general anaesthetics Flashcards
three main categories of anaesthetic
local, regional and general
what is anaesthesia
the reversible loss of awareness in pain
local anaesthesia
small area has sensation blocked, patient remains conscious
regional anaesthesia
pain sensation in region of body are blocked.
Allows more extensive procedures to take plain but maintains the advantage that patients are conscious. Is safer than general anaesthesia
general anaesthesia
general: patient is given a drug that causes them to loose consciousness (and enter a state or altered consciousness)
Can essentially be viewed as a medically induced coma
Allows major surgery to take place
-that may be too painful or traumatic for the patient (or too difficult for the surgeon) if the patient were conscious
historical general anaesthetics
nitrous oxide, chloroform, ether
the first ‘modern’ anaesthetic
haloethane
problems with ether
highly flammable
problems with chloroform
hepatoxic and causes cardiac dysrhythmias
problems with haloethane
It causes liver damage with repeated use because (unlike other inhlaed agents) a substantial fraction (20%) is metabolised in the liver.
The product of this metabolism is trifluroacetic acid, which causes hepatitis.
This is a problem not just for patients, but for operating theatre staff who breathe in “waste” halothane.
stage 1: induction/ analgesia
patient is conscious but drowsy
they have reduced response to pain
stage 2: excitement
patient may become delirious and hypersensitive to pain (pain responses preserved)
may have increased gag reflex making intubation difficult
concerns in this phase: choking, breath holding, movement and vomiting
-important to limit the amount of time patient is in stage 2
stage 3: surgical anaesthesia
desired stage for surgery
there are 4 substages (‘planes’) in stage 3
as you move through the phases there is progressive shallowing of breathing and loss of muscle tone and reflex
plane 3 is said to be the ideal state for surgery, because there is relaxation of the thoracic and abdominal muscles
stage 4 results in apnea due to diaphragm paralysis
stage 4: anaesthetic overdose
in this stage there is medullary paralysis, cessation of respiration and loss of vasomotor control
without rapid intervention, the patient will die
goals of an anaesthetist
Achieve a pleasant, rapid induction
Spend as little time in stage II as possible
Get the patient into stage III as quickly as possible
Make this surgery as easy as possible for the surgeon
Stay out of stage IV
Achieve a rapid recovery from anaesthesia, with minimal post operative pain
pre-operative/ sedative anxiolytic
midazolam
induction of anaesthesia
propofol (IV)
maintenance of anaesthesia
isoflourane/ nitrous oxide mixture (inhaled)
relax tracheal muscles to facilitate intubation
suxamethonium
post operative analgesia
fentanyl
overton and myer
reported that the potency of the general anaesthetic is directly proportional to the lipophilicity
lipid theories
fluidizaition
volume expansion
These changes were presumed to affect the behaviour of the ion channels and receptors in the membrane.
However, the lipid theories explain drug action in terms of the AMOUNT of anaesthetic that accumulates in the membrane (which is related to the drug’s lipid solubility).
fluidization
Anaesthetic causes the membrane to become more fluid. As normal operation of the channel depends on its interactions with the solvent it is dissolved in (the membrane), its function is altered and it closes
volume expansion
The general anaesthetic causes the membrane to thicken. This alters interactions between the membrane and the channels/ receptors within it, causing their function to change
problems with lipid theories
The potency of alkyl alcohols increases up to around 13 carbons in length, but this is the cut off point
-suggests binding to a pocket of a defined size within a protein
Stereoisomers of anaesthetics have identical effects on membrane but can differ in their anaesthetic potency
Temperature changes fluidise membranes, but do not produce effects similar to general anaesthetics
Not all lipophilic molecules are general anaesthetics
current view of how anaesthetics work
protein theories
seems more likely that anaesthetics alter the way the protein moves between different conformational states.
-For example, an ion channel might have a higher likelihood of opening in the presence of a general anaesthetic.
Protein theories explain the lipophilic nature of general anaesthetics by proposing that:
the binding sites on target proteins are located in their membrane regions.
Thus, the drug would have to dissolve in the bilayer to be able to access its target site
how can the myer-overton correlation be explained in terms if we hypothesise actions of GA are protein dependent
that anaesthetics have to cross the blood brain barrier in order to exert their actions, and this depends on lipophilicity.
GA target proteins
Potentiating GABAA receptors and strychnine-sensitive glycine receptors
-extrasynaptic GABAA receptors may be particularly important targets of general anaesthetics
Potentiating two-pore-domain potassium channels
Inhibiting ionotropic glutamate receptors
two pore-domain potassium channels
Potassium channels that are open at resting membrane potential
-determine the resting membrane potential
Have two pore-forming domains in each subunit (and 4 transmembrane domains)
Assemble as dimer with 2 pore forming domains from each subunit contributing to the lining of the channel
Compounds that potentiate the function of these channels (more potassium moves out of cell) will produce neuronal inhibition
types of anaesthesia
inhalation
intravenous
neurolept
dissociative
inhalation
Requires use of volatile agent, that can be mixed with air or oxygen and delivered to patient via a mask
advantages of inhalation
by adjusting the mixture of anaesthetic drug reaching the patient, its relatively easy to maintain a certain level of anaesthesia
there will be rapid equilibration between the inhaled gas and the patient’s tissues
Most general anaesthetics undergo only limited metabolism in the patient’s body, and they will leave by the same route that they entered: the patient’s lungs. This can give rapid emergence from anaesthesia
potency of general anaecthetics
For an injected or orally administered drug, we would normally express potency as an ED 50 with units of mg/kg.
-we cannot do this for an inhaled drug.
inhaled anaesthetic potency is expressed as its minimum alveolar concentration (MAC).
minimum alveolar concentration
This is the minimum concentration of the anaesthetic at 1 atm pressure that is needed to prevent movement in 50% of subjects in response to an incision.
