Local Anesthetics: Review

Question 1

Local anesthetics interrupt neural conduction by

Answer 1

inhibiting Na+ influx through channels or ionophores within neuronal membranes

Question 2

When the neuron
is stimulated, the channel assumes a ___/___ state, in which sodium ions diffuse into the cell, initiating depolarization.

Answer 2

activated/open

Question 3

What happens in the inactivated state?

Answer 3

further influx is denied

active transport returns sodium ions
to the exterior

repolarization

Question 4

Local anesthetics have greater affinity for receptors within sodium channels during

Answer 4

their activated and inactivated states

rather than when they are in their resting
states

Question 5

(Larger/smaller) fibers are generally more susceptible to LAs.

Answer 5

smaller
a given volume can more easily block the requisite number of sodium channels & entirely interrupt signal transmission

Question 6

which fibers are most sensitive?

Answer 6

Most to least:
tiny, rapid-firing autonomic fibers

sensory fibers

somatic motor fibers

(most susceptible: Ag spindle efferents, Ad nociceptive
resistant: myelinated C)

Question 7

recovery from spinal anesthesia:
Order of returning fxns?

Answer 7

First to last:
voluntary motor fxn
sensation
autonomic control (ie: micturition)

Question 8

How do sensory fibers vary in their sensitivity?

Answer 8

Easiest → hardest to block:
sympathetic
temperature
pain fibers
pressure & proprioception
motor

Ex: pt may feel unpleasant pressure despite
complete anesthesia of pain fibers

Question 9

The molecular structure of all local anesthetics consists of (3)

Answer 9

lipophilic aromatic ring
intermediate ester or amide linkage
tertiary amine

Question 10

concentrations that range typically from

Answer 10

0.5 to 4%
d/t differences in lipid solubility

Question 11

Which is more potent?
bupivacaine
articaine

Answer 11

bupivacaine is more lipid
soluble & potent

available as 0.5% [ ] (5 mg/mL)

Question 12

diffusion through nerve sheaths and neural
membranes is determined by

Answer 12

aromatic ring and its substitutions

Question 13

the most important factor that determines the onset of anesthesia

Answer 13

proportion of molecules in a lipid-soluble rather than a water-soluble state

Question 14

When is an amine charged? uncharged?

Answer 14

Tertiary (3 bonds) = lipid soluble

Quaternary (4 bonds) = water soluble; + charge

Question 15

In their packaging, LAs exist as ___. Why does this affect onset of action?

Answer 15

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)

Question 16

T/F
higher pka = faster onset

Answer 16

False
higher pKa = less molecules in lipid-soluble form

This will delay onset

Question 17

The intermediate chain/linkage tells us…

Answer 17

classification
&
elimination

Question 18

Amide metabolism

Answer 18

biotransformed in the liver

aromatic hydroxylation
amide hydrolysis
N-dealkylation

Question 19

Ester metabolism

Answer 19

hydrolyzed in the bloodstream by plasma esterases

Question 20

Which amide is metabolized as if it was an ester?

Answer 20

Articaine
amide according to its intermediate linkage, but also contains an ester side chain on its aromatic ring.

Question 21

Local anesthetics vary in their duration of action due primarily to differences in their …

Answer 21

affinity for protein

Question 22

T/F
local anesthetics irreversibly bind to plasma proteins while circulating in the bloodstream

Answer 22

False
reversibly bind

Question 23

LA’s percentage of protein binding correlates with

Answer 23

its affinity for protein within sodium channels

Question 24

T/F
greater protein binding = shorter neural blockade

Answer 24

False
will prolong blockade

Question 25

bupivacaine vs mepivacaine protein binding

Answer 25

bupivacaine 95% mepivacaine 55%

Question 26

Which drug shortens its own duration by dilating local vasculature?

Answer 26

Lidocaine

Question 27

Plain lidocaine formulation limitations

Answer 27

useful for brief procedures following infiltration but efficacy for nerve block is poor

Question 28

How do LAs affect seizure activity?

Answer 28

Low serum [ ]: suppress 🩷 arrhythmias & status seizures higher [ ]: induce seizure activity

Question 29

the initial life-threatening consequence of local anesthetic overdose

Answer 29

convulsive seizures

Question 30

How does LA toxicity cause convulsive seizures?

Answer 30

selective depression of central inhibitory tracts ↓ uncontrolled excitatory tracts

Question 31

LA toxicity will first cause ___. If [ ]s increase further what else happens?

Answer 31

convulsive seizures all pathways are inhibited coma, respiratory arrest, CV collapse

Question 32

Lidocaine toxicity [ ]s

Answer 32

>5 mcg/mL (S/S start) >10 mcg/ml (convulsive seizures)

Question 33

Monitor for .... when using LAs with sedatives & opioids.

Answer 33

respiratory depression they potentiate any respiratory depression a/w sedatives & opioids

Question 34

LAs are CNS ___

Answer 34

depressants

Question 35

Which clinical conditions lowers the minimum serum [ ] for LA induced seizures?

Answer 35

hypercarbia caution w/ respiratory depression by concurrent use of sedatives and opioids!

Question 36

greater potential for direct cardiac toxicity than other agents

Answer 36

bupivicaine (~greater affinity for inactive & resting Na channel → dissociates more slowly)

Question 37

When using lidocaine or other anesthetics, regardless of their formulated concentration, one must consider ___ administered, not the ___

Answer 37

dose (milligrams) volume (milliliters)

Question 38

In adults, we use ____ to avoid toxicity. In peds, this value is expressed as ___.

Answer 38

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)

Question 39

metabolite of prilocaine

Answer 39

o-toluidine can oxidize Hgb iron ferrous ( Fe 2+) → ferric ( Fe 3+)

Question 40

Patients appear cyanotic and become symptomatic when the proportion of methemoglobin exceeds

Answer 40

15%

Question 41

prilocaine contraindctns

Answer 41

hereditary methemoglobinemia

Question 42

Methemoglobinemia treatment

Answer 42

methylene blue reduces the hemes to their normal state

Question 43

How does Methemoglobinemia affect oxygen monitoring?

Answer 43

low pulse oximetry ( SpO2 ) despite effective oxygenation and ventilation ex: SpO2 90%, but PaO2 is normal

Question 44

Why do pts sometimes falsely assume they're allergic to an LA?

Answer 44

1) syncopal episode a/w the injection 2) 🩷 palpitations from the epi (in the solution or released endogenously)

Question 45

Likely cause of true LA allergy

Answer 45

Preservatives (methylparaben) antioxidants (sulfites)

Question 46

Methylparaben

Answer 46

preservative in multidose vials to prevent microbial growth

Question 46

Sulfites

Answer 46

antioxidants prevent the [O] of vasopressors (epinephrine or levonordefrin)

Question 47

Allergies Type I Reactions

Answer 47

occur w/in minutes mediated by antibodies or immunoglobulin E ( IgE ) produced by B lymphocytes most commonly provoked by components of the formulation

Question 48

Allergies Type 4 reactions

Answer 48

delayed for several days mediated by sensitized T lymphocytes rare

Question 49

Drugs must be ... to cause allergic rxn, but most do so by...

Answer 49

large MW w/ multiple valences combining w/ carrier molecules (most drugs are too small)

Question 50

Have the PABA structure in common and risk cross sensitivity

Answer 50

sulfa antibiotics methylparaben ester LAs

Question 51

T/F The ester linkage causes the allergic rxn a/w ester LAs

Answer 51

False a molecular component joined by this linkage is the culprit

Question 52

patients claiming allergy to these foods may experience cross-reactions with LA solutions containing vasopressors bc they contain these same sulfites

Answer 52

fresh fruits and vegetables

Question 53

Meperidine "allergic" response

Answer 53

Meperidine simulates histamine release and NSAIDs may promote synthesis of leukotrienes Pt response = pseudoallergic (vs true allergy, which is immune-mediated)

Question 54

How to assess LA allergy

Answer 54

Question 55

unverified LA "allergy" what should we use?

Answer 55

mepivacaine or prilocaine without vasopressor (avoids esters & sulfites from 'pressors)

Question 56

Good for length procedures

Answer 56

Bupivacaine but more pain injection

Question 57

Most widely used LA in US

Answer 57

Lidocaine

Question 58

Vasopressors are drugs that provide constriction of blood vessels by

Answer 58

activating alpha-1 adrenergic receptors

Question 59

Why include Vasopressors with LAs

Answer 59

hemostasis in operative field delay absorption (reduces systemic toxicity risk & prolongs effect)

Question 60

Epi causes considerable cardiac stimulation d/t its..

Answer 60

Beta 1 adrenergic agonist (in addition to the usual Alpha 1)

Question 61

Epi concentrations greater than 1 : 200,000 (5 mg/mL )

Answer 61

does not reduce LA serum [ ]

Question 62

Increasing Epi [ ] to 1 : 100,000 (10 mg/ mL ) and 1 : 50,000 (20 mg/mL )

Answer 62

may increase site hemostasis

Question 63

Standard Epi [ ]

Answer 63

1 : 100,000

Question 64

Epi receptor sites

Answer 64

alpha, beta-1, and beta-2

Question 65

Norepi vs Epi

Answer 65

Norepi lacks activity at beta-2

Question 66

T/F Avoid vasopressors in a pt that regularly uses cocaine

Answer 66

True Not an absolute contraindcation

Question 67

Can increase cardiotonic effects of vasopressors

Answer 67

tricyclic & MAOI antidepressants digoxin thyroid hormone any sympathomimetics for weight control or attention deficit disorders (not a contraindication)

Question 68

Vasopressors in a pt using nonselective B-blocker

Answer 68

selective agents only block beta-1 🩷 receptors nonselective also block vascular beta-2 pressors' alpha agonist action increases ↑↑↑DBP & MAP ↓ sudden reflex ↓HR

Question 69

T/F vasopressors are contraindicated in patients taking nonselective beta blockers

Answer 69

False use caution