L2- Neurophysiology Flashcards
Local Anesthesia Definition
loss of sensation in a circumscribed area of the body caused by a depression of excitation or conduction process in peripheral nerves
Six methods of inducing local anesthesia
- mechanical trauma
- low temperature
- anoxia
- chemical irritants
- neurolytic agents such as alcohol and phenol
- chemical agents such as local anesthetics
Desirable properties of LA in terms of effectiveness?
Effective regarldess of whether it is injected into the tissue or is applied locally to mucouos membranes
time of onset should be as short as possible
duration should be long enough to complete the procedure
non irritant
no permanent alteration of nerve structure
low systemic toxicity
Bennett’s other desirable properties of an ideal LA
- should have a potency sufficient to give complete anesthesia without the use of harmful concentrated solutions
- relatively free of allergic reactions
- it should be stable in solution and should readily undergo bio-transformation in the body
- should be sterile or capable of being sterile
Two types of basic neurons and parts
- sensory (affaretn)
- motor (efferent)
Parts
- dendritic zone
- axon
- cell body
cell body in a sensory neuron
located at a distance FROM the axon
it is NOT involved in the process of impulse transmission
its primary function is provide vital metabolic support for the entire neuron
motor neurons - basic
nerve cells that conduct impulses from the CNS to the periphery
cell body location of motor neuron
interposed between the axon and dendrites
difference in cell body of motor vs sensory neuron
MOTOR - cell body IS MAJOR COMPONENT OF THE IMPULSE TRANSMISSION SYSTEM and also provides metabolic support for the cell - located between the axon and dendrites
Sensory - location is at distance from the axon and it IS NOT INVOLVED IN TRANSMISSION OF IMPULSE and its major role is for metabolic process
resting state of neuron
slightly permeable to sodium ions (Na+)
freely permeable to potassium ions (K+)
freely permeable to chloride ions (Cl-)
why does K+ stay within the membrane at rest?
due to the negative charge of the nerve membrane
why does Cl- remain outside at rest?
due to the negative charge of membrane
at what point is the primary effect of LA on the nerve and how does it work / primary action
the effect occurs during the DEPOLARIZATION PHASE
- decreasing the rate of depolarization *
producing CONDUCTION BLOCKS - to decrease the permeability of the ion channels to sodium ions
*nondepolarizing nerve block
two main theories that are recognized on how local anesthetics works
membrane expansion and specific receptor
specific receptor theory is more widely held
membrane expansion theory
the LA molecules diffuse to hydrophobic regions of excitable membranes, producing a disturbance of the membrane structre, and thus preventing an increase in permeaility to sodium ions
- changes the membrane, and so sodium cannot go through
specific receptor theory - describe it and what happens to permeability
LA act by binding to specific receptors on the sodium channel
action is direct
either on the external or internal axoplasmic surface of the sodium channels
*once the LA gains access to the receptors, the permeability to sodium ions is decreased or eliminated, and nerve conduction is interrupted
most common/ accepted mechanism
where are the tertiary amine LA working?
within sodium channel
biotoxins work where?
at the outer surface of the sodium channel
- tetrodotoxin, saxitoxin
what works at the activation or inactivation gate?
scorpion venom
Class A
Definition and chemical substance
agents acting at receptor site on EXTERNAL surface of nerve membrane
Biotoxins - tetrodotoxins, saxitoxin
Class B
Definition and chemical substance
Agents acting at receptor site on INTERNAL surface of nerve membrane - closer to the cytoplasm
structure : quarternary ammonium analogs of lidocaine
scorpion venom
Class C
Definition and chemical substance
Agents acting by a receptor - independent physio-chemical mechanism
Benzocaine (may be one of the membrane receptor theory?)
Class D
Definition and chemical substance
ONES WE FOCUS ON MOST
Agents acting by combination of receptor and receptor independent mechanisms
Chemical substance - articaine, lidocaine, mepivacaine, prilocaine)
most clinically useful anesthetic agents
local anesthetics are classified as? where are each metabolized?
Amides = in the liver
Esters = in the blood - more likely to cause allergic reaction and not used as much clinically
dissociation of local anesthetics
and available as what?
available as SALTS - which allow them to be dissolved in sterile water for clinical use
in this solution it exists as one uncharged base RN and 2 positive charge molecules RNH+ called the cation
1 BASE - RN
2 CATION - RNH+
so RNH + goes to RN and H+
dissociation Constant pKA
pKa is a measure of a molecules affanity for hydrogen ions
when the pH of a solution has the same pKa as the local anesthetic, exactly half of the drug will exist in teh RNH+ and exactly half in the RN form
human physiologic pKA
- 4
- so if LA has pKa of 7.4 half will exist as base and half will exist as cation
mechanism of base and cation in the LA
Base- diffuse into the channel / nerve sheath and the cation will BIND AT RECEPTOR SITE will block it - so no depolarization
rate of onset of LA related to?
the pKa of the LA
- the pka determines the rate of onset
- closer the pka is to the ph the quicker the onset
- an LA with a lower pKa has a greater number of lipophilic FREE BASE MOLECULES to diffuse through the nerves sheath, but intracellular
if have decreased tissue pH
may not have adequate anesthetic in area
what determines the ease with which LA moves from site of administration in the axoplasm of the nerve cell?
pH of the extracellular fluid
*note the intracellular pH remains stable and independent of extracellular pH
adequate blockade of the nerve in inflammed or infected tissue?
harder to achieve because of the smaller number of molecules to be able to cross the nerve sheath
mantle bundles
these are located near the surface of the nerve, exposed to the highest concentrations
tend to innervate more proximal regions
MOLARS in an IANB - think closer to the nerve in proximal / distal
molars are first to get anesthetized and last to wear off
Core bundles
closer to the CENTER of the nerve
LONGER to onset, and lower concentration of LA
Tend to innervate more DISTAL points of nerve innervations - incisors, canines with an IANB
- takes longer to anesthetize but will wear off sooner than molars
quicker onset?
when the pka and ph are more similar
Factor - pKA
Action effected?
Description
Action Affected – onset
Description : Lower pKA more rapid onset of action - more RN molecules present to diffuse through nerve sheath; thus onset time is decreased
Factor - Lipid Solubility
Action effected?
Description
Related to the intrinsic potency
Action Affected: anesthetic potency * increased lipid solubility = increased potency
Description: with more lipid solubility - the drug is more potent
Factor - protein binding
Action effected?
Description
Action Affected: Duration
Description: Increased protein binding allows the anesthetic CATION (RNH+) to be more firmly attached to proteins located at receptor sites; thus the duration of action is increased
Factor - Nonnervous tissue diffusibility
Action effected?
Description
Action Affected: ONSET - if increased diffusibility there is a LOWER time of onset - able to diffuse into the tissue more
Description:
Factor - Vasodilator Activity
Action effected?
Description
Action Affected: Anesthetic potency and duration
Description: the greater the vasodialtor activity –> the increased blood flow to a region and this leads to more rapid REMOVAL of anesthetic molecules from the injection site –> thus the anesthetic potency and duration are decreased
recovery from LA Block
The first to come out of anesthesia are those in the center (core fibers/bundles) - incisors and canines will come out first
the mantle - molars will stay anesthetized longer
recurrence of immediate profound anesthesia
combination of residual local anesthetic in the nerve fiber and the newly deposited supply
difficulty re-achieving profound anesthesia
if readministration of anesthesia does not produce the effect this may be due to tachyphylaxis
Tachyphylaxis
‘an increased tolerance to a drug that is administered repeatedly’
this could be due to edema, localized hemorrhage, clot formation, transduation, hypernatremia, and decreased pH of the tissues
duration of the anesthesia - general factors effecting
Longer acting - more firmly bound in the nerve membrane (due to increased protein binding)
vascularity of the injection site
presence or absence of vaso-active substance
if recovery is slow?
LA is bound to the nerve membrane
perineurium
the SHEATH of connective tissue surrounding a fascile or bundle of nerve fibers within a nerve
* this is the main barrier to diffusion of local anesthetics into a nerve
Potassium, sodium, and chloride intracellular, extracellular concentrations
Potassium – K+ is higher inside (b/c membrane is negative so stays in)
Sodium - higher concentration on the outside
chloride - higher concentration on the outside
- most freely permeable to potassium and chloride
- but doesnt just go in and out because the charge is negative on the inside so keeping the chloride out and the potassium in at rest
what happens when the transmembrane potential decreases by 15 mV from resting potential?
RAPID depolarization occurs
how much nerve needs to be covered by anesthetic solution to ensure a thorough blockade?
at least a minimum of 8-10 mm of nerve
