LA Flashcards
Define LA
Loss of sensation ins specific area of the body by depression of excitation in nerve endings or an inhibitor of the conduction process in peripheral nerves
List some qualities of the ideal LA (12)
Specific and reversible Non-irritant produces no permeant damage no systemic toxicity high therapeutic ratio active topically and by injection Rapid onset suitable duration of action Chemically stable and sterilisable Combine with other agents Non-allergic Non-additive
Of the 12 qualities of an ideal LA, what is the hardest to achieve?
Specificity
What is the consequence of the lack of specificity of LAs?
It will affect transmission of any excitable tissue they come into contact with e.g. CNS, cardiac, motor system
List 4 uses of LA in dentistry?
Operative pain management
Post-operative pain management
Diagnosis
Haemostasis
How can LA be used in diagnosis?
If tooth ache cannot be localised can give infiltrations adjacent to each tooth and see which one gets rid of the pain
Why is LA not commonly used for diagnosis of tooth ache anymore?
Pulp sensibility testing is available (EPT, ethyl chloride)
How is LA used for haemostasis?
Uses the adrenaline within the LA to cause vasoconstriction of the BV in that area - reduce bleeding
Name the 2 theories of LA action?
Membrane expasnion therory
Specific receptor theory
Describe generally how LA works?
Blocks/inhibits sensory signals from tooth to brain
Describe an action potential
Resting potential - the inside of the cell is negative compared to the outside fo the cell. 3K+ out for 1Na+ in
Depolarisation - voltage gated sodium ion channels open due to electronic stimulus - Na+ move into the cell and the inside of the cell becomes positive compared to the outside of the cell. If the membrane potential reaches the threshold potential the maximum response will be elicited.
Repolarisation - once the action potential has occurred voltage gated Na+ channels close. the positive charge in the cell causes voltage gated K+ channel to open, K+ move down electrochemical gradient out of the cell. Membrane returns to resting potential. depolarisation tends to overshoot - making the inside of the cell more negative = hyperpolarisation = refractory period where another AP cannot occur
What part of an action potential is targeted by LA?
Voltage gated NA+ channels
Name the gates within voltage gated Na+ channels?
M gate and H gate
Make and halt
Describe the membrane potential and positioning of the voltage gated Na+ channel at rest
Inside of the cell -ve compared to outside
M gate closed, H gate open
How does the voltage gated Na+ channel change during depolarisation?
M gate opens, Na+ flood in - inside of cell = +ve
How does voltage gated Na+ channel change during repolarisation?
H gate closes
This stops Na+ moving into the cell
The inside fo the cell is +ve - this opens voltage gated K+ channels and K+ moves out of the cell making the inside -ve
Describe membrane expansion theory
La enters the nerve cell membrane, this causes the membrane to expand, this blocks the Na+ channels and stops Na+ entering the cells, this stops depolarisation = no AP
Describe specific receptor theory
Specific receipt int he H gate of the VG Na+ channel.
LA bind to this receptor
Stops the H gate opening - keeps Na+ channel closed - hold the cell in the refractory period - no AP can be fired
In what subunit does NA pass through the VG Na+ channel?
alpha
Describe the position of the M gate on the VG Na+ channel
Alpha subunit split into 4 domains, each contains 6 subunits
M gate is the 4th subunit
Describe the position of the H gate on the VG Na+ channel
Link of protein between domain 3 and 4 within the alpha subunit
Name the 3 parts fo an LA molecule
Aromatic group, intermediate chain, substituted amino terminal
Function of the aromatic group on LA?
Makes it lipophilic
Function of substituted amino terminal on LA?
Makes it hydrophilic