Nagelhout Video Local Anesthetics 1 - Exam 2 Flashcards
What are 2 main types of local anesthetics?
esters and amides
-esters have 1 “i” and amides have 2 (lidocaine = amide, procaine =ester)
3 parts of LA structure
Lipophilic Benzene Ring (aromatic group)
Hydrophilic Quaternary Amine (base)
Intermediate chain in between them (made of ester or amide)
-if chain has a N in it = amide
-if chain has 2 oxygen groups = ester
Which LA class has a higher allergy potential?
Ester
-metabolites are in common household items so pts can have ester allergies without having been exposed before
T/F If pt has an allergy to an ester, they can just have a different ester
false
T/F If pt has an allergy to an amide, they can just have a different amide
true
-can also have an ester too
How are amide LAs metabolized?
in liver by CYP1A2 and CYP3A4
-if pt is ultrarapid metabolizer will have a significant blood level
How are ester LAs metabolized?
catalyzed by plasma and tissue cholinesterase via hydrolysis
-does this rapidly
Are esters synthetic or natural?
mostly synthetic
-except cocaine
Which LA are longer acting and why?
amides
-more lipophilic and protein-bound, require transport to liver to metabolize
Longest acting LA ester?
Tetracaine
Examples of ester LAs
Cocaine
Procaine (Novacaine)
Chloroprocaine (Nesacaine)
Tetracaine (Pontocaine)
Benzocaine (Anbesol, Cepacol)
Examples of amide LAs
Lidocaine (Xylocaine)
Prilocaine (Citanest)
Ropivacaine (Naropin)
Bupivicaine (Marcaine, Sensorcaine)
Mepivicaine (Cabocaine)
The fatter the nerve, the _ it is to block.
harder
-Alpha a (motor and proprioception) is larger and is blocked last, comes back first
-heavy myelination makes it harder to block too
Order of nerve blocks by type (first to last):
-B (pre ganglionic- autonomic**)
-A Delta + C fibers (C>A deltapost ganglionic-pain/temp/touch)
-rest of A fibers (gamma>beta>alpha-proprioception +motor)
Neuraxial fiber recovery order occurs in _.
reverse
-motor/proprioception function comes back 1st
-A alpha>beta>gamma
-A delta > C
-B
***Neuraxial sensorimotor function block order:
sympathetic function
pain
temp, touch, pressure
proprioception
motor function
If LA is in tertiary form it is _ (non/ionized) and if it is in its quaternary form it is (non/ionized)
nonionized
ionized
T/F When injected into skin, LA becomes ionized.
False
-it is both
T/F When in the skin, ionized LA crosses into the nerve cells
False,
NON IONIZED
T/F When in the nerve cell, LA splits up again into ionized and nonionized versions and the ionized version travels to the sodium channel and blocks it from inside.
TRUE!!!
Which part of the LA molecule is ionized or hydrophilic?
Q Amine
Which part of the LA molecule is nonionized or hydrophobic?
Tertiary Amine
All LA are both lipophilic and hydrophilic and are weak _ (acids/bases)
bases
-all LA are bases bc they have a N group
How do LA work?
Block Na+ channels
The lower a LA’s pKa, the _(faster/slower) its onset will be bc the closer the pKa is to 7.4, the _ (smaller/ larger) its portion of NONionized drug is
faster
larger
-nonionized part penetrates the nerve
-EXCEPTION: Chloroprocaine, this is bc its given in such high concs which make it fast
T/F The higher the pKa on a LA, the faster it works
false
The more protein bound LA is, the _ (shorter/longer) its duration is
longer
-protein binding helps it stick around tissue and nerves longer
Long duration LAs:
-Cocaine
-Tetracaine
-Ropivacaine
-Etidocaine
-Bupivacaine
When adding vasoconstrictors to LA, the drug is usually Epi at a concentration of 1: _ or _mcg/mL
1:200,000
5mcg/mL
Adding vasoconstrictors to LA increases the _ and _ of them while decreasing their risk of _
depth and duration
toxicity
Extent in which epi prolongs the duration of regional and epidural anesthesia is dependent on which 2 factors?
-type of LA
-site of injection
-spinal anesthesia is actually a slower onset with epi
Why is the peak concentration of an LA decreased when you add Epi?
vasoconstriction slows the absorption of LA into system, prolonging its effect in tissue/nerves
Lidocaine 1% and 2% MAX with and without epi:
Lido: 4mg/kg
Lido + Epi: 7mg/kg
Bupivacaine 0.75% MAX dose with and without epi:
Bupi: 2.5mg/kg
Bupi + Epi: ~3mg/kg
Max dose of cocaine is _ mg and it can only be given _.
200mg MAX - not per kg
topically
Cocaine blocks the reuptake of _ and _ causing sympathomimetic effects
epi and norepi
In LA overdose, resp depression occurs, causing _ and _.
resp. depression
hypoxia
acidosis
In LA over dose causing acidosis from respiratory depression, the acidosis could cause _ (increased/decreased) ionized LA in the brain which _ (increases/decreases) its ability to leave.
increased
decreases
-overdose is potentiated by the acidosis it causes by preventing it from leaving BBB bc its more ionized; higher CNS toxicity
How to fix LA toxicity?
fix the acidosis is causes first, then treat toxicity
-can’t leave BBB with acidosis bc LA is more ionized
Why would a fetus retain more LA than its mother?
fetal pH is lower, and more acidotic, so LA ionizes and leaves fetal system slower
-especially if mom is acidotic too.
What will happen if LA is injected accidentally into septic tissue?
it will not reach the site of action due to the ACIDOTIC infected environment, it will ionize in the skin and linger
Adding CO2 to LA has what effect?
Will diffuse readily into nerve, once in the nerve it will more readily accept H+ and ionize more, so there is a higher conc of LA at the site of action
-faster onset
Adding bicarb to LA has what effect?
Improves diffusion of LA by making it more basic, increasing its NONionized portion which goes into nerve quicker = quicker onset!
-base+ base = NON ionized
Lipid solubility of an LA is correlated with which factor?
A. Potency
B. Onset
C. Metabolism
D. Duration
A. Potency
-higher lipid solubility = better diffusion = needs less mg dose to work well
Dissociation constant (pKa) of an LA is correlated with which factor?
A. Potency
B. Onset
C. Metabolism
D. Duration
B. Onset
-lower pKa = higher portion of tertiary (diffusible/nonionized) state = faster onset
Chemical linkage (ester/amide) of an LA is correlated with which factor?
A. Potency
B. Onset
C. Metabolism
D. Duration
C. Metabolism
-esters = HYDROLYZED in plasma
-amides = BIOTRANSFORMED in liver
Protein binding of an LA is correlated with which factor?
A. Potency
B. Onset
C. Metabolism
D. Duration
D. Duration
-higher affinity for protein at receptor site = prolonged presence of LA at site of action
The MORE lipid solubility an LA has, the _ (more/less) it diffuses and the _ (higher/lower) dose is required to be effective
more
lower
The LOWER the pKa LA has, a _ (smaller/larger) amount of tertiary (nonionized) molecules exist which can diffuse and _ (speed/ slow) the onset.
larger
speed
Of the 2 kinds of LAs,
_ are hydrolyzed in the plasma and _ are biotransformed in the liver
esters
amides
The HIGHER affinity an LA has for protein, the _ (shorter/ longer) the presence lasts at the site of action
longer
LAST Lido classic progression
Therapeutic level/ Stage 1
-plasma conc (mcg/mL)
5mcg/mL
-lightheadedness, tinnitius, circumoral or tongue numbness
LAST Lido classic progression
Stage 2
-plasma conc (mcg/mL)
-s/s
5-10mcg/mL
-muscle twitching, visual changes
LAST Lido classic progression
Stage 3
-plasma conc (mcg/mL)
-s/s
10-20mcg/mL
-convulsions, coma, unconsciousnes
LAST Lido classic progression
Stage 4
-plasma conc (mcg/mL)
-s/s
20-25+mcg/mL
-resp arrest, CVS depression
T/F Bupivacaine can be used for IV regionals
FALSE HELL NAH
-doesn’t follow classic LAST progression like Lido (CNS s/s -> cardiac s/s)
-cardiac-specific binding causes extreme cardiac s/s (arrest) as 1st signs of LAST
How is Ropivacaine different than Bupivacaine?
same MOA but does NOT possess same cardiac toxicity, so doesn’t have the same horrible cardiac LAST s/s
T/F A pt experiencing LAST will always show CNS s/s first.
False
-not always
The most common CNS s/s during LAST is _
seizures
-lots of arrhythmias as well, brady/asystole most common
Most cases of LAST happen within _ min/s.
LESS THAN 1 min
-could be while injecting!
LAST
-factors influencing plasma conc.
-dose
-rate absorbed
-site injected/ use of adjuncts
-biotransformation or elimination of drug
LAST
-pvn
-US GUIDANCE
-benzos as premedication can lower seizure rate but mask s/s
-be ready for anything
-LA and resusc drugs close by
-double check dose(give LOWEST effective dose)
-deliver in increments (3-5ml w/ 15-30s pause between)
-aspirate Q injection!
-TEST DOSE! (45mg Lido 15mcg Epi!)
-VERBAL communication w pt
LAST
-Tx, resp
O2-mask, LMA, ETT
LAST
-Tx CV/meds
-lift legs, fluids, BP meds
-anticonvulsants (benzos, prop, thiopental)
-standard arrhythmia drugs (EXCEPT CCB, sodium valproate, phenytoin, vasopressin, and other LAs)
LAST
-lipid infusion
if pt unresponsive to standard resusc. but can give immediately after securing airway*
-bolus
-infusion
-CHEST COMPRESSIONS TO CIRCULATE
-repeat bolus Q 3-5 up to 3mg/kg
-leave infusion on until CV stable
LAST
-Intralipid 20% bolus dose
Pt <70kg :
1.5mL/kg IBW over 2-3minv
repeat bolus x3 for persistent CV collapse; upper limit 12mL/kg in 1st 30 min
Pt >70kg
20% Interlipid
100mL over 2-3 min
LAST
-Intralipid infusion
Pt<70kg:
0.25-0.5mL/kg /min
Pt >70kg:
200-250mL over 10-20 min
-keep on for at leas t10 min after CV stable
LA toxicity requires close control on what factor due to the factor’s influence on inotropic/chronotropic effects?
O2 + ventilation
-hypoxia, acidosis, and hypercarbia worsen this
LAST
-TEST DOSE concentrations and actual dose
3mL of 1.5% Lidocaine + 1:200,000 Epi
= 45mg Lido + 15mcg Epi
T/F My pt’s IV is just aight… they should be fine for a spinal block, right?
FALSE
-if they develop LAST you’re SOL
-have a GOOD IV and resusc tools ready
T/F Negative needle aspiration means you definitely aren’t going intravascular with a LA
false!
there is a ~2% false negative aspiration rate
When using a fixed needle approach for LA, the time between injections should encompass 1 circulation time which is ~ - sec
30-45sec
-give longer intervals for larger doses of LA
Intravascular injection of a test dose of Epi (10-15mcg/mL) causes ~ _ beat increase in HR and ~ _ mmHg increase in BP
10+ beat
15+mmHg
-beta blocker, active labor, old age, and GA can mask this!
Subtoxic test doses of intravascularly injected LA can cause s/s of mild systemic toxicity like:
excitation, auditory changes, metallic taste
-if fentanyl is part of test dose for laboring pts = sedation
all of this is true only if pt is NOT premedicated
LAST
-early s/s
CAN BE MASKED IF PREMEDICATED W BENZO
-dizzy
-tongue numb*
-difficulty focusing
-tinnitis**
-confusion
-muscle twitching
LAST
-late s/s
-ton/clon sx
-coma
-resp + cardiac arrest
T/F A pt experiencing LAST can present initially with CNS and cardiac s/s at the same time
true
-could also just completely bypass CNS effects as well
Delayed (1-5min) presentation of LAST s/s indicates suggests _ or _ intravascular injection
partial or intermittent
Immediate (<60sec) presentation of LAST suggests intravascular injection of LA with direct access to the _
brain
LAST can present > _ min after injection so it’s important for CRNA to monitor them for _ mins afterwards.
> 15 min
30 min
T/F LAST has a higher association with pts suffering from underlying diseases
true
-watch out for your older ASA 3-5 pts more closely
You successfully gave a test dose of LA with no problem, however, when you give our pt a spinal injection, they start experiencing a reaction. Their symptoms almost resemble late signs of LAST but you’re not 100% positive. How will you proceed?
Absolutely treat this like it’s LAST.
-keep a low threshold to treat for LAST especially if atypical symptoms arise and they received more than a test dose
Goal of LAST airway management:
prevent hypoxia and acidosis by maintaining their airway/ventilation
1st line treatment for a seizure during LAST:
benzos!
-give versed, let them relax if possible, let LA wear off and either try again or cancel case if pt unstable
Your pt starts seizing after receiving a standard dose of LA spinal injection. They appear to be breath-holding and their SpO2 is dropping. What’s your next move?
-stop seizure (benzos, small doses propofol (if not hypotensive), or sux)
-give O2/ LMA/ intubate
Why should large doses of propofol be avoided in a pt seizing who is experiencing LAST ?
cardio depressive, will bottom out BP when pt reaches their postictal state
Which drugs should be avoided during ACLS on a pt experiencing LAST?
-standard dose epi (use 10-100mcg boluses)
-VASOPRESSIN
-CCB/ Beta blockers
-LIDOCAINE/PROCAINAMIDE :) lol
-Amio is the DOC for ventricular arrhythmias
If pt does not respond to lipid emulsion or vasopressors during ACLS when experiencing LAST, what is the next option for them?
cardiopulmonary bypass
-if at a smaller hospital, not a bad idea to call for a neighboring hospital for a transfer as soon as cardiac s/s come up
Which type of LA is more likely to cause LAST?
Amides
LA block voltage-gated _ channels which interrupts the _ and _ of nerve impulses in axons.
Na+ channels
initiation and propagation
If LA is put in a basic solution, it _ (will/will not) carry a charge, and if it’s put in an acidic solution, it _ (will/will not) carry a charge.
will not (nonionized)
will (ionized)
CPR is especially hard with which LA drug’s cardiac toxicity?
Bupivacaine
