Local Anaesthetics Flashcards
What is a local anaesthetic?
a local, reversible loss of sensation without loss of consciousness
what is LA mechanism of action
By blocking nerve conduction:
Small diameter nerve fibres are blocked more readily than large fibres.
Nocicptive (Pain fibres) impulses are carried by Aδ and C fibres (small)
The LA affects these small fibres at lower concentrations than larger fibres.
How do LA block nerve conduction
LA block Na+ channels form opening
LA enchance Na+ inactivation
What is the site of LA binding on the Na channel
The Na channel has 4 subunits each have 6 transmembrane domains
Tyrosine and Phenylalanine → interacts with LA hydrophobic γ
Process of LA interaction with phenylalanine
Drug binds to protein and alters the shape of phenylalanine via the benzyl ring. LA gives phenylalanine a positive charge Result: 1. Blockage of pore 2. Enhance inactivation
Drugs that have Local anaesthetic properties at high concentrations
- Morphine
2. Propranolol
What two forms do local anesthetics come in
charged
uncharged
What is the uncharged LA form important for
- Penetration of neural sheath (rate of onset of action).
2. Crossing the plasma membrane (access to site of action).
What is the charged LA form important for
Interacting with the Na+ channel.
What determines the percrntage of LA molecules that are ionised?
pH
pKa of the local anaesthetic (most are weak bases with a pKa in the range of 8-9)
If the pKa for Local anaesthetics is 8-9 at physiological pH of 7.4 what oercentage of LA molecules are ionised?
[LA] = 20% [LAH+] = 80%
What happens to the percentage of ionised LA as the pH drops in inflammed tissue where the pH is more acidic
The amount of ionised LA increases
Give 2 examples of atypical local anaesthetics
Benzocaine
QX-314
What is the mechanism of action of Benzocaine
Ester group, no amine group therefore unprotected (0%) ionised) works via hydrophobic pathway only
no use dependance i.e. the more often a neuron fires the greater the degree of block
What is the mechanism of action of QX-314
Permanently charged – 100% ionised.
Blocks Na channels only if introduced into cells (experimental tool).
• Cannot cross membranes.
• No therapeutic use
Give examples of LA
Mepivacaine Bupivacaine Prilocaine Tetracaine Articaine
What is the onset and duration of Mepivacaine
Rapid onset
Medium duration
Does Mepivacaine need to be administrated with a vasoconstrictor?
No as Less vasodilation
What is the onset and duration of Bupivacaine
Slow onset
Long duration
Why is Bupivacaine widley used?
less cardiotoxicity
What is the onset and duration of Prilocaine
Medium onset
Medium duration
What is the onset and duration of Tetracaine
Slow onset
Medium duration
What is the onset and duration of Articaine
Rapid onset. Short duration
When is Articaine used
dentistry
What can be a side effect of Articaine
In a small proportion of patients it can induce parathesia (burning, tingling and sharp shooting pains)
Numbness that outlasts the presence of the drug in the body.
What is used for surface anaesthesia?
Lidocaine: spray for nose/ mouth/ upper respiratory
Lidocaine, Tetracaine: solution for cornea
Which LAs can be used for infiltration anaesthesia
Most LAs
When is infiltration anaesthesia used
For minor surgery
With adrenalina/ vasopressin which are vasoconsrictors so prolong the action of the LA
Which LAs are used for intravenous regional anaesthesia
Lidocaine
Prilocaine
When is intravenous regional anaesthesia used?
Limb surgery
Which LAs are used for intravenous administration
lidocaine
When is intravenous administration used
neuropathic pain
Which LAs are used for nerve-block anaesthesia
Most LAs
When are nerve-block anaesthesias used
Dentistry
surgery
Which LAs are used for spinal anaesthesia
Lidocaine
Tetracaine
When are spinal anaesthesia used
surgery of abdomen, pelvis or leg
Which LAs are used for Epidural anaesthesia
Bupivacaine
Lidocaine
Adverse CNS effects of LAs if high plasma concentration (accidental injection into artery or vein)
Confusion
Convulsions
Respiratory depression
Adverse CVS effects of LAs if high palsma concentration (accidental injection into artery or vein)
Decreased blood pressure due to decreased heart contractility (block of Na channels in cardiac muscle)
