inhalation agents Flashcards
define critical temperature
the temperature above which a substance exists as a gas regardless of the pressure applied.
below this the substance is a vapour
above this the substance is a gas
define critical pressure
the pressure that needs to be applied to liquify a gas at its critical temperature
what is the saturated vapour pressure?
the pressure exerted by the vapour phase of a gas when it is in equilibrium with liquid phase.
At specified temp & pressure
how is the boiling point defined?
the temp at which SVP = atmospheric pressure
what are the 2 chemical groups for inhaled agents?
mosts ethers - have O - sevo, des, iso, enflurane
some halogenated hydrocarbons - chloroform and halothane
how does structure of an inhalation agent affect chemical properties?
Size
- smaller the more lipid soluble - newer agents are less potent as bigger
Electronegativity of halide ion - F is more electronegative than Cl - hence desflurane differs from iso by F vs cl. therefore desflurane has stronger intermolecular forces - less lipid soluble and takes longer to metabolise
hydrocarbon chain - more hydrocarbon to halogenated groups, the more lipid soluble
Overall more lipid soluble, the more potent
how do isoflurane and enflurane compare structurally ?
structural isomers
altered position of Cl and F
this makes isoflurane more lipid soluble, less water soluble, takes longer to metabolise.
what is the blood:gas partition and what does this determine?
defined as the ratio of the amount of anaesthetic agent in blood and gas when the two phases are of equal volume, pressure and in equilibrium at 37°C.
water solubility
speed of onset
what is the oil gas partition? what does this determine?
defined as the ratio of the amount of anaesthetic agent in oil and gas when the two phases are of equal volume, pressure and in equilibrium at 37°C.
lipid solubility
potency and MAC
what factors affect speed of onset of anaesthesia with inhaled agent?
alveolar conc reflect brain conc - therefore the faster build up of anaesthetic agent in alveolar, the fast in the brain and the faster the speed of onset.
Can be divided into patient factors, drug factors, equipment and delivery factors
drug factors:
- lower water solubility the faster - i.e. lower blood:gas partition
- the more volatile i.e. the higher SVP , the quicker
- higher the MAC (i.e. less potent) the faster.
patient factors:
- cardiac output - the larger cardiac ouput, the more is removed from alveoli therefore slower onset.
- alveolar minute volume
- high FRC dilutes agent - slower onset
- CBF - the faster the blood flow to brain, the quicker the onset
equiptment and delivery:
- inspired conc and FGF
- deadspace in equiptment
- second gas effect
what graph is drawn to compare speed of onset of volatiles?
FA/ FI
Fraction in alveolus / fraction inspired
when FA=FI = 1
the speed of onset will be how quickly FA /FI gets to 1 i.e. the steeper the rise in gradient.
order the speed of onsets for the inhalation agents including 20% N20 and 70% N20
fastest - 70% N20
desflurane
20% N20
sevo
iso
halothane - slowest
a small proportion of the inhaled gases are metabolised - by what?
CYP 2E1
what % are the different agents metabolised and what do they produce?
halothane - 20% - F, Cl, Br, Trifluroacetic acid
sevoflurane 3-5% - F, hexafluroisopropanol
enflurane - 2% - F, Cl, Trifluroacetic acid
isoflurane - 0.2% - F, Cl, Trifluroacetic acid
desflurane - 0.02% - F and trifluroacetic acid
how are wash out curves drawn ?
y axis - FA/ FAE
x axis - time
FAE = the partial pressure in the lungs at the point when the vaporiser isfirst turned off. i.e. starts at 1
negative exponential
what are the different theories of how volatile agents work?
older hypothesis
- meyer overton hypothesis
- lipid bilayer expansion theory
- lateral phase separation theory
newer hypothesis:
- interactions with ion channels through lipid binding sites on ion channel.
what is the Meyer and Overton hypothesis / lipid solubility hypothesis?
meyer and overton hypothesised that because potency correlated with lipid solubility, volatile agents must work through dissolving in lipid bilayers of neurons to exert their effects
what is the Critical volume hypothesis / lipid bilayer expansion theory?
developed from meyer and overton…
anaesthetic agents exert their effects through dissolving in bilayer and distrupting bilayer structure i.e. distortion which disrupts functioning of ion channels and hence AP propagation.
the more space in a membrane that is taken up by anaesthetic, the more effect. hence potency relates to lipid solubility but also molecular struture.
which membrane receptors are volatiles thought to interact with?
GABA A
glycine
NMDA
2 pore K channels - leads to hyperpolarisation
nAChR - reduce currents through this
However they have lipophilic binding sites which explains why lipid solubility correlates with potency
positive allosteric modulation of inhibitory gaba and glycine
what is the definition of MAC?
minimum alveolar concentration is defined as the concentration of anaesthetic agent needed to prevent movement response to standard skin incision in 50% of subjects aged 40 when breathing 100% O2 at 1atm.
in the absence of other analgesic or anaesthetic agents. Historically this was a midline incision in the abdomen.
measure of potency
Define mac -awake
concentration required to prevent 50 % of subjects responding to a verbal command. MAC-awake is usually about 0.4 MAC.
define MAC BAR
concentration required toBlockAutonomicReflexes to nociceptive stimuli in 50 % of subjects. (no tachycardia, no hypertension, pupils constricted in response to pain). Usually around MAC 1.5.
define MAC 90
MAC 90 - MAC is the minimum alveolar concentration of an anaesthetic agent that prevents movement in response to a standard skin incision in standard conditions in 90% of subjects
define MAC amnesia
level needed to prevent memory of noxious stimulus. Occurs at 0.25 MAC
define mac intubation
the amount needed to intubate with inhaled agent alone e..g seen in children at MAC 1.3. In adults would need 3 MAC which is not possible hence use muscle relaxants (in paeds you don’t need to
what are the MAC values of the different agents?
halothane = 0.75
isoflurane = 1.17
sevo - 2
des = 6.6
nitrous =103
xenon = 71
which factors have no influence on MAC?
gender
alkalosis
Mg/K
anaemia
HTN
what does Na do to MAC?
hypernatraemia increases MAC (the need for anaesthetic)
hyponatremia decreases MAC
what does metabolic acidosis do to MAC?
decreases amount of anaesthetic needed
decreases MAC
what does clonidine do to MAC?
decreases it
which of inhalation agents is airway irritant and which is good for bronchodilation?
sevo = good - bronchodilation and reduces airway resistance
desflurane & iso - pungent smell and airway irritatant.
which of the metabolites of the volatiles is toxic?
trifluroacetic acid
whcih is the most and least cardiac stable?
most - sevoflurane (although can cause long QT)
Iso is used in cardiac surgery - potent vasodilator (reduces afterload) and myocardial conditioning protecting from ischaemia
least - halothane
why cant sevo be stored in glass bottles?
glass is a sorce of lewis bodies which causes breakdown of sevo into hydrofluric acid
what are the risk factors for fulminant hepatitis in halothane use?
Risk factor – obesity, middle aged, rfremale, repeat exposure
how is N20 made?
Ammonium nitrate is heated to 250 degrees causing it to decompress
if temperature is not controlled carefully during production, contaminants may accumulate in the gas (e.g. nH3, n2, no, no2 and Hno3).
any impurities are removed through alkaline washes (NO and NH3 by acid wash) prior to storage.
can N20 be used as an agent alone to anaesthesise someone?
MAC 103% - hence would need to be 100% of the atmospheric pressure
therefore would need all of the inhaled gas to be N20 - hypoxic. and this will only anaesthetise 50% of population. i.e. give MAC of 1.
however in elderly requirements are lower so potentially possible
OR can increase atmospheric pressure i.e hyperbaric chamber. (it is the partial pressure that exerts its effect so need a pp around 103 kpa. so if atm 200 kpa - would give 50% of N20 but this would be around 103kpa)
how does N20 have its analgesic effects?
opioid receptor on descending pathways
- it is antagonised by naloxone
which vapouriser is needed for ether?
EMO (Epstein, Macintosh, Oxford) draw-over vaporizer.
what is the environmental impact of volatiles?
greenhouse gases
ozone depletion - N20
overall most harm done by N20
desflurane persists in atmosphere for the longest time
which agents MAC is not affected by hyperthermia?
n20
which agents are structural isomers?
enflurane
isoflurane
which agent is epileptogenic?
enflurane
what does a low latent heat of vapourisation suggest in terms of boiling point?
A low latent heat of vaporisation facilitates easy vaporisation.
which inhalation agent has lowest MAC?
halothane
what is MAC like in neonates/ children?
low in neonates
high in children
what are the early signs of MH?
he first clinical signs are tachycardia, increasing ETCO2 and increased oxygen consumption. Pyrexia is a late sign.
what is the genotype of MH?
chrom 19
auto dom
what is the filling ratio of a cylinder of N20?
UK - 0.75
hotter climates 0.67
what temp is SVP quoted at?
20 degrees
define critical temperature…
This is the temperature above which it is not possible to return a vapour to a liquid, regardless of the pressure
is Ethers B:G high or low?
high - 12
how does N20 affect the heart rate? what are the CVS effects like
may increase it slightly
may mildly decrease SVR
overall minimal effects CVS compared to other agents
how is N20 stored?
It is stored in French blue cylinders at a gauge pressure of 52 bar
how is n20 made?
heating ammonium nitrate to 250
what type of anaemia can N20 cause?
megaloblastic
a type of macrocytic anaemia
is n20 and xenon flammable?
only n20
what are the boiling points of xenon and N20?
N20 = -88
Xeno =-108
what do the 3 older theory’s of inhalation agent mechanism work?
The main descriptor of the Meyer-Overton Hypothesis is lipid-solubility.
The main descriptor of the Critical Volume Hypothesis is a change in membrane volume.
The main descriptor of the Lateral Phase Separation Hypothesis is a change in membrane fluidity.
what type of receptor is the glutamate receptor?
Ionotropic Receptors: NMDA, AMPA, and Kainate receptors, which are ion channels mediating fast synaptic transmission.
Metabotropic Receptors: mGluRs (Groups I, II, and III), which are G-protein-coupled receptors involved in modulating neuronal excitability and synaptic plasticity through slower, second messenger systems.
which anaesthetic agents can influence nAChR?
propofol , ketamine
isoflurane, sevo
ether
