L18: Local anaesthetics Flashcards
What is general anaesthetics?
Act on the brain to numb the whole body
What is local anaesthetics?
Involves numbing an area of the body
What are nociceptors?
Specialised sensory nerves that detect tissue damage
How do we sense & feel pain?
Nociceptors detect tissue damage
- This triggers AP along sensory nerve to the brain via spinal cord
- When AP reaches brain, we perceive pain
How does local anaesthetics prevent pain?
Stopping action potentials being triggered/propagating along sensory nerves
Action of local anaesthetics blocking APs
LA target (voltage-dependent Na+) channel
- Drugs ‘plug’ the channel pore, preventing Na+ entry & initiation of AP
What does local anaesthetic molecules consist of?
Aromatic head linked to a basic side chain by an amide OR an ester bond
What can the ester bond be destroyed by to be shorter acting?
Esterase enzymes
How are amide-linked LAs long-acting?
Metabolised in the liver
Are local anasthetics weak or strong bases?
Weak bases (pKA = 8.0)
What forms do LA’s exist in at pH (7.4)?
Ionised & unionised forms
Can ionised/unionised form of LA cross the lipid membrane to reach N channel binding site?
Unionised
- Low pH increases ionisation, reducing effectiveness
How do LAs block voltage-depdent Na+ channels?
What are the features of the outer mouth & inner mouth?
Binding to a site deep within the ion channel pore
Outer mouth: Too narrow to allow drug through
Inner mouth: Guarded by activation/inactivation gates
What is the hydrophobic pathway?
Basic, non-ionised form of drug can penetrate membrane & access Na+ channel
What is the hydrophilic pathway?
When inside the cell, drug establishes a new equilibrium between ionised & unionised forms
- Ionised drugs can enter ONLY when the channels are open
Why is hydrophilic pathway use dependent?
When drug enters the channel when its open, there is more channel use & more block
Why is the hydrophobic pathway NOT use-dependent?
Drug enters Na+ channel from lipid membrane & not from channel’s opening, so channel state doesn’t matter
Why is lignocaine longer acting than amethocaine?
Lignocaine has amide/ester bond
Action of outer/inner mouth of voltage-dependent Na+ channels
Outer mouth: Too narrow to allow drug molecules through
Inner mouth: Guarded by activation/inactivation gates
Describe *use dependence *
More the ‘use’ of the channel, the more readily the drug can gain access
Why is the hydrophobic pathway NOT use-dependent?
Drug enters the Na+ channnel from lipid membrane and doesn’t matter as the it can enter either it is closed/open
Which pathway is available when the channel is closed?
Only hydrophobic pathway
Which pathway is available when the channel is open?
Both hydrophobic & hydrophilic
What is the molecular target for local anaesthetic drugs?
Voltage-dependent Na+ channels
Describe surface anaesthesia
Drug applied to the mucosal surfaces (e.g urinary tract, cornea, inside nose)
- Not very affective on skin as it takes ~1 hour to take effect
Side effects:
If applied over large area/damaged skin
Describe infiltration anaesthesia
Local anesthetic injected into tissues around sensory nerve teminals & branches
e.g minor surgery, dentistry
Describe nerve-block anaesthesia
Local anaesthetic is injected around nerve trunks
- Requires less drug than infiltration but affects wider area
- Requires accurate placement
e.g brachial plexus in the neck to anaesthetise the arm
What is the brachial plexus?
Bundle of nerves that supplies the shoulder, arm & hand with feeling & movement
Describe spinal/epidural anaesthesia
Local anaesthetic is injected into spinal OR around epidural the spinal cord
- Blocks nerve as they enter/rise within spinal cord
- Widespread effect (BELOW site of injection blocked)
Describe intravenous regional anaesthesia (Bier block)
Local anaesthetic injected into a limb isolated from the rest of circulation using a pressure cuff
- Limit duration of procedure
e.g limb surgery
Side effects of local anaesthetics
All are toxic
- High concentrations can cause life-threatening side effects
How are drugs removed from their site of action?
Being broken down (ester bond) OR entering into general circulation to be diluted
How can duration of action using ‘nerve block’ or ‘infiltration’ anaesthesia be increased?
Co-administrating a vasoconstrictor (e.g adrenaline) to prevent the drug entering the general circulation
Why does spinal anaesthesia have the most widespread effects?
All nerves entering the cord BELOW the site of injection are blocked
Which form of local anaesthesia might be used to reset a broken arm?
Intravenous regional anesthesia (Bier block)
Why do local anaesthetic preparations sometimes contain adrenaline?
Prevent drug entering the general circulation
