Principles of local anaesthesia Flashcards
Define “local anaesthetic”
Drug which reversibly blocks neuronal conduction when applied locally
Describe the chemical structure of local anaesthetics
Aromatic region
Tertiary amine side chain
2 regions either bound by ester or amide bond
Give examples of a local anaesthetic drug for both ester- and amide-bound aromatic and amide groups in their structures
Ester bond: cocaine
Amide bond: lidocaine
What is the trade name of lidocaine?
Xylocaine
Give one example of a local anaesthetic that does not share the normal structure of local anaesthetics and describe how it differs
Benzocaine
No tertiary amine side chain
What is the main use of benzocaine and why?
Surface local anaesthetic
Pretty weak
Describe the pH of local anaesthetic drugs
Weakly basic
pKa 8-9
What barriers must the local anaesthetic drug pass through to affect a neuron, and in what state must this occur?
Connective tissue sheath and axon membrane
Unionised
Recall the 2 possible MOAs of local anaesthetics and which of these is the main one
Hydrophillic (main one) and hydrophobic
Recall the hydrophillic MOA of local anaesthetics
- Enters neuron
- Forms cation
- Binds WITHIN the sodium channels
- Stereochemically inhibits Na+ pasage
Why does the hydrophillic MOA of local anaesthetics give rise to use-dependency?
Bind within the channels so the channel has to be open in order for the drug to bind
Recall the hydrophobic MOA of local anaesthetics
- Enters neuron
- Drop straight into the ion channel due to high lipophilicity, without first ionising
- Become ionised within the channel, blocking it
Describe the effect of local anaesthetics on neuronal membranes
- Prevents AP generation
- Influences channel-gating
- DO NOT influence resting potential
How do local anaesthetics influence channel gating in neuronal membranes?
They bind preferentially to Na+ channels in the inactive state, holding them in this configuration for longer
Which elements of local anaesthetic selectivity make them show preference for nociceptive fibres?
Selective for small diameter fibres - like A-delta and C fibres
Selective for non-myelinated fibres - like C fibres
Why is it more difficult to anaesthetise infected tissue?
Infected tissue tends to be acidic, which pushed local anaesthetics towards their ionised state
Recall the 6 possible routes of local anaesthetic administration
SIRENS Surface Infiltration Regional IV Epidural Nerve-block Spinal
To where is surface anaesthesia applied? Give examples
Mucosae
Mouth
Eyes
Bronchial tree
What is the main risk associated with surface anaesthesia?
High concentrations can cause systemic toxicity
How is infiltration anaesthesia applied?
Injected straight into tissue you want to anaesthetise
What is the main use of infiltration anaesthesia?
Minor surgery
What is co-administered with infiltration anaesthesia and why?
Adrenaline to keep anaesthetic at site of injection
In which routes of administration should adrenaline be co-administered?
Infiltration, nerve-block
Describe the method for IV regional administration of local anaesthesia
- Add pressure cuff
- Insert IV line distally
- Leave cuff for 20 mins to ensure administration does not become systemic
- Remove cuff when LA has diffused into tissues
What is the main indication for administering local anaesthetic using the IV regional route?
Limb surgery
Which route of administration is used in dental surgery?
Nerve-block
Where do you inject in nerve-block anaesthesia?
Close to nerve trunks eg dental trunks
Recall an advantage and a disadvantage of nerve-block anaesthesia
Advantage: can use low doses
Disadvantage: Slow onset (mins)
Where is spinal anaesthesia injected?
Intrathecally at L34 - into the subarachnoid space
What are the side effects associated with spinal anaesthesia?
Sudden hypotension
Prolonged headache
What is the cause of hypotension in spinal anaesthesia?
Sensitive pre-ganglionic SNS neurons with a small diameter are triggered to up SNS outflow and thus vasodilate
How can spinal anaesthesia be localised to one place?
Mix with glucose to increase its specific gravity
Where is epidural anaesthesia administered
Outside all of the layers of mater
Recall 2 advantages and 2 disadvantages of epidural anaesthesia compared to spinal anaesthesia
Advantages: Less likely to... 1) diffuse up spinal cord 2) Affect BP Disadvantages: 1) Higher doses 2) Slower onset
Recall the main type of reaction involved in lidocaine metabolism
Hepatic N-dealkylation
Compare the plasma half life of cocaine and lidocaine
Cocaine: 1 hour
Lidocaine: 2 hours
Recall and EXPLAIN the side effects of lidocaine
On the CNS:
Restlessness, confusion, tremor
Explanation: GABA neurons are more sensitive to the anaesthetic than CNS neurons
On the CVS: myocardial depression, vaodilation, hypotension
Explanation: Na+ channel blockade
Compare the site of metabolism of lidocaine and cocaine
Cocaine = plasma and liver Lidocaine = liver only
Recall and EXPLAIN the side effects of cocaine
On the CNS: euphoria and excitation
On the CVS: Opposite to lidocaine
increased CO, vasoconstriction, hypertension
Explanation: actions on the SNS
