K2i / 17B11 / 15B14: Describe the pharmacology of Propofol

17B11: Exam Report

Describe the pharmacology of propofol.

76% of candidates passed this question.

A structured approach proved a good basis to answer this question. It was expected candidates would outline the uses such as anaesthesia, more prolonged sedation or possible additional roles in patients with seizures or head injuries. Discussion of the presentation and pharmaceutics, including a comment on antibacterial preservatives or lack thereof was expected. The mechanism of action should have been described. It was expected candidates could provide an indication of the usual dose (and how it differs in the more unwell / elderly patient population). A maximal rate and possible toxicity was expected.

A discussion on the pharmacodynamics by major organ systems was expected and credit was given for additional comments about hyperlipidaemia, urine colour changes or metabolic alterations. It was expected that candidates would mention propofol infusion syndrome at some point in their answer with some mention of clinical features or pathophysiology.

The important aspects of its pharmacokinetics should have been mentioned (high protein binding, large volume of distribution, termination of effect by redistribution, hepatic metabolism, context sensitive half life). A mention of adverse effects would complete the answer.

15B14: Exam Report

Describe the pharmacology of propofol.

60% of candidates passed this question.

Those candidates who did poorly lacked any structure for answering a pharmacology question. Pharmacokinetics was generally poorly handled and many answers revealed a lack of knowledge about this drug. Adverse effects and mechanism of action were generally well
known. Doses of the drug were often incorrectly stated.

Important aspects such as dose or pharmacodynamics were often omitted and a structured approach helps avoid this.

K2i / 17B11 / 15B14: Describe the pharmacology of Propofol


Non-barbiturate phenol derivative IV anaesthetic agent


  1. Induction & maintenance anaesthesia
  2. Sedation
  3. Cerebral protection in ICU
  4. PONV
  5. Hx of malignant hypertension


20mL lipid emulsion

1% propofol (200mg)

  • Egg lethicin 1% → emulsify intralipid
  • Glycerol 2.25% → isotonicity
  • Soyabean 10% → intralipid
  • NaOH → brings pH >7
  • Benzyl alcohol → retards bac/fungal growth
  • PPF is insoluble in H2O → must be mixed in a lipid emulsion to make it soluble (this is expensive)
  • pKa 11 (50% ionised, 50% unionised) = weak organic acid = 99% UNIONISED at pH 7.4
  • A weak acid moving into a more acidic enviro becomes less ionised
  • Highly lipid soluble


Induction → 2mg/kg

Maintenance → 6 – 10mg/kg/hr

Sedation → 2 – 4mg/kg/hr

PONV → 0.6mg/kg/hr


IV only → pain on injection


  • Extremely rapid
  • 1-arm-brain-circulation time ~15secs
  • Short effect site equilibration ∴ LOC ~30 sec
  • Peak effect 2 mins


Rapid distribution & elimination = rapid recovery

Awakening occurs at [PPF] 1mcg/mL

Short C5HT <40 mins for 8hr infusion


  • Unclear → ∴ no antidote
  • Potentiates actions of GABA & Glycine (main inhibitory NT of CNS/SC)



  • Sedation & hypnosis
  • Amnesia (same as midaz, Fent has more)
  • Anticonvulsant
  • Cerebral protection: ↓CMRO2 → coupled to metabolic rate, there is a ↓CBF & ↓ICP
  • ↓intraocular P


  • ↓BP (myocardial depression & ↓SVR)
  • ↓SVR
  • ↓CO
  • Direct -ve inotrope (↓Ca2+ release)

NB: ↓ symp CV & ↓ Ca2+ availability


  • ↓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)



  • IV admin only


  • Short effect site equilibrium time (2 mins)
  • Mixes rapidly in central blood volume
  • Distributed to tissues quickly according to BF & diffusion
  • After a single bolus, plasma levels ↓rapidly due to redistribution & elimination
  • High VD = 4L/kg → prolonged clearance

*** huge, the largest of all IV induction agents

  • PPB = 98%

Crosses placenta rapidly (but rapidly cleared)


  • Clearance = 30mL/kg/min
  • Exceeds HBF → ∴ extrahepatic metabolism
  • Hepatic metabolism → rapid + extensive
  • All metabolites inactive → H2O soluble sulphate & glucuronic acid metabolites


  • Inactive sulphate & glucuronic acid metabolites excreted by kidney
  • Organ dependent metabolism → liver & extra-hepatic
  • <1% excreted unchanged
  • ↓elimination with renal disease

Adverse Effects


  • Expensive → complex mixture requiring lipid emulsion due to low H2O solubility
  • High E content → caution with prolonged infusion & disorders of fat metabolism
  • Formulation supports growth & needs to because discarded quickly following being drawn up (<6hrs)
  • Glass ampoule! Accidents! Occupational hazard!
  • Preservatives → allergic potential
  • Pain on injection


MoA unclear so no antidote


  • Narrow therapeutic index: sedation → GA
  • ↓CPP
  • Excitatory phenomena → vivid dreams
  • Abuse potential & addiction described


  • HR unaffected → but 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 depression (dose related)
  • ↓ventilatory response to ↑PCO2 & ↓PO2
  • Suppresses laryngeal & cough reflexes


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


  • Pain on injection
  • Anaphylaxis
  • Propofol infusion syndrome: metabolic acidosis, rhabdo, MOF


  • IV admin only
  • High PPB → ∴ affected by [plasma proteins] & other drugs with high PPB
  • High lipid solubility → crosses placenta (but this is what allows it to act rapidly in lipid-rich CNS neurons which mop it up to drive the [ ] gradient)
  • High VD → prolonged clearance
  • Decreased elimination w renal disease