local anesthetics Flashcards
which LA is manufactured as a single enantiomer
ropivicaine (pure S enantiomer), less neuro toxicity and cardio toxicity than its racemic mixture
which LA is manufactured as a single enantiomer
ropivicaine (pure S enantiomer), less neuro toxicity and cardio toxicity than its racemic mixture
where is
epineurium
perineurium
endoneurium
ID parts of the axon
a alpha
myelination
function
diameter
velocity
block onset
myelination: heavy
function: skeletal muscle- motor proprioception
diameter: 12-20
velocity: +++++
block onset: 4th
a beta
myelination
function
diameter
velocity
block onset
myelination: heavy
function: touch, pressure
diameter: 5-12
velocity: ++++
block onset: 4th
a gamma
myelination
function
diameter
velocity
block onset
myelination: medium
function: skeletal muscle- tone
diameter: 3-6
velocity: +++
block onset: 3rd
a delta
myelination
function
diameter
velocity
block onset
myelination: medium
function: fast pain, temperature, touch
diameter: 2-5
velocity: +++
block onset: 3rd
b fibers
myelination
function
diameter
velocity
block onset
myelination: light
function: preganglionic ANS fibers
diameter: 3
velocity: ++
block onset: 1st
C sympathetic
myelination
function
diameter
velocity
block onset
myelination: none
function: post ganglionic ANS fibers
diameter: 0.3-1.3
velocity: +
block onset: 2nd
C dorsal root
myelination
function
diameter
velocity
block onset
myelination: none
function: slow pain, temperature, touch
diameter: 0.4-1.2
velocity: +
block onset: 2nd
LA’s inhibit peripheral nerves in the following order
B fibers > C fibers > small diameter A fibers > large diameter A fibers
LA’s can bind to VG channels in which states
active and inactive states
LA’s bind to which subunit on VgNa channel
alpha
describe resting state
-70mV, channel is closed
describe active state
-70 to +35mV
when threshold potential is reached, channel opens
open channel allows Na to follow concentration gradient (outside to inside)
describe inactive state
channel is closed
inactivation gate plugs channel until RMP is re established
restoration of RMP converts channel from inactive state to resting state. at this point, the nerve is ready to be stimulated again
what do LA’s do to RMP and TP
have no effect on TP and RMP
3 things that influence RMP
- chemical force (concentration gradient)
- electrostatic counter force
- Na/K/ATPase (3 Na out for every 2 K in)
what does decreased serum K do to RMP
becomes more negative
what does increased serum K do to RMP
becomes more positive
TP and primary electrolyte
-55, Ca2+
repolarization
occurs when K leaves the cell or Cl- enters the cells
cell is resistant to subsequent depolarization during during refractory period because Na channels are in the closed inactive state
henderson hasslebach equation
primary determinant of onset of LA
pKa
-if the pKa is further away from pH of blood, less lipophilic availability and therefore longer OOA
primary determinant of potency of LA
lipophilicity (via aromatic ring)
-easier time diffusing through epineurium
-more lipophilic means more potent and longer DOA
does the ionized or non ionized species of LA bind to VgNa channel
ionized
what do vasoconstrictors do to LA activity
prolong effect by decreasing uptake
are LA’s acids or bases?
is the pH low or high
weak base with low pH to guard against precipitation
why can we predict that >50% of LA will exist in ionized state when it enters the blood stream
weak based with pKa > physiologic pH so a greater fraction will exist in the ionized state
what 3 paths can a LA travel after its injected near a peripheral nerve?
- can diffuse into nerve
- can diffuse into surrounding tissue and bind to neighboring proteins
- can diffuse into systemic circulation
basic structure (3 parts) of a LA molecule includes what and what is their significance
true allergy is more likely with
esters because of para amino benzoic acid (PABA) metabolite
is there cross sensitivity in the amide group
no, not like the ester group
COO
ester
NHCO
amide
does the ionized or non ionized species bind to the alpha subunit of the inside of the VgNa channel
the non ionized
explain why chlorprocaine has a fast onset
the pKa is high which means its further from the blood pH and less ionized species are available which would make you think the OOA is increased. However, because it it not potent it is given in large doses and the more molecules creates a mass effect which explains why it still has a rapid onset
why does .75% bupiv have a faster OOA than .25% bupiv
more molecules
what happens to a LA with more intrinsic vasodilating ability
increase rate of uptake and shorten DOA by up to 1/3
acid does what to a proton
donates
HA–> H+ + A-
base does what to a proton
accepts
B+ + H- = BH+
ionization is dependent on 2 factors
pKa of drug
pH of solution
in an acidic solution, weak bases are
more ionized and water soluble
in an acidic solution, weak acids are
more nonionized and lipid soluble
in a basic solution, weak bases are
more non ionized and lipid soluble
in a basic solution, weak acids are
more ionized and water soluble
amide type, pKa, ionization at 7.4%, protein binding (%) for
bupivicaine
levobupivicaine
ropivicaine
lidocaine
prilocaine
mepivicaine
ester type, pKa, ionization at 7.4%, protein binding (%) for
procaine
chlorprocaine
tetracaine
which LA’s have higher pKa values in general
esters (8.5-8.9) over amides (8.1 is the highest)
benzocaine pKa
3.5. “odd man out”
-non ionized at physiologic pH
-metHGBemia is significant risk
factors that influence vascular uptake and plasma clearance of LA’s
site of injection
tissue BF
physiochemical properties of LA
metabolism
addition of vasoconstrictor
site of LA injection and highest to lowest plasma concentration (Cp) and pneumonic
I think I can push each bolus super slowly for safety
IV, tracheal, intercostal, caudal, paracervical, epidural, brachial plexus, subarachnoid/sciatic, femoral, SQ
LA’s preferentially bind to which protein
alpha 1 acid glycoproteins (but will also bind to albumin)
what does the addition of precedes do to a brachial plexus block
extends DOA
max dose of exparel and how it is dispensed
266mg
133mg in 10mL or
266mg in 20mL
rules for giving exparel (and lidocaine) to a patient
after infiltrating lidocaine, no liposomal bupiv for at least 20m
after infiltrating liposomal bupiv, no lidocaine (in any form) for 96h
levobupivicaine max dose in mg and mg/kg
2mg/kg or 150mg
bupivicaine max dose in mg and mg/kg
2.5mg/kg or 175mg
bupivicaine and epinephrine max dose in mg and mg/kg
3mg/kg or 200mg
ropivicaine max dose in mg and mg/kg
3mg/kg or 200mg
lidocaine max dose in mg and mg/kg
4.5mg/kg or 300mg
mepivicaine max dose in mg and mg/kg
7mg/kg or 400mg
lidocaine and epinephrine max dose in mg and mg/kg
7mg/kg or 500mg
prilocaine max dose in mg and mg/kg
8mg/kg or if <70kg, 500mg. if >70kg, 600mg
procaine max dose in mg and mg/kg
7mg/kg or 350-600mg
chlorprocaine max dose in mg and mg/kg
11mg/kg or 800mg
chlorprocaine and epi max dose in mg and mg/kg
14mg/kg or 1000mg
most frequent sx of LA toxicity and exception
seizure
bupiv is exception, cardiac arrest before seizure
what to expect with 1-5mcg/kg Cp of lidocaine
analgesia
what to expect with 5-10mcg/kg Cp of lidocaine
tinnitus, skeletal muscle twitching, numbness of lips and tongue, restlessness, vertigo, blurred vision, HoTN, myocardial depression
what to expect with 10-15 mcg/kg Cp of lidocaine
seizures, loss of consciousness
what to expect with 15-25mcg/kg Cp of lidocaine
coma, resp arrest
what to expect with >25mcg/kg Cp of lidocaine
CV collapse
factors that increase risk of LA CNS toxicity (3)
hypercarbia (increases CBF and drug delivery to brain, decreases protein binding and increases free fraction of LA)
hyperkalemia (raises RMP making neurons more likely to depol)
metabolic acidosis (decreases convulsion threshold and favors ion trapping inside the brain)
LA’s create CV toxicity by
decrease automaticity, conduction velocity, AP duration, and effective refractory period
depress myocardium by impairing intracellular calcium regulation
produce a biphasic effect on vascular smooth muscle. low concentration LA causes vasoconstriction while high concentration LA causes vasodilation and a reduction in SVR
two features determine extent of cardiotoxicity
- affinity for VgNa channel in active and inactive states
- rate of dissociation from receptor during diastole
difficulty of cardiac resuscitation based on LA in order from greatest to least
bupiv>levobupiv>ropiv>lido
risk off bupiv toxicity is increased with
pregnancy, BB’s, CCB’s, digitalis
tx of LAST
- manage aw (100% FiO2, hypoxia and acidosis will worsen sx of LAST)
- tx seizures with benzos (avoid prop, can give succ to tx muscle contraction)
- ACLS with specific modifications (epi is no bueno, but if you have to then keep dose below 1mcg/kg, avoid vasopressin, amio is agent of choice for ventricular dysrhythmias)
- 20% lipid emulsion therapy (if patient is over 70kg, 100mL bolus over 2-3m, infusion 250mL over 15-20m. if patient remains unstable, repeat bolus and/or double infusion. if patient is <70kg, bolus of 1.5mL/kg over 2-3m then .25mL/kg/min infusion. if patient remains unstable, same as above)
max recommended dose of 20% lipids
12mL/kg
proposed MOA of lipid emulsion therapy
lipid sink: intravascular reservoir that sequesters LA and reduces plasma concentration of LA
metabolic effect: enhanced myocardial fatty acid metabolism
inotropic effect: increased calcium influx and intracellular calcium concentration
membrane effect: impairs LA binding to VgNa channels
dose for 20% lipid emulsion therapy
if patient is over 70kg, 100mL bolus over 2-3m, infusion 250mL over 15-20m. if patient remains unstable, repeat bolus and/or double infusion. if patient is <70kg, bolus of 1.5mL/kg over 2-3m then .25mL/kg/min infusion. if patient remains unstable, same as above
for tumescent anesthesia, max dose of lidocaine is
55mg/kg
GA is recommended if ________ of tumescent is used
2-3L
which LA’s can be responsible for methemoglobinemia
benzocaine
prilocaine (O toluidine)
lidocaine
cetacaine
EMLA (50/50 prilocaine, lidocaine)
what does methgbemia do to oxyhgb dissociation curve
to the left makes it easier for HgbA to bind to O2 but makes it more difficult to release it at the tissue level
% methgbemia and sx
SpO2 and PaO2 for methgbemia
SpO2 decreased in setting of normal PaO2
dose of methylene blue should not exceed
7-8mg/kg
glucose 6 phosphate reductase deficiency
dont give methyline blue
what is required to dx methgbemia
co oximeter
presentation of methemoglobinemia
hypoxia
cyanosis (slate grey pseudo cyanosis)
chocolate colored blood
tachycardia
tachypnea
mental status changes
coma and death
how does methylene blue work in the setting of methemoglobinemia
it is metabolized by methgb reductase to form leucomethylene blue. this metabolite functions as an electron donor, which reduces metHGB back to HGB
population at higher risk for methylene blue toxixity
neonates.
5% emla cream is
50% 2.5 prilocaine and 50% 2.5 lidocaine
0-3 months or <5kg and max dose of EMLA, max area of application
max dose 1g, max area of application 10cm^2
3-12mo and >5kg and max dose of EMLA and max area of application
max dose 2g, max area of application 20cm^2
1-6y and >10kg max dose of EMLA cream and max area of applicatoin
10g, 100cm^2
7-12y and >20kg max dose of EMLA cream and max area of application
20g, 200cm^2
drugs that prolong LA DOA
epinephrine
dexamethasone
dextran
drugs that provide supplemental analgesia with LA
clonidine (100mcg)
epinephrine
opioids (neuraxial only)
drugs that shorten onset time of LA
sodium bicarb (1mL of 8.4% in 10mL LA)
drugs that improve LA diffusion through tissues
hyaluronidase
causes of methemoglobinemia
