Local anaesthetics Flashcards
What are the unwanted effects of cocaine overdose?
CNS - excitation, euphoria CVS - increased CO, hypertension, vasoconstriction (all sympathetic actions)
What are the unwanted effects of lidocaine overdose?
CNS - restlessness, confusion, tremor (paradoxical) CVS - myocardial depression, vasodilation, hypotension (caused by Na channel blockade)
How can local anaesthetics be administered?
- Surface - mucosal (mouth, bronchial tree), spray/powder 2. Infiltration = directly into tissues - sensory nerve terminal 3. IV regional - distal to pressure cuff 4. Nerve block 5. Spinal 6. Epidural
When would LAs be administered by infiltration?
Minor surgery
Why are LAs by infiltration co-administered with adrenaline?
Adrenaline causes vasoconstriction So LA doesn’t spread (decreases systemic toxicity) And increases duration of action
What is a local anaesthetic?
A drug which reversibly blocks neuronal conduction when applied locally
What is a problem with surface LAs?
Have to use a high concentration Can cause systemic toxicity
When would LAs be administered by regional IV?
Limb surgery
If the pressure cuff is released prematurely when LAs are administered by regional IV, what issue could arise?
Systemic toxicity
Where are epidural LAs injected?
Into fatty tissue of epidural space Spinal roots
When may an epidural LA be used?
Childbirth Abdominal, pelvic, lower limb surgery
When may a spinal LA be used?
Abdominal, pelvic, lower limb surgery
Where are spinal LAs injected?
Sub-arachnoid space Spinal roots
Why are spinal LAs injected with glucose
To increase specific gravity
What are the disadvantages of epidural LA over spinal LA?
Slower onset Higher doses need to be used More restricted action - less effect on BP
When may nerve block LA be used?
Dental work
What is co-injected with nerve block LA?
A vasoconstrictor
Where is nerve block LA injected?
Close to target nerve trunks
Are LAs acids or bases?
Weak bases PKa 8-9
What are the effects of local anaesthetics?
- Prevent generation and conduction of action potentials - May influence channel gating - Selectively block nociceptive pain fibres - small diameter fibres (A-delta and C-neurones have small diameter axons), non-myelinated fibres (pain C fibres)
Do LAs influence resting membrane potential?
No
Why is infected tissue harder to anaesthetise?
Infected tissue tends to be acidic Larger proportion of LA in ionised state (BH+)
What are the side effects of spinal anaesthesia?
Decreased BP Prolonged headache
What are the pharmacokinetics of lidocaine?
- Good absorption at mucous membranes - 70% plasma protein binding - Hepatic metabolism by N-dealkylation - Plasma half life = 2 hours
What are the pharmacokinetics of cocaine?
- Good absorption at mucous membranes - 90% plasma protein binding - Hepatic and plasma metabolism by non-specific esterases - Plasma half life = 1 hour
Compare the plasma half lives of lidocaine and cocaine
Lidocaine = 2 hours Cocaine = 1 hour
Compare the absorption at mucous membranes of lidocaine and cocaine
Both good
Compare the plasma protein binding of lidocaine and cocaine
Lidocaine = 70% Cocaine = 90%
Compare the metabolism of lidocaine and cocaine
Lidocaine = hepatic, N-dealkylation Cocaine = hepatic and plasma, non-specific esterases
Are LAs largely unionised or ionised at physiological pH?
Largely ionised
What is the general structure of a LA?
Aromatic region + basic amine side-chain Linked by either an ESTER or AMIDE bond.Benzocaine, relatively weak but a useful surface local anaesthetic(NOTE: it is the exception to the whole general strucure rule). Bupivacaine is an important one.
How do the structures of lidocaine and cocaine differ?
Cocaine has an ester bond Lidocaine has an amide bond
Explain the hydrophilic pathway of LA action
- Only unionised (lipid soluble) LA (B) can pass through connective tissue sheath and thr axon membrane - LA can only work from inside the neurone (as ionised form - BH+) 1. Unionised LA (B) passes across connective tissue sheath + axon membrane into neurone 2. Equilibrium established btwn B + BH+ 3. Cationic form (BH+) of LA is formed inside 4. BH+ can only bind w/Na channel when channel is open bc binding site is inside channel 5. Once inside channel, it stereochemically inhibits passage of Na ions from outside to inside of cell = HYDROPHILIC PATHWAY = main MOA = gives rise to use-dependency of LA
Summarise an action potential
- Depolarisation 2. Resting Na channels open, Na enters cells 3. Na channels close (inactivation), K channels open, K leaves cell 4. Na channels restored to resting state but K channels still open tf cell refractory 5. Na and K channels restored to resting state tf cell will respond normally to further depolarising stimulus
What is use dependency of LAs?
The more active the cell is, the more frequently its Na channels will be open and the more it will be blocked bc the binding site for cationic LA (BH+) is INSIDE the channel
Why is use dependency a useful feature of LAs?
Gives LAs a greater degree of selectivity for nociceptive neurones When conducting pain, nociceptive neurones fire rapidly
You would think that something that blocks nerve transmission would be a CNS depressant. Why is the CNS stimulated by lidocaine?
- GABA system is very sensitive to LAs - GABA signalling is reduced - Causes CNS excitation - GABA is main inhibitory NT
Why does spinal anaesthesia cause a prolonged headache?
LA mixes in with CSF Can diffuse towards brain
How can you control the level of spinal anaesthesia?
- Add some glucose w/LA - Increases specific gravity - LA stays more or less in one place - Can be moved by tilting patient rather than freely diffusing through CSF
Why does spinal anaesthesia cause a drop in blood pressure?
- Inject into CSF - Preganglionic sympathetic neurones are v susceptible to block by LA - Reduced sympathetic outflow to heart and vasculature - Drop in BP
Explain the hydrophobic pathway of LA action
- Only unionised LA can pass through connective tissue sheath and thr axon membrane - LA can only work from inside the neurone 1. LA can also pass into neuronal membrane in unionised form (B) 2. Some highly lipid soluble LAs can drop straight into Na channel 3. They then become ionised in Na channel and block channel = HYDROPHOBIC PATHWAY
