Lecture 5 - Local Anesthetics Physiology Flashcards
the 3 types of anesthesia listed in the notes
general, neuraxial, peripheral nerve block
peripheral nerve block:
used for surgeries of the _____;
local anesthetic is placed typically near one of 2 locations…
extremities;
brachial or lumbar plexus
neuraxial anestheisa:
2 spaces where the anesthesia is placed =
used for surgeries of the ____ and _____
CSF (spinal), epidural space;
abdomen, lower extremity
general anesthesia:
only type of the anesthesias that causes what?
usually is instrumented along with a ______
loss of consciousness;
endotracheal tube
_____ anesthesia is used to sedate an area of the skin. then a subcutaneous injection can be used
topical
why did cocaine not end up being the best local anesthetic?
blocks dopamine and NE transporters
local anesthetics block what kind of channel?
voltage gated Na channels (NaV)
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
4;
6 (S1-S6);
S5, S6
NaV channel:
the inactivation gate is a loop connecting the S__ of section ___ and the S__ of section ____
S6 of section 3;
S1 of section 4
most anesthetics bind to what part of the Na channel?
intra or extracellular?
inactivation gate;
intracellular
NaV channels: subtypes are based off the ____ subunit. which channel is found in cardiac muscle and explains the severe cardiac toxicity of some anesthetics?
alpha;
NaV5
NaV channels:
types 1, 2, 3, and 6 are found in the ____. Type 4 is found in _____
CNS;
skeletal muscle
NaV channels:
Na7, 8, 9 are found in ____ neurons of the PNS. they are associated with ____ chance for CNS toxicity
afferent;
reduced
resting potential:
high ___ in cell;
high ____ extracellular;
high proteins in or outside of cell?
K;
Na;
in (negatively charged)
the Na/K ATPase:
pumps ___ K ____ the cell;
____ Na ___ the cell
2 in;
3 out
also K+ leak channel contributes to negativity
Action potential:
depolarization is due to opening of ____ channels;
repolarization is due to ____ efflux;
Na, K
after depolarization, Na channels enter an ____ state due to the ____ gate. after 20 msec- 10 seconds, the channel reverts to its resting ___ state
inactivated;
inactivation (blocks Na entry);
closed
action potentials occur in one direction due to presence of a ____ period, where Na channels are in the ___ state
refractory;
inactivated
ie Na only diffuses forward
Na channel blockers prevent full ____. in addition, less Na diffuses down the axon, further preventing ____
depolarization;
conduction/propagation
2 exceptions to the general rule that local anesthetics (LA) bind intracellularly:
natural peptides and alkaloid toxins bind the extracellular side
to cross cell membranes for binding, LA’s are usually weak ____. They cross membranes when they are protonated or non-protanated?
bases (ie pKA 7.5-9);
non-protanated
adding bicarb to anesthetics ____ the pH of extracellular space. this ____ the non-ionized form and _____ entry into cells
increases; increases; increases
inflamed tissue is at an ____ pH. LA’s are typically in the ____ form = harder or easier to enter?
acidic;
protanated;
harder
intracellular pH is ____ than extracellular pH. thus, inside the cell, most LA’s are in the ____ form = ____ binding
lower (ie more acidic);
protanated, increased
