Local Anesthetics

Question 1

Neurophysiology of pain involves what three things?

Answer 1

initiation

propagation

perception

Question 2

Define local/peripheral analgesics

Answer 2

analgesia close to the source of the pain

ie) Novocaine, cocaine, NSAIDs

Question 3

Define central analgesics

Answer 3

analgesia through supraspinal and spinal sites

ie) morphine, NSAIDs

Question 4

Define general anesthetics

Answer 4

Loss of consciousness, amnesia, +/- analgesia

ie) propofol, etomidate, barbituates

Question 5

What are pain receptors also called?

Answer 5

Nociceptors

Question 6

Provide an example of a pain receptor

Answer 6

TRP channels

(transient receptor potential)

Question 7

What are the two types of pain fibers?

Answer 7

C fibers and alpha delta fibers

Question 8

What NT is released at synapse of alpha delta fibers?

Answer 8

Glutamate

Question 9

What is the NT released at the synapse of C fibers?

Answer 9

Substance P

(and a little bit of glutamate)

Question 10

Are C fibers unmyelinated or myelinated?

Do they have fast or slow AP propagation?

Answer 10

Unmyelinated

Slow propagation

Question 11

Are alpha delta fibers unmyelinated or myelinated?

Do they have fast or slow AP propagation?

Answer 11

myelinated

fast, saltatory conduction

Question 12

Character of first pain?

What fiber is responsible for first pain?

Answer 12

Sharp, Stinging, High Intensity Pain

fast alpha delta fibers

Question 13

Character of second pain?

What fiber is responsible for second pain?

Answer 13

Dull, Aching, Low Intensity Pain

slow C fibers

Question 14

How do NSAIDs work to decrease sensitization of C and alpha delta fibers?

Answer 14

NSAIDs inhibit production of PGs by blocking COX2 in proinflammatory cells

Question 15

What is TTX?

Answer 15

tetrodotoxin

from pufferfish

Question 16

How does TTX work?

Answer 16

it blocks Na+ channel via the extracellular side

extracellular Na+ channel blockage

THUS, since it is bound to the outer pore,

it blocks Na+ entry no matter what stage/state Na+ channel is in (resting, activated, inactivated)

Question 17

How do local anesthetics bind differently than TTX to the Na+ channels?

Answer 17

local anesthetics are lipophilic so they get into cell and then wait around inside cell until Na+ channel is activated and then LAs go in and bind to Na+ channel and block Na+

So intracellular channel blockage

Question 18

Blockage of Na+ channel occurs in what state for TTX?

resting and/or activated and/or inactivated

Answer 18

resting &

activated &

inactivated

Question 19

Blockage of Na+ channel occurs in what state for local anesthetics?

resting and/or activated and/or inactivated

Answer 19

Blockade occurs when channel is in activated state

(M gate opens up and allows LA to gain entry into inner Na+ channel and block it)

Blockade can also occur during inactivated state

(LA can gain access to this inner pore of Na+ channel and block during inactivated state too)

Question 20

Why do local anesthetics (and not TTX) lead to use-dependent blockade?

Answer 20

local anesthetics cannot bind and block during resting state

they can bind and block only in activated and inactivated states

Question 21

Graph of use-dependent blockade of Na+ currents by local anesthetics

Answer 21

See picture

Question 22

In the presence of TTX, the Na+ current trace following the 1st stimulation of the neuron would look like?

See Picture

Answer 22

trace 25

Question 23

True or false:

Increased lipophilicity of local anesthetic means greater potency of local anesthetic and earlier onset of action of local anesthetic

Answer 23

true

Question 24

What local anesthetics are esters?

Do they have a short or long duration of action?

Answer 24

See picture

Question 25

What local anesthetics are amides? Do they have a short or long duration of action?

Answer 25

See picture

Question 26

True or false: For every 10 local anesthetics that form as cationic, one forms as uncharged and can cross the membrane and block Na+ channels

Answer 26

True

Question 27

Infected tissue has lower pH leading to more charged local anesthetic, so this anesthetic is more or less able to cross the cell membrane?

Answer 27

less So less potency in these areas and takes longer to work/onset of action

Question 28

The charged or uncharged local anesthetic can cross the membrane?

Answer 28

uncharged

Question 29

The charged or uncharged local anesthetic blocks the Na+ channel?

Answer 29

charged

Question 30

Small or large diameter fibers are blocked most easily by local anesthetics?

Answer 30

small

Question 31

myelinated or unmyelinated fibers (of the same diameter) are blocked more readily?

Answer 31

myelinated fibers are blocked more readily

Question 32

True or false: The more the fiber fires, the more it is blocked by local anesthetics

Answer 32

True use dependent thing

Question 33

Are fibers in the interior or exterior more or less readily blocked by local anesthetics?

Answer 33

fibers in interior are less readily blocked by local anesthetics and fibers on the exterior are more blocked by local anesthetics

Question 34

Name six routes of administration of local anesthetics

Answer 34

topical infiltration bier block peripheral nerve block epidural spinal

Question 35

When does systemic toxicity occur with local anesthetics?

Answer 35

when the LAs get absorbed into the vasculature and reach high enough concentrations in the heart and/or brain to disrupt cardiac and CNS function probablility of this happening increases when LAs are administered into tissues with dense vasculature (high vascularization) intercostal \> caudal \> epidural \> brachial plexus \> sciatic nerve (low vascularization)

Question 36

Symptoms of systemic toxicity of brain

Answer 36

anxiety confusion tremors convulsions

Question 37

Symptoms of systemic toxicity of cardiovascular system

Answer 37

depressed myocardial contractility bradycardia vasodilation hypotension (**exception:** cocaine: tacycardia, vasoconstrction, and hypertension due to its abilit to block catecholamine reuptake at sympathetic nerve termini: that revolving door NET: NE transporter)

Question 38

Administration of what reduces the likelihood of systemic toxicity by causing vasoconstrction and consequently prolongs duration of action of local anesthetics?

Answer 38

Epinephrine (many LA formulations contain epinephrine)

Question 39

What can direct injection into vasculature of local anesthetics cause?

Answer 39

temporary blindness aphasia hemiparesis convulsions (treated with benzodiazepines) respiratory depression coma cardiac arrest

Question 40

What are some local adverse reactions to local anesthetics?

Answer 40

range from pain to tissue necrosis at site of injection

Question 41

What are allergies most associated with, esters or amides?

Answer 41

rare but most associated with esters (It is the PABA: para-aminobenzoic acid derivatives produced by metabolism of local anesthetic through pseudocholinesterases)

Question 42

What drug given in adjunct therapy to reduce pain transmition?

Answer 42

Clonidine See picture

Question 43

Highlights of Cocaine

Answer 43

ester used in nose and throat procedures high abuse potential can cause tachycardia can cause vasoconstriction

Question 44

Highlights of Procaine (Novocaine)

Answer 44

first sythetic local anesthetic ester slow onset short duration relatively low systemic toxicity commonly used for infiltration and peripheral nerve blocks

Question 45

Highlights of Lidocaine (Xylocaine)

Answer 45

most commonly used amide xylidine derivative rapid onset intermediate duration causes vasodilation and is therefore combined with epinephrine this compound is also used as a class 1B anti-arrhythmic due to its capacity to inhibit cardiac Na+ channels

Question 46

Highlights of Ropivacaine (Naropin)

Answer 46

**synthesized in only the S-isomer** S-isomer has low affinity for cardiac Na+ channels (R-isomer has high affinity for cardiac Na+ channels) lower cardiac toxicity compared to other local anesthetics

Question 47

Drug Summary Table

Answer 47

See picture

Question 48

Drug summary table

Answer 48

See picture