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True IV induction agents produce loss of consciousness within  one arm-brain circulation time Approximately 30 seconds Induction agents  induce anaesthesia    but a single dose will  wear off after a few minutes Keeping the patient “asleep”  requires maintenance (additional agent)

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Rapidly –Acting “true induction agents” Slower-acting Thiopentone Etomidate Propofol Ketamine Benzodiazepines Neuroleptic-anaesthetics Opioids (in large doses)

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Rapid onset of action More pleasant & acceptable for the patient Pollution free Low incidence of side-effects Smooth induction with rapid transfer through the classic stages of anaesthesia

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Requires intravenous access It is easy to give too much .... side-effects No removal of drug via the lungs as with  inhalationals Recovery requires Redistribution Metabolism Excretion  Sudden loss of normal protective reflexes

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Most  sedative hypnotics exert their effect via the  inhibitory GABA A  receptors GABA –  γ   (gamma)- aminobutyric acid Increased chloride conductance → hyperpolarisation → neuronal inhibition Some  inhibit the release of glutamate , an excitatory amino acid, in brain Not clearly understood

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Pharmacokinetics  refers to the processes by which a drug is: Taken up by the body (absorption) Distributed to various tissues (distribution) Metabolised  (usually via the liver) Excreted ( e.g  kidneys, GIT) Pharmacodynamics  refers to the drug’s effects on the body

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Pharmacokinetics of Intravenous Anaesthetics

The  onset of action  depends on the drug reaching the effect site (the brain) by crossing the Blood-Brain Barrier Arm-brain circulation time  is determined by Speed of injection Lipid solubility Protein binding Blood flow to brain Recovery  is determined by Redistribution  from vessel-rich to vessel-poor organs (brain → muscle  etc ) Metabolism and excretion

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Following IV Induction, the patient will wake up after a few minutes  due to  REDISTRIBUTION  of the drug from brain to other tissues that are less well perfused Rapid awakening is  not  due to metabolism or excretion Low concentrations of the drug will remain in the brain for a while This impairs concentration and higher functioning Recommended not to drive or make important decisions for 48-72 hours post anaesthesia

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Smooth and rapid onset of action Rapid recovery No pain on injection Minimal side-effects / toxicity Inexpensive

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Reduce pain on injection IV lignocaine 10-20mg in syringe when giving propofol New, large-bore, free-running IV line Titrate to effect ..... You can always give more Less in elderly .... More in children

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“True Induction Agents” Propofol Thiopentone Etomidate Ketamine (unique: dissociative  anaesthetic  & analgesic) Benzodiazepenes Midazolam The international  colour  coding for all true IV induction agents is  YELLOW The international  colour  coding  forIV  sedatives is  ORANGE

The Intravenous Anaesthetic Agents

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