Neurophysiology of LA Flashcards
How do neurons compare to other cells?
· The neuron is similar to other cells in that it has a cell membrane a nucleus, and other organelles
· It differs in that it has specialised part like the dendrites and axon, and that it can generate action potentials
· In dentistry, we usually deal more with sensory neurons
What are the types of nerves?
What are the pain fibres of the teeth
· Myelinated: Myelin sheath (composed of lipids and proteins). Nodes of Ranvier = fast conduction. Very sensitive, a very small Na+ influx will excite the neuron. Sufficient LA needed to block ion channels
· Unmyelinated: small diameter, nerve impulses are slow
· Pain fibres of the teeth: A- delta and C fibres
Describe A delta fibres
Myelinated
- Responsible for dentinal pain
- Sharp pain
- Cavity preps, air drying stimulates it
- Dentinal sensitivity
Describe C fibres
Unmyelinated
- Responsible for pulpal pain
- Dull pain
- Heat stimulates it
- Pulpal inflammation
Briefly describe the generation of an action potential
· Neurons/ nerves at rest is -70 m. Obv, it is more negative inside the neuron than outside. This is its “polarised” state
· Neurone has high concentration of K+ ions inside and low Na+
· To generate action potential, the membrane needs to depolarise to 40. mV
· Hyperpolarisation: refractory period during which action potentials cannot fire until resting potential has been regained
· Repolarisation: occurs via Na+/ K+ pump being activated; sodium pumped out and potassium pumped in
Name the parts of LA
· Aromatic ring
· Intermediate chain
· Amino group
Describe the aromatic ring of LA
· Lipophilic
· Un-ionised
· Can cross membrane
· AKA as base form
Describe the intermediate chain of LA
Differentiates the types of anaesthetic as either ester or amide. It is important to consider for metabolism.
Describe the amino group of LA
· Hydrophilic
· Ionised
· AKA as cation form
· Largely responsible for Na+ blockade as this part of it enters the inner-pore of the sodium channel and docks with it
Describe disassociation and pKa in terms of LA
· Disassociation is when an acid separates into it’s separate components. For example, AH. –> A- + H+
· pKa measures the strength of an acid (in -Log). A strong acid = an acid which mostly ends up disassociating
· Remember that LA molecule has an ionised part and unionised part
· The lower the pKa the stronger the acid, and the faster acting the LA
· Body pH is around 7. The closer the pKa is to the body pH, the better/faster acting it is
Briefly describe what happens when you inject LA
· Deposition of solution in tissue
· LA molecules achieve equilibrium (between cation form RNH+ and base form RN, H+)
· Diffusion of solution to reach nerve fibres
· Lipid soluble form (base) enters nerve cell membrane
· Dissociated ionised form (cation) inside the cell binds to the sodium channel, thus preventing sodium ions entering channel and preventing depolarisation
List the order of things LA works on in terms of blocking order
· Pain · Cold · Heat · Touch · Pressure
What are the three clinical . effects that need to be considered when thinking about LA
Time of onset of action
Duration
Potency
Describe the “time of onset of action” regarding LA
- Higher pKa: decrease amount of RN/ base available to pass through cell membrane
- Lower pKa: increased amount of RN/ base available to cross membrane
- The closer the pKa of the drug is to normal pH, the faster onset of action
What affects onset?
• Distance of diffusion to nerve fibre
• Anatomical barriers
• Adequate concentration and volume of LA
Changes in tissue pH can alter dissociation of LA
• Inflamed tissue has lower pH; more LA will exist in cationic form. This reduces cell membrane permeation from the base = doesn’t work
Inject away from infection and inflammation
Describe the “duration” regarding LA
• Duration of anaesthesia (and depth) primarily influenced by volume and concentration
• Need sufficient LA molecules to dock with the inner pore of the sodium channel
• Protein binding: In general, agents with greater protein binding have a greater attraction for receptor sites and remain within sodium channels for a longer period of time
• Amount of local anaesthetic used: The larger the amount, the longer it will take for it to be removed by the bloodstream, and for it to be metabolised
• Intravascular injection: Short duration or ineffective anaesthesia
Rate of metabolism in the tissues
