W2: LA- Neurophysiology and MOA Flashcards
Looking at
- basic nerve structure
- sodium channels
- nerve pulse/ AP
Neuron
like a cell
- has special parts: dendrites and axons that talk with other cells by chemical transmitters
What is the epineurium layer responsible for in a nerve cell?
contains bunch of axons called fasicles
What is neuron cell membrane?
proteins embeded in PLB
3 main ions and conc to know
K, Na, Cl
difference in conc out/in cell= result in voltage
rest: inside is negative -70mv
how is resting Mem Pot maintained?
pumps
voltage gated channel on mem called? importance?
sodium channel important bc LA molecule sticks here. has 3 parts
- green out vestibule
- selectivity
- inner pore (LA binds here)
What happens when sharp tip of probe pokes your gums?
pain signal to brain
- Na open progressively (at first just bit open, then more)
- influx Na come in cell
- positive membrane potential (from -70 to +40)
depolarisation
going from -70 to +40 (threshold level -55mv which by influx of Na which goes rapid)
membrane becomes more permeable
Repolarisation
when reach full depol at +40mv, the membrane will get back to resting MP
through ATP Na/K pumps
Refractory period
- when another AP cannot be done during refractory period
- AP only gen at hyperpol
summary
- rest -70mv
- stimulus- sharp poke. Na come in. slow depol
3.threshold by 15 mv, BOOM rapid depol +40 - active pumping of ions
- repole
- rest
AP direction
wave of AP travel down axon.
only move forward bc as gen, there is a refractory period where you cannot gen another AP
Myelination effects
myeline= big jumps, no need to propogate all down nerve section by section= faster
‘sultatory conduction’ = bouncing signal (phenomenon)
When you inject LA to myelinated nerve, what happens?
LA only works at nodes where there is no Myeline. where gaps exposed.
If inject to unmyelinated nerve= blocks whole nerve
what fibre types are there, what should you know?
main subtypes to know: a-delta which are small myelinated fibres
- c even smaller unmyelinated fibres (slower)
Pain fibres of teeth
a-delta= dental pain like sharp shooting pain is from dentine sensitivity. pain when drilling cavity with no LA, go bit in dentine= sharp pain = a fibres.
c fibres= pulpal, dull aching, always in background.
basic chemical structure of LA
like Na channel , there is 3 parts
- fat (lipophilic)
- middle chain
- water loving part
2 main groups
1. Amides:
2. Esters:
- aromatic= lipic= pass thru cell, fat part can pass thru cell membrane
- middle chain: ester or amide= affects metabolism
- love water= can be present in extra/intracellular fluid = prevents it from precipitating in solution
design: pass through fat PLB, present in water
Middle chain of LA can be
ester or amide.
diff in metabolism and clearance
Why is acid added to anaesthetic?
they are acidified to form salts so they are more stable. when dissolve in solution present
1. RN- uncharged
2. RNH+= charged
inject dissolved salts in LA cartridge, will inject partial uncharged and charged particles into pt.
- inject
- RNH +- positive bit= outside cell mem, allows
- RN passes through fat PLB, then combines with
-H ions other side, reform a molecule to binds to - inner pore of Na channel (green oval)
- effectively block Na channel
when stimulus comes, will not open Na channels bc blocked, no AP. this block IS REVERSIBLE
basically: positive bit distracts pore, so RN uncharged comes in, joins with H and blocks the pore, NO AP.
what form of LA can pass through cell membrane?
RN uncharged.
reforms to cation by H, which binds to inner pore of Na channel.
stops Depol and AP
summarise in one line LA MOA
LA bind to inner pore of Na channel, no AP bc can’t depol. this is reversible (does it’s job for only limited time, body clears it)
3 important ft of LA
- time: how long, pt will ask how long will it last? pKa = dissoc constant
- duration MOA: 1-3 hours (some surgeons use one for 8+ hrs), depends on protein binding of LA to inner pore (reversible, but strength of binding determines duration of action)
-potency: how strong LA is (related to lipid solubility) gotta pass through mem, more inside and easily pass= more binding to Na channel. more potent= need less. less potent= need more.
Onset time of LA. What influences onset of LA action? (how long it takes for LA to work)
determined by pKa. lower value= quicker it works.
how much acid wants to give up ions
give up H easily= stronger acid
lower pKa value= shorter the onset time
higher pKa= longer
e.g. mepivicaine= lowest 7.7. pKa, shortest onset of action compared to procaine.
- LA with lower pKa = more the acid (salt solution in LA), more it will br8k to base molecules= stronger acid. want to give up H more.
infection
pH of tissues affect LA
infection= more acidic more H ions, so more LA needed bc less of it is going through membrane.
If you have La with high pKa…
weak acid, loves to hold onto H more.
less RN, so less RNH on inside so less Na channel gets blocked
which LA has similar pKa levels?
similar onset 2-4 mins. first 3.
If the LA is closer to normal to body pH, this means that it will…
More likely disassociate. There is more of the uncharged base form ‘RN’ formed more quickly, so it will work with a shorter onset time.
What other factors affect onset/dissoc of LA to uncharged RN version?
pKa and pH
normal pH of tissue: 7.4
inflammation tissue: lower pH will mean lot more H, more acidic which drives rxn in other way, decrease in dissoc of LA, less RA, less base molecule, less pass thru cell mem, less of it works.
infection prevents dissociation
infected tissue, what do you do?
infection prevents dissociation
LA wont work. block don’t infiltrate.
don’t inject to inflamed tissue- LA won’t work well IT WILL HURT. avoid area, inject at diff site.
block nerve at main trunk.
all the branches will be blocked.
IAN don’t infiltrate at branch.
normal vs inflamed. Why is pH important factor for onset?
prevents LA dissoc to RN and binding with H+
25 % vs 1% (lil decrease in pH is huge affect on LA)
allows you to change technique to block not infiltrate
other factors affecting onset time aside from pH and pKa
- distance of nerve, further you inject, longer for LA to diffuse across
- accuracy of injection/ anatomy. e.g. mandible is physical barrier bc it has cortical bone.
- enough conc/vol amt of LA. if you don’t give enough it wont work.
What 4 main factors determines how LONG LA works?
binding of protein.
Strong = longer duration, affected by amount of LA you give. more LA more in tissues, more it takes to remove.
Vascular tissue: if you inject to bunch of BV’s, means blood constantly flowing, so blood keeps taking it away. this will lower duration. (LA is also vasodilator, that’s why adrenalin added)
is LA a vasodilator or constrictor?
LA is vasodilate= opens vessels
in area with lots of BV= enhances flow away
so thats why adrenalin is added to vaso constrict
Duration of blockage in relation to amt
more vol= more LA
less vol when there is high conc.
What determines the strength of the LA? Give an example of a strong LA.
determined by how easy fat passes. greater fat loving, easier to pass and bind NA channel
high fat loving = binding more
Which LA is potent?
ones that love fat
articaine, ligno
ligno (more potent)
bupivacaineL 30 = 6-8hrs
ligno vs mep
ligno is 4 times more potent
Summaries the action potential and LA mechanism of action:
- rest -70 to -55 threshold - rapid depol +40mv reverses quick, rapid repol –> creeps back to resting mem potential (refractory period no AP can happen)
- base form crosses cell mem (RN unionised) reassoc with H, binds with inner pore of Na channel, blocks it. reversible
- pKa determines onset time, duration (protein binding), potency (how fat passes easilt)
