Midazolam

Class

• • short-acting benzodiazepine

Indications

• • procedural sedation (often in combination with an opioid, such as fentanyl)

  • preoperative sedation

  • induction of general anesthesia

  • sedation of ventilated patients

Administration/Absorption

• • Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl)

  • Oral

    • poorly absorbed orally with only 50 percent of the drug reaching the bloodstream

Dosage

Distribution

Mechanism

• • Benzodiazepines bind at the interface of the α and γ subunits on the GABA_A receptor

    • Requires that alpha subunits contain a histidine amino acid residue, (i.e., α₁, α₂, α₃ and α₅ containing GABA_A receptors)

    • Benzodiazepines show no affinity for GABA_A receptors containing α₄ and α₆ subunits with an arginine instead of a histidine residue.^[118]

  • Benzodiazepine ligand locks the benzodiazepine receptor into a conformation in which it has a greater affinity for the GABA neurotransmitter

  • This increases the frequency of the opening of the associated chloride ion channel and hyperpolarizes the membrane of the associated neuron

  • The inhibitory effect of the available GABA is potentiated, leading to sedatory and anxiolytic effects.

Excretion

• • short-acting benzodiazepine in adults with an elimination half-life of one to four hours

  • Midazolam is metabolised into an active metabolite alpha1-hydroxymidazolam

    • However, the active metabolite of midazolam is minor and contributes to only 10 percent of biological activity of midazolam.

  • Metabolised by cytochrome P450 (CYP) enzymes and by glucuronide conjugation

Side effects

Interactions

Contraindications