Anaesthesia

• Anaesthesia 


  Loss of sensation with or without loss of consciousness of the whole body or parts of it
• local anaesthesia

  affects only one part of the body, the local nerves
• general anaesthetics 


  Affects the whole body by depressing the CNS and consciousness
• what is a general anaesthesia?

  it is a medically induced coma with loss of protective reflexes caused by the administration of one or more general anaesthetic agents
• why is general anaesthesia carried out?

  to allow intolerably painful medical procedures to take place
• Examples of inhaled anaesthetics

  Haloethane

  desflurane

  sevoflurane

  isoflurane
• inhaled anaesthetics

  introduced as a gas or nebulised liquid
• what is minimum alveolar concentration?

  the fraction of the compound in the lungs needed for a lack of response to pain
• IV anaesthetics

  introduced as a suspension or solution

  often used for induction
• examples of IV anaesthetics

  propofol - primarily acts on gaba a receptors

  etomidate

  ketamine
• function of propofol

  Enhances GABAergic neurotransmission in the CNS

  acts at GABA-A receptor complex, different site to BZD
• PKA of propofol

  11 at pH 7-8.5
• features of propofol

  poorly soluble - octanol:water partition coefficient is 7000:1

  one of the most commonly used parenteral anaesthetics
• dose of propofol

  2-2.5 mg/kg
• onset of action of propofol

  hypnosis occurs with 30-60 seconds, with effects lasting 10-15 mins

  quickly and extensively metabolised

  quick onset and quick recovery
• What is fospropofol?

  It is the prodrug for propofol - much more soluble than propofol

  phosphate ester pre drug - undergoes metabolic conversion
• what is released after the metabolic conversion of fospropofol?

  phosphate, formaldehyde, propofol
• dose of fospropofol

  6.5 mg/kg
• onset of fospropofol

  onset delayed by 4-10 mins as the hydrolysis has to take place
• ketamine onset of action

  Potent and rapidly acting anaesthetic agent

  short duration of action - 10-25 mins
• effects of ketamine

  recovery accompanied by visual, auditory, and confusional illusions

  disturbing dreams and illusions for 24 hrs after administration
• where does ketamine act?

  does not act on GABA-A receptors

  non competitive antagonist at glutamate receptor, NMDA receptor

  binds to mu and kappa opioid receptors
• issue with ketamine

  significant potential for abuse
• features of etomidate

  carboxylates imidazole

  r enantiomer more potent

  positive modulation of GABA receptors

  not water soluble
• how is etomidate administered?

  2mg/ mL in 35% propylene glycol
• what type of anaesthetic is etomidate?

  general anaesthetic
• where does etomidate go?

  rapidly penetrates the CNS due to its lipid solubility
• how is etomidate metabolised?

  liver esterase
• how is etomidate eliminated?

  75% of the drug is eliminated in the urine as the inactive hydrolysed carboxylic acid
• discovery of local anaesthetics

  coco leaves in Peru chewed to feel good

  saliva from chewed leaves used to relieve painful wounds
• active constituent of coco leaves

  alkaloid cocaine
• effects of cocaine

  mood swings

  paranoia

  insomnia

  psychosis

  high blood pressure

  panic attacks
• Features of coca tropane alkaloids

  Tropane moiety - not ideal

  basic amine

  carboxymethoxy group

  benzoyl group - ester + aromatic group
• cocaine is


  unstable and is hydrolysed to 3 compounds which athletes can be tested for in drug testing
• effects of cocaine on the CNS

  loss of contact with reality, an intense feeling of happiness or agitation
• physical symptoms that occur when taking cocaine

  fast heart rate, sweating, large pupils

  high doses can cause high bp or body temp
• Primary metabolite of cocaine

  Benzoylecgonine - formed by carboxylesterases and excreted in urine
• Benzoylecgonine use


  used to detect and identify illegal cocaine usage
• what has cocaine been used to do?

  local anaesthetics have been developed based on cocaine
• Examples of local anaesthetics derived from cocaine (cocaine derivatives)

  Benzoyltropine

  procaine

  lidocaine

  bupivacaine