Local anaesthetics Flashcards
What are local anaesthetics?
Reversibly block nerve conduction when applied to a restricted area of the body to enable a procedure to take place without loss of consciousness.
Drugs end in -caine.
How do local anaesthetics work?
Target Voltage gated Na channels (VGNaC) on nociceptors to stop the electrical signals from the periphery going to the brain.
This stops us feeling pain.
What is the chemical nature of local anaesthetics?
Aromatic ring - Linkage - basic amine group.
The linkage can be an amide or ester, and will determine the rate of metabolism and half-life.
See picture
What is the importance of the chemical nature of local anaesthetics?
Aromatic ring - lipid solubility - can cross biological membranes.
Amine group - can add H+ to make the molecule ionised.
Ionisation state is important for the drug functioning.
What are the characteristics of some local anaesthetics?
Procaine, ester linkage, short duration (minutes).
Lidocaine and prilocaine, amide linkage, medium duration (few hours).
Bupivacaine, amide linkage, long duration (6 hours).
Why are local anaesthetics weak bases?
The ionisation state is determined by pH.
At normal pH, there are more molecules in the ionised state than the unionised state.
An unhealthy body would impact the degree of ionisation.
Unionised and ionised proportions depend on the pH.
What is the equilibrium of local anaesthetics?
Drug + H2O <—> Drug+ + OH-.
Forwards direction is increased acidity.
Reverse direction is increased alkalinity.
e.g. increasing alkalinity means a higher proportion of unionised drug.
What are nociceptive neurones at rest?
When there is no stimulus, the VGNaC are shut.
The Na+ are outside of the neurone.
What happens to nociceptive neurones when a stimulus is applied?
Action potentials are generated in sensory neurones which transmit action potential up axon.
Depolarisation of membrane causes VGNaC to open so Na flows from outside to inside of compartment.
What happens to a nociceptive neurone when local anaesthetic is injected?
Local anaesthetic given in solution, some equilibrium between ionised and unionised form.
The anaesthetic molecules diffuse across the membrane and into the axon.
It must be lipid-soluble to cross the phospholipid membrane, and so must be unionised.
In the cell, more ionisation, the ionised molecule enters and blocks the VGNaC.
What is a use-dependent block?
The ionised anaesthetic molecules are blocking an open VGNaC.
The more active the nociceptive neurone, the more open channels (VGNaC), and the more effective block.
How does tissue pH affect the effectiveness of local anaesthetic?
In inflammation and infection, bacteria produces acidic products and causes acidic conditions.
Local anaesthetic injected into infected area would cause more ionisation at increased acidity.
More ionisation so less can diffuse across the membrane, so there is poor anaesthesia.
How does the sensitivity of neurones change?
Axon diameter:
Alpha motor fibres have the largest diameter, and are well myelinated.
A delta and C fibres have the smallest diameter, and no to little myelination.
Delta and C fibres carry the nociceptor messages, and are highly sensitive to local anaesthetic.
But almost impossible to only selectively block the small fibres - affect motor fibres as well.
What are the routes of administration of local anaesthetic?
Topical - applied to gums, skin, eyeballs as lipid soluble.
Infiltration - injection into extracellular space.
Nerve block - also extracellular space.
Epidural - spine to anaesthetise large area of body.
Spinal
Regional
What are non-specific side effects of local anaesthetic?
Hypersensitivity reactions due to the solution that the local anaesthetic is in.
