General anaesthetics Flashcards
what are chemical anaesthetics?
inhalational: nitrous oxide, ether and chloroform, isoflurane
- ether and chloroform are volatile - low temperature when they vaporise but are highly flammable so too dangerous to use
intravenous: halogenated carbons
- barbiturates: thiopental
- steroids: alphaxalone
what are physical anaesthetics?
- low atmospheric pressure
- hypothermia
how does lipid solubility affect general anaesthetics (GAs)?
- GAs can cause membrane expansion by entering the lipids of the plasma membrane and making them more fluid
- direct correlation between lipid solubility of GAs and the conc at which it can render 50% patients unresponsive to a surgical incision
- minimal alveolar concentration to abolish response of patients
- the more lipid soluble the GA, the lower the conc of drug required to render patient unresponsive
what is the relationship between anaesthetic effect and conc of GA?
anaesthetic effect is directly proportional to the molar concentration of agent in lipid
what is the lipid theory of GA mechanism of action?
Advantages: GA effectiveness is related to its lipid solubility
disadvantages:
- lipid becomes less fluid in colder temps
- if binding sites are saturated, GAs have less effects
- GAs cause increase in GABAa receptor affinity for agonists
INCORRECT THEORY
what is the protein theory of GA mechanism of action?
- GAs exert effect by interacting with a protein
- binding site for GA on the protein is only accessible within the plasma membrane
- explains why lipid solubility is important in determining what conc of drug is needed to reach the membrane
CORRECT THEORY
how do GAs regulate the activity of neuronal ion channels?
- GAs increase action of GABAa: volatile GAs bind to alpha and beta subunits, and intravenous GAs bind to beta subunit only
- low concs of volatile GAs activate Two-Pore Domain K+ channels, causing the resting membrane potential to become more hyperpolarised and less excitable
- ketamine and nitrous oxide block NMDA receptors (glutamate ionotropic receptor)
what are the molecular mechanisms of GAs?
- GAs can directly regulate synaptic transmission, as they can inhibit synaptic machinery
- with increasing conc of GA, voltage-gated Na+ channel current is decreased as they are inhibited
- GA causes the amplitude of APs to decrease
- GAs may also interfere with exocytotic machinery, as they reduce fusion of vesicles to presynaptic membrane and inhibit neurotransmitter release
how do low concs of GA affect neurotransmission?
low concs bring about an overally decrease in CNS activity and reduction in synaptic transmission:
- increase in inhibitory neurotransmission by GABAa receptor
- inhibition of transmission in reticular formation -> unconsciousness
- inhibition of transmission in hippocampus -> short-term amnesia
- inhibition of thalamic sensory relay nuclei -> analgesia
- can inhibit spinal reflexes
what do high concs of GA lead to?
all brain functions are affected:
- loss of motor control
- loss of all reflexes involved in respiration and autonomic regulation of heart
- leads to death
what are the 4 stages of anaesthesia?
- analgesia - patient shows reduced pain response but are still partially conscious (nitrous oxide can achieve this)
- excitement - patient has exaggerated reflexes e.g. they may kick out
- this is an undesirable state as it may cause complications in surgery - surgical anaesthesia - unconsciousness, loss of response to pain stimuli, loss of motor and autonomic reflexes, short-term amnesis
- this stage is desirable and is aimed to be maintained during surgery - medullary paralysis - loss of cardiovascular and respiratory mechanisms, leading to death
- this stage must be avoided
what are the desirable effects of anaesthesia?
- induction from stage 1 to 3 just be rapid
- analgesia
- muscle relaxation to make surgery easier
- rapid recovery/reversible
stage 2 and 4 must be avoided
give examples of intravenous anaesthetics:
propofol
thiopental (barbiturate on GABAa)
etomidate
alphaloxone (steroid)
what are the advantages of intravenous anaesthetics?
- easy to administer
- rapid induction (20-30s)
- propofol has rapid metabolism: 2-4 min half-life so rapid recovery and less hangover
what are the disadvantages of intravenous anaesthetics?
- pain at injection site
- complex pharmacokinetics
- thiopental has high lipid solubility so rapid induction but short duration due to redistribution, and hangover due to accumulation in fat
- side effects: respiratory and cardiovascular depression
etimodate does not have these effects
