16-11-21 - Local Anaesthetics Flashcards
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?
How do all of these vary? => type of action/ onset
- 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?
Sure! Let’s break down the information about local anesthetics and their mechanisms in simpler terms:
Local Anesthetics and Their Forms:
Local anesthetics are weak bases, which means they can exist in two forms:
1. Protonated (charged) form – occurs at low pH (acidic environments).
2. Neutral (non-ionized) form – occurs at higher pH (alkaline environments).
How Local Anesthetics Work:
1. Neutral Form Diffuses:
The neutral (non-ionized) version of the local anesthetic can cross the cell membrane. This is because the neutral molecules can easily pass through the fatty, lipid-based membrane of cells, while the charged (protonated) molecules cannot.
-
Ionization Inside the Cell:
Once the anesthetic is inside the cell, it gets exposed to the cell’s internal environment (which is typically more acidic), and it becomes ionized (charged). The charged form is the one that can act on the sodium channels. -
Blocking Sodium Channels:
The ionized form of the anesthetic binds to sodium channels inside the cell. These sodium channels are important for nerve signaling. By blocking these channels, the anesthetic prevents sodium from entering or leaving the cell, which stops nerve signals and causes numbness.
Pathways for Local Anesthetics to Block Sodium Channels:
Local anesthetics can block sodium channels through two main pathways:
-
Hydrophilic (Use-Dependent) Pathway:
- These anesthetics work by binding to sodium channels only when they are open or actively used (during nerve impulses).
- They are called use-dependent because their effectiveness depends on how often the sodium channels are opening and closing (i.e., how frequently the nerve is firing).
- Faster firing neurons (like pain neurons) will get blocked more quickly, which means the anesthetic works faster in these neurons.
-
Hydrophobic (Non-Use-Dependent) Pathway:
- These anesthetics can bind to sodium channels whether they are open, closed, or resting (not actively firing).
- They don’t rely on the channel’s activity (hence, non-use-dependent).
- These anesthetics are effective at blocking sodium channels regardless of how frequently the neuron is firing.
Summary:
- Local anesthetics block sodium channels to stop nerve signals, but the way they do it can depend on whether the sodium channels are actively opening (use-dependent) or whether they can block the channels in any state (non-use-dependent). The neutral form of the anesthetic gets inside the cell, where it becomes charged and can block the sodium channels.
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 vasodilation, 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?
R
T
C
R
D
- 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
