Local Anaesthetics Flashcards
Give named examples of local anaesthetics
Amide-containing
- Lidocaine
- Prilocaine
- Bupivacaine / Levobupicaine
- Articaine
Ester-containing
- Tetracaine
- Chloroprocaine
- Benzocaine
Lidocaine
Medium acting
Rapid onset
[amide containing]
Prilocaine
Medium acting
No vasodilation
Used in epidurals
[amide containing]
Bupivacaine
Long-acting
Slow onset
[amide containing]
Articaine
Short-acting
Rapid onset
[amide containing]
Mepivacaine
Dental use
[amide containing]
Tetracaine
Long-acting
Very slow onset
[ester containing]
Tetracaine feature
Poor solubility
More hydrophobic and so stays around site for longer than procaine.
Longer duration of action
Chloroprocaine
Medium acting
[ester containing]
Benzocaine
Atypical mechanism of action
e.g. Throat lozenges
[ester containing]
Eryrthroxylon coca
Cocaine
Local anaesthetic
Explain the clinical uses of local anaesthetics
When loss of consciousness is neither necessary or desirable.
As an adjunct to surgery to avoid high-dose general anaesthetics.
Post-operative analgesia
For major surgery, with sedation.
Basic structure of local anaesthetics
They all have :
- Aromatic region
- an ester OR amide bond
- basic amine side-chain
Feature of local anaesthetics
They are lipophilic
Why are amides-containing anaesthetics more commonly used in anaesthetics than ester-containing anaesthetics?
Esters are more unstable and can be metabolised into compounds associated with allergic reactions.
Amides are more commonly used as they are less likely to be metabolised.
Mechanisms of action of local anaesthetics
Local anaesthetics stop the spread of pain and work by reversibly blocking voltage gated sodium channels.
- stabilises excitable membranes
- prevents membranes form being depolarised (excited)
Structure of a peripheral nerve
Consists of fibres of different function, diameter and insulation.
All can be blocked by Local Anaesthetics, but at different rates.
Order of Loss when using a LA
Pain
Temperature
Proprioception
Skeletal muscle tone
Explain the factors that affect the probability that a local anaesthetic will block an impulse.
- Diameter of fibre
- Myelination status
- Length of nerve exposed to drug
- Length of time exposed to drug
- Concentration of drug
Local anaesthetics have different fibre types and sensitivity to local anaesthetics.
Diameter of fibre effect from LA
Smaller nerve fibres blocked more easily than large fibres.
Myelination status effect from LA
Myelinated fibres are blocked more easily than unmyleinated.
Describe voltage gated sodium channels
3 stages
- Resting
- Open
- Inactivated
Where are sodium gated voltage channels found ?
They are not exclusive to pain fibres, they are also found anywhere that has excitable tissue:
- Sensory, motor and autonomic fibres
- Skeletal and cardiac muscle
What pH do local anaesthetics have ?
Almost all local anaesthetics are weak bases.
They can exist as neutral or pronated.
They are pH dependent on the degree of ionisation.
Recognise features of weak base structure
They can exist as neutral or pronated.
They are pH dependent on the degree of ionisation.
Weak base interaction with pH
They need to enter the cell to block the voltage gated sodium channels.
Local anaesthetics block when ionised via an intracellular binding site, but can’t pass through membrane when ionised.
What is pKa ?
The pKa is the pH at which 50% of the drug is ionised.
Describe the pKa of local anaesthetics
Most local anaesthetics have pKa values between 8 and 9.
BH+ <=> B + H+
Where :
BH+ = The ionised form to block the channel
B = Weak base, i.e. the local anaesthetic
H+ = Ionising agent
Henderson - Hasselbalch equation
pKa - pH = log10 [BH+]/[B]
Explain why different local anaesthetics have varying time courses of actions
Many local anaesthetics show use-dependence.
Duration of action dictated by rate of removal.
Describe the use-dependence of local anaesthetics
They binds to open or inactive channels
Related to the frequency of neuronal firing
- faster onset in faster firing neurones
Explain how the duration of action of a local anaesthetic is dictated by the rate of removal
Factors such as the following can affect the rate of removal:
Blood flow
Action of plasma esterase (ester-linked LA’s only)
Hydrophobicity of drug
What do most local anaesthetics cause ?
Vasodilation resulting in :
- Increased blood flow to the area
- this increases they chances of destruction
How can the varying time courses of action be modified ?
To increase the duration of action :
Cocaine and Prilocaine both cause vasoconstriction.
Also ADH and Adrenaline.
Note :
Decreased blood flow to the area means a decreased rate of removal.
Describe the function of adrenaline
Vasoconstriction (adrenaline)
Can increase the duration of local anaesthetics by around 2x.
Can also decrease bleeding during surgery
Although risk of ischaemic damage at extremities.
Different routes of administration of local anaesthetics
Surface
Infiltration
Nerve block
Intravenous regional
Extradural (epidural)
Subarachnoid
Surface administration examples
Nose, Mouth, Bronchial tree, Cornea, Urinary tract
Infiltration administration examples
Injection into tissues to reach nerve branches / terminals.
Nerve block administration examples
Small or large regional block by injection around the nerve.
Intravenous regional administration examples
Double cuff method to contain local anaesthetics to a limb.
Extradural (epidural) administration examples
Used in thoracic, lumbar and sacral regions.
Subarachnoid (intrathecal) administration examples
Drug is injected into the subarachnoid space. (CSF)
EMLA
Eutectic Mixture of Local Anaesthetics
Topical numbing cream
Used for dermal anaesthesia
EMLA composition
Lignocaine and Prilocaine
Features of EMLA
Melting point of mixture is lower than that of the individual chemicals.
Therefore, higher concentration of both can be used.
More chance more will get across the skin.
Predict the dangers and side-effects of local anaesthetics
Local anaesthetics are not specific to nerves, hence side effects.
Unwanted effects due to entry into systemic circulation.
Effects in the Cardiovascular system as well as the CNS
Although, side effects have been sed therapeutically (e.g. epilepsy and some heart conditions)
Side effects on the Cardiovascular system
Dysrhythmias
Sudden fall in blood pressure, due to effects on the heart and vasculature.
Side effects on the CNS
Inhibits muscle tissue
Restlessness
Tremors
Convulsions
Respiratory centre depression
Death
