Basic Local Anesthetics Flashcards
Local anesthetics prevent the _______ and _______ of nerve impulses
Generation and conduction
How do local anesthetics prevent generation and conduction of nerve impulses?
By blocking Na ion influx
Which voltage -gated channels do local anesthetics work?
Na channels
What do local anesthetics prevent the transmission of?
advancing wave of depolarization down the length of the nerve
Do LAs alter the resting transmembrane potential?
No
Do LAs have a little or large effect on the threshold potential?
Little
Which subunits are located on the the voltage gated sodium channels?
Alpha subunits
Beta subunits
What are the 3 states of the voltage gated sodium channel?
Activated
Inactivated
Resting
What is another name for the activated state of voltage gated sodium channels?
Open
Which 2 states do LAs have a higher affinity for?
Activated & Inactivated
Do LAs have a higher affinity for resting states over the actived & inactivated?
No
Repeated ______ facilitates encounter of LA with the sodium channels that are ______ as opposed to the ______
Repeated DEPOLARIZATION facilitates encounter of LA with the sodium channels that are ACTIVATED as opposed to the RESTING
Which nerve state is least sensitive to LAs?
Resting
Are LAs more or less sensitive to a resting nerve state than a state of repeated stimulation?
Less sensitive
In high or low doses of LAs, does increasing or decreasing the stimulation frequency create an increase or decrease in Na flow?
In LOW doses of LAs, INCREASING the stimulation frequency create a DECREASE in Na flow?
What channels contain the LA binding site?
Voltage gated sodium channel
Which nerves do LAs work on?
peripheral nerves
Are Na channels integral membrane proteins?
Yes
Where do Na channels initiate and propagate action potentials?
axons
dendrites
muscle tissue
Na channels _____ & _____ membrane potential oscillations
Na channels INITIATE & MAINTAIN membrane potential oscillations
Which specialized cells do Na channels work on?
Heart and brain cells
Do Na channels shape and filter synaptic inputs?
Yes
What is the common structural feature found in Na channels and other gated ion channels?
6 Transmembrane helical segments
Are Na channels tetrameres?
Yes
How many alpha subunits are on a Na channel?
1 larger alpha subunit
How many beta subunits are on a Na channel?
1 or 2 smaller beta subunits
Which subunit on a Na channel is larger, alpha or beta?
Alpha are larger
Blocking of impulses in a nerve fiber requires that a defined length of nerve become ______
Blocking of impulses in a nerve fiber requires that a defined length of nerve become INEXCITEABLE
As the LA concentration increase, should it be applied to a longer or shorter length of nerve to prevent impulse conduction?
As the LA concentration increase, should it be applied to a SHORTER length of nerve to prevent impulse conduction
Is there a difference in the way LAs inhibit conduction between myelinated and unmyelinated nerve fibers? Or is it the same?
Different
How does conduction work in myelinated fibers?
impulse jumps from one ranvier node to the next
In order to block an impulse in a myelinate nerve fiber, how many Na channels in ranvier nodes need to be inhibited?
3 successive ranvier nodes
Must the 3 ranvier nodes be successive when blocking?
Yes, they should be successive
Do unmyelinated fibers conduct more quickly or slowly than myelinated?
More slowly
Are unmyelinated fibers resistant to LAs? Why?
Yes, because they have dispersive Na channels throughout their plasma membranes
Are unmyelinated fiber larger or smaller in diameter to myelinated?
Smaller
When an action potential occurs, do Na channels open?
Yes
When Na channels open, does Na flow extracellular to intracellular or intracellular to extracellular?
extracellular to intracellular
Does depolarization occur when Na channels open and there is an influx of Na ions?
Yes
Do Na channels remain open for long?
No, they remain open for a short period of time - milliseconds
What is another name for Na channels return to resting conformation?
Repolarization
What is the term for when ion channels go from conducting to nonconducting forms?
gating
Gating is assumed to result from movements of _______ in response to changes in potential
Gating is assumed to result from movements of DIPOLES in response to changes in potential
Do LAs bind irreversibly or reversibly?
reversibly
Is LA binding concentration dependent?
Yes
Where is the predominant binding site of LAs - in the cell?
near cytoplasmic side of the plamsa membrane
Can LA molecules pass through the channel itself to reach the binding site?
No
What is this - soluble & diffuse rapidly in both hydrophilic & hydrophobic environments?
Effective LA
What is the chemical structure of LAs?
Amino amide & esters
Do Amino amide & esthers LAs have a tertiary amine group?
yes
Are unionized base forms of LAs uncharged or charged?
uncharged
Are unionized base forms of LAs lipophilic or hydrophilic?
lipophillic
Do unionized base forms of LAs permeate more rapidly through the phospholipid membrane?
Yes
Are ionized forms of LAs uncharged or charged?
charged
Are ionized forms of LAs lipophilic or hydrophilic?
hydrophillic
Do ionized forms of LAs bind with greater affinity to open Na channels?
Yes
Between ionized forms and unionized base forms, which has a greater affinity to open Na channels?
ionized
Between ionized forms and unionized base forms, which permeates more rapidly the phospholipid membrane?
unionized
Which LA form is the predominantly active species at the binding sites on Na channels? Ionized or unionized?
Ionized
Is the LA change from ionized to unionized a quick occurance?
yea, it happens in a fraction of a second
What does the meyer overton theory hypothesize about?
mechanism of action of LAs
What does the hypothesis of the meyer overton theory suggest?
That lipid soluble portion of the LA molecule expand the cell membrane & interferes with rapid Na conductance
LAs _____the influx of _____ by altering the ______ of membrane
LAs INHIBIT the influx of SODIUM by altering the PERMEABILITY of membrane
LAs bind to specific ____ within the ____ channel to _____ the threshold potential
LAs bind to specific SITES within the SODIUM channel to INCREASE the threshold potential
LAs provide a _____blockade that is ______ when molecules ______ from the ______ site
LAs provide a REVERSIBLE blockade that is TERMINATED when molecules DIFFUSE from the NERVE site
