K2i / 19B09: Propofol v Midazolam

19B09: Exam Report

Compare and contrast the pharmacology of propofol and midazolam.

77% of candidates passed this question.

Highlighting important similarities and differences between the drugs scored higher marks than listing the pharmacology of each drug separately. More pharmacokinetic information was required than simply stating both drugs “are metabolized in the liver and excreted by the kidney”.

K2i / 19B09: Compare and contrast the pharmacology of Propofol and Midazolam

Chemical

Propopfol

Midazolam

Use

Propopfol

Induction & maintenance anaesthesia
Sedation
Cerebral protection in ICU
PONV
Hx of malignant hypertension

Midazolam

Sedation
Hypnosis
Anxiolysis
Anticonvulsant
Anterograde amnesia

PPF can be used as an alternative GA when volatile anaesthesia is not possible

Midazolam has no anti-emetic properties

Both confer some cerebral protection

Both can be used for sedation

Both confer no analgesia. Midazolam has amenesic properties

Presentation

Propopfol

Complex emulsion

Midazolam

Sedation costs using PPF much lower cf Midazolam in ICU

Route

Propopfol

Midazolam

IV/IM/CNB

Midaz can be given IM in an emergency/no IV access, PPF IV only

MoA

Propopfol

Unclear

Potentiates actions of GABA & Glycine (main inhibitory NT of CNS/SC)

Midazolam

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

Midazolam has a known MoA w antidote

PD

Propopfol

CNS

Sedation & hypnosis

NO ANALGESIA

Amnesia (same as midaz, Fent has more)

Anticonvulsant

Cerebral protection: ↓CMRO₂ → coupled to metabolic rate, there is a ↓CBF & ∴ ↓ICP

↓intraocular P

CVS

↓BP (myocardial depression & ↓SVR)

↓SVR

↓CO

Direct -ve inotrope (↓Ca²⁺ release)

NB: ↓ symp CV & ↓ Ca²⁺ availability

Resp

↓Resp depression (dose related)

↓ventilatory response to ↑PCO₂ & ↓PO₂

Suppresses laryngeal & cough reflexes

Anti-emetic (D₂ receptor antagonism)

↓RBF 2° ↓CO

Green urine (prolonged infusions, due to phenols in urine)

NB: does not affect renal function (the green or the ↓ RBF)

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

Both have anticonvulsants and cerebral protection

Midazolam is more cardio stable. Very effective at reducing the dose of PPF when used together, with added benefit of amnesia for induction/RSI

Both confer respiratory depression

No anti-emesis for Midaz

PK

Propopfol

A

D

High V_D = 4L/kg

→ prolonged clearance

PPB = 98%

Short effect site equilb 2mins

M

Clearance = 30mL/kg/min

Heptic & Extrahepatic

E

Inactive

metabolites

<1% excreted

unchanged

Midazolam

A

D

95% PPB (albumin-base)

V_D 1.5L/kg

High lipid solubility

Short DoA 2° redistribution

M

Hepatic 3A4 hydroxylation

5% to OXAZEPAM = active metabolite

E

Metabolites renally cleared

High PPB of both. Potential for interaction with other drugs w high PPB

Both have hepatic metabolism.

PPF has no active metabolites

Adverse Effects

Propopfol

High energy content ampoule which supports bac growth

Pain on injection

CVS

1/100,000 → profound brady + asystole on induction

↓myocardial contractility

Bradycardia → asystole (SNS > PNS suppression)

↓HBF/RBF/CBF 2° ↓BP

Direct -ve inotrope (↓Ca²⁺ release)

Resp

↓Resp depression (dose related)

↓ventilatory response to ↑PCO₂ & ↓PO₂

Suppresses laryngeal & cough reflexes

Immuno

Allergy → should not be given to patients with soya/egg allergy

Other

Propofol infusion syndrome: metabolic acidosis, rhabdo, MOF

Midazolam

Both may cause pain on injection

Both ascribed abuse potential. Midazolam is a class 8 which will delay access in an emergency

PPF has potential for bradycardia & asystole and is a direct negative inotrope

Both supress ventilatory drive and suppress laryngeal reflex

Midaz is not a risk for MOF with prolonged high dose infusions