16-11-21 - Local Anaesthetics Flashcards
Learning outcomes
- To give named examples of local anaesthetics and explain their clinical uses
- To recognise the features of the weak base structure and the interaction with pH, which account for the mechanisms of action of local anaesthetics
- To explain why different local anaesthetics will have varying time courses of action and how this can be modified
- To identify the different routes of administration of local anaesthetics
- To predict the dangers and side-effects of local anaesthetics
What are 4 situations local anaesthetics are used in?
1) When loss of consciousness is neither necessary or desirable (general anaesthetic)
2) As an adjunct (supplementary) to surgery to avoid high doses of general anaesthetics
3) Post-operative analgesia (pain relief medication)
4) For major surgery, with sedation
What is the basic structure of local anaesthetics?
How do these structures differ?
- Local anaesthetics have an aromatic region linked to a basic amine sidechain with either an ester or amide bond
- Esters are more unstable can be metabolised into compounds associated with allergic reactions
What type of local anaesthetic is most commonly used?
What are the 4 types of amid containing local anaesthetics?
What are the 3 ester-containing?
How do all of these vary?
- Amide containing local anaesthetics are more commonly used than ester containing, which are rarely used
- Amide containing local anaesthetics:
1) Lidocaine (lignocaine) – medium acting, rapid onset
2) Prilocaine – medium acting, no vasodilation
3) Bupivacaine/levobupivacaine – long acting, slow onset
4) Articaine – short acting, rapid onset
• Ester-containing local anaesthetics:
1) Tetracaine – long acting, very slow onset
2) Chloroprocaine – medium acting
3) Benzocaine – atypical mechanisms of action
• All of these local anaesthetics vary in time of onset and duration of action
What is the mechanism of action of local anaesthetics?
What does this cause?
What do peripheral nerves contain?
What is the order of sensation loss caused by local anaesthetics?
What are local anaesthetics not exclusive to?
- Local anaesthetics work by reversible binding voltage gated Na+ channels
- This prevents the membranes from being depolarised, and stabilises the membranes
- Peripheral nerves consist of fibres of different function, diameter, and insulation
• Order of loss in sensation caused by local anaesthetics:
1) Pain (pain neurons blocked earliest)
2) Temperature
3) Proprioception
4) Skeletal muscle tone
• Local anaesthetics are not exclusive to pain fibres and can work on any neuron conducting action potentials e.g skeletal and cardiac muscle
What are local anaesthetics?
What forms can they exist in?
Describe the mechanism by which local anaesthetics work?
What are the 2 pathways for local anaesthetics blocking voltage gated sodium channels?
What local anaesthetics use each pathway?
How do they each work?
- Almost all local anaesthetics are weak bases
- They can exist in a neutral or protonated state depending on the pH (protonated at low pH, neutral at high pH)
1) A non-ionised (neutral) version the local anaesthetic diffuses across the cell membrane (only neutral version can diffuse across, as charged molecules are repelled by charges on the membrane)
2) Once inside the cell, the local anaesthetic must become ionised (only ionised form can bind to sodium channels)
3) This ionised form of local anaesthetic can then bind intracellularly to a binding site on Na+ sodium channels, which blocks them, and prevents any Sodium moving into or out of the cell
- Hydrophilic pathway
- Local anaesthetics that use this pathway are known as use dependent local anaesthetics
- Use dependent local anaesthetics have an effective block that is related to the frequency at which these voltage gated sodium channels try to open
- They can only bind to the sodium channel when it is in a particular state, either closed or open during an impulse (one or the other depending on the LA)
- This means they have faster onset in faster firing neurons
- Hydrophobic pathway
- Local anaesthetics that use this pathway are no use-dependent
- These can bind to the pump when it is activated or resting
What is pKa value of a drug?
What is the pKa of most LAs?
Why is intracellular and extracellular pH and pKa important for the function of LAs?
What does the Henderson Hasselback equation allow us to calculate?
- The pKa value is the pH at which 50% of the substance dissociates into ions/ when 50% of the drug is ionised
- Most LAs have a pKa value of 50%
- Intracellular and extracellular pH and pKa is important as LAs can only diffuse across the membrane in their non-ionised state, and bind to sodium channels in the cell in their ionised state
- The Henderson Hasselback equation allows us to calculate the ratio of ionised to non-ionised LA in the intracellular and extracellular environment
- This also allows us to work out the speed of onset, and the effectiveness of the block we except to see from local anaesthetics inside the cell
What is duration of action dictated by?
What are 3 factors that affect this?
What do most local anaesthetics cause?
What is an exception to this?
What can be taken in conjunction with LAs to avoid this?
What are 2 positives of this? What is a negative?
- Duration of action is dictated by the rate of removal
- This can be affected by:
1) Blood flow
2) Action of plasma esterase’s (only degrades ester-linked LAs)
3) Hydrophobicity of the drug
- Most LAs cause vasoconstriction, which increases blood flow and the rate of removal
- An exception to this is cocaine and prilocaine, which cause vasoconstriction
- LAs can be taken in conjunction with adrenaline, which is a vasoconstrictor
- This decreases blood flow to the area, which decrease rate of removal, and can extend the duration of the LA by about 2xThis can also decrease the risk of bleeding during surgery
- This can also increase the risk of ischaemic damage at extremities
What are the6 different routes of administration of LAs?
1) Surface
• Nose, mouth, bronchial tree, cornea, urinary tract
2) Infiltration
• Injection into tissues to reach nerve branches/terminals
3) Nerve block
• Small or large regional block by injection around the nerve
4) Intravenous regional
• Double-cuff method to contain LA to a limb
5) Extradural aka epidural (particularly bupivacaine)
• Injection into back to stop feeling pain in part of the body
• Used in thoracic, lumbar, and sacral regions
6) Subarachnoid (intrathecal)
• Drug injected into the subarachnoid space (CSF)
What is Eutectic Mixture of Local Anaesthetics (EMLA) used for?
What does it consist of?
Why is it better than individual chemicals?
What does this increase chances of?
- EMLA is a gel used for dermal anaesthesia
- It is a mixture of lignocaine and prilocaine
- The melting point of the EMLA mixture is lower than that of the individual chemicals, so higher concentrations of both chemicals can be used
- This increases the chance more LA will cross the skin
What 2 side effects can LA have on the cardiovascular system?
What 5 side effects can LAs have on the CNS?
• Side effects on cardiovascular system:
1) Dysrhythmias – abnormality on heartbeat/rhythm
2) Sudden fall in blood pressure – due to effects on heart and vasculature
• Side effects on CNS:
1) Restlessness
2) Tremors
3) Convulsions
4) Respiratory centre depression
5) Death
