Local Anesthetics Flashcards
Is blockade from local anesthetics specific to nociceptors?
Nope
Infiltration
Injected at site to be operated on
Field block
Subcutaneous – anesthetizes region distal to injection
Nerve block
Injected near peripheral nerve or plexus
Epidural
Injected into epidural space
Spinal
Injected into CSF in lumbar region
Local anesthetic structure
Has:
Aromatic group
Linker (ester or amide)
Amino group to accept proton
How to tell if local anesthetic is ester or amide?
All amides have ‘i’ before the caine.
Molecular target of LA?
Vg Na channel, they bind within the pore
What contributes to adverse effects of local anesthetics?
Lack of specificity for types of Na channels.
Which form (protonated vs unprotonated) has a higher affinity for Na binding site?
Protonated, because can enter from aqueous environments.
Are most LAs acid or base?
Weak base (pKa between 7.5 and 9)
Henderson Hasselbalch eq
pH + log (proton/unproton) = pKa
If pH is lower than 7.4, the effect of an LA is…(greater or weaker)?
Weaker, less is protonated.
Two routes to LA binding site?
Intracellular moving into pore through cytoplasm. Membrane delimited (moving from membrane to pore).
What is use-dependent inhibition?
Access of an LA to a pore through the cytoplasmic route requires the pore to open. So, if a axon is stimulated in the presence of an LA with a high number of preceding pulses, the channel will be inhibited more greatly, because the drug doesn’t have time to dissociate between spikes.
Is access to channel from membrane use-dependent?
No. So even inactive neurons can be inhibited by this route.
Barriers to therapeutic binding site?
Drug must pass between a series of liquid/aqueous phases.
Epineurium, perineurium, endoneurium, cell membrane
Potency is determined by?
The hydrophobicity of the base. More hydrophobic, more potent, because the drug accumulates in the lipid bilayer. This creates a reservoir of drug that can be protonated and then enter the channel.
Do highly hydrophobic drugs block fast or slow?
Slow, because lower concentrations are used.
Most sensitive fibers to LA? Why?
C-fibers, then Ad fibers. Larger fibers are relatively spared. Small fibers have faster AP decay if Na channels are blocked. Also, spike threshold is higher normally.
Effect of LA on vessels?
Normally vasodilators because they inhibit sympathetic postgangionic fibers.
Problem with vasodilation with local anesthetics?
Flushes drug away into systemic circulation.
Solution to vasodilation?
Vasoconstriction w/ epinephrine.
Problem with ester LAs?
Metabolized to PABA in plasma, which can cause hypersensitivity reaction in some patients. Vasoconstrict, chance of problem is reduced.
How are amides metabolized?
Metabolized partly by CYP450 in liver. Terminated by systemic distribution, so greater risk of systemic adverse effects.
For which class of LA is chance of systemic side effects greater?
Amides
What patients should avoid amide LAs?
Hepatic disease
CNS effects of LA
Sedation, seizures, LOC
Cardiac effects
Occur at higher doses than CNS symptoms. Arrythmias (av block, ventricular arrest),
Cocaine
Naturally occurring, vasoconstrictor, prevents monoamine reuptake. Mainly used on mucous membranes.
Procaine
Devoid of abuse potential. Low potency, slow onset, short duration. Can’t use topically, only infiltration.
Tetracaine
Slow onset, but more potent and longer lasting. Used mainly for spinal block and topically.
Benzocaine
Unique structure that lacks an ionizable group. Poor aqueous solubility, strictly used for surface anesthesia.
Lidocaine
Amide, commonly used, rapid onset, moderately hydrophobic. Elimination is flow-limited, so caution w/liver disease.
Prilocaine
Only a weak vasodilator, epi not usually required. Large Vd. Rapid systemic elimination. Can cause methemoglobinemia.
Bupivacaine
Blocks sensory over motor neurons. Useful in labor. More cardiotoxic than lidocaine. Can cause PVCs. There’s a extended release formula thats good for post surgery.
Ropivacane
Derived from the r enantiomer of bupivacane. Less cardiotoxic.
