Analgesia: Local Anaesthetics Flashcards
how does conduction of an electrical impulse through a nerve occur?
all or nothing event called the action potential
what is an action potential?
all or nothing event that facilitates conduction of electrical impulse through nerves
what is an action potential caused by?
voltage dependent opening of sodium and potassium channels in the cell membrane
what ion channels are involved in the creation of an action potential?
Na+ and K+
describe the Na+ concentration outside a nerve cell
high
describe the K+ concentration outside a nerve cell
low
describe the Na+ concentration inside a nerve cell
low
describe the K+ concentration inside a nerve cell
high
how is the concentration of sodium and potassium within a nerve cell maintained?
Na+/K+ pump uses ATP to move 2 potassium ions and 3 sodium ions against their concentration gradients
how many sodium and potassium ions are exchanged by the Na+/K+ pump?
2K+ ions into the cell and 3Na+ ions out
what is the method of cell transport used in the Na+/K+ pump?
active transport
why is active transport required in the Na+/K+ pump?
as sodium and potassium are being moved against their concentration gradient
what causes the nerve cell membrane to become depolarised?
rate of Na+ entry to the cell exceeds K+ exit
what is occurring when a nerve cell becomes depolarised?
membrane looses negative electrical gradient
what is set off by the depolarisation of nerve cell membranes?
Na+ positive feedback which causes more voltage gated Na+ channels to open to cause the membrane to become even more depolarised
what is caused by increasing number of voltage gated Na+ channels opening in response to membrane depolarisation?
more voltage gated Na+ channels open to cause the membrane to become even more depolarised
what is the threshold for generation of an action potential?
15mV higher than RMP
what happens when the membrane potential reached 15mV higher than RMP?
an action potential is generated
when does the cell membrane repolarise following generation of an action potential?
when Na+ channels become inactivated and K+ channels open to allow K+ to exit the axon
how is the membrane potential returned to -70mV following generation of a action potential?
Na+ channels become inactivated and a set of K+ channels open to allow K+ to leave the axon
Na+ cells regain resting excitable state and Na+/K+ pump returns membrane potential to normal
describe how an action potential is generated
rate of Na+ entry to the cell exceeds K+ exit
membrane looses negative electrical gradient
Na+ positive feedback causes more voltage gated Na+ channels to open to cause the membrane to become even more depolarised
when a threshold of 15mV higher than RMP is reached an action potential is generated
how do local anaesthetic drugs affect action potential generation?
block Na+ channels and prevent generation of action potential
where are voltage operated Na+ channels found in the body?
all excitable tissue (not just nerve tissue)
what are voltage operated Na+ channels sensitive to?
membrane potential
what is the role of voltage operated Na+ channels?
selective passing of Na+ ions
what effect on the membrane are local anaesthetics said to have?
membrane stabilising
why are local anesthetics said to be membrane stabilising?
less likely that Na+ will move into the cell and begin membrane depolarisation
what are the 3 broad nerve types?
motor
sensory
autonomic
what are the types of motor nerves?
alpha
beta
gamma
what are the types of sensory nerves?
proprioceptors
mechanoreceptors
nociceptors
what types of nerve fibre are proprioceptors?
Aalpha
Abeta
what types of nerve fibre are mechanoreceptors?
Abeta
Adelta
what types of nerve fibre are nociceptors?
Adelta
C
what are the types of autonomic nerves?
preganglionic B
postganglionic C
what axons are more resistant to LA block?
larger diameter
why are larger diameter axons more resistant to LA block?
more heavily myelinated
why does level of myelination affect LA block efficacy?
myelin slows/resists movement of LA into nerve cells
what nervefibre types are more susceptible to LA block?
C fibres and Adelta
why are C fibres and Adelta fibres more susceptible to LA block?
C fibres are unmyelinated
Adelta fibres are only thinly myelinated
what fibres are preferentially blocked?
C fibres
Adelta fibres
why does preferential blocking occur?
due to sensitivity of some nerve fibres to LA block because of their level of myelination
what nerve fibres are blocked first due to preferential blocking?
nociceptive
what order will nerve blocking occur in due to preferential blocking?
nociceptive
proprioceptive
mechanoreceptive
motor
where is LA site of action
within nerve cells at the Na+ channel
where on the cell does LA have its action>
within the cell rather then on the outside
what are LA drugs made up of?
aromatic group (lipophillic)
basic side chain / tertiary aimide (hydrophillic)
linkage by either ester or amide
what are the aromatic group and basic side chain / tertiary aimide of a LA drug linked by?
ester or amide linkage
what type of molecules are LA drugs?
weak bases
what is the pKa of most LA drugs?
8-9
what form of LA can enter cells?
only the uncharged form can cross the lipid membrane
in order to have maxiumum LA effect what form does the drug need to be in?
uncharged
what is the proportion of uncharged LA governed by?
pH of the solution the LA is in
pKa of the LA
Henderson-Hasselbach equation
what affects how much of the LA is uncharged?
pKa of LA itself
pH of the solution it is in
what will lead to more uncharged fraction of LA?
if solution is closer to the pKa of the LA
what can lead to more ionised / charged LA?
more acidic solution so pH is further from pKa
what does pKa affect?
onset of LA action
what is the pKa of lidocaine?
7.8
what is the pKa of bupivacaine?
8.1
what is the pH of plasma?
7.4
of lidocaine and bupivacaine which has the slower onset of action?
bupivacaine
why does bupivacaine have a slower onset of action than lidocaine?
at plasma pH a greater proportion of bupivacaine is ionized and so less is able to cross into the cell
why is a greater fraction of bupivacaine than lidocaine ionised in plasma?
plasma pH is further from bupivacaine pKa
in what type of tissue is LA less effective?
inflamed tissue
why is LA less effective in inflamed tissue?
pH is decreased so a greater proportion of LA is ionised and so less can penetrate the cell membrane to bind to the Na channel
what is the effect of inflammation on tissue pH?
decreases - more acidic
what is drug potency a measure of?
drug activity expressed in terms of the amount required to produce an effect of given intensity
what is the potency of lidocaine?
2
what is the potency of bupivacaine?
8
what happens to LA toxicity as potency increases?
increases
what are the factors which affect LA duration of action?
lipid solubility
strength of binding to the channel
speed of drug removal
metabolism of LA
why does lipid solubility affect duration of action?
ease of penetration of membrane
amount of drug reaching Na+ channel
what is the speed of removal of LA dependent on?
tissue perfusion
what does metabolism of the LA depend on?
ester or amide linkages
what can be added to LA drugs to reduce speed of removal?
vasoconstrictors
what vasoconstrictor is often added to LA drugs?
adrenaline
what is the benefit of adding adrenaline to LA drugs?
vasoconstriction reduces blood flow to and from the area which reduces the removal of LA
how can you identify LA drugs that have an ester linkage?
no i before caine
how can you identify LA drugs that have an amide linkage?
i before caine
how stable are ester linkages?
unstable
how stable are amide linkages?
more stable than ester
what are ester linkages broken down by?
plasma pseudocholinesterase
how long is the plasma half life of ester linkage LAs?
short - rapidly broken down by plasma pseudocholinesterase
how long is the plasma half life of amide linkage LAs?
longer than ester
how are amide linkage LAs broken down?
subject to biotransformation with conjugation in the liver
how do plasma esterases breakdown ester linked LA?
hydrolysis of ester link
what is formed as a result of the hydrolysis of the ester link in LA drugs?
PABA
why is there a risk of allergic reactions with ester linked LA drugs?
PABA is produced by the hydrolysis of ester link which can cause allergic reactions
where in the body are esterases not found?
CSF
what enzyme breaks down amide linkages?
cytochrome P450
what disease may contraindicate the use of amide linkage LA drugs?
hepatic
why may hepatic disease contraindicate the use of amide LA drugs?
can prolong or limit LA metabolism
what effect can barbiturates have on amide LA breakdown?
increase drug breakdown
what drugs may cause an increase in amide LA breakdown?
barbiturates
how can barbiturates increase amide LA breakdown?
induce enzymes in the liver that breakdown the LA
what drugs can inhibit amide LA breakdown?
midazolam
why may midazolam inhibit amide LA breakdown?
inhibit P450 enzymes that breakdown amide linkage
what are the main formulations of lidocaine available?
sterile solution for parenteral use
aerosol or spray
topical patches
why are LAs often supplied in a salt solution?
as they are poorly water soluble
what is the effect to the patient of placing local anaesthetics in a salt solution?
lowers pH so can cause stinging on injection
what is baricity?
weight of one substance compared to the weight of an equal volume of another
what is the comparator substance for baricity for spinal anaesthesia?
CSF
why must baricity be considered in local anaesthesia?
dont want LA to spread high into the epidural space and affect muscles of respiration
how can upward spread of LA in spinal anaesthesia be avoided?
ensuring LA is heavier / has higher baricity than the CSF
how is baricity of LA increased for spinal anaesthesia to prevent spread?
glucose is added to make then heavier
why is adrenaline commonly added to LA?
vasoconstrictor to prolong duration
reduction of risk of toxicity
reduction of bleeding
when should LA with vasoconstrictors in be used with caution?
end arterial sites (e.g. tail/toes) as risk of ischemia
what is the issue with LA being absorbed systemically?
available for systemic effects including toxicity
what is required for a drug to be systemically active?
unbound and unionised
what does plasma protein binding of LA depend on?
concentration
pH
when does percentage binding of plasma proteins to LA decrease?
as concentration rises
as pH falls
what is the effect of low plasma protein on LA toxicity?
less protein = more free, unbound LA
leads to more systemic effects
in what species is lidocaine licensed?
cats
dogs
horses
what is the onset of action of lidocaine?
2-5 minutes
what is the duration of action of lidocaine?
20-40 minutes
how cardiotoxic is lidocaine when compared to bupivacaine?
less as less potent
what species is bupivacaine licensed for use in?
no veterinary species so should be used under cascade
what is the duration of action of bupivacaine?
up to 6 hours
what is the onset of action of bupivacaine compared to lidocaine?
linger
is EMLA licenced?
no
what is EMLA made up of?
lidocaine and prilocaine
what leads to maximum absorption of EMLA into the skin?
covering with an occlusive dressing
when is full effect of EMLA seen?
30-45 mins after application
what are the main areas of LA toxicity?
neurotoxicity
cardiotoxicity
what is the safe maximum dose for lidocaine?
8-10mg/kg
what is the safe maximum dose for bupivacaine?
1-2mg/kg
what is the main risk factor for LA toxicity?
overdosing
how can LA toxicity be avoided?
never exceed safe dose limits
consider injection site
care with small patients
use correctly sized syringes
are CVS or CNS toxicity signs seen at lower concentrations of LA?
CNS
what is seen with CNS LA toxicity?
generalised CNS depression proportional to unbound drug in bloodstream
minor behavioural changes
muscle twicthing and tremors
tonic-clonic convulsions
CNS depression/respiratory depression and death
how is LA CNS toxicity treated?
symptomatic
benzodiazepines to control seizures
O2 supplementation
intubation and ventilation if needed
what can LA CVS toxicity lead to?
hypotension
dysrhythmias
how does LA CVS toxicity lead to hypotension?
depression of myocardial contractility
direct relaxation of vascular smooth muscle
loss of vasomotor sympathetic tone
how does LA CVS toxicity lead to dysrhythmias?
lipophilicity means rapid entry of LA to open sodium channels during systole
drug remains bound to the sodium channel during diastole
how does LA CVS toxicity present as arrhythmias?
re-enterant arrhythmias
what LA most commonly causes arrhythmias if cardiotoxicity occurs?
bupivacaine
how is LA CVS toxicity treated?
symptomatic
manage bradycardia
fluid therapy with inotropic support if needed
intralipid IV
how should brady cardia be managed?
anticholinergic
how can LA toxicity be prevented?
don’t exceed safe maximum dose
dilute LA with 0.9% NaCl if larger volume needed
use appropriately sized syringes
use appropriately sized needles to minimise tissue trauma
aspirate before injection
what is the role of intralipid IV in CVS LA toxicity?
mop up unbound LA
according to the RCVS guidance on the VS act (1966) what LA blocks can RVNs carry out?
any block that doesn’t enter a body cavity
cannot perform epidural/pleural block
what are the main loco-regional techniques?
epidural
regional/local
topical
infiltration
where is epidural anesthesia placed?
into epidural space after L7 / around sacrum
what structure are spinal and epidural anaesthesia both performed within?
the vertebral canal
what is the epidural space?
space within vertebral canal which surrounds the sac containing spinal cord, nerves and CSF
what is spinal anaesthesia?
injection into sac containing CSF, spinal cord and nerves
what is epidural anesthesia?
injection into the epidural space
can epidural anaesthesia be performed by an RVN?
no involves entry into a body cavity
in what patients is epidural anaesthesia more complex?
pregnant
obese
those were anatomical landmarks have been affected
how should the skin be prepped for epidural?
sterile prep
when should epidural not be performed?
if sin infection at puncture site
sepsis
coagulation impairment
what LA must be used for epidurals?
sterile
preservative free
what may be added to LA in an epidural?
opioids (may use alone)
ketamine
medetomidine
what are the side effects of epidural?
hypotension
hypothermia
urinary retention
infections
slowed hair regrowth
define local anaesthesia
infiltration - small discrete action
define regional anaesthesia
blocking a larger area (e.g. brachial plexus)
what is the role of local / regional anesthesia?
surround a specific peripheral nerve or set of nerves to provide anaesthesia
what are 4 examples of local/regional blocks?
ophthalmic
dental
limb nerve blocks
wound soaker catheters
what forms may topical LA come in?
spray / cream /liquid
what are 3 examples of topical LA?
eyedrops
intubeeze
EMLA
what topical LA products are licensed for veterinary use?
none except for intubeeze
where can infiltration LA occur?
anywhere on the body provided there is enough tissue to infiltrate
what are 4 examples of infiltration LA?
ring block of distal limb/tail
around skin tumour to be excised
incisional line block
intraperitoneal
how is infiltration LA performed?
injection into either V-shape or inverse pyramid
how is intraperitoneal LA infiltration performed?
instilled into peritoneal space of open abdomen before closure (more difficult if abdomen closed
can RVNs perform infiltration LA blocks?
some - not any that require entry into a body cavity but could at as VS hands (e.g. under instruction do intraperitoneal while scrubbed in)
