Local Anaesthetics Flashcards
Define Local Anaesthetic.
Drugs that reversibly block neuronal conduction when applied locally
What is the rapid depolarisation stage of the action potential caused by?
Opening of voltage-gated sodium channels
Influx of Na+
What are the three components that make up all local anaesthetics?
Aromatic region
Basic amine side-chain
Amide or ester link
What are the two types of local anaesthetics? Give an example of each.
Ester = COCAINE Amide = LIDOCAINE
Name a local anaesthetic that doesn’t fit the structure of all other local anaesthetics.
Benzocaine: has an alkyl group rather than an amine side chain
Thus it’s relatively weak but highly lipid soluble (good for surface anaesthesia)
What are the two pathways of local anaesthesia? State which one is more important.
HYDROPHILIC – most important
Hydrophobic
Describe the hydrophilic pathway.
Unionised LA from the blood crosses the axon membrane + gets into the axon
Within the axon it forms the cation form of the LA
Cation then binds to the inside of the VGSCs (when open) + block Na+ entry
Blocks AP conduction
What feature of local anaesthetics helps make it more selective for nociceptive neurones? Can they block motor neurones?
Use-dependency
Can block MN’s but less intensely (fire less + are myelinated)
Describe the hydrophobic pathway. What is advantageous about this pathway?
Very lipophilic LAs move into the cell membrane (in unionised form) + drop straight into the sodium channel
Then transition to cation form in the sodium channel
+ will block Na+ influx
VGSCs don’t need to be open for LA to bind
What effect do local anaesthetics have on resting membrane potential?
No effect on resting membrane potential
Explain the effect of local anaesthetics on channel gating.
Suggestion: LA’s bind more strongly to the VGSCs in their inactive state
Once bound it holds it in the inactive stage for longer thus increasing the refractory period + reducing the frequency of APs
Describe the selectivity of local anaesthetics.
Preference for small diameter axons (e.g. nociception neurones)
Tend to block non-myelinated axons
Describe the pKa of all local anaesthetics. What does this mean for local anaesthetics acting at our physiological pH?
8-9
All local anaesthetics are WEAK BASES
Only small % will be unionised + can pass into neurones
Explain why it is difficult to anaesthetise infected tissue.
Infected tissue is ACIDIC
So less anaesthetic will be unionised
What are the 6 methods of administration of local anaesthetics?
Surface anaesthesia Infiltration anaesthesia Intravenous regional anaesthesia Nerve block anaesthesia Spinal anaesthesia Epidural anaesthesia
What are the consequences of using high doses in local anaesthesia?
Can cause systemic toxicity- go to heart then brain
What is infiltration anaesthesia?
Injection of anaesthetic directly into tissue near the sensory nerve terminals
Used for minor surgery
What is often coadministered with infiltration anaesthesia and what are the benefits of this? When is this avoided?
Adrenaline: causes vasoconstriction + increases the duration of action of LA meaning a lower dose can be used
Also slows bleeding at site of injection + reduces the amount of LA going into the systemic circulation
Avoided in LA of extremities as risk of ischaemic damage
What is intravenous regional anaesthesia and how can this cause systemic toxicity?
LA administered intravenously, distal to pressure cuff (which restricts blood flow)
Used in limb surgery
Removing pressure cuff too early can lead to a bolus of anaesthetic entering the systemic circulation
What is nerve block anaesthesia? Describe the dosage and onset.
Inject anaesthetic close to the nerve trunks
Low doses + slow onset
What is coadministered with nerve block anaesthesia?
A vasoconstrictor e.g. adrenaline
What is another name given to spinal anaesthesia?
Intrathecal
Where is the anaesthetic inserted in spinal anaesthesia?
Into the subarchnoid space (into the CSF)
Which parts of the body can be anaesthetised effectively with spinal and epidural anaesthesia?
Abdomen, pelvis, lower limbs
How does spinal anaesthesia affect blood pressure and why does it have this effect?
Can cause drop in BP due to effects on preganglionic sympathetic nerves (have small diameter)
Leads to reduced sympathetic output + hence a drop in BP
Can cause prolonged headaches
What trick can anaesthetists do to get better control over the location of the spinal anaesthesia?
Add glucose to the anaesthetic mixture
Increases specific gravity of the LA meaning the patient can be tilted to move the bolus of anaesthetic to target site
Describe the difference in metabolism of lidocaine and cocaine.
Lidocaine: hepatic – N-dealkylation
Cocaine: hepatic + plasma by non-specific cholinesterases
Describe the difference in half-life between lidocaine and cocaine.
Lidocaine: 2 hours
Cocaine: 1 hour
What are 4 CNS side-effects of lidocaine? Explain why it has these effects.
CNS stimulation Restlessness Confusion Tremor Paradoxical- GABA system (inhibitory effect on CNS) is very sensitive to LA's so effected 1st
What are 3 CVS side-effects of lidocaine? Why do they arise?
Myocardial depression
Vasodilation
Decrease in BP
Due to sodium channel blockade
What are the CNS side-effects of cocaine? Why do they arise?
Euphoria + excitation
Due to blockade of monoamine transporters
What are the 3 CVS side effects of cocaine? Explain why it has these effects.
Increased CO
Vasoconstriction
Increased BP
Due to increased sympathetic drive caused by blockade of monoamine transporters
Where does surface anaesthesia act? How is it often administered?
Mucosal surfaces e.g. mouth
Spray or powder
Where is the anaesthetic inserted in epidural anaesthesia?
Fatty tissue of epidural space
needle doesn’t pierce dura
What are the uses of epidurals?
Abdominal, pelvic + lower limb surgery
Painless childbirth
What is the disadvantage of using epidural anaesthesia?
Slower onset so higher doses are required
Thus more likely to cause systemic toxicity
What are the advantages of epidurals over spinal anaesthetics?
Epidurals have more restricted action as doesn’t diffuse into CSF + less likely to effect BP
Describe the absorption across mucous membranes and plasma protein binding of lidocaine and cocaine
Both have good absorption
Both highly PPB
Name a local anaesthetic with a longer duration of action (~6 hours)
Bupivicaine
