RESUMEN
Human carboxylesterases 1 and 2 (CES1 and CES2) catalyze the hydrolysis of many exogenous compounds. Alterations in CES sequences could lead to variability in both the inactivation of drugs and the activation of prodrugs. The human CES1 gene encodes for the enzyme carboxylesterase 1, a serine esterase governing both metabolic deactivation and activation of numerous therapeutic agents. Some of theses drugs are the antiviral oseltamivir used to treat some types of influenza infections and the methylphenidate employed in the treatment of patients with attention deficit. The Gly143Glu polymorphism in CES1 gene has been shown to reduce enzyme activity. The aim of the present study was to develop an easy and cheap method to detect this polymorphism. For this, we studied a group of people from Córdoba, a Mediterranean area from Argentina. Our results show that our methodology could detect the presence of this polymorphism with a frequency around 1.8%, only in the heterozygote form. These results could be relevant to patients before the treatment with some drugs where the CES1 enzyme is involved.
Asunto(s)
Antivirales/farmacocinética , Hidrolasas de Éster Carboxílico/genética , Estimulantes del Sistema Nervioso Central/farmacocinética , Metilfenidato/farmacocinética , Oseltamivir/farmacocinética , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Sustitución de Aminoácidos , Antivirales/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Hidrolasas de Éster Carboxílico/metabolismo , Estimulantes del Sistema Nervioso Central/uso terapéutico , Femenino , Frecuencia de los Genes , Ácido Glutámico/genética , Glicina/genética , Humanos , Inactivación Metabólica/genética , Gripe Humana/tratamiento farmacológico , Masculino , Metilfenidato/uso terapéutico , Persona de Mediana Edad , Oseltamivir/uso terapéutico , Adulto JovenRESUMEN
Pharmacological treatment for attention deficit hyperactivity disorder, although highly effective, presents a marked variability in clinical response, optimal dosage needed and tolerability. Clinical and neurobiological investigations have juxtaposed findings on both response to medication and etiologic factors, generating the hypothesis that genetic factors may underlie differences in treatment outcome. Over the last decade, research has focused on the catecholaminergic system to investigate a potential role of genotype on pharmacological effect. Despite an increasing number of associations reported (for methylphenidate, nine in 2005, 24 in 2008 and 52 reported in the current article), the identification of clinically relevant genetic predictors of treatment response remains a challenge. At present, additional studies are required to allow for a shift from a trial-and-error approach to a more rational pharmacologic regimen that takes into account the likelihood of treatment effectiveness at the individual level.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/genética , Adolescente , Inhibidores de Captación Adrenérgica/farmacocinética , Inhibidores de Captación Adrenérgica/uso terapéutico , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Catecol O-Metiltransferasa/genética , Catecol O-Metiltransferasa/metabolismo , Estimulantes del Sistema Nervioso Central/farmacocinética , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Humanos , Metilfenidato/farmacocinética , Metilfenidato/uso terapéutico , Farmacogenética , Propilaminas/farmacocinética , Propilaminas/uso terapéutico , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos alfa 2/metabolismo , Receptores de Dopamina D4/genética , Receptores de Dopamina D4/metabolismoRESUMEN
OBJECTIVE: To assess ADHD symptoms after switching from Methylphenidate Immediate-release (MPH-IR) to Methylphenidate Spheroidal Oral Drug Absorption System (MPH-SODAS) in clinically stable patients with ADHD and to identify predictors of dissatisfaction with MPH-SODAS. METHODS: This is an 8-week open clinical trial. Patients were assigned to MPH-SODAS according to their pre-study dose of MPH-IR. Assessments at baseline were conducted using the Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV), and the Barkley's Side Effect Rating Scale (SERS). Potentials predictors of treatment response were evaluated. RESULTS: From 62 patients, 47 completed the protocol. There was no significant change in the total score at the SNAP-IV (F (1,51.26) = 0.01; P = 0.91) and its subscales scores during the trial. Although no significant effect on the SERS total score (F (1,111.49) = 0.75; P = 0.39) was found, one adult patient with a previous cardiovascular condition presented a hemorrhagic cerebral vascular accident resulting in her obit. Overall, 46 (74.2%) patients reported to be satisfied. No factor assessed predicted dissatisfaction in univariated analyses. CONCLUSION: Results suggested that switching from MPH-IR to MPH-SODAS did not affect stabilization of ADHD symptoms in the majority of patients. MPH prescription in patients with previous cardiovascular conditions must be extremely careful. Further studies with long-acting MPH including larger samples and patients not responsive to MPH-IR are needed especially in countries outside the US.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/administración & dosificación , Metilfenidato/administración & dosificación , Administración Oral , Adulto , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Déficit de la Atención y Trastornos de Conducta Disruptiva/diagnóstico , Déficit de la Atención y Trastornos de Conducta Disruptiva/epidemiología , Estimulantes del Sistema Nervioso Central/farmacocinética , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Comorbilidad , Trastorno de la Conducta/diagnóstico , Trastorno de la Conducta/epidemiología , Preparaciones de Acción Retardada , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Esquema de Medicación , Femenino , Humanos , Masculino , Metilfenidato/farmacocinética , Metilfenidato/uso terapéutico , Encuestas y CuestionariosAsunto(s)
Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/terapia , Quimioterapia , Relaciones Padre-Hijo/etnología , Metilfenidato/administración & dosificación , Metilfenidato/uso terapéutico , Metilfenidato/farmacocinética , Trastornos de la Conducta Infantil/fisiopatología , Trastornos de la Conducta Infantil/psicología , Trastornos de la Conducta Infantil/terapia , Crecimiento/efectos de los fármacos , Antidepresivos/uso terapéutico , Antihipertensivos , AntipsicóticosRESUMEN
Os psicoestimulantes vêm sendo empregados como potencializadores de drogas antidepressivas no tratamento de transtornos do humor refratários. Mesmo nao associados a antidepressivos, os estimulantes sao considerados úteis no paciente deprimido portador de doença física e no idoso deprimido apático, nos quais os antidepressivos encontram obstáculos, especialmente efeitos colaterais e longa latência para o início da açao terapêutica. Sao particularmente interessantes para o paciente deprimido portador de doença física crônica terminal, como a AIDS e o câncer, e para o deprimido portador de lesao encefálica residual. No transtorno de déficit de atenção e hiperatividade residual do adulto, os psicoestimulantes sao indicados. Pacientes com transtornos do humor relacionados ao complexo demencial da AIDS também parecem beneficiar-se de terapêutica com psicoestimulante. Em casos da síndrome de fadiga crônica, psicoestimulantes também têm sido considerados úteis