug-resistant forms of the disease (DRE), with a significant increase in morbi-mortality. OBJECTIVE: Our objective was to assess the impact of some genetic factors and its possible association with treatment response and adverse drug reactions (ADRs) to phenytoin in 67 adult Colombian patients with epilepsy. METHODS: We conducted an analytical, observational, prospective cohort study to screen four polymorphisms in pharmacogenes: CYP2C9*2-c.430C>T (rs1799853), CYP2C9*3-c.1075A>C (rs1057910), ABCB1-c.3435T>C (rs1045642), and SCN1A-IVS5-91G>A (rs3812718), and their association with treatment response. Patients were followed for 1 year to confirm the existence of DRE (non-response) and ADRs using an active pharmacovigilance approach, followed by a consensus in order to classify ADRs according to causality, preventability, intensity and their relation with phenytoin dose, the duration of treatment, and susceptibility factors (DoTS methodology). RESULTS: A little more than half of evaluated subjects (52.2%) were non-responding to phenytoin. Regarding the genotype-phenotype correlation there was no association between polymorphisms of SCN1A and ABCB1 and DRE (non-response) (p = 0.34), and neither with CYP2C9 polymorphisms and the occurrence of ADRs (p = 0.42). We only found an association between polymorphic alleles of CYP2C9 and vestibular-cerebellar ADRs (dizziness, ataxia, diplopia, and dysarthria) (p = 0.001). Alleles CYP2C9*2-c.430C>T and CYP2C9*3-c.1075A>C were identified as susceptibility factors to ADRs in 24% of patients. CONCLUSIONS: Decreased function alleles of CYP2C9 were highly predictive of vestibular-cerebellar ADRs to phenytoin in our study (p = 0.001). However, the genetic variants CYP2C9*2-c.430C>T, CYP2C9*3-c.1075A>C, ABCB1-c.3435T>C, and SCN1A-IVS5-91G>A, were not associated with treatment response in our study.

Cognitive and Behavioral Disorders in Children with Neurofibromatosis Type 1.

AIM: The last systematic review of research on the behavior of children with neurofibromatosis type 1 (NF1) was in 2012. Since then, several important findings have been published. Therefore, the study aim was to synthesize recent relevant work related to this issue. METHOD: We conducted a systematic review of the literature. Relevant articles were identified using the electronic databases PubMed, PsycINFO, and Scopus and a manual search of references lists. Thirty of 156 articles identified met the inclusion criteria. A quality evaluation of the articles was performed and the information was synthesized using a narrative approach. RESULTS: Compared with controls, children and adolescents with NF1 present significant alterations in language, reading, visuospatial skills, motor function, executive function, attention, behavior, emotion, and social skills. The prevalence of attention-deficit/hyperactivity disorder (ADHD) is important and can affect cognition and executive function variables. A high prevalence of autistic traits and autistic spectrum disorder were reported. The benefits of using statins to treat cognitive deficits are unclear. However, children with NF1 and ADHD seem to benefit from methylphenidate treatment. The presence of hyperintensities in brain magnetic resonance imaging data seem to be related to poor cognitive performance. Analysis of these lesions could help to predict cognitive alterations in children with NF1. INTERPRETATION: There has been important progress to evaluate cognitive characteristics of children with NF1 and to determine the physiological mechanisms of the concomitant disorders. However, discrepancies in relation to intelligence, learning disabilities, attention deficits, and treatment remain. Further investigations on this topic are recommended.

Nuevos enfoques farmacológicos en el manejo de la angina de pecho estable / New pharmacological approaches in the management of stable angina

RESUMEN En años recientes han sido introducidos nuevos antianginosos al mercado con mecanismos de acción novedosos, complementarios a los del arsenal farmacoterapéutico existente. Aunque el tratamiento de primera línea continúan siendo los betabloqueadores, antagonistas de canales de calcio y nitratos, el descubrimientos de nuevos aspectos fisiopatológicos de la enfermedad permitieron el desarrollo de blancos terapéuticos innovadores a nivel celular y molecular. El nicorandil, la trimetazidina, la ivabradina y la ranolazina se consideran nuevos fármacos antianginosos y constituyen la segunda línea de tratamiento de la angina de pecho estable; están indicados en pacientes que persisten sintomáticos a pesar del manejo de primera línea o en aquellos que presentan intolerancia o contraindicación a los betabloqueadores o antagonistas de canales de calcio. La trimetazidina, a través de su mecanismo de acción metabólico, mejora la tolerancia al ejercicio y puede ser útil en pacientes con falla cardíaca y contraindicación al uso de digitales; la ivabradina tiene un efecto cronotrópico negativo sin afectar el inotropismo ni la tensión arterial por lo que se puede usar en pacientes con taquiarritmias o falla cardíaca concomitante; en contraste, la ranolazina no afecta el cronotropismo por lo que se usa en pacientes con bradiarritmias aunque puede generar prolongación del intervalo QTc. La elección de alguno de estos medicamentos antianginosos de primera o segunda línea debe ser individualizado para cada paciente y se basa en las comorbilidades, contraindicaciones y preferencias del paciente. MÉD.UIS. 2016;29(3):79-93.

ABSTRACT In recent years, new antianginal agents with novel mechanisms of action have been launched to the market, as a complement to the existing therapeutic arsenal. Even though the beta-blockers, calcium channel blockers and nitrates continue to be the first line of treatment, recent discoveries of pathophysiological aspects of the disease led to the development of innovative therapeutic targets on both cellular and molecular level. Nicorandil, trimetazidine, ivabradine and ranolazine are novel antianginal drugs and constitute the second line of treatment of stable angina; these drugs are indicated for those patients who persist symptomatic despite treatment with first line agents or in those with contraindication or intolerance to beta-blockers o calcium channel blockers. Trimetazidine, through its metabolic mechanism of action, improves exercise tolerance and might be useful in patients with concomitant heart failure and contraindication to digitalis; ivabradine can be used in patients with concomitant tachyarrhythmias due to its negative chronotropic effect without affecting inotropism or blood pressure; in contrast, ranolazine doesn't affect chronotropism and can be used in patients with bradyarrhythmias, however, it might cause prolongation of the QTc interval. The choice of treatment with either of the first line or second line antianginal agents must be individualized for each patient and based on comorbidities, contraindications and patient's preference. MÉD.UIS. 2016;29(3):79-93.

Automedicación en estudiantes de medicina de la Universidad del Rosario en Bogotá D. C., Colombia / Self-medication in medical students at the Universidad del Rosario in Bogota D. C., Colombia

Introducción. La automedicación es un problema de salud pública frecuente en población estudiantil, el cual se da sobre todo en estudiantes de medicina, dado su mayor conocimiento en farmacología. Por tratarse de los futuros prescriptores, es importante establecer la magnitud del problema en esta población. Materiales y métodos. Se realizó un estudio de corte transversal mediante una encuesta aplicada a 276 estudiantes de medicina, en el que se indagaron datos demográficos, antecedentes patológicos, hábitos, frecuencia de automedicación, medicamentos automedicados, porcentaje de automedicación responsable, razones para automedicarse y conocimiento sobre esta conducta. Resultados. De las 276 encuestas realizadas, se analizaron 270. La prevalencia de automedicación fue del 79,3%. El único factor con asociación estadística fue pertenecer a un semestre clínico (p = 0,020). Los medicamentos automedicados con mayor frecuencia son acetaminofén (10,8%), e ibuprofeno (3,9%). Entre los medicamentos automedicados, el 70,6% requiere prescripción médica. Las indicaciones más frecuentes fueron cefalea (10,6%), resfriado común (4,2%) y dismenorrea (3,4%). El 39,1% de los encuestados cumplen los criterios de automedicación responsable. Conclusión. La prevalencia de automedicación en la población evaluada es alta, y la mayoría de los medicamentos utilizados requieren fórmula médica. Los factores influyentes se relacionan con la edad y el semestre que cursan. La mayoría de estudiantes se automedica de manera inadecuada.

Introduction. Self-medication is a common public health problem among students, mainly among medical students who have greater knowledge in pharmacology. We consider that it is important to establish the magnitude of the problem in future prescribers. Materials and methods. We performed a cross-sectional study through a survey of 276 medical students. We analyzed demographic data, medical history, habits, frequency of this behavior, drugs used as self-treatment, percentage of self-medication, reasons for self-medication and knowledge about this behavior. Results. Of the 276 surveys 270 were analyzed. We found a prevalence of 79.3% self-medication. The only associated factor with higher statistical significance was students who were in clinical practice (p = 0.020). Drugs that were mostly used were: acetaminophen (10.8%) and ibuprofen (3.9%). 70.6% of the mentioned drugs require a medical prescription. Most frequent reasons were: headache (10.64%), common cold (4.20%) and dysmenorrhea (3.37%). Only 39.1% of respondents met criteria for responsible self-medication. Conclusion. Prevalence of self-medication among medical students is high. Most of used drugs need a medical prescription. The factor influencing this behavior is the year of medical school to which they belong. Self-medication is mostly found when students are in clinical practice. Most students do not self-medicate responsibly.