Midazolam

Chemical

Short acting BZD

Use

  1. Sedation
  2. Hypnosis
  3. Anxiolysis
  4. Anticonvulsant
  5. Anterograde amnesia

Presentation

Clear, colourless solution

1mg/mL in 5mL ampoule

H2O soluble

pH solution 3.5

  • pH <4 = imidazole ring open (H2O soluble)
  • pH >4 = imidazole ring closed (lipid soluble)

@ pH 7.4 → 89% UNIONISED

Dose

0.1 – 0.2mg/kg → depends on indication

  • ANXIOLYSIS 20% receptor occupied
  • SEDATION 50% receptor occupied
  • UNCONSCIOUSNESS >60% receptor occupied

Route

IM, IV, SC, CNB (intrathecal/epidural)

Onset

Slow 2 – 3 mins, wide individual variability

MoA

  • Bind BZD receptor which are closely linked with GABA receptors
  • Facilitates GABAergic inhibition
  • ↑frequency of Cl– channel opening

PD

CNS

  • Anterograde amnesia
  • Dose related ↓CMRO2 & CBF
  • Potent anticonvulsant
  • Sedation
  • Anti-nociceptic in SC/Epidural

CVS

  • Blunts CV response to intubation
  • Small ↓SVR

RESP

  • Stable MV
  • Dose dependent resp depression
  • ↓response to ↑PaCO2

PK

A

OBA 40% (large 1st pass)

IM availability 80%

D

95% PPB (albumin-base)

VD 1.5L/kg

High lipid solubility

Short DoA 2° redistribution (because lipophilic)

M

Hepatic 3A4 hydroxylation → same as Alfentanil

∴ together have ↑DoA

Then glucuronidation for renal excretion

5% to OXAZEPAM = active metabolite

E

Metabolites renally cleared

Clearance 7mL/kg/min

Adverse Effects

  • May have pain on injection
  • Apnoea

Flumazenil = antagonist