Local Anesthetics Flashcards
What two things affect nerve conduction velocity
myelin
diameter (^diameter > ^ conduction velocity)
order of block onset in nerve types
- B fibers
- C fibers
- Alpha Gamma and delta fibers
- Alpha alpha and beta
what is nerve resting membrane potential and it’s primary determinant?
-70mv and K is the primary determinant
what is nerve typical threshold potential? and it’s primary determinant?
-55mv and Ca++ is the principal determinant
LA mech of action
reversibly bind alpha subunit inside the voltage gated sodium channels.
can only bind channels in the open/active or close/inactive state. cannot bind channels in the resting state
After injection the lipid soluble uncharged base portion diffused through the nerve. a new equilibrium is established and the conjugate acid is what actually bind the sodium channel.
what are the three main compents of LA chemical structure? which ones determines LA class?
benzene ring
intermediate side chain - determines ester vs amide class
tertiary amine
Name the Ester LAs
benzocaine
cocaine
procaine
tetracaine
name the amide LAs
“two is”
bupivicaine
dibucaine
lidocaine
mepivicaine
ropivicaine
how are amide LAs metabolized?
P450 system
how are ester LA metabolized?
pusdocholinesterase
which LA class exhibits cross sensitivity throughout the class?
ester types
if allergy to ester LA don’t use any ester LAs
if allergy to one amide LA okay to use another amide LA but make sure it is preservative free
allergy to which class of LA is more common? what causes the allergic reaction?
more common to esters
Ester LA are derivatives of para-aminobenzoic acid, which is typically what causes the allergic reaction
why must you avoid LAs with preservatives is a pt has any allergy to ANY LA?
methylparaben is a preservative and is similar to PABA so it could also cause an allergic reaction.
What are primary and secondary determinants of LA onset of action?
primary is Pka
seconday: dose and concentration
what are primary and secondary determinants of LA potency?
primary: lipid solubility
secondary: intrinsic vasodilating activity
primary and secondary determinants of LA duration of action?
primary: protein binding
secondary: lipid solubility, intrinsic vasodilating capabilities, addition of vasoconstrcitors
describe LA vasoconstrictive/vasodilating properties
in small doses (sub clinical use) LA cause vasoconstrcition.
in larger doses (clinical use dose) LAs cause vasodilation. Some cause more than other
Cocaine: exception, intense vasoconstricting properties
cocaine mech of action
inhibits re-uptake of NE
which two LA have no intrinsic vasodilating properites according to some texts?
ropivicaine
chloroprocaine
which LA has zero protein binding?
chloroprocaine
how does the Pka of ester LA compare to amide LAs?
Pka of all ester LAs is higher than Pka of amide LAs
which two factors affect drug ionization?
pH of solution
pKa of the drug
when is ionziation greatest in relation to pH and Pka?
greatest ionization when Pka is far from pH
how is onset affected by Pka and pH? what is the exception?
the closer Pka is to pH the faster the onset.
Exception: chloroproaine becuase it is so concentrated still has a fast onset even though pKa is not close to pH.
List area from most to least vascular uptake
“I think illogical imposters cant educate but fabulous schools should”
IV
tracheal
intrapleural
intercostal
caudal
epidural
brachial plexus
femoral
sciatic
subcutaneous
Exparel max dose
266mg
what can exparel be mixed with?
LR, NS, or bupivicane
when is exparel contra indicated?
paracervical use in obsetric population
when/where is exparel use not reccomended?
epidural, intrathecal, intrarticular, or during pregnancy
what happens if exparel is mixed with LA other than bupiviane?
will disrupt liposomal structure and can cause immediate release of bupivicane
rules of exparel use with lidocaine and bupivicane?
after lidocaine infiltration must wait 20min before exparel admin
after exparel infiltration: no bupivicane in any form for at least 96hrs
Amide LA max doses
levobupi. 2mg/kg or 150mg
bupivicane 2.5mg/kg or 175mg
bupi with epi. 3mg/kg or 200mg
ropi 3mg/kg or 200mg
lidocaine. 4.5mg/kg or 300mg
mepivicaine 7mg/kg. or 400mg
lido with epi 7mg/kg or 500mg
prilocaine. 8mg/kg. or 500mg <
70kg and 600mg > 70kg
Ester LA max doses
procaine 7mg/kg or 350-600mg
chloroprocaine 11mg/kg or 800mg
chloroprocaine w epi. 14mg/kg or 1,000mg
what is abnormal about benzocaine? what is a significant risk with its use?
Pka is 3.5 so it is totally non-ionized at physiologic pH. all other LA work by the conjugate acid binding the sodium channel.
methemoglobinemia is a significant risk
most common cause of LAST?
intravascular injection during regional
what is the most frequent, as well as the first symptom of last? waht is the exception?
seizure
exception: first symptom of last with bupivicaine is cardiac arrest
is last more common with PNBs or epidurals?
PNBs
symptoms of plasma Lidocaine concentration 1-5mcg/ml
analgesia
symptoms of plasma Lidocaine concentration 5-10mcg/ml
Neuro:
tinnitus
skeletal m. twitching
perioral numbness
restlessness
vertigo
blurred vision
CV:
hypotension
myocardial depression
symptoms of plasma Lidocaine concentration 10-15mcg/ml
seizure
loss of consciousness
symptoms of plasma Lidocaine concentration 15-25mcg/ml
coma
resp arrest
symptoms of plasma Lidocaine concentration >25mcg/ml
CV collapse
what 3 things increase risk of CNS toxicity from LAs and why?
- hypercarbia
- hyperkalemia
- metabolic acidosis
- increases cerebral blood flow so ^ drug delivery to the brain. Also decreases protein binding so there is more free fraction of drug available to enter brain
- increases resting membrane potential and neurons are more likely to depolarize
- decreases conduction threshold and favors ion trapping in the brain
what three things decrease risk of CNS toxicity for LAs?
- hypocarbia
- hpokalmeia
- CNS depressants - raise seizure threshold
which two things affect LA ability to cause CV toxicity?
- affinity for voltage gated Na chanels in active and inactive states
- rate of dissociate form receptors during diastole
why does bupi have a higher risk of CV toxicity than lidocaine?
bupi has a greater affinity for receptors and a slower rate of disocciation during diastole
list the LAs in order from most to least difficult to resuscitate following CV toxicity
bupi>levobupi>ropi>lidocaine
what is the main risk of Cocaine toxicity?
SNS stimulation
what drugs warrant avoidance of cocaine?
MAOIs
TCAs
sympathomimetic drugs
how to treat cocaine toxicity?
alpha blockers before beta blockers
cocaine dose
1.5-3mg/kg or < 150-200mg
LAST tx
- manage airway
- tx seizure
- ACLS with modification
- Intralipid (20% lipid emulsion)
how should you manage airway during last?
100% FiO2 because hypoxia worsens symptoms
how to treat seizures from last
give benzo, dont give propofol
if benzos are ineffective can give small dose sux or roc. this will decrease muscle contraction and associate increase in oxygen consumption avoiding hypoxemia and acidosis. this won’t stop seizure activity in the brain though
ACLS modifications for LAST
avoid epi, it hinders effectiveness of intralipid. if you must give, keep dose <1mcg/kg
avoid: vaso, lidocaine, procanamide, BB, and CCB
amio is agent of choice for vent dysrhythmias
if ACLS is unsuccessful prep for cardiac bypass.
Lipid Emulsion dosing for LAST
> 70kg
100ml bolus over 2/3 min
250ml infusion over 15-20min
<70kg
1.5ml/kg bolus over 2-3min
0.25ml/kg infusion
if pt remains unstable repeat bolus and double the infusion
continue for 15min after CV stability
lipid emulsion recommended max dose?
12ml/kg
lipid emulsion mech of action
lipid sink
impairs LA binding to voltage gated Na channels
is lipid emulsion therapy safe in pregancy?
yes
what is a theoretical concern with intralipid use?
pacreatitis 2ndary to hyperlipidemia and hypermylasemia (amylase)
most common cause of death from liposuction?
PE
why is tumescent anesthesia used during liposuction?
for patient comfort
what is tumescent lidocaine made up of?
NS
lidocaine
bicarb
epi
Tumescent lidocaine max dose
55mg/kg
with liposuction serum lidocaine levels seldom get higher than?
1.5mcg/ml
when doe plasma concentrations peak from tumescent lidocaine and when is it totally eliminated from the body?
peak 12 hours
elminiated at 36hours
when should tumescent lidocaine dose me reduced?
when taking any medications that inhibit CYP 3A4 or CYP1A2
when can you do MAC vs GA for lipsuction?
if tumescent volume small MAC is okay
if volume >2-3L GA is reccommended
what are two complications that can occur from tumescent lidocaine?
fluid overload and pulm edema
How is methemoglobin formed?
when iron molecule (Fe+2) on hgb is oxidized to ferrous form Fe+3
what two ways does methemoglobinemia decrease O2 carrying capacity?
- methgb can’t bind O2
- shifts oxy-hgb diss curve to the left
drugs than can cause methgb?
benzocaine
cetacaine
prilocaine
EMLA cream
phenytoin
nipride
nitro
s/s of methgbemia
hypoxia not fixed by ^ FiO2
cyanosis
chocolate colored blood
tachycardia
tachypnea
changes is LOC
spo2 ready with methgbemia
85%
what do you need to diagnois methgbemia?
co-oximieter
cyanosis in the presence of normal to high PaCO2 suggests what?
methgbemia
methgbemia tx
methyleme blue
1-2mg/kg over 5min
max dose is 7-8mg/kg
how does methylene blue treat methgbemia?
reduces methgb back to hgb
when will methyele blue be ineffective in treating methgbemia? how do you treat in this situation?
pt with glucose-6phosphate reductase deficiency. treat with exchange transfusion
patient population that is at higher risk for methgbemia and why?
neonates because they are relatively deficient in methgb reductase
What is EMLA cream made of?
50% lidocaine
50% prilocaine
EMLA cream can provide analgesia how quickly? and peaks when?
analgesia within 1hr and peaks in 2-3hours
what skin conditions increase risk of toxicity from EMLA cream?
psoriasis, eczema, and skin wounds can increase risk of toxicity
how can EMLA cream cause methgbemia?
prilocaine is metabolized to 0-toluidine which oxidzes hgb to methgb
who are more likely to become toxic form emla cream?
infants and small children
where can you apply EMLA cream?
only to intact skin and never to mucous membranes
EMLA dosing
0-3mo or < 5kg 1g
3-12mo & > 5kg. 2g
1-6yrs & >10kg. 10g
7-12yrs & > 20kg. 20g
EMLA max area of application
0-3mo or < 5kg 10cm square
3-12mo & > 5kg. 20cm sqaured
1-6yrs & >10kg. 100 cm squared
7-12yrs & > 20kg. 200 cm squared
which additive increase DOA of LAs
epi decadron dextran
how does dextran increase DOA?
it decreases systemic uptake just like epi
what additive increase onset of LA
sodium bicarb
which additive provide supplemental analgesia with LAs?
clonidine
epi
opioids (neuraxial only)
which additives ^ LA diffusion through tissue?
hyaluronidase
Epis ability to increase DOA is more effective with LAs with intermediate or long DOA?
intermediate
i.e extends lidocaine better than bupivicane
how does decadron increase LA duration of action?
how much does it increase DOA and of which blocks?
glucocorticoid activity > decreaesd uptake of LA.
can extend BP block by up to 50%
which LA decreases effectivness of opiods in the epidural space?
chloroprocaine
how does bicarb speed onset of LAs? how do you actually add bicarb to LA and how much do you add?
it increases number of lipid soluble molecules.
add 1ml 8.4% sodium bicarb to 10ml LA
if you add more it will precipitate
