2015B04 Discuss the concepts of half life and context-sensitive half times
with examples from anaesthetic pharmacology.



For each:

·      Intro

·      Use

·      Limitation

·      Graphs

·      (Equation)

·      Factors increasing it

·      Factors decreasing it


Half life:


·  Half life: time taken for plasma concentration C -> C/2

o t1/2α: during distribution phase ( 1/distribution x metabolism)

o t1/2β: during terminal elimination phase ( redistribution / metabolism)

·  Time constant: time taken for plasma concentration C -> C/e

·  These are fixed values


·  Provide some indication of likely time to offset

·  Determine dosing frequency: e.g. every half life

·  Determine time to steady state: 5 x t1/2, 3 x τ


·  Poor indication of time to offset after bolus or short infusion


·  t1/2 = τ x loge2

·  τ = 1/k

·  Cl = k x VD

·  Hence t1/2 = VD/Cl x loge2


Increased if

·  ↑VD:

o Small

o Non-polar (e.g. propofol)

o Low plasma protein binding

o ICF sequestration (e.g. amiodarone)

·  ↓Metabolism

o Low HER: e.g. thiopentone Cl 3.5mL/kg/min

Decreased if

·  ↓VD:

o Large (e.g. suxamethonium)

o Polar (e.g. heparin)

o High plasma protein binding (e.g. warfarin)

·  ↑Metabolism

o High HER (e.g. propofol)

o Ubiquitous enzyme (e.g. adenosine deaminase, plasma cholinesterase for suxameth)


Context-sensitive half time:


·  Time taken for plasma concentration C > C/2 as a function of duration of infusion

·  Not fixed but dependent on duration of infusion

·  Approaches but in theory does not reach t1/2β


·  Better than half life as an indicator of likely duration of action

·  Predict suitability for short infusion:

o e.g. fentanyl (highly LS 600x morphine -> large VD 4L/kg)

·  Predict suitability for long infusion:

o e.g. remifentanil: small VD 0.3L/kg, high Cl (40mL/kg/min), max CSHT <10 mins

·  TCI modelling: estimate time to propofol emergence (e.g. Cet 1mcg/mL)


·  No account of active metabolites (e.g. diazepam)

·  No account of prolonged receptor effects (e.g. aspirin)


(using two compartment model)

(Note not a textbook graph, just my interpretation)

Increased if

·  Long infusion

·  Other factors as for t1/2

Decreased if

·  Short infusion

·  Other factors as for t1/2




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