16A24: Exam Report
Describe the ideal sedative agent for an Intensive Care patient (50% of marks). How does midazolam compare to this (50% of marks)?
60% of candidates passed this question.
Candidates who had a structured approach (i.e. pharmaceutical, pharmacokinetic, pharmacodynamic) provided more content and scored higher. Candidates who also approached pharmacodynamic effects in an organ system based approach scored higher. Relating a pharmacokinetic property of midazolam (e.g. volume of distribution or half-life) to a un/desirable attribute e.g. offset of action and accumulation displayed a greater understanding of the question. For many candidates, the description of an ideal drug contained more detail and candidates were not able to adequately state how midazolam compares.
K2i / 16A24: Describe the ideal sedative for an ICU patient (50 marks) + How does midazolam compare to this (50 marks)
Physical
Ideal
Midazolam
Stable in H2O
H2O soluble
Stable in solution
pH solution 3.5
pH <4 = imidazole
ring open (H2O soluble)
pH > 4 = imidazole ring closed (lipid soluble)
No reconstitution before use
None required
Stable in air & light
Yes
Long shelf
Yes
Stored room temp
Yes
Doesn’t support bacterial growth
Does not
Compatible with drugs & fluids
Incompatible with some drugs
No additives
Cheap. But only more cost effective than PPF if using it for prolonged sedation in ICU
PK
Ideal
Midazolam
Onset
Ideal
Rapid onset
Midazolam
~10 mins
Wide individual variability
VD
Ideal
High oiL/H2O solubility
Midazolam
At physiological pH, highly lipophilic with small VD 1.5L/kg
C5HT
Ideal
Short
Midazolam
Not ideal
360 min after 9hrs
Metabolism
Ideal
Completely metabolised
Organ independent
Active & inactive metabolites
Midazolam
Liver 3A4
Hydroxylation & then glucuronidation
5% to OXAZEPAM = active metabolite
Elimination
Ideal
Rapid clearance with short DoA
Midazolam
Short DoA 2° redistribution (highly lipophilic)
Metabolites excreted in urine, renal impairment has little effect
Clearance 7mL/kg/min → lasts ~60mins
PD
Ideal
Midazolam
MoA
Ideal
Known with antagonist
↓CMRO2, ↓CBF, ↓ICP
Midazolam
Binds B2D receptor
Potentiates GABA
↑frequency Cl – channel opening
Flumazenil = antagonist
Yes
CNS
Ideal
Anxiolysis
Amnesia
Analgesia
Ability to progress to GA
Midazolam
Yes
Anterograde
None
Large dose required
CVS
Ideal
Minimal CVS depression
Midazolam
Small ↓SVR
Blunts CVS response to intubation
Resp
Ideal
Minimal resp depression
Midazolam
Apnoea
↓response to ↑PaCO2
GI
Ideal
No N&V
Midazolam
↓PONV
Pain on Injection
Ideal
None
Midazolam
Occasional discomfort
Histamine Release
Ideal
None
Midazolam
None
Allergy/ Anaphylaxis
Ideal
None
Midazolam
Rare