Genetal Anaethetics Flashcards
What is the triad of GA
Need for unconsciousness
Need for analgesia
Need for muscle relaxation - loss of reflexes
Facts about inhalation anaesthesia
Compounds used are simple and unreactive
Short chain molecules
No one chemical class
GA mechanism of action what are the two theories which one is more accepted
Lipid theory and protein theory - protein more accepted
Lipid theory
Where did the evidence come from
What in this theory is thought to cause the GA actions
Meyers experiments with tadpoles - added GA compounds to tadpole with water and oils at different concentrations. Concentration of agents required to anaesthetise the tadpole was inversely proportional to its lipid:water partition coefficient
Lipid solubility was key to need less GA
Concentration of 0.05mM of anaesthetic in cell membrane leads to anaesthesia
Lipid volume expansion of 0.4% causes anaesthesia
Thought that these processes interfere with the conduction of nerve impulses which causes anaesthesia
Protein theory - where does lipid solubility fit it
Why are the proteins thought to be needed
Proteins mechanism
Lipid solubility is thought to be required for the transmission of the GA across the cell membrane for it to the attach onto the a protein either a transport channel or receptor
Protein and lipid Meyer curves for the action of GA are the same
Cut off phenomenon at a certain carbon length the GA potency stops if it was just to do with lipid solubility then the increase in carbon length would not have any effect on the decrease in potency this suggests a binding pocket of a certain size
Stereoselectivity - the same atoms but a different arrangement in space. This effects the potency of the GA if this was just lipid based this wouldn’t have an effect but as it does it is thought the proteins have a specific binding pocket which can lead GA effects
GA bind to hydrophobic pockets on proteins -> where lipid solubility is important for access
Molecular targets for inhaled/gaseous targets
Ion channels - no single target/ indirect action
GABAA receptor ligand gated channel in inhibition and enhance other inhibitory ligand gated -glycine
K+ channel activation decreases membrane excitability
Inhibits function of excitatory ligand gated channels - NMDA (glutamate), 5HT, Ach nicotinic
Stages of anaesthetic
1 analgesia :
Drowsiness, reflexes in tact, still conscious
2 Delirium: induction phase
Excitement, delirium, inconvenient speech, loss of consciousness unresponsive to non-painful stimuli
Dangerous phase - muscle rigidity, spasmodic movements, arrhythmia, vomiting and choking
3 surgical anaesthesia:
Unresponsive to painful stimuli, breathing regular, abolition on reflexes, muscle relaxation, synchronised EEG
4 medullary paralysis - od
Pupillary dilation
Respiration/circulation ceases
EEG wanes -> death
What are the concentration dependent effects of anaesthesics
Molecular size affects potency
Concentration of the GA effects potency
Inc conc more effect it has
However narrow therapeutic window between loss of movement and CV function lost
Large window between consciousness and movement
Only 2-3x clinical dose can lead to od- CV failure and death
Properties of a good anaesthetic
Potent and fast acting
GA potency measured?
MAC - minimal alveolar concentration- measurement of anaesthetic potency in man
Is the concentration of anaesthetic required to produce immobility in 50% of patients when exposed to a noxious stimulus
Variables that need to be considered
Sex, height, weight, red hair and alcoholic status
Expressed as % of inspired air (%v/v)
Assumed at equilibrium
Inspired air= alveolar conc
Alveolar conc= brain conc
Mac dircectly or inversely proportionate to lipid solubility
Inversely
More lipid soluble Dec MAC
Lipid solubility main determinant of anaesthetic potency
What does fast acting mean?
What influences how fast acting a GA is
High speed of induction and recovery
This is important for control of depth of anaesthesia
It is influenced by:
Properties of the GA - blood:gas partition coefficient solubility in blood
Oil: gas partition coefficient solubility in lipid
Physiological factors - cardiac output and alveolar ventilation rate
What can the speed of induction be increased by in the transfer to the alveoli
Increase in concentration of anaesthetic
Increase in ventilation rate
Speed of induction increased by - transfer to the blood
Blood: gas partition coefficient
Solubility
Less soluble in blood the less needs to be saturated to inc partial pressure therefore speed of induction to the brain is faster
If it is highly soluble in blood the blood needs to be saturated before inc conc in brain
Need low solubility - low blood:gas partition coefficient inc speed of induction
What inc transfer of GA from blood to tissue
Determined by the tissue:blood partition coefficient - how soluble in tissue
In lean tissue grey matter in brains and lead muscle the partition coefficient is 1 so the conc in brain can rise quickly
In adipose tissue higher than 1 so has a high capacity for anaesthetic Dec speed of induction can lead to accumulation
However blood flow in adipose tissue much less than grey matter in brain so the GA cannot reach adipose as much as lean tissue so leads to faster transfer and induction in lean tissue
