local anesthetics Flashcards
a fundamental use of of local anesthetics is
blockade of nerve fxn (both centrally and peripherally)
application may be for blockade of ____ _____ _____ for ___________ or blockade of ________ ________ for a specific limb analgesia, or central blockade for a truncal blockade
cardiace nerve fxn
dysrhythmia
peripheral nerves
local anesthetics derive their effect from
interrupting the sodium channel action potential in the nerve
depolarization of a receptor channel can be through ________ or ________ __________
voltage or ligand gating
with voltage gating, an _________ arrives at the channel causing it to open and a NT or substance such as _________ enters the cell for effect
impulse
sodium
a ligand gate opens when a ______ (___) in the environment of operation ______ __ __ _________ and causes it to open.
ligand (NT)
binds to the channel
ACh in the NMJ is an example of:
ligand gating
local anesthetics operated with _________ gating on the ________ channels
voltage gating
sodium channels
LAs operate in _____ dependent fashion with a larger amount of LA blocking a respectively larger number of channels
dose-dependent
as greater blockade occurs, so is the prominence of the blockade through interruption in depolarization _______ __________
impulse propagation
the inability of an impulse to propogate or carry a signal results in the
inability of that nerve to carry the signal to its destination
since different nerve fibers have different signal functions, blocking some nerves will result in lack of _______ fxn past the point of blockade and other fibers will not transmit _______ signals pas the blockade
sensory
motor
there is a functional threshold for LAs, that is, until a minimum dose is met, there will be ___________
no effect
nerve fibers are blocked in order of their _______ and _________ variables
size and myelination
LA effect is __________ and __________ dependent
concentration and volume
transmission through tissue in a concentration gradient sufficient to penetrate the nerve sheath is _________ to gaining effect
essential
esters
cocaine
benzocaine
procaine
chloroprocaine
tetracaine
amides
lidocaine
mepivacaine
bupivacaine
prilocaine
ropivacaine
(2 i’s in amide)
2 primary divisions of LAs are created by their chemical structure:
lipophilic (lipid soluble) is an aromatic benzene ring
hydrophilic (water soluble) is a tertiary amine
joining these 2 elements: lipophilic (aromatic benzene ring) and hydrophilic (tertiary amine) is a
hydrocarbon chain
the link between the ________ ________ and the __________ is the key to classifying the types of LAs
lipophilic ring and the hydrocarbon
ESTERS bind the lipid side to the chain with _____
CO
AMIDES bind the lipid side to the chain with ______.
NHC
ESTERS are metabolized by
pseudolchilinesterases
AMIDES are metabolized by
the liver
pts with pseudocholinesterase deficiencies will have ______ _________ and risk _________
slower metabolism and risk toxicity
recall that AChE drugs are found in the ________ for metabolism of ACh
NMJ
The presence of enzymes that break down ester LAs are found in the _______ and are referred to as _________ __________
plasma
plasma cholinesterases - bc they are found outside the the NMJ they can also be called pseudocholinesterases
___________ metabolism is generally slower than _________ metabolism
amide
esterase
the true metabolism of the drugs becomes pertinent after it is ______________________ from the site of injection
taken up into circulation
once this “uptake” occurs, _______ _________ for esters and _________ dysfunction for amides metabolize the LA
plasma cholinesterase
liver
a _______ uptake into circulation can _______ the chance of toxicity by preventing a large, less metabolizable bolus from effecting the CNS and CV system.
slow
decrease
an exception on route of metabolism is the ester local __________ which is metabolized by the liver
cocaine
______ are more likely to cause allergic reactions than _______
esters
amides
the ester metabolite ______________ (____) is the offending agent
p-aminobenzoic acid (PABA)
because __________ such as __________ are used with amide drug packaging, they too may have an allergic response
preservatives
methylparaben
true allergic patients may benefit from using a _________ _______ ________ LA
preservative free amide LA
_________, which is not as readily available anymore is the more common culprit for allergic responses of the amides
prilocaine
___________ is the active LA in “hurricane spray” and is more likely to cause this response than other amides
benzocaine
methemoglobinemia correlates with these 2 LAs
prilocaine and benzocaine
the formation of methemoglobin is abnormal ______ given the normal amount of this form of ______ is trace
Hgb
Hgb
when these LAs are given, especially in high doses, the normal Hgb is susceptible to
change to MetHgb
A left shift to the oxygen hemoglobin dissociation curve results and the inability of this Hgb to
carry oxygen
__________ is often used for topical anesthesia during GI procedures, TEE exams, and oral procedures
benzocaine (hurricane spray)
treatment for HetHgb
methylene blue given at 1-2 mg/kg IV
Since LAs have both non-ionized (lipophilic) and ionized (hydrophilic) components, it is valuable to know the respective ____ of each drug
pKa
the pKa is the ______ at which half of the drug is non-ionzed and other half is ionized
pH
if a pH solution is _____ than the pKa of the drug, then the LA becomes ______ ionized and is less able to enter the nerve and have its effect
lower
more
clinically, patients with infections have _____ effect of the drug when injected
less
if pH is lower than the pKa of the drug, then the LA becomes MORE ionized and less able to effective
if an ankle block is needed for a toe debridement, and the foot is infected, the pH will be lower and thus the drug becomes more __________ and ____ _________ bc _______ drug enters the nerve
ionized
less effective
less
making the onset _______ and ______ dense
slower and less dense
the addition of _______ ________ to LAs has been demonstrated to increase speed of onset by keeping more drug in the non-ionized state
sodium bicarbonate
one additional benefit of adding bicarbonate is the reduced ____ __ ______
pain on injection
This MOA for reduced pain with bicarb is not certain but perhaps related to decreased sensitivity of _____ _______ to ______________ drug
nerve fibers to non-ionized
when a drug has a high pKa, it becomes more _________________________
difficult to enter the nerve for action
(drug with high pKa difficult to enter the nerve for action)
this is exaggerated when the patient pH is _________ and when ________/__________ make the _______ lower
lower
additives/preservatives
lower
bc the alkalization of LA increases the _______ soluble nature, it is able to enter the cells more easily (instead of reaching the nerve)
lipid
the more ______ soluble the LA, the more potent and longer duration of action.
lipid
most LAs have a non-ionized component that is _______ soluble and an ionized portion that is _______ soluble
lipid
water
when the non-ionized portion enters the nerve, it then equilibrates its non-ionized and ionized portion and the ionized portion is able to bind to the ______ _______
sodium receptor
thus to speed onset, making the lipophilic portion more ________ by the addition of __________, you assist the speed of onset
prominent
bicarbonate
3 factors determine the longevity of action in the LAs
- dose to start
- tissue distribution and lipid solubility
- drug metabolism
the larger the _____, the _________ duration of action
dose
longer
lipid soluble drugs have _________ duration of action than less soluble drugs
longer
increased ______ ______ is inversely related and _______ _______ solubility is directly related to duration of action
blood flow (means less on site time)
lipid solubility (means increased time on site)
systemic absorption (uptake from tissue to plasma level) is affected by:
site of injection
dose
specific drug properties
vessel rich sites generally absorb more quickly than vessel poor
larger dose increase the concentration gradient of the LA
properties (lipid solubility/pKa) can increase absorption vs uptake
one way to consider the functional duration of action is to think of what keeps the drug from being _____ ______ from the site.
taken away
lipophilic properties promote _____
absorption
epinephrine decreases ______ ______ for uptake
blood flow
high protein binding increases _______ to the tissue
adherence
injection of LA into tissue (not IV) results in it eventually moving into __________ (this is _____)
moving into circulation
this is uptake
the uptake of LA represents the duration of _________ utility
clinical
lungs remove a large portion of LA, especially _________
lidocaine
protein binding results in drug being __________, versus free drug in the ________
sequestered
plasma
metabolism occurs by the two primary methods of:
pseudocholinesterase activity
the liver
_______ ________ then occurs following metabolism
renal excretion
we think of clinical duration of action as how long will this drug stay in the tissue around the nerve before it gets _________ and taken away for _________
absorbed
metabolism
sites of absorption (rates of uptake from fastest to slowest)
tracheal > intercostal > caudal > epidural > brachial plexus > femoral/sciatic
TICEBS
drug uptake into circulation initiates metabolism of the drug more quickly in _______ than ______________ sites, thus the clinical effect at the _______ is shorter bc its taken up into circulation from that site
tracheal
brachial plexus
trachea
rate of uptake is important when considering _______ doses
toxic
several ______ are found to potentiate the effect of LAs.
drugs
__________ decreases uptake and therefore prolongs effect
epinepherine
___________ by ____________ decreases blood flow to the area and decreases circulatory uptake (and thus metabolism) of the LA
vasoconstriction by epinephrine
the use of epi is found to increase duration of ________, ________, and __________ in absorption into tissue in some blocks through vasoconstrictive nature.
action, potency and reduction in absorption
___________ & ___________ as well, increase the potency and duration of the blocks by delaying repolarization
clonidine and dexmedetomidine
interestingly, _________, like ___________, has alpha 2 agonist properties
epinephrine
clonidine
_________ can potentiate LA and have been found to increase intensity and speed of onset for blocks by way of their own mechanism of blockade of _______ transmission
opioids
pain
regarding metabolism of pseudocholinesterase, the LA, ___________, disables this enzyme
dibucaine
exposing a patients pseudocholinesterase to dibucaine should __________ the action of the enzyme. Normal is ________ _________
inhibit
80% inhibited
dibucaine is NOT used ___________, but to test for the presence of ___________ __________
anesthetically
abnormal pseudocholinesterase
for abnormal pseudocholinesterase, dibucaine only inhibits _______%
20%
20% inhibition by dibucaine implies that abnormal pseudocholinesterase wont break down drugs at the normal speed, thus _______ LAs and drugs metabolized by this process (remi, esmolol, SCh) will have significant ________ in duration of action over their nominally short duration of action.
ester
increases
the ________ the dibucaine number, the more normal the enzyme and likelihood that it breaks down at a normal rate
higher
__________ is often noted in the CNS due to crossing the BBB
toxicity
toxicity is due to the _________ of the inhibitory neurons
depression
__________ & _________ are the hallmarks of toxicity
seizures and hyperexcitation
_______________, ____________, & ______________ is followed by excitation and seizures
ringing in the ears, circumoral numbness, and tongue numbness
subsequent excitatory blockade results in excitatory block with ____________ & _________ collapse
respiratory and cardiac collapse
acute and significant uptake may result in __________ arrest
respiratory
the ____________ features are secondary (though timing may be varied) due to blockade of the excitatory neurons resulting in ________ _________ and ________
cardiotoxicity
cardiac dysrhythmia and arrest
CV effects may include decreased __________ and __________ through the same inhibitory mechanism of action on sodium channels
contractility and conductivity
at higher concentrations, smooth muscle relaxation occurs which may be helpful in the _________, but causes systemic __________.
lungs
systemic hypotension
cardiac toxicity, likely related to high _____ ______ is more associated with longer acting drugs, particularly ___________
protein binding
bupivicaine
in most cases, occurrence of toxicity is _____
rapid
most often less than 1 minute and majority less than 5 minutes from time of injection
rapid toxicity is often due to direct injection of the LA ____________ rather than into ___________
intravascularly rather than tissue
efforts to avoid intravascular injection include:
frequent needle aspiration
avoidance of excessive dosing
use of ultrasound
test-dosing for epidurals
incremental dosing
maximum bupivicaine dose
2.5 mg/kg = 2.5 mg/ml
2.5 mg/kg max dose for bupivicaine (or 2.5 mg/ml) means that the patient’s weight in kg is the ________ ________
maximum volume, or half the volume if 0.5% is used
_______ ________ ________ is a form of toxicity in the intrathecal space which can be caused by LA in prolonged exposure as well as mechanical processes such as infection, compression, hematoma, or structural changes
cauda equina syndrome
this process tends to be ________ lasting, if not _________
longer lasting, if not permanent
loss of _______, ________, or _______ and ________ fxn are consistent along with intractable pain inconsistent with __________ or absence of noxious ___________
sensory, motor, or bowel and bladder
stimulus, stimulus
_______ _________ _________ are resolvable syndromes that have similar features
transient neurologic symptoms
________, _________, lower extremity ________ and ________ deficits are the hallmarks of these two processes (CES/TNS)
bowel, bladder, lower extremity motor and sensory deficits
________ _________, particularly with _________ have been associated with TNS
subarachnoid catheters
lidocaine
___ ___________ for SAB has fallen out of favor even for single injection blocks
5% lidocaine
often indistinguishable, the _______ resolves within a few weeks whereas the _______ does not
TNS
CES
several factors influence increase the risk for systemic toxicity. _______ ________ into circulation is a risk for any LA. This achieves potentially toxic level in the shortest amount of time
unintended uptake
_______ _________ is reportedly reduced by the use of ultrasound for constant visualization of the needle tip
vascular injection
fast uptake from highly perfused areas can result in toxicity when ______ _______ of LA are near the ______
large quantities
near the site
toxicity parallels _______
potency
drugs that are very lipophilic are _____ _____, with the most prominent drug being _______
more toxic
bupivacaine
_______ toxicity generally precedes _________ and is related to level of drug
CNS
cardiotoxicity
since the increase in level can change quickly during (unintended) IV injection, _____ ______ _ ______ can occur in short succession
both types of toxicity
keep in mind that toxicity is not a “ _______ _____”, it is a ______ that enters circulation and the brain ________ than it can be cleared
“large dose”
dose
faster
large doses CAN be used for protracted effect but within the confines of the ______ _______ ________
peripheral nerve space (outside the vasculature)
prevention by use of ________, _________ dosing, use of _______ for blockade, _____ dosing, and knowledge of toxic levels are key
aspiration, incremental dosing, use of US for blockade, test dosing, and knowledge of toxic levels are key
Initial toxic response is often _________
seizures/ CNS toxicity
___________ are the most common therapy though ________ can be effectively used.
benzos
propofol
caution with propofol d/t _______ ______ effect
myocardial depressant
decreased ________ ________ and peripheral ____________ are effects of the propofol by itself and may be more prominent in the presence of LA toxicity
myocardial contractility and peripheral vasodilation
_______ may stop external muscle activity, but they don’t affect cerebral excitation
paralytics
_______ toxicity is more difficult to address with traditional resuscitation
Cardiac
ACLS is used in standard workflow but some recommendations include using smaller doses of _________
epinephrine - 100 mcg rather than 1000 mcg
______ ______ is the most complicated but best method to sustain the patient until drug is metabolized
cardiac bypass
the newest mechanism of therapy is use of _____ ______ ______
20% lipid solution
use of lipids absorbs the LA which ________ the removal of the LA from the _______ receptors and has resulted in many anecdotal resuscitations
accelerates
cardiac
the _______ is inversely related to the seizure threshold
PaCO2
if person is hypoventilating, the _______ will increase and consequently _________ threshold
CO2
lower
additional factors include ________, ________, and _________ which can worsen LAST
acidosis, hypoxia, hyperkalemia
an intuitive response for suspected or known LAST is control of the ______ with ______ and _______ to prevent these issues
control of the airway with oxygenation and ventilation
prilocaine
unique metabolite, o-toluidine. pre-cursor for MetHgb
benzocaine can also cause __________
MetHgb
benzocaine is a __________ amine (most LAs are ______ amines)
secondary
tertiary
benzocaine is permanently _________ and stays ______ soluble and crosses into the _______ and attaches to the _____ channel directly
non-ionized
lipid
cell
Na
(this may account for its rapid onset and is most commonly used in the aersolized form for topical use in airway analgesia)
5% lidocaine (concentrated form) can be, and historically was used for ______
SAB
lidocaine has fallen out of favor for spinals due to reports of _______, specifically _________ when catheters were used to continuously infuse the medication
neurotoxicity, specifically CES
_______ from single injections of 5% lidocaine have been reported with spontaneous resolution of symptoms
TNS
_________ has a particular propensity to cause cardiac effects more than other LAs
bupivacaine
in addition to prominent cardiac toxicity, the prolonged duration makes bupivacaine more concerning bc it doesnt “____ ____”. pay attention to ____ ______
wear off
max dose
ropivacaine behaves similarly to ___________ with respect to _____/______/_______ however it has less cardiotoxic effects and generally has less pronounced ______ _____ potency
bupivacaine
onset/time/duration
motor block
Eutectic mixture of LA
EMLA cream
eutectic means
lower melting point
_____ & _______ are the combo used for topical EMLA, and must be applied an _______ in advance
lidocaine and prilocaine
hour
liposomal bupivicaine (exparel) is a ______ ______ LA
sustained release
designated for infiltration, exparel is found to have prolonged duration of action, presumably from _______ ______
delayed uptake
exparel is also being used with _______ ________ _______ for increased duration of action
peripheral nerve blocks
(24-48 hours reportedly)
_________ has become the preferred method of providing long acting pain relief for orthopedic sx (a single injections perform as well/better than pain catheter that must be removed/monitored)
exparel
several drugs when added to LAs improve their fxns
steroids
alpha2 agonists
opioids
bicarbonate
steroids - particularly ________ has been shown to increase duration of action of blocks. studies have compare _________ and _________ injections and found similar effects on the block when either route is used
decadron
IV and perineural
alpha2 agonist - _________, address pain directly but also ______ ______ _______ ________ conduction in the ___ and ___ fibers thus prolonging and improving blockade. the synergistic effect of the two mechanisms of action make it a popular _________.
clonidine
inhibit peripheral nerve signal
A and C fibers
additive
opioids - have been added to blocks to increase _______. the _____ of the block likely wont change and neither will the total _______ __ ______, but some suggest there is ___________ or ________ effect
potency
density
duration of action
potentiation or cumulative
opioids are recognized by some providers as an ______ in speed of onset in certain central blocks. others suggest there are more consistencies and fewer ______ ______ in the presence of opioids
increase
spotty blocks
bicarbonate - the addition of an ____________ agent is deigned to increased _____________ portion of the drug to allow access to the nerve. this process improves both the pain of ___________ and the ___________ of the block
alkalyzing
non-ionized
injection
efficacy
in addition to selective nerve blockade, LAs have additional application: inhibition of ______ ______, reduction in ______ ______ _______ (for high _____ during intubation), and pain ________ ________ are a few examples
ventricular dysrhythmias
reduction in cerebral blood flow (for high ICP during intubation)
pain management therapy
specific to anesthesia is the use of lidocaine to blunt ______ _______ by ______ _______ relaxation
respiratory stimulation
smooth muscle
______, _______, and ________ applications have been described
IV, inhaled, and topical
for dysrhythmia applications, the disruption of conduction in the cardiac cycle can address _____ _______ sites by blocking ______ _____
aberrant ectopic
Na channels
however, in the presence of conduction delay or heart block, lidocaine can actually cause _______ ______ ______
complete cardiac standstill
complete cardiac standstill with lidocaine is exacerbated in the presence of concurrent therapy with _____ _____ and/or ________ _____ ________
beta blockers
calcium channel blockers
our focus is on the use of LAs to provide __________ nerve blockade and provide __________ nerve blockade
peripheral
central
how do we pick what drug to use?
onset/duration
safety factor
goals for regional should include understanding of (5)
peripheral nerve anatomy
LAs
US equipment
nerve blockage techniques
practice with tools for block delivery
benzocaine technique/concentration/max/duration
technique - topical
concentration - 20%
max - NA
duration - NA
chloroprocaine - technique/concentration/max/duration
technique - epidural, infiltration, peripheral nerve block, spinal
concentration - 1%, 2%, 3%
max - 12mg/kg
duration - short
cocaine - technique/concentration/max/duration
technique - topical
concentration - 4%, 10%
max - 3 mg/kg
duration - short
tetracaine (amethocaine) - technique/concentration/max/duration
technique - spinal, topical (eye)
concentration - 0.2%, 0.3%, 0.5%, 1%, 2%
max - 3 mg/kg
duration - long
bupivacaine - technique/concentration/max/duration
technique - epidural, spinal, infiltration, PNB
concentration - 0.25%, 0.5%, 0.75%
max - 2.5 mg/kg
duration - long
lidocaine - technique/concentration/max/duration
technique - epidural, spinal, infiltration, PNB, IV regional, topical
concentration - 0.5%, 1%, 1.5%, 2%, 4%, 5%
max - 4.5 mg/kg (7 mg/kg with epi)
duration - medium
mepivacaine - technique/concentration/max/duration
technique - epidural, infiltration, PNB, spinal
concentration - 1%, 1.5%, 2%, 3%
max - 4.5 mg/kg (7 mg/kg with epi)
duration - medium
ropivacaine - technique/concentration/max/duration
technique - epidural, spinal, infiltration, PNB
concentration - 0.2%, 0.5%, 0.75%, 1%
max - 3 mg/kg
duration - long
