Local Anaesthetics Flashcards
Local anaesthesia
Regional anaesthesia
The goal is to reversibly
block sensory perception
of pain, with the patient’s
consciousness maintained
A good LA should be
Soluble in water and stable in
solution preparations
Cocoa was derived from
Cocaine
Due to cocaines structure, LA have 3 structural requirements:
- Lipophillic group (aromatic
ring) - intermediate bond (ester
or amide linkage) - hydrophillic group (basic
amine side chain; either
tertiary or quaternary
amino group).
Common LAs
The ‘Caines’
Procaine,
Lidocaine
Bupivicaine, and
Tetracaine
Procaine
Less toxic and not addictive like cocaine!
very long time of onset of anaesthetic,
wore off too quickly,
was not nearly as potent as cocaine.
causes vasodilation, so is quickly
absorbed away from injection site.
is an ester, and has a very high potential
to cause allergic reactions ~(1:100).
Procaine treats
procaine is combined with penicillin and used in deep intramuscular
injection for slow absorption
Esters (except cocaine) are inactivated by:
plasma esterases, and excreted via urine.
Cocaine is metabolized in liver
Lidocaine
is an amide and hypoallergenic
as the amide linkage does not
sensitize patients.
anaesthetic effect occurs quickly,
causes vasodilation at the injection
site, so is quickly absorbed away
Amide LAs are degraded by
CYP450s
in the liver, so hepatic disease
requires caution in use.
How do we resolve the vasodilation issue with
procaine and lidocaine/lignocaine?
Cocaine blocks noradrenaline reuptake
transporters as well, which increases NA and
leads to vasoconstriction.
these LAs lack this NA effect, causing
vasodilation of the local blood vessels,
increasing the blood flow in the area and
absorption into circulation before it have
complete effect, increasing adverse effects.
Therefore, these synthetic anaesthetics are
always mixed with low concentrations of
adrenaline which causes vasoconstriction and
slows blood flow through the area, keeping
anaesthetic in position long enough to
produce long-lasting numbness (1-2 hours).
All local anaesthetic agents are weak bases T/F
True
At physiological pH (7.4) all local anaesthetics are
more ionised than un-ionised as all
pKa values are greater than 7.4.
Ionised molecules of any size are
much less likely to cross the nerve sheath and
axonal phospholipid bilayer of the neuron unassisted by transport proteins.
Un-ionised molecules may be
hydrophobic/lipophillic enough to enter/cross the
neuronal membrane without assistance.
Commercial LA solutions are designed to have an
acidic pH, which maximises
water solubility and chemical stability – increasing shelf-life.
Prior to injection, alkali (sodium bicarbonate) can be added to raise pH to that of
tissues (pH 7.4).
This increases the proportion of non-ionised drug present, and reduces pain felt by the patient
Un-ionised drug will enter the neuron more readily than ionised drug. T/F
True
Why shouldnt you inject a LA into inflammed tissue?
Infected tissue may also have an increased
blood supply and hence more anaesthetic
may be removed from the area before it can
affect the neurons.
The target of LAs
Voltage-dependant sodium ion channels
LAs have greater affinity for inactivated channels, and by binding to them, they
prevent channels from re-opening. Thus, there appears to be a “loss of ion
channels (and ion current)” during a train of pulses.
LAs have greater affinity for inactivated channels, and by binding to them, they
prevent channels from re-opening. Thus, there appears to be a “loss of ion
channels (and ion current)” during a train of pulses.
90% of LA block occurs via the
Hydrophillic pathway
only if the charged form of the LA can enter sodium ion channels from the inside when they open, as they bind to a site within the pore region when inactivated
If a neuron is actively firing
action potentials,
these sodium ion channels will open frequently, allowing greater access of the LA molecule to the inner pore region
10% of LA block occurs via the
Hydrophobic pathway
The blocking site within the sodium ion channel is thought to be reached directly from the membrane by the uncharged B, and the molecule will become charged upon arriving in the cytoplasm (BH+) (10% of action)
