Uses and Actions of Local Anaesthetics* Flashcards
define a local anaesthetic
Local anaesthetics reversibly block nerve conduction when applied to a restricted area of the body to enable a procedure to be carried out without loss of consciousness.
why is a local anaesthetic reversible?
Reversible: so your sense can return afterwards – last until necessary
This is hugely contrasting to general (body wide) anaesthesia
Why might we want to use local anaesthetics?
They relieve or reduce pain in a specified area e.g. mouth, throat, eye.
what are receptors that detect pain called?
nociceptors
how would local anaesthetics help prevent pain?
Sensory receptors detect stimulus –> generate APs –> brain
We must stop that AP reaching the brain to prevent pain from being registered
They target the voltage-gated Na+ channels
what is the naming convention of local anaesthetics?
-caine
This is because the very first local anaesthetic was cocaine so they now all end the same way
Cocaine is no longer used due to the psychoactive effects
synthetic version of cocaine (procaine) has been produced which will not exhibit these effects
what is the chemical nature of local anaesthetics?
All local anaesthetics the same common structure:
- similar functional groups
- similar bonds
what is the chemical structure of a LA?
aromatic ring
linkage
amine group
what properties does the aromatic ring have that makes the drug the way it is?
Makes the drug lipophilic
Cells are surrounded by phospholipid bilayer; this allows the drug needs to cross the cell membrane of neurones
what are the 2 linkages and what properties do they have?
Linkage = amide or ester
Site of metabolism - where the molecule is broken down into the aromatic ring and amine group by enzymes. This stops the drug from being present in the body forever (reversible)
Ester linkage:
metabolised more quickly - doesn’t last in the body for long so it has limited clinical use.
Metabolites formed from drugs with ester linkage gave people allergic reactions.
Amide linkage:
Used more commonly
what are the properties of an amine group in a drug?
Amine groups can be neutral or have a net positive charge by associating with another hydrogen ion. Charged molecules are lipophobic and hydrophilic.
name:
4 drugs
their linkages
their duration
what does equilibrium in the context of LA mean?
Equilibrium means that both charged and uncharged forms are present in the extracellular space.
how do LA exist in equilibrium?
The amine groups are weak bases – they can accept H+ ions
Therefore local anaesthetics exists in an equilibrium of ionised and non-ionised forms
If alkalinity increases (increase in pH), eqm shifts to left (unionised form)
If acidity increases (decrease in pH), eqm shifts to right (ionised form)
At physiological pH (body pH), what form would the LA be in?
more ionised form of local anaesthetic
explain the steps of adding the LA to nociceptors?
- The unionised version is lipid soluble so quickly diffuses through the membrane into the axon
- The pH inside an axon will be roughly equal to outside so when unionised molecules enter a new equilibrium will be set up meaning both ionised and unionised anaesthetic molecules exist inside the axon.
- The ionised version physically blocks the voltage gated Na+ channel, even if they are open Na+ cannot enter the axon and cause depolarisation –> action potential ceases, no message to brain and so no feeling of pain
explain use-dependent block?
the ionised LA blocks OPEN VG Na+ channels
As pain increases, more APs are generated
This means more VG Na+ channels open
Therefore, local anaesthetics bind to and block more VG Na+ channels
So, blockage is to same degree of pain so changing degree of pain won’t be felt.
what are the factors affecting the effectiveness of LA?
Inflammation/infection: Bacteria produce acidic bi products, this creates acidic conditions - acidosis
A lower pH means an even greater proportion of ionised LA molecules
For molecule to get inside the cell, they must be uncharged
Fewer uncharged molecules means less LA diffuses across the membrane which causes poorer anaesthesia, thus dentist may prescribe antibiotics before carrying out the procedure if area is infected
what is the difference in sensitivity of neurones to LA?
All neurones are sensitive to LA.
Luckily sensory neurones are more sensitive to LA than motor neurones due to their small diameter.
However, all sensory neurones are usually blocked by LA so as well as not feeling pain you won’t feel touch either.
how does the area that the LA is administered affect the area that is anaesthetised?
The more proximal the site of administration is to the CNS, the greater the area that will be anaesthetised
what are the 5 different routes of administration?
Topical (surface) anaesthesia
Infiltration anaesthesia
Nerve block Anaesthesia
Epidural anaesthesia
Spinal anaesthesia
what is Topical (surface) anaesthesia?
near the sensory terminal of the axon
just lathering it on the skin but it only works well on certain areas e.g. with thin epithelia and places where diffusion is possible so it is limited in usage.
what is Infiltration anaesthesia?
injection into tissue (avoids skin barrier)
ring of injections around site = ‘ring block’ - ensures whole area anaesthetised.
This is usually done when a wound needs to be sewn up.
Can also be used to anesthetise just one tooth.
what is Nerve block Anaesthesia?
injection is close to the nerve course - more proximal to spinal cord so more axons are affected - so large area is anaesthetised. E.g. one injection can anaesthetise one side of whole jaw.
what is Epidural anaesthesia?
Anaesthesia put in epidural space to bathe the nerve roots exiting in the spinal cord.
This is commonly done to anaesthetise nerve that supply pelvis to minimise pain during childbirth.
Need a long-lasting anaesthesia.
what is Spinal anaesthesia?
Even closer to the spinal cord - into the CSF in the subarachnoid space to effect spinal nerves/spinal cord.
Anaesthesia of extensive parts of the body e.g. pelvis and lower abdomen and legs allowing major surgery but patient is still conscious.
what is regional anaesthesia?
Introduced IV – Bier’s block can be used to anaesthetise large area
First force the blood out of the extremity (e.g. forearm) a tourniquet placed on to keep the blood out.
LA is then injected into vein in a precise area e.g. sometimes Ultra sound is used to guide and it then diffuses into the local tissue.
Blood circulation into the arm would cause anaesthetic to circulate the entire body
what are the 3 different types of side effects you can get from anaesthetics?
Non-specific
Specific
Affects other excitable tissue
what is non-specific side effects of LA?
not related to anaesthesia itself
Hypersensitivity/redness reactions to the preservatives mixed in with the anaesthetic
what are specific side effects of LA?
relate to blockade of VG Na+ ion channels
A too high a dose can cause problems
Injected into wrong place can cause problems e.g. injected into a vein which means they circulate around body blocking Na+ VG channels all over e.g. heart which can cause heart attack.
what are side effects of LA that affect other excitable tissue?
CNS (brain spinal cord) –> tremor, convulsions, respiratory failure
Cardiovascular system:
- If it effects cardiac muscle –> less contraction
- Blood vessels being injected with LA can cause specific side effects –> they will dilate, and BP will drop
- Bupivacaine -most cardiotoxic LA
give examples of other drugs that are administered with LA?
done to reduce effect to surrounding tissue
Vasoconstrictions usually found in solutions with the LA as LA causes dilation
This causes smooth muscle cells to constrict to localise LA and stop it flowing around the body – remain where injected.
E.g. adrenaline/felypressin
By localising the LA:
Less likely to get unwanted effects, only effects target tissue
Longer duration of action (reduce rate of LA metabolism) so lower dose can then be given –> minimises side effects
what would happen if LA was given in extremity?
if LA was given in extremity e.g. finger or toe then reducing blood flow to an area via vasoconstrictors can be problematic
what are properties of good local anaesthetics?
- Reversible
- Block nerve conduction in nociceptive neurones
- Effective for time of procedure – use different ones for time needed.
- Low toxicity
