W5: Locl Anaesthetics Flashcards
What do local anaesthetics do?
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.
What is nociception?
Sensory receptors that detect damage or harm to the body perceived as pain. Generates action potentials which are sent to the brain.
How to prevent pain
Preventing signals being sent to the brain. Target of drugs = voltage gated sodium ion channels to stop generation of APs
Naming local anaesthetics
They end in -caine
Chemical structure of local anaesthetics
Aromatic ring, amine group, with an amide or ester bond linking them.
Where do enzymes act to break down local anaesthetic molecules/where is the site of metabolism?
At the ester or amide bond
Are esters or amides broken down faster?
Esters
What might happen after local anaesthetics are broken down?
They might form potentially harmful metabolites.
What are the implications for clinical use of producing harmful metabolites from breakdown?
We need a drug that will be available in the body for a certain period of time and do not want potentially allergic metabolites.
Property of the aromatic ring
Lipid soluble
Thus will target neurones which have a phospholipid bilayer.
Property of the amine group
Amine groups can exist charged or uncharged. Thus all local anaesthetic molecules are weak bases and can accept a proton when dissolved in water.
Can the ionised or unionised version of LA block VGNa+ channels?
Ionised
What does the LA do in the presence of an action potential at a nociceptive neurone?
- presence of LA will be outside the axon in the extracellular fluid and there will be an equilibrium of ionised and unionised versions.
- the aromatic ring allows the molecule to be lipid soluble if uncharged (unionised version)
- unionised version moves into the axon, creating a new equilibrium such that some become ionised
What is a use-dependent block?
The degree of the block is dependent on whether the channels are being used. The ionised molecule blocks open channels. Channels are only open if there is a stimuli generating APs. Therefore if there is a more painful stimulus, we may expect more action potentials, thus more open channels and thus a better block.
How can pH affect effectiveness of LA?
pH determines the ionisation states of the molecules. Tissue pH is normal stable but sometimes disrupted.
What can cause lower tissue pH?
When there is lots of inflammation, e.g., due to bacterial infection, bacteria are multiplying and respiring producing acidic byproducts, lowering tissue pH.
What affect does the lower pH have on LA effectiveness?
Increased acidity drives the ionisation reaction to the right, creating a greater proportion of ionised LA molecules, so it is less likely that there are unionised molecules to cross the membrane to bring about the action of blockage, hence poorer effect of anaesthetic. Thus best to clear infection first.
Formula for amine ionisation and how pH affects it.
molecule + H2O <—> molecule+ + OH-
Increased acidity shifts reaction right
Increased alkalinity shifts reaction left
How do neurones affect effectiveness or LA?
Axons with a small diameter are nocipetic (Adelta and C). The largest axons found are alpha motor neurones.
Large alpha motor neurones are definitely myelinated so have a thickened wall but the nociceptic neurones vary.
If LA is used to alleviate pain, we want it to target Adelta and C neurones since these are nociceptic. They have higher sensitivity to LA so will be more targeted, but other motor neurones can also be affected hence loss of sensation in the affected areas.
General rule for the route of administration of LA
The more proximal (closest to the centre thus the spinal cord) the site of administration, the greater the area anaesthetised.
5 routes of administration of LA (refer to image)
Topical anaesthesia Infiltration anaesthesia Nerve block anaesthesia Epidural anaesthesia Spinal anaesthesia
Describe topical anaesthesia
Anaesthetising surfaces. Nerve terminals are branching to cover the skin area. Not very effective since skin is made up of many layers and is dense so it is difficult for the LA molecules to diffuse across the skin.
Describe infiltration anaesthesia
LA is injected into the skin. Sometimes done as multiple injections so all of the neurones supplying that area are anaesthetised. Can be used in some forms of dental work for anaesthetising one tooth.
Describe nerve block anaesthesia.
Injection given quite proximally so it is targeting quite a large mixed nerve so all of the axons are affected within that nerve.
