general anaesthetics Flashcards
what are stages of anaesthesia
stage 1: analgesia, still conscious
stage 2: excitement, delirium and respiration becomes irregular
stage 3: surgical anaesthesia: unconscious, respiration and reflexes become progressively depressed as anaesthesia deepens
stage 4: medullary depression, no spontaneous respirator and depressed vasomotor centres, coma and death follow in absence of artificial respiration and circulatory support
what are 2 main categories of general anaesthetics
those that are inhaled as vapour or gas (volatile anaesthetics)
intravenous anaesthetics
what are examples of volatile anaesthetics
neither ether (explosive) or chloroform (damages liver) are used any longer
N20, nitrous oxide is used
most are volatile liquids such as halothane, enflurane and isoflurane
what are examples of intravenous anaesthetics
thiopentone is most common, it is a thiobarbiturate
other agents are used such as propofol
how are volatile anaesthetics absorbed and excreted
both absorption and excretion is via lungs
how is potency of volatile anaesthetics expressed, what determines potency
potency is expressed as minimum alveolar concentration (MAC) of anaesthetic which will, when equilibrium has been attained, prevent movement in response to surgical incision in 50% of individuals (essentially an ED50)
MAC is expressed by %volume in the alveoli, measure in percentage atmospheres
mmHg= percentage atmx760
higher solubility in blood will cause an anaesthetic to be more potent
potency is also correlated with lipid solubility
how is solubility of volatile anaesthetics expressed
the blood: air partition coefficient, termed lamda
this is ratio of concentration of anaesthetic in blood:air at equilibrium, an anaesthetic which has a concentration of n times higher in blood than air at equilibrium will have a lamda value of n
what is the product of MAC and lamda value directly proportional to
blood concentration of anaesthetic at equilibrium when 1 MAC is administered
how do solubility/potency of anaesthetics compare
nitrous oxide is least potent, is far less potent than halogenated hydrocarbons such as halothane and enflurane
MAC of nitrous oxide is 105%, which is not achievable at atmospheric conditions, considering a patient needs at least 15% oxygen
out of halothane, enflurane and N2O: halothane has lowest MAC (0.75), then enflurane (1.6) then N2O (105)
how blood: air partition coefficients relate of some anaesthetics
highest in halothane (2.3) then enflurane is 1.8, and 0.47 for nitrous oxide
how is MAC related to lamda value
generally an inverse relationship
what is rate of onset and rate of recovery of an anaesthetic dependent on
rate of onset is faster in anaesthetics with a high MAC, since there is a larger concentration gradient between air in lungs and blood at time of administration, thus less soluble anaesthetics are faster
rate of recovery is faster is anaesthetics with low solubility as well so have low lamda values
what properties would an ideal anaesthetic have
high MAC (quick onset) and low lamda (quick recovery), thus low solubility anaesthetics
why is methoxyflurane no longer used
large lamda value so had long recovery rate
how does rate of elimination relate to onset, what may effect this
rate of elimination is inverse rate of onset
rate of elimination may be slower in patients which large fat depots
high lipid solubility causes slower recovery as it accumulates in fat
what is mechanism of volatile anaesthetics
although potency is correlated with lipid solubility mode of action does not involve insertion into lipid bilayer
they bind to hydrophobic regions of proteins, selective effects on certain ion channels have been demonstrated
halogenated hydrocarbons at anaesthetic doses selectively effect synapses between neurones over axons
GABAa receptors and 2 pore (leak) potassium channels that control neuronal excitability are shown to be important targets
effect of glycine at glycine receptors is also enhanced
ketamine, nitrous oxide and xenon are examples of anaesthetics which block NMDA receptors
what are side effects of volatile anaesthetics
all agents produce respiratory depression (especially halothane) and fall in blood pressure caused by myocardial depression and vasodilation
incidence of serious toxic effects is quite low, however therapeutic index for general anaesthetics is quite low; dose does not need to be increased much to move from surgical anaesthesia to respiratory paralysis
safety depends on skill of the anaesthetist
use of a mixture of halogenated hydrocarbon with nitrous oxide may minimise vasomotor depression
describe metabolism of volatile anaesthetics
halogenated agents are to some extent metabolised
about 60-80% of halothane is exhaled unchanged during first 24 hours after administration, up to 20% of halothane broken down into compounds such as trifluoroacetic acid
other volatile anaesthetics are broken down to a smaller extent (up to 3%)
what is an example of an intravenous anaesthetic, what are they usually used for
thiopentone, very commonly used to induce anaesthesia as they have very high speed of action
what are pharmacokinetics of thiopentone
often reffered to as ultra short acting barbiturate, however not actually short lasting
metabolised quite slowly in the liver, half life for catabolism is 4.6 hours
it has very rapid onset and recovery after a single dose
how does thiopentone concentrations in various tissues relate to time
very lipid soluble and can cross cellular barriers including blood brain barrier very quickly; therfore concentration in brain along with other tissues with large blood supply peaks soon after peak in blood concentration
blood peak is very short for thipentone as it redistributes to other less well perfused tissues quite quickly, drop in blood concentration causes drop in brain concentration, causing quick recovery
lean tissues and fat are last tissues to peak
if repeated doses of thiopentone are given, the blood and hence the braine concentration will remain high and thiopentone will be quite long lasting and slowly metabolised
what are pharmacokinetics of most intravenous anaesthetics and how does this relate to their use
quick onset, slow metabolism
normally only used for induction since anaesthetist needs to be able to control level of anaesthesia from moment to moment and best control is obtained with anaesthetics
how does mode of action of thiopentone compare to volatile anaesthetics
mode of action is very similar
however it has no analgesic effects and respiratory depression is profound
effects are via GABAa receptors
what is main hazard of thiopentone
solution of thiopentone is very alkaline, can cause serious tissue damage if it is not injected properly
how is propafol used
iv anaesthetic
fast onset and recovery
administration via continuous slow intravenous infusion, controlled by computer to avoid overdose
is an irritant at site of injection, causing pain
how is ketamine used
is a dissociative anaesthetic
disadvantages: slow recovery and causes hallucinations (less in children)
used in pediatric surgery and as pediatric sedative after trauma
widely used in vetinary practice
widely abused and can cause bladder damage with chronic use
produced incomplete anaesthesia, however very good analgesic
causes dissociation from surrounding and light sleep, for when co-operation is needed
lethal overdose is rare
can be used in combat zones or acute trauma outside hospital settings such as in bombings
orally active
how is epidural anaesthesia used
use of local anaesthetic such as bupivacaine (long duration), in combination with narcotic analgesic such as fentanyl
only gives pain control below site of epidural
uses of epidural: childbirth, minor surgery, lower limb surgery, post operative pain control
how are drugs used peri-operatively
premedacation for surgery: analgesics, anxiolytics, anti-emetics and anti-muscarinics
induction of anaesthesia: intravenous anaesthetic
maintenance: inhaled anaesthetic
muscle relaxants are also used to reduce amount of anaesthetic needed
