Clonazepam
PsicodepresoresC55-(2-chlorophenyl)-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one
Estructura molecular
Datos: PubChem CID 2802 — National Library of Medicine
Efectos
Mecanismo de acción
Se une con alta afinidad al sitio benzodiazepínico del receptor GABA-A. Potencia la acción inhibitoria del GABA al aumentar la frecuencia de apertura del canal de cloruro, produciendo hiperpolarización neuronal. Tiene actividad anticonvulsivante, ansiolítica, sedante, miorrelajante y amnésica.
Vida media
Vida media de eliminación de 30-40 horas. La farmacocinética es dosis-independiente en el rango terapéutico.
Toxicidad
IDENTIFICATION AND USE: Clonazepam is off-white to light yellow crystalline powder with a faint odor. It is a Schedule IV Controlled Substance. It is anticonvulsant and gamma-aminobutyric acid (GABA) modulator. A significant increase in the illegal use of clonazepam has been seen. HUMAN STUDIES: Overdosage of clonazepam may produce somnolence, confusion, ataxia, diminished reflexes, or coma. The shortcomings of clonazepam therapy include tolerance, withdrawal symptoms, and adverse effects such as drowsiness, dizziness, and confusion leading to increased risk of falls. Inter-individual variability in the incidence of adverse events in patients partly originates from the differences in clonazepam metabolism due to genetic and nongenetic factors. Because of experience with other members of the benzodiazepine class, clonazepam is assumed to be capable of causing an increased risk of congenital abnormalities when administered to a pregnant woman during the first trimester. In a study of 118 liveborn infants, there were 6 (5.1%) with major malformations, 4 of whom were prenatally exposed to clonazepam monotherapy and all of whom were full term infants. These included two with bilateral inguinal hernias requiring surgery, one with bilateral communicating hydroceles requiring surgery, one with midline pit over the nasal bridge, one with a uretero-pelvic junction obstruction requiring surgery and one with a PDA and ASD diagnosed at one day of age for which no follow-up is available. Sixty five (55.1%) of liveborn infants received a dysmorphological exam performed by an examiner who was blinded to the prenatal exposure. Although 16 (13.6%) children had 3 or more minor malformations, only one of the 16 was exposed to monotherapy. It is notable that 3 fullterm infants, all of whom were prenatally exposed to clonazepam monotherapy, had either inguinal hernias or communicating hydroceles requiring surgery. ANIMAL STUDIES: No adverse maternal or embryo-fetal effects were observed
Farmacología
Benzodiazepina de acción prolongada con potentes propiedades anticonvulsivantes. Indicada para epilepsia (ausencias, mioclonías, Lennox-Gastaut), trastorno de pánico y distonías. Vida media larga (30-40 horas) permite dosificación 1-2 veces/día. Alto potencial de dependencia con uso prolongado. Efectos adversos: sedación, ataxia, deterioro cognitivo.
Efectos en el organismo
Farmacocinética
Vida media de eliminación de 30-40 horas
1-4 horas
6-12 horas (efectos clínicos)
20-60 minutos (oral)
~90% (oral)
Hígado (CYP3A4)
Renal
Absorción oral rápida y completa. Biodisponibilidad absoluta del 90%. Volumen de distribución de 1.5-4.4 L/kg. Unión a proteínas plasmáticas del 85%. Se distribuye ampliamente en tejidos, incluyendo el SNC.
Cronología farmacocinética
Riesgos para la salud — Calculadora de dosis
Advertencias
- No suspender abruptamente
Combinaciones peligrosas
Riesgo Individual (IPRS)
Moderado
IPRS v4 · escalar normalizado [0, 1]
ModeradoModelo IPRS calculado: 20 de octubre de 2018
Fuentes de datos de dosificación
Los rangos de dosificación fueron compilados a partir de Goodman & Gilman's (14ª ed.), Rang & Dale (9ª ed.) y publicaciones indexadas en PubMed. Los valores representan promedios poblacionales para la vía de administración principal y no consideran variabilidad individual, tolerancia, peso corporal ni interacciones.