Flashcards in Local anaesthetics Deck (16)
What do local anaesthetics exist as?
All LAs are weak bases; existing in unionised (B) and ionised (BH+) forms.
How do local anaesthetics reach the target site and act?
They diffuse across the lipid cell membrane in their unionised form, where they are ionised by the (more) acidic intracellular cytosol and bind/block the VGSC from the inside.
What forms can LAs derived from cocaine exist in, and what enzymes metabolise them?
Amide and ester variants:
Amides: metabolised by liver amidases (implication for liver failure)
Esters: metabolised by cholinesterase
Are LAs more ionised or unionised at physiological pH?
LAs are more ionised at physiological pH (7.4) than unionised; all pKa values are greater than 7.4.
What pKa is preferable for LAs to act, and what does a more pKa mean for the drug action?
As close to a pKa of 7.4 as possible (where there'd be 50% 1:1 ratio ionised/unionised due to pH 7.4); Lidocaine has pKa 7.9 = 25% unionised, Bupivacaine has pKa 8.1 = 15% unionised; Lidocaine thus has a more rapid onset of action (passing through lipid cell membrane more).
Can the ionised LA pass back through the membrane back to the extracellular fluid?
Not readily; its ionised state means it is 'trapped', thus increasing the length it is bound and blocking VGSC's exerting their therapeutic effect.
What type of nerve fibres are LAs most efficacious for/are the target for?
C fibres (slow pain) are most sensitive; myelinated and thicker axons (e.g. Aα, Aβ, Aγ, Aδ) are more difficult to penetrate for LAs than thin, unmyelinated axons (C).
Aα, Aγ, C, Aδ, Aβ. Order them according to LA sensitivity.
What are the different sites of LA action?
- Surface anesthesia
- Infiltration (most LAs; injection into tissues to reach nerves)
- IV regional
- Nerve block
Give examples of targets for surface anesthesia and example LAs.
Mucus membranes & corneal drops (sprays)
- Lidocaine, tetracaine
Skin (not v effective - cream)
- EMLA (Eutectic Mixture of Local Anaesthetics; lidocaine & prilocaine)
Describe LAs in Infiltration.
- Injection into tissues to reach nerves
- Minor surgery (most LAs)
What might be added to LAs to complement Infiltration, and when is it not added?
Adrenaline; vasoconstriction (reducing perfusion) preventing diffusion away from site, keeping LA at target.
- Not for fingers/toes due to risk of ischaemia
Describe LAs in Nerve block and their applications.
Injection close to nerve trunks reducing sensation peripherally, used in surgery/dentistry.
Describe LAs in Spinal and their applications.
Injection into subarachnoid space (containing cerebrospinal fluid; CSF) depressing spinal roots/cord.
- Surgery on: abdomen, pelvis, leg (if general anaesthetic not possible)
What might be added to LAs to complement Spinal application and why? Any other precautions and why?
Glucose; increases density, limiting spread of LA.
Can also tilt patient; risk of CVS effects/respiratory depression (VGSCs present) thus limit spread to brain in CSF.