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Midazolam
- indication:For use as a sedative perioperatively.
- pharmacologypharmacology:
- mechanism: It is thought that the actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the brain. Benzodiazepines increase the activity of GABA, thereby producing a calming effect, relaxing skeletal muscles, and inducing sleep. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening.
- toxicity: LD<sub>50</sub>=825 mg/kg (Orally in rats). Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs.
- absorprion: Rapidly absorbed after oral administration (absolute bioavailability of the midazolam syrup in pediatric patients is about 36%, and intramuscular is greater than 90%).
- halflife: 2.2-6.8 hours
- roouteelimination: Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, α-hydroxymidazolam, followed by glucuronidation of the α–hydroxyl metabolite which is present in unconjugated and conjugated forms in human plasma. The α- hydroxymidazolam glucuronide is then excreted in urine. No significant amount of parent drug or metabolites is extractable from urine before beta-glucuronidase and sulfatase deconjugation, indicating that the urinary metabolites are excreted mainly as conjugates.
- volumedistribution: * 1.24 to 2.02 L/kg [pediatric patients (6 months to <16 years) receiving 0.15 mg/kg IV midazolam,]
- clearance: * 9.3 to 11 mL/min/kg [pediatric patients (6 months to <16 years old)]