Local Anaesthetics Flashcards
What was the first topical, local and spinal anaesthesia?
Cocaine!
Draw a nerve conduction to another nerve!
- if you can a threshold depol. then the axon depolarises down to the next nerve
- Depolarisation occurs at each point due to voltage gated ion channels.
How doe voltage-gated ion channels work?
They are ‘pores’ through the membrane, that have a resting membrane potential of -90mV.
Once the membrane reaches the threshold depolarisation of -65mV then the activation gate will open and there will be an large/fast influx of Na+ down their electrochemical gradient.
As soon as the positive potential is achieved there is an automatic deactivation (deac. gate closes)
Recovering period occurs
What does the membrane potential look like during the depolarisation/repolarisation cycle?
How do Local Anaesthetics work?
By physciallly blocking voltage-gated sodium channels in excitable cell membranes, therefore blocking action potentions.
It works from within the neuron. It’s a weak base that exists in a solution in its un-ionised form (which is what can cross cell membranes), in the cell it ionises and this is what can block the channel!
What is the basic stucture of a local anaesthetic
- Hydrophobic aromatic group
- Hydrophilic amine group
- An amide (modern, longer lasting) or ester (old, vunerable) link
What does the ester or amide bond determine for the local anaesthetic?
The link determines the site of metabolism and the potential to produce allergic reactions.
Esters: more rapidly metabolised, shorter acting and more allergenic :(
Out of Esters and Amides, what more likely to be topical and whats more likely to be injected?
Esters: topical use eg; cocaine cream (plasma cholinesterases)
Amides: Injected often (metabolised by liver)
” All anaesthetics are weak _____.”
What does this mean…
- Therefore if you suspend them in fluid they will exist in two forms; ionised LAH+ and unionised free base LA
- Only free base can cross membranes and enter cells, and the amount of free base depends on the pKa of the drug.
“More free base present = faster the onset”
What is the pKa of a drug?
When the ionised and un-ionised free base is 50:50.
Low pKa: favours the free base (faster onset as the faster it can get in)
High pKa: favours the ionized form
Based on these pKa values, which local anaesthetic will have the fastest speed of onset?
Lignocaine, as it is an aminehas the lowest pKa and therefore the highest % of free base able to enter the cell.
Why do you have a poor quality block when a LA is injected intoacidic infected tissue?
Because LAs with pKa closest to physiological pH have the fastest onset of action
How do you make a LA drug more potent?
Lengthing alkyl chain increases lipid solubility
the more lipid soluble = more potent
How does protein binding of LA’s relation to their duration of action?
The better the protein binding tendancy of a drug, the longer they last.
Eg; bupivancaine is the longest lasting
Explain some properties of Lignocaine
- Amide; standard comparitable agent
- ‘Low’ lipid solubility and low potency
- ‘Low’ pKa, high non-ionised therefore fast onset
- ‘Low’ protein bind and short duration of action
Ideal to cover short surgical procedures eg; mole removal
Describe the properties of Bupivacaine
- Amide
- High lipid solubility → more potent then lignocaine
- High protein binding → longer duration of action than lignocaine
Ideal for nerve blocks for analgesia
Describe
Cocaine:
Prilocaine:
Ropivacaine:
Cocaine: ester, topical to nose, vasoconst.
Prilocaine: amide, safest, IV use
Ropivacaine: Amide, slow onset, long acting, less cardiac toxicity then bupiv.
What type of LA toxicity can you get? WHich is usually due to inadvertent IV administration
Allergic - rare with amides
Dose-dependent CNS toxicity: seizures, usually first, so acts as a red flag
Dose-dependent cardiac toxicity (worse): heart block and ventral fibrillation
Cardiotoxicity of local anesthetics can be compared using the CC/CNS dose ratio that is the ratio of the dose causing cardiac collapse (CC) to the dose causing seizure/convulsions. The lower the number the more cardiotoxic the drug (ex. The CC/CNS for bupivacaine is approximately 3 versus 7 for lidocaine). SO you need to use 3x more bupiv to get a cardiac event then a cerebral. and vice verse for ligno, but 7 (so wider margin of safety)
What is the point of using adrenaline with your local anaesthetic?
It vasoconstricts and reduces systemic absorbtion so you can give more of the drug safely and it lasts longer!
How does topical to skin administration work?
EMLA: eutectic mixture of LAs
- mix of ligno. and prilo. as an oil that allows most to be a free bease → easily crossing the skin
- For insertion of IV cannulae in children
What LA do we use topical to mucus membranes?
- Cocaine
- Ligno. spray and viscous preperations
means you can intubate whilst the patient is awake!
Why do we administer LAs via soft tissue infiltration
- For minor interventions eg; mole removal
fast acting short duration agent eg; lignocaine - For post op pain relief
slow acting, long duration agent eg; bupiv.
How does a peripheral nerve block work and why would we need one?
- LA is infiltrated around a specific nerve; eg a brachial plexus blcok for surgery on the arm.
- in a mixed nerve, small sensory fibres more susceptible, but motor fibres can be affected
- For surgery without general anaesthesia, or for post-op pain relief
How does a spinal nerve block work and why would we need one?
- LA injected into the intrathecal space into CSF, only below L2 where spinal cord terminates
- Profound distal motor and sensory blockade
- Allows major surgery in awake patient as from there down they go numb/weak
How does a epidural nerve block work and why would we need one?
- Small catheter inserted into the epidural space and LA infused through the catheter. Affects spinal nerves passing through space
- Distal sensory and motor blockade
- good block op/labour analgesic
