Local Anesthetics

Question 1

Local anesthetics: are _________, with pKa values of ∼7.7 – 9

Answer 1

weak bases

Question 2

The LA intermediate chain is key determinant for:

Answer 2

onset speed, duration, potency

Question 3

LA general structure

Answer 3

aromatic moiety- (lipophilic)
intermediate chain
amino group- (hydrophilic)

Question 4

*Note: amides have ______ in their names, esters have one

Answer 4

two i’s

Question 5

Cocaine:

Answer 5

a natural product first employed as LA in 1884
• Still used clinically, for procedures on nasal passages and lachrymal glands
• Procaine (Novocain): synthetic LA developed, first employed in 1904

Question 6

Local anesthetics work by blocking ___________and

consequently, action potentials

Answer 6

NaV channels

Question 7

faster onset, lower pKa,

more potent, have:

Answer 7

higher lipid solubility,
longer-lasting LAs and greater protein binding

Correlation of potency, speed and duration of LA action
with physico-chemical properties of LAs

Question 8

Esters are hydrolyzed in the

Answer 8

plasma (primarily by pseudocholinesterase) and in the liver.

Question 9

Amides are metabolized only in the

Answer 9

liver

Question 10

patients with hepatic insufficiency, use of ________ local anesthetics may be contraindicated.

Answer 10

amide-linked

Question 11

Describe the role of pH in determining the effectiveness of local anesthetics.

Answer 11

Weak bases (neutral). Can be protonated (cationic). Need both forms for drug action.

lower pKa = better (↑ neutral LA%, more drug can get into the nerves)

Question 12

The NaV channels gate (on the intracellular side) must open to allow ___________, thereby obstructing Na+ flux through the channel.

Answer 12

LA+ to enter the channel and bind within

Question 13

NaV channels must first open in order to allow LA block, LA action is said to
be:

Answer 13

“use-dependent.”

Question 14

LA fx?

Answer 14

Enters the nerve

Question 15

LA+ fx?

Answer 15

Blocks Na channel

Question 16

Use-dependent block:

Answer 16

the more NaV channels are used, the more they become blocked

Question 17

LA strongest block?

Answer 17

C fiber- no myelin

Question 18

LA weakest block?

Answer 18

Aa, AB- heavy mylin

Question 19

Excretion of (primarily the charged form of) local anesthetics occurs via the

Answer 19

kidney.

Question 20

plasma level of _________ binds much of the injected LA-

Answer 20

α1-acid glycoprotein

–> amount of amide delivered to the liver for metabolism is variable–> variable degree
of local anesthetic toxicity.

Question 21

Topical anesthesia

Answer 21

application directly onto skin/cornea/mucous membranes of

nose, mouth, throat.

Question 22

Infiltration anesthesia

Answer 22

injection of LA into tissue without consideration of the
location of cutaneous nerves

Lidocaine, procaine and bupivacaine .

Question 23

Nerve block anesthesia:

Answer 23

injection of a LA near peripheral nerve

Question 24

Intravenous regional anesthesia (Bier’s Block):

Answer 24

blood is squeezed out of a limb using a tight elastic bandage, and a tourniquet is placed proximally. LA is injected via a catheter, and limb anesthesia develops within 5-10 minutes.

Lidocaine is most commonly employed in this technique.

more cardiotoxic drugs, such as bupivacaine,
are contraindicated.

Question 25

Spinal anesthesia

Answer 25

LA injection into CSF bathing lumbar spinal cord

Lidocaine for shorter procedures, bupivacaine for intermediate procedures, and
tetracaine (a long-lasting ester-linked drug)

Question 26

Epidural anesthesia:

Answer 26

LA injection just outside dura-enclosed spinal canal.

Lidocaine for shorter duration procedures, bupivacaine for longer procedures.

Question 27

EMLA cream

Answer 27

a eutectic mixture of lidocaine and prilocaine that exists as an oil at room temperature and can thereby penetrate intact skin, producing anesthesia up
to a depth of 5 mm

Question 28

Co-application of the vasoconstrictor epinephrine w/ LA

Answer 28

LAs can block sympathetic activity, causing vasodilatation.

Coapplication of epinephrine reduces this action, helping retain LA near injection site.

Question 29

LAs can block NaV channels and action potentials ___________,
including brain and heart.

Answer 29

in all nerve and muscle tissue

Question 30

LA overdose can produce ______ via action on inhibitory interneurons of the
CNS.

Answer 30

convulsions

Question 31

LAs often interfere with :

Answer 31

autonomic nervous system function.

Question 32

LAs block cardiac NaV channels, causing ________;

Answer 32

cardiac arrhythmia

bupivacaine is particularly cardiotoxic.

Question 33

Para-aminobenzoic acid (PABA) is a metabolic product of ester-linked LAs; this is
the primary culprit in:

Answer 33

local anesthetic hypersensitivity.

Question 34

In patients allergic to both amide and ester LAs, high doses of__________
can be used as a local anesthetic.

Answer 34

promethazine

antihistamine at lower doses

Question 35

Tetrodotoxin and saxitoxin:

Answer 35

block NaV channels by

plugging the extracellular channel entrance

Question 36

_________ is a small organic toxin found in some kinds of fish (Japanese puffer fish), newts and frogs (Atelopus).

Answer 36

Tetrodotoxin

Question 37

__________ is produced by marine dinoflagellates, which are consumed by, and retained in the flesh of, clams and other shellfish.

Answer 37

Saxitoxin

Question 38

Although chemically

distinct from one another, tetrodotoxin and saxitoxin both act by binding to and blocking the

Answer 38

extracellular entrance of voltage-gated Na+ channels

Question 39

Tetrodotoxin and saxitoxin

therefore cause death by paralyzing:

Answer 39

respiratory muscles, and not by an action on the heart

Question 40

Drug List

Esters

Answer 40

tetracaine
benzocaine
procaine
cocaine

Question 41

Amides Drug List

Answer 41

lidocaine
bupivacaine
prilocaine