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Pharm 101: Propofol

Pharmacodynamics
  • Multiple organ system effects, most notably central nervous system (CNS), cardiovascular and respiratory
  • CNS:
    • Hypnotic
    • Anticonvulsant
    • Decreases intracranial pressure (due to decrease in both cerebral metabolic rate and cerebral blood flow)
    • Note no analgesic effect
  • Cardiovascular:
    • Decreases preload and afterload, causing hypotension. This effect is increased with increasing age and reduced intravascular volume
    • Also some inhibition of normal baroreceptor reflex, leading to minimal reflex tachycardia
  • Respiratory:
    • Dose-related central depression of respiratory drive, with reduced respiratory rate, and reduced response to hypercapnoea and hypoxia
    • Reduction in tidal volume
    • Reduction in upper airway reflexes
  • Other:
    • Anti-emetic effect
Pharmacokinetics
  • IV administration
  • Rapid onset and offset due to redistribution from the brain to skeletal muscle and fat (c.f. metabolism)
  • Distribution half life 2-4 minutes
  • Metabolism and elimination:
    • Rapid metabolism in liver, some extra-hepatic (lung) as total body clearance is greater than hepatic blood flow
    • Excreted in urine as glucuronides and sulphates, <1% unchanged
    • Elimination half life of 4-23 minutes
  • Duration of action 3-8 minutes
Clinical uses
  • Procedural sedation
    • 0.5-1.0mg/kg single bolus or 10-20mg aliquots titrated
    • Use in conjunction with an analgesic agent
  • Rapid Sequence Induction
    • 1-2.5mg/kg in adults
    • 2.5-3.5mg/kg in children
  • Maintenance of anaesthesia
Adverse effects
  • Adverse effects are often an extension of propofol’s pharmacodynamic effect
  • Hypotension
    • Negative isotropic effect and venodilation
  • Apnoea
  • Loss of airway reflexes causing obstruction and aspiration
  • Pain on injection
  • Allergic cross-reactivity to egg/soy products
  • Propofol infusion syndrome
    • Metabolic acidosis and tachycardia
Precautions/contraindications
  • Elderly patients
  • Poor cardiovascular reserve
  • Haemodynamic instability
Further Reading

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Adult/Paediatric Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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