Local Anesthetics

Question 1

Describe what type of impulse each of the classes of

nerve fibers conducts.

Answer 1

A-alpha: motor and proprioception, A-beta: touch, and pressure
sensation, A-gamma: muscle spindle innervation and reflexes,
A-delta: pain, cold temperature, and touch, B: preganglionic
autonomic nerves, C: pain, warm temperature, touch.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 128.

Question 2

How do local anesthetics block neuromuscular

transmission?

Answer 2

Local anesthetics block nerve impulse transmission by binding
reversibly to voltage-gated ion channels which produces a
concentration-dependent decrease in the peak sodium current.
This effect on the sodium channels disrupts the propagation of
action potentials along the nerve fiber.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 564-565.

Question 3

What is pKa and how does it affect the onset of

action of a local anesthetic?

Answer 3

The pKa is the pH at which the ionized and non-ionized forms of
the drug are present in equal concentrations. Local anesthetics
with a pKa closest to physiologic pH will have higher
concentrations of the non-ionized form. Because it is the nonionized
form that is able to pass through the lipid membrane of
the cell, drugs with a pKa closest to physiologic pH will also
have a faster onset. Commonly used local anesthetics have a
pKa range from 7.6 to 9.0.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 268-269.

Question 4

Does the ionized or the non-ionized form of a local
anesthetic bind with the sodium receptor on the
inside of the cell membrane?

Answer 4

Although it is the non-ionized (lipid soluble) form of the drug that
crosses the membrane to the site of action, it is the ionized
(water soluble) form that is able to bind to the sodium receptor.
After the non-ionized form crosses the membrane, it reaches
equilibrium with the ionized form. The ionized form is then able
to bind to the receptor.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 269.

Question 5

What is the principal factor that determines the onset

of action of a local anesthetic?

Answer 5

The principal factor that contributes to the onset of action of a
local anesthetic is the amount of the drug that exists in the nonionized
form versus the ionized form. It is the non-ionized form
that is able to cross the cell membrane and act on sodium
channels.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 269.

Question 6

What characteristic of a local anesthetic determines

the potency of the drug?

Answer 6

Potency is associated with the lipid solubility of the drug. The
lipid solubility of local anesthetics increases as the number of
carbon atoms in the molecule increases.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 269.

Question 7

In general, how is the chemical structure of local

anesthetics organized?

Answer 7

Local anesthetics are all weak bases consisting of a lipophilic
group (often a benzene ring) that is connected to a positivelycharged
hydrophilic group such as a tertiary amine by either an
amide link or an ester link. It is this link that is used to classify
local anesthetics as either amide local anesthetics or ester
anesthetics.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 267-268

Question 8

What two factors are principally responsible for the

degree of nerve blockade by local anesthetics?

Answer 8

Local anesthetic concentration and volume are the primary
factors that determine the degree of neural blockade.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 565.

Question 9

What is differential blockade?

Answer 9

Differential blockade is the interruption of different modes of
nerve transmission in an unequal fashion. For example, local
anesthetics produce an ordered progression of blockade of
temperature sensation first, then proprioception (kinesthetic
sense), motor function, sharp pain, and light touch.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 565-566.

Question 10

How can you easily remember which local

anesthetics are esters and which are amides?

Answer 10

Chloroprocaine, tetracaine, procaine, benzocaine, and cocaine
are amino ester local anesthetics. Lidocaine, bupivacaine,
mepivacaine, ropivacaine, etidocaine, prilocaine, and dibucaine
are amino amide local anesthetics. Notice that amide
anesthetics all have two I’s in their name. Ester anesthetics
only have one I in their name.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 767.

Question 11

Rank the different classes of nerve fibers in order

from greatest to least according to their diameter.

Answer 11

A-alpha fibers: 12-20 microns, A-beta: 5-12 microns, A-gamma:
3-12 microns, A-delta: 1-5 microns, B fibers: < 3 microns, and C
fibers: 0.3-1.3 microns.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 1074.

Question 12

How do pKa, protein binding, and lipid solubility
correspond with the potency, onset of action, and
duration of action of a local anesthetic?

Answer 12

The onset of a local anesthetic correlates with its pKa, the
potency correlates with its lipid solubility, and the duration of
action correlates with the degree to which the drug is protein
bound.
Yao FF. Anesthesiology: Problem-Oriented Patient
Management. 7th ed. Philadelphia: Lippincott, Williams, and
Wilkins; 2012: 1067.

Question 13

How does the diameter of a nerve and the degree of

myelination affect its sensitivity to local anesthetics?

Answer 13

The smaller the diameter of a neuron and the less myelin it has,
the more sensitive it is to local anesthetics.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 266.

Question 14

How does protein binding affect local anesthetic

duration of action?

Answer 14

The duration of action of local anesthetics is dependent
primarily upon their binding to alpha-1 acid glycoprotein.
Increased binding to this protein prolongs the duration of action.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 269.

Question 15

Which nerve fiber types are myelinated or not

myelinated?

Answer 15

A fibers (including A-alpha, A-beta, A-gamma, and A-delta) and
B fibers are myelinated. C fibers are nonmyelinated.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 128.

Question 16

How does the metabolism of ester and amide local

anesthetics differ?

Answer 16

Ester anesthetics are metabolized by plasma cholinesterases
and amides are metabolized by hepatic carboxylesterases and
the cytochrome P450 system.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 570.

Question 17

Are amide local anesthetics or ester local
anesthetics more ionized at physiologic pH? What
can you infer about the pKa based on this
information?

Answer 17

The ester anesthetics are more ionized at physiologic pH. For
example, procaine and chloroprocaine are 97% and 95%
ionized at physiologic pH, respectively. Bupivacaine and
ropivacaine have the highest degree of ionization in the amide
group at 83%. The drugs with the highest pKa also have the
highest degree of ionization at physiologic pH. Bupivacaine and
ropivacaine both have a pKa of 8.1 whereas chloroprocaine has
a pKa of 8.7 and procaine has a pKa of 8.9.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 566-567.

Question 18

Rank the following sites from greatest to least
according to the speed at which injected local
anesthetics enter the systemic circulation:
subcutaneous, intercostal, intravenous, tracheal,
epidural, brachial plexus, paracervical, and caudal.

Answer 18

From greatest to least, the rate at which an injected local
anesthetic enters the systemic circulation at the following sites
are: intravenous> tracheal> intercostal> caudal> paracervical>
epidural> brachial plexus> sciatic> subcutaneous.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 270.

Question 19

How does acidosis affect the pharmacokinetics of

local anesthetics?

Answer 19

Acidosis and/or hypercarbia will decrease the convulsive
threshold of procaine, mepivacaine, prilocaine, lidocaine, and
bupivacaine. Acidosis decreases the plasma protein binding,
which increases the free form of the drug in the bloodstream
which results in an increased amount available for diffusion into
the brain.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 778-
779.

Question 20

What are the respiratory effects of local anesthetics?

Answer 20

Local anesthetics such as lidocaine can depress the ventilatory
response to hypoxia, relax bronchial smooth muscle, and block
the bronchoconstrictive reaction that may accompany
intubation. Apnea is a possible effect if the phrenic nerve or
medullary respiratory center is directly exposed to local
anesthetics.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 273.

Question 21

What are the symptoms of local anesthetic toxicity in
awake patients and in what sequence do they
develop?

Answer 21

Early symptoms of local anesthetic toxicity include dizziness
and paresthesias around the mouth and tongue. Tinnitus and
blurred vision may occur next followed by excitatory signs such
as nervousness and agitation. The symptoms of CNS excitation
are a precursor to slurred speech and unconsciousness.
Muscle twitching often heralds tonic-clonic seizures and
respiratory arrest.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 135.

Question 22

Name three factors that contribute to the negative
inotropic and chronotropic effects of local anesthetic
toxicity.

Answer 22

Hypoxia, hypercarbia, and acidosis are the three major factors
contributing to the negative chronotropic and inotropic effects of
local anesthetics.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 136.

Question 23

Which local anesthetic displays the greatest
tendency towards cardiotoxicity and what symptoms
would you expect to see with a cardiotoxic reaction
with this agent compared to other local anesthetics?

Answer 23

Bupivacaine is the most cardiotoxic of the local anesthetics.
Large doses of bupivacaine and most other local anesthetics
will reduce the duration of the refractory period, cause
depression of myocardial contractility and conduction velocity,
slow spontaneous phase IV depolarization (automaticity) and
result in bradycardia, hypotension, heart block, and potentially
cardiac arrest. It also impairs regulation of cardiovascular
system by the CNS by disrupting the arterial baroreflex system.
Whereas early cardiotoxic signs of lidocaine may include
hypotension, bradycardia, and hypoxia, the first sign of a
cardiotoxic reaction involving bupivacaine may be cardiac arrest
due to ventricular arrhythmias that is resistant to resuscitation
efforts.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 573-575.

Question 24

Why is the threshold for local anesthetic toxicity
lower when injected intra-arterially than when
injected intravenously?

Answer 24

The lung extracts a significant amount of local anesthetic, thus
intravenous injection is associated with a much higher dose
before toxicity is reached than intra-arterial injection.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 270.

Question 25

Plain 2% lidocaine has a specific gravity between
1.0004 and 1.0066. In relation to cerebrospinal fluid,
would this solution be hypobaric, isobaric, or
hyperbaric?

Answer 25

CSF has a specific gravity of 1.003 to 1.008. 2% plain lidocaine
is hypobaric in relation to CSF.

Question 26

What is accomplished by mixing hyaluronidase with

local anesthetics?

Answer 26

The addition of hyaluronidase facilitates the spread of the local
anesthetics into the tissue.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 133.

Question 27

What are the effects of adding bicarbonate to a local

anesthetic prior to injection?

Answer 27

The addition of bicarbonate to local anesthetics increases the
non-ionized portion of the drug which facilitates the passage of
the drug across the neuronal lipid membrane. By doing so, the
onset of the drug is more rapid. It also prolongs the duration of
action and reduces pain on injection.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 132-133.

Question 28

What is the usual concentration of epinephrine
added to local anesthetics to prolong epidural
blockade?

Answer 28

The usual concentration is 1:200,000 or 5 mcg/mL
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 132.

Question 29

How does the addition of epinephrine affect the

duration of lidocaine? Bupivacaine?

Answer 29

The addition of epinephrine does not significantly affect the
duration of action of bupivacaine, etidocaine, or prilocaine
whereas mepivacaine and lidocaine are significantly prolonged.
The addition of epinephrine has little effect on the duration of
bupivacaine, whose long duration of action is due to a high
degree of protein binding.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 270.

Question 30

All local anesthetics cause relaxation of vascular

smooth muscle except for three. Name them.

Answer 30

All local anesthetics cause vasodilation except for cocaine,
ropivacaine, and lidocaine.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 131.

Question 31

How does intravenous lidocaine affect cerebral blood

flow?

Answer 31

Intravenous lidocaine decreases cerebral blood flow.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 271-272.

Question 32

What local anesthetics have been implicated in

cauda equina syndrome?

Answer 32

The repeated use of 5% lidocaine and 0.5% tetracaine via
infusion through small-bore continuous spinal catheters has
been implicated in the development of a type of neurotoxicity
known as cauda equina syndrome.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 273.

Question 33

What two local anesthetics can result in
methemoglobinemia? What patients are most
susceptible to this effect? What is the treatment for
methemoglobinemia?

Answer 33

Prilocaine and benzocaine are both capable of converting
hemoglobin to methemoglobin. Neonates of mothers who have
received prilocaine are particularly susceptible, as are patients
with cardiopulmonary disease who would be more likely to feel
the effects of the decrease in oxygen transport.
Methemoglobinemia is treated with 1-2 mg/kg of a 1% solution
of methylene blue administered over a period of five minutes.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 271.

Question 34

What ester local anesthetic is not metabolized by

plasma cholinesterases?

Answer 34

Although cocaine is an ester anesthetic, it is metabolized by the
liver and excreted unchanged in the urine and does not undergo
metabolism by pseudocholinesterase.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 271.

Question 35

What factors can prolong the half-life of ester local

anesthetics?

Answer 35

Because ester anesthetics are metabolized by plasma
pseudocholinesterases, atypical plasma cholinesterase, the
administration of succinylcholine, and severe liver disease can
result in a prolonged half-life of these drugs.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 134.

Question 36

What are the two primary factors that determine the
rate of elimination of amide local anesthetics?
Based on these factors, what are the major
conditions that predispose amide anesthetics to a
prolonged duration of action?

Answer 36

The two major factors that determine the rate of elimination of
amide local anesthetics are hepatic enzyme activity and hepatic
blood flow. Any pathologic condition that results in reduced
hepatic blood flow or enzymatic activity will prolong the action of
amide anesthetics. For example, severe hepatic disease
reduces both hepatic blood flow and enzymatic activity. As a
result, the elimination half-life of lidocaine is increased from 1.6
to 4.9 hours. Because it results in decreased hepatic blood
flow, congestive heart failure will also prolong the plasma halflife.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 134.

Question 37

What is responsible for the alpha phase of decay

seen with local anesthetics? The beta-phase?

Answer 37

Local anesthetics are rapidly distributed to the highly perfused
organs (lungs, brain, heart, liver, and kidneys) resulting in a
rapid decrease in plasma concentration. This is referred to as
the alpha phase of decay. Of the organs listed, the lungs play
the greatest role in the decrease in the plasma concentration of
the local anesthetic. The slower fall in plasma concentration
that follows, known as the beta phase of decay, reflects drug
metabolism, excretion, and distribution into tissues with a more
limited blood supply.
Miller RD. Miller’s Anesthesia. 7th ed. Philadelphia: Churchill
Livingstone; 2010: 931

Question 38

What arrhythmias would warrant serious
consideration before administering a large volume of
local anesthetics? Why?

Answer 38

Because stabilization of cardiac cellular membranes by local
anesthetics may result in decreased conduction in electrical
depolarization and prolongation of the PR interval and an
increase in the degree of heart block, a history of type I or type
II second degree heart block or third degree heart block with or
without a pacemaker may require choosing another anesthetic
technique.
Miller RD. Miller’s Anesthesia. 7th ed. Philadelphia: Churchill
Livingstone; 2010: 932-933.

Question 39

What are the contraindications to performing

peripheral nerve blocks?

Answer 39

The contraindications to peripheral nerve blocks are generally
the same as for neuraxial anesthesia (patient refusal, systemic
anticoagulation, infection at the site of infection) except that
peripheral nerve blocks do not produce the high-degree
sympathectomy associated with neuraxial blocks and therefore
would not be contraindicated in stenotic cardiac valve lesions or
increased intracranial pressure.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 977.

Question 40

What is responsible for most of the allergic reactions

associated with amide local anesthetics?

Answer 40

Allergic reactions to amide local anesthetics are infrequent and
typically due to the preservative methylparaben.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 274

Question 41

Do local anesthetics block sodium channels located
on the outside of the neuron membrane or on the
inside?

Answer 41

Local anesthetics bind to the alpha-subunit on sodium channels
on the inside of the cell membrane and block the large influx of
sodium into the cell associated with depolarization.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 264