Local Anesthetics: Review Flashcards
Local anesthetics interrupt neural conduction by
inhibiting Na+ influx through channels or ionophores within neuronal membranes
When the neuron
is stimulated, the channel assumes a ___/___ state, in which sodium ions diffuse into the cell, initiating depolarization.
activated/open
What happens in the inactivated state?
further influx is denied
active transport returns sodium ions
to the exterior
repolarization
Local anesthetics have greater affinity for receptors within sodium channels during
their activated and inactivated states
rather than when they are in their resting
states
(Larger/smaller) fibers are generally more susceptible to LAs.
smaller
a given volume can more easily block the requisite number of sodium channels & entirely interrupt signal transmission
which fibers are most sensitive?
Most to least:
tiny, rapid-firing autonomic fibers
sensory fibers
somatic motor fibers
(most susceptible: Ag spindle efferents, Ad nociceptive
resistant: myelinated C)
recovery from spinal anesthesia:
Order of returning fxns?
First to last:
voluntary motor fxn
sensation
autonomic control (ie: micturition)
How do sensory fibers vary in their sensitivity?
Easiest → hardest to block:
sympathetic
temperature
pain fibers
pressure & proprioception
motor
Ex: pt may feel unpleasant pressure despite
complete anesthesia of pain fibers
The molecular structure of all local anesthetics consists of (3)
lipophilic aromatic ring
intermediate ester or amide linkage
tertiary amine
concentrations that range typically from
0.5 to 4%
d/t differences in lipid solubility
Which is more potent?
bupivacaine
articaine
bupivacaine is more lipid
soluble & potent
available as 0.5% [ ] (5 mg/mL)
diffusion through nerve sheaths and neural
membranes is determined by
aromatic ring and its substitutions
the most important factor that determines the onset of anesthesia
proportion of molecules in a lipid-soluble rather than a water-soluble state
When is an amine charged? uncharged?
Tertiary (3 bonds) = lipid soluble
Quaternary (4 bonds) = water soluble; + charge
In their packaging, LAs exist as ___. Why does this affect onset of action?
quaternary/water-soluble
-unable to penetrate the neuron
-onset: directly r/t proportion of molecules that convert to tertiary/lipid-soluble @ physiologic pH (H&H equation)
T/F
higher pka = faster onset
False
higher pKa = less molecules in lipid-soluble form
This will delay onset
The intermediate chain/linkage tells us…
classification
&
elimination
Amide metabolism
biotransformed in the liver
aromatic hydroxylation
amide hydrolysis
N-dealkylation
Ester metabolism
hydrolyzed in the bloodstream by plasma esterases
Which amide is metabolized as if it was an ester?
Articaine
amide according to its intermediate linkage, but also contains an ester side chain on its aromatic ring.
Local anesthetics vary in their duration of action due primarily to differences in their …
affinity for protein
T/F
local anesthetics irreversibly bind to plasma proteins while circulating in the bloodstream
False
reversibly bind
LA’s percentage of protein binding correlates with
its affinity for protein within sodium channels
T/F
greater protein binding = shorter neural blockade
False
will prolong blockade
bupivacaine vs mepivacaine
protein binding
bupivacaine 95%
mepivacaine 55%
Which drug shortens its own duration by dilating local vasculature?
Lidocaine
Plain lidocaine formulation limitations
useful for brief procedures following infiltration
but
efficacy for nerve block is poor
How do LAs affect seizure activity?
Low serum [ ]: suppress 🩷 arrhythmias & status seizures
higher [ ]: induce seizure activity
the initial life-threatening consequence of local anesthetic overdose
convulsive seizures
How does LA toxicity cause convulsive seizures?
selective depression of central inhibitory tracts
↓
uncontrolled excitatory tracts
LA toxicity will first cause ___. If [ ]s increase further what else happens?
convulsive seizures
all pathways are inhibited
coma, respiratory arrest, CV collapse
Lidocaine toxicity [ ]s
> 5 mcg/mL (S/S start)
> 10 mcg/ml (convulsive seizures)
Monitor for …. when using LAs with sedatives & opioids.
respiratory depression
they potentiate any respiratory
depression a/w sedatives & opioids
LAs are CNS ___
depressants
Which clinical conditions lowers the minimum serum [ ] for LA induced seizures?
hypercarbia
caution w/ respiratory depression by concurrent use of
sedatives and opioids!
greater potential for direct cardiac toxicity than other agents
bupivicaine
(~greater affinity for inactive &
resting Na channel → dissociates more slowly)
When using lidocaine or other anesthetics, regardless of their formulated concentration, one must consider ___
administered, not the ___
dose (milligrams)
volume (milliliters)
In adults, we use ____ to avoid toxicity.
In peds, this value is expressed as ___.
adults: have max dose in mg (regardless of age and weight)
peds: max dose is in mg/kg
(large children: dot exceed max dose when calculating mg/kg)
metabolite of prilocaine
o-toluidine
can oxidize Hgb iron
ferrous ( Fe 2+) → ferric ( Fe 3+)
Patients appear cyanotic and become symptomatic when the proportion of methemoglobin exceeds
15%
prilocaine contraindctns
hereditary methemoglobinemia
Methemoglobinemia treatment
methylene blue
reduces the hemes to their normal state
How does Methemoglobinemia affect oxygen monitoring?
low pulse oximetry ( SpO2 ) despite effective oxygenation and ventilation
ex: SpO2 90%, but PaO2 is normal
Why do pts sometimes falsely assume they’re allergic to an LA?
1) syncopal episode a/w the injection
2) 🩷 palpitations from the epi (in the solution or released endogenously)
Likely cause of true LA allergy
Preservatives (methylparaben)
antioxidants (sulfites)
Methylparaben
preservative
in multidose vials to prevent microbial growth
Sulfites
antioxidants
prevent the [O] of vasopressors
(epinephrine or levonordefrin)
Allergies
Type I Reactions
occur w/in minutes
mediated by antibodies or immunoglobulin E ( IgE ) produced by B lymphocytes
most commonly provoked by components of the formulation
Allergies
Type 4 reactions
delayed for several days
mediated by sensitized T lymphocytes
rare
Drugs must be … to cause allergic rxn, but most do so by…
large MW w/ multiple valences
combining w/ carrier molecules
(most drugs are too small)
Have the PABA structure in common and risk cross sensitivity
sulfa antibiotics
methylparaben
ester LAs
T/F
The ester linkage causes the allergic rxn a/w ester LAs
False
a molecular component joined by this linkage is the culprit
patients claiming allergy to
these foods may experience cross-reactions with LA solutions containing vasopressors bc they contain these same sulfites
fresh fruits and
vegetables
Meperidine “allergic” response
Meperidine simulates histamine release
and NSAIDs may promote synthesis of leukotrienes
Pt response = pseudoallergic
(vs true allergy, which is immune-mediated)
How to assess LA allergy
unverified LA “allergy”
what should we use?
mepivacaine or prilocaine
without vasopressor
(avoids esters & sulfites from ‘pressors)
Good for length procedures
Bupivacaine
but more pain injection
Most widely used LA in US
Lidocaine
Vasopressors are drugs that provide constriction of blood vessels by
activating alpha-1 adrenergic receptors
Why include Vasopressors with LAs
hemostasis in operative field
delay absorption (reduces systemic toxicity risk & prolongs effect)
Epi causes considerable cardiac stimulation d/t its..
Beta 1 adrenergic agonist
(in addition to the usual Alpha 1)
Epi concentrations greater than 1 : 200,000 (5 mg/mL )
does not reduce LA serum [ ]
Increasing Epi [ ] to 1 : 100,000 (10 mg/
mL ) and 1 : 50,000 (20 mg/mL )
may increase site hemostasis
Standard Epi [ ]
1 : 100,000
Epi receptor sites
alpha, beta-1, and
beta-2
Norepi vs Epi
Norepi lacks activity at beta-2
T/F
Avoid vasopressors in a pt that regularly uses cocaine
True
Not an absolute contraindcation
Can increase cardiotonic effects of vasopressors
tricyclic & MAOI antidepressants
digoxin
thyroid hormone
any sympathomimetics for weight control or attention deficit disorders
(not a contraindication)
Vasopressors in a pt using nonselective B-blocker
selective agents only block beta-1 🩷 receptors
nonselective also block vascular
beta-2
pressors’ alpha agonist action increases
↑↑↑DBP & MAP
↓
sudden reflex ↓HR
T/F
vasopressors are contraindicated in patients taking nonselective beta blockers
False
use caution
