Lecture 5 - Local Anesthetics Physiology

Question 1

the 3 types of anesthesia listed in the notes

Answer 1

general, neuraxial, peripheral nerve block

Question 2

peripheral nerve block:
used for surgeries of the _____;
local anesthetic is placed typically near one of 2 locations…

Answer 2

extremities;

brachial or lumbar plexus

Question 3

neuraxial anestheisa:
2 spaces where the anesthesia is placed =
used for surgeries of the ____ and _____

Answer 3

CSF (spinal), epidural space;

abdomen, lower extremity

Question 4

general anesthesia:
only type of the anesthesias that causes what?
usually is instrumented along with a ______

Answer 4

loss of consciousness;

endotracheal tube

Question 5

_____ anesthesia is used to sedate an area of the skin. then a subcutaneous injection can be used

Answer 5

topical

Question 6

why did cocaine not end up being the best local anesthetic?

Answer 6

blocks dopamine and NE transporters

Question 7

local anesthetics block what kind of channel?

Answer 7

voltage gated Na channels (NaV)

Question 8

NaV channel:
the alpha subunit consists of ___ sections that each have a ____ transmembrane compenent;
the S__ and S__ regions combine to form a pore that allows Na entry

Answer 8

4;
6 (S1-S6);
S5, S6

Question 9

NaV channel:

the inactivation gate is a loop connecting the S__ of section ___ and the S__ of section ____

Answer 9

S6 of section 3;

S1 of section 4

Question 10

most anesthetics bind to what part of the Na channel?

intra or extracellular?

Answer 10

inactivation gate;

intracellular

Question 11

NaV channels: subtypes are based off the ____ subunit. which channel is found in cardiac muscle and explains the severe cardiac toxicity of some anesthetics?

Answer 11

alpha;

NaV5

Question 12

NaV channels:

types 1, 2, 3, and 6 are found in the ____. Type 4 is found in _____

Answer 12

CNS;

skeletal muscle

Question 13

NaV channels:

Na7, 8, 9 are found in ____ neurons of the PNS. they are associated with ____ chance for CNS toxicity

Answer 13

afferent;

reduced

Question 14

resting potential:
high ___ in cell;
high ____ extracellular;
high proteins in or outside of cell?

Answer 14

K;
Na;
in (negatively charged)

Question 15

the Na/K ATPase:
pumps ___ K ____ the cell;
____ Na ___ the cell

Answer 15

2 in;
3 out

also K+ leak channel contributes to negativity

Question 16

Action potential:
depolarization is due to opening of ____ channels;
repolarization is due to ____ efflux;

Answer 16

Na, K

Question 17

after depolarization, Na channels enter an ____ state due to the ____ gate. after 20 msec- 10 seconds, the channel reverts to its resting ___ state

Answer 17

inactivated;
inactivation (blocks Na entry);
closed

Question 18

action potentials occur in one direction due to presence of a ____ period, where Na channels are in the ___ state

Answer 18

refractory;
inactivated

ie Na only diffuses forward

Question 19

Na channel blockers prevent full ____. in addition, less Na diffuses down the axon, further preventing ____

Answer 19

depolarization;

conduction/propagation

Question 20

2 exceptions to the general rule that local anesthetics (LA) bind intracellularly:

Answer 20

natural peptides and alkaloid toxins bind the extracellular side

Question 21

to cross cell membranes for binding, LA’s are usually weak ____. They cross membranes when they are protonated or non-protanated?

Answer 21

bases (ie pKA 7.5-9);

non-protanated

Question 22

adding bicarb to anesthetics ____ the pH of extracellular space. this ____ the non-ionized form and _____ entry into cells

Answer 22

increases; increases; increases

Question 23

inflamed tissue is at an ____ pH. LA’s are typically in the ____ form = harder or easier to enter?

Answer 23

acidic;
protanated;
harder

Question 24

intracellular pH is ____ than extracellular pH. thus, inside the cell, most LA’s are in the ____ form = ____ binding

Answer 24

lower (ie more acidic);

protanated, increased

Question 25

LA forms:
when in an ointment or cream form, usually in a ____ form;
when in a solution for injected, usually a _____;
the ____ form penetrates membranes. the ____ form blocks channels

Answer 25

freebase;
salt;
non-ionized;
ionized

Question 26

4 factors that influence LA efficacy:

____ of transmission, _____ of peripheral axons, ___, ____ of target tissue

Answer 26

frequency, size/class; pH;

vascularity

Question 27

Na blockers have high affinity for the ____ state of the Na channel. thus, increased efficacy with fibers with a ____ Frequency of depolarization

Answer 27

activated/open;

high

Question 28

order the 4 groups in order of blockade (ie first blocked = 1): small/large; unmyelinated/myelinated:

Answer 28

1. small myelinated
2. small unmyelinated
3. large myelinated
4. large unmyelinated

Question 29

order of loss (for temperature, pressure, touch, pain)

Answer 29

1. pain
2. temperature
3. touch
4. pressure

Question 30

____ blood flow = faster absorption of LA

Answer 30

greater

but also faster metabolism = potentially shorter action

Question 31

slow vs fast firing nerve block:
drug completely dissociates between spikes = 
block accumulates each spike - 
activity is preserved = 
activity is suppressed =

Answer 31

slow,
fast,
slow,
fast

Question 32

larger or smaller nerve fibers have easier access for LA’s?

myelinated or unmyelinated nerves fire faster = more binding?

Answer 32

smaller;

myelinated

Question 33

LA's with pkas closer to physiologic pH (7.4) =
more non-ionized or ionized?
faster or slower penetration?
faster or shorter onset?
longer or shorter half life?

Answer 33

non-ionized = faster penetration;
shorter onset;
longer (evades degradation)

Question 34

2 target areas with relatively low vascularity

Answer 34

subcutaneous, sciatic

Question 35

LA’s can be given along with _____ (_____ usually) to enhance local action. these ____ diffusion and local metabolism and _____ duration of action

Answer 35

vasoconstrictors (Epinephrine);
decrease;
prolong