Interruption of neurotransmission in dental treatments

What sensation does the periphery specialised sensory receptors detect

normal sensation:

- pressure 

- vibration 

- touch 

That does 2 point discrimination mean

- your ability to tell whether your cream touched in 1 or 2 spots 

- the specialised periphery sensory neurons have this 

How are sensation detected and responded 

1.  sensory receptors detect the sensation

2.  They activate sensory neurones 

3. The neurones enter the spinal cord 

4. There’s a synapse between first and second neurone in the dorsal horn 

5.  Second order neurones take the info from thalamus to somatosensory cortex (in brain) 

What are the signs of the periphery tissue becoming inflamed after damage and  the function 

redness 

Swelling 

Heat

Pain 

Loss of function 

- this allows the tissue to heal so no more damage 

What are the 3 steps for your brain to send signals to make a muscle contraction 

1. The upper motor neurones that cell varies are Duran in the motor cortex send signal to the lower motor neurones 

2. They synapse at the ventral horn of the spinal chord 

3.  Lower motor neurones release ACH (acetylcholine) which activates the mainly fibres to contract  

How are side effects caused by local anaesthetics 

The voltage gated Na+ channels are found in many tissues.

The side effects are minimised any applying it to a local area 

What is the concentration of local anaesthetic needed to block an action potential in a sensory nerve 

0.1 — 1mM

What is the lethal systemic plasma concentration of Local Anaesthetics

40 — 60 micro meters

( this is the amount of LA in the whole body blood circulation that is lethal ) 

Are local anaesthetics strong or weak bases

Weak bases 

What are local anaesthetic made up of ( chemistry )

Aromatic head - basic side chain 

Likes by an animated or ester bond 

At physiological pH ( 7.4 ) do the LA excise as ionised, non ionised or both 

Both ( it becomes provided by releasing a H+)

which from uncharged and charged molecules can pass through the cell membrane

uncharged can 
charged cant 

describe what in the membrane blocks the local anaesthetic from beinfg able to enter the membrane  

the extracelluar side pore of the membrane is too narrow to allow LA to enter

the intracellular side pore of the membrane has a gate that can be activated or deactivated 

what is the ionised and non ionised form of LA ( the equation)

LA (the basic non ionsied version)+ H+ -> LAH+ (the acidic ionised version) 

what is the hydrophobic pathways of the LA to enter a membrane

the basic non ionised LA can directly diffuse into the mmebrane through the pore

what does decreasing the PH do to the degree of ionisation of LA

it increases 

what is the hydrophilic pathway for the LA to enter the membrane 

once the non ionised LA is through the first pore it can becoem ionsed becoming LAH+ then only if the gates are open there is an equilibrium betweej ionised and non ionised so th eionised can pass the gate

if the chanle is closed whic pathway can occur

hydrophobic 

if the channel is open whic pathway/s can occur

hydrophobic and hydrophilic 

explain what "use dependence" means with the hydrophilic pathway 

the gates in the intermolecular side of the cell membrane are Na+ gates. the more action potentials the more the sodium ion channels oopen so the more LA enters and can block nerve signalling

which pathway is use dependant  

hydrophilic not hydrophobic 

how does low PH effect LA effect

it decreases it as more are ionised so less hydrophic pathways so less moveemnt of LA in the cell

why do inflamed tissues have less effective LA 

tehy have a low ph so more ionsied LA less move into the cell 

are smaller or larger diameter nerve fivre more susceptible to LA 

smaller diametr nerve fibres `s theres less sodium ion channels to block( like Aδ- and C-fibres )

what is supraperiosteal infiltration used to anaesthetize

an individual tooth or group of teeth

what location is the anaesthetic injected 

adjacent to the lateral (buccal) alveolar bone supporitng the tooth 

for which type of anesthesia is it injected into the tissues aorund the sensory nerve terminals and branches

infiltration 

for which type of anesthesia is it injected aroud the nerve trunks 

nerve block anaesthesia

what deos duration of action mean

 the rate of loss of local anaesthetic from the site of adminstration    

what are the 2 ways the local anesthic can be removed form thier site of action 

1. being briken down 

2. entering the general blood circulation where it becomes dilutes

are local anaesthetics inherntly toxic

yes

why do side effects occur with LA 

if they are in high cincentrations in the gneneral circulations

what are some side effects 

1. tinitus 

2. slurred speech

3. metalic taste

4. trmore 

5. vasodialiation - which leads to drop in blood pressure 

6. cardiac arrest 

7. bradychardia 

8. allergy

when having both LA and adrenaline/noradrenaline 

tachycardia whic is due to the catecholamine entering gernal circulation that then speeds up the cardiac pacemaker 

what is botulism and what are the sympotoms of botulism 

• when a toxin blocks the release of acetylcholine at neuromuscular junctions 

• double vision (diplopia)

• blurred vision 

• drooping eyelids 

• surred speech 

• difficulty swallowig

• dry mouth 

• paralysis of breathing muscles

• flacid paralysis (muscle weakness)

whats the link between botulism and LA 

botulism is caused by blocked nerves

what are the steps in a neuromuscular junction to release a neurortransmitter (overview)

1. AP reaches the presynaptic terminal ( bouton)

2. this depolarises the presyanptic membrane 

3. the voltage gated Ca2+ channels open and ca2+ moves in 

4.  increased calcium ion conc causes vesicile fusion with the SNARE complex 

5. fusion releases neurotransmitters

what is the snare complex needed for ( simple)

make a vesicle fuse with the cell membrane so it can release neurotransmitters 

what are the 4 proteins used in the SNARE complex

synaptobrevin  -  vesicle protein 
synataxin  -    membrane protein
SNAP-25  -   membrane protein
synaptotagmin  - calcium sensor

explain what  happens in the SNARE complex

used to release neurotransmitters

1. synaptobrevin binds to syntaxin and SNAP-25 to bring the vesicle close to the membrane

2. synaptotagmin is actiavted when theres a rise in calcioum concentration 

3. this triggers the SNARE complex making the vesicle fuse 

4. once the vesicle fuses the ACh can be released

what bacterium is Botulinum Toxin produced by

clostrdium botulinum 

what causes botulism

botulinum toxin

what does botulinum toxin do and whats the consequences 

• it blocks the SNARE complex so the vesicle cant fuse with the membrane 

• no ACh reelased = no muscle contraction =  flaccid paralysis

how many differnt types of botulinum toxins are 

6 
ABCDEF

which type of Botulinum toxin attacks SNAP-25 and what deos this cause

A    E

it cuts the SNAP-25 protein so the vesicel cant fuse with the membrane 

what type of Botulinum toxin effects synaptobrevin 

B D F 

they cut synaptobrevin stoping vesicle from fusing 

what type of botulinum toxin effects syntaxin 

C

it cuts syntaxin which makes rhe vesicle not be able to fuse with the membrane 

what are 5 uses of Botulinum Toxin (botox)

1. cosmetic uses

2. sweatign/salivary disorders

3. headaches

4. focal dystonia- when a muscle contracts involunaterly e.g cervical dystonia (neck muscle tightened)

5. spasticity - when your muscel is too stiff/tight usually after a stroke, cerebral palsy or multiple sclerosis (MS)

when is botulinum toxin (BTX) used in dentistry 

to treat
- tempromandibular joint disprder (TMJ) e.g-

• bruxism (clenching of teeth) 

• mandibular spasm 

- chronic sialorrhea (drooling) 

- facial aesthetics

how do dentist prevent toxicity when using botulinum toxin

- using low doses ( 100 units`)
- injecting locally 

what are side effects of using botulinum toxin in dentistry

• muscle weakness 

• vision problems 

• breathing problems

• trouble speaking/swallowing 

• loss of bladder controll

What receptors detect tissue damage? 

Nociceptors

What do local anaesthetics block?

Voltage gated Na+ channels in the sensory neurones that are involved in pain transmission 

They stop action potential

Describe the structure of a local anaesthetic. 

An aromatic head joined to a basic group by an amide or ester bond. 

Why are local anaesthetics with an ester bond shorter lasting? 

They are broken down by esterase enzymes in tissue or plasma

What is the pKa of a local anaesthetic usually around? 

8.00 ( weak base)

Why does a low pH affect the efficacy of an anaesthetic? 

More of the anaesthetic is availible in its charged form, and therefore it is not able to diffuse across a lipid membrane as it is hydrophilic. 

What does the hydrophilic pathway of movement of local anaesthetics involve? 

The uncharged local anaesthetic enters the cell via the hydrophobic pathway, then establishes a new equilibrium between the charged and uncharged molecule. The charged molecule can then enter the channel if the activation gates are open. 

What is the name of the technique used for local anaesthesia for a single tooth or small group? 

Supraperiosteal infiltration

What is the name of local anaesthesia that blocks a wider area than infiltration anaesthesia? 

Nerve-block anaesthesia

Where are drugs with ester bonds metabolised ( broken down) ? What about those with amide bonds? 

Ester - tissues and blood
Amide - liver

How can the duration of action of a local anaesthetic increase? 

Co-administer with a vasoconstrictor like adrenalineto delay the drug entering general circulation. 

What are the clinical uses of botox? 

Paralyse muscle, decrease secreations, suppress pain. 

What is botox used to treat in dentistry? 

TMJ disorders & chronic sialorrhia (excessive saliva)

How does BoTN/A1 work? 

It binds to and degrades SNAP-25 (part of SNARE proteins) so exocytosis cannot occur. 

Why does BoNT/A1 last for a long time (3-4 months)? 

It is trapped in the nerve terminal, it is very stable, and only a small fraction of SNAP-25 needs to be disrupted to suppress neurotransmitter release.