K2i / 19A07: Midazolam v dexmedetomidine
19A07: Exam Report
Compare and contrast the pharmacokinetics and pharmacodynamics of midazolam and dexmedetomidine.
27% of candidates passed this question.
Most candidates used the effective tabular format presenting pharmacokinetics and pharmacodynamics of each drug side by side. Many answers demonstrated a lack of correct detail with respect to the pharmacokinetics and pharmacodynamics of these two level 1 drugs.
Many included pharmaceutics which attracted no marks as it was not asked.
K2i / 19A07: Compare and contrast the pharmacokinetics and pharmacodynamics of midazolam and dexmedetomidine
Chemical
Midazolam
Dexmedetomidine
Use
Midazolam
- Sedation
- Hypnosis
- Anxiolysis
- Anticonvulsant
- Anterograde amnesia
Dual benefit of anticonvulsant activity w sedation. Less marked CVS effects
Dexmedetomidine
- Sedation
- Anxiolysis
- Analgesia
- Antihypertensive
Route
Midazolam
IM, IV, SC, CNB (intrathecal/epidural)
Multiple modes of delivery make it more robust for administration
Dexmedetomidine
IV
Onset
Midazolam
2 – 3 mins
Faster onset, more amenable to emergencies
Dexmedetomidine
15 mins
MoA
Midazolam
- Bind BZD receptor which are closely linked with GABA receptors
- Facilitates GABAergic inhibition
- ↑frequency of Cl– channel opening
Both have completely separate MoA
Dexmedetomidine
- Activates pre-synaptic α2 adrenoreceptors in CNS → ↓NA release
∴ ↓symp outflow
- α2 agonism in CNS → sedation & anxiolysis
- α2 agonism in AS/C fibres → analgesia
- α2 agonism in CNS/SC → ↓symp outflow → ↓HR, VD
PD
Midazolam
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
Dexmedetomidine
CNS
- Sedation
- Anxiolysis
- But does not cause Resp D
- Gives sedation in a cooperative & semi-rousable state
Resp – none
CVS – ↓MAP, ↓HR
Essentially, the biggest difference here is the awake co-oeprative patient with the haemodynamic consequences which can be favourable or not.
Midazolam also aids neuroprotection
PK
Midazolam
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
Dexmedetomidine
A
IV only
Unpredictable PO
D
High PPB 94%
Low VD 1.3L/kg
M
Hepatic, extensive glucuronidation & N-methylation
E
Metabolites in urine
t ½ B – 2hrs
Clearance 39L/hr
Both have similar Vd, liver metabolism and renal metabolite clearance.
Midazolam has a much longer CSHT owing to its lipophilicity
No known active metabolites
Adverse Effects
Midazolam
- May have pain on injection
- Apnoea
Flumazenil = antagonist
Dexmedetomidine
- Hypotension
- Bradycardia
- Nausea
- Dry mouth
- Author: Krisoula Zahariou