Local Anesthetics

Question 1

Is blockade from local anesthetics specific to nociceptors?

Answer 1

Nope

Question 2

Infiltration

Answer 2

Injected at site to be operated on

Question 3

Field block

Answer 3

Subcutaneous – anesthetizes region distal to injection

Question 4

Nerve block

Answer 4

Injected near peripheral nerve or plexus

Question 5

Epidural

Answer 5

Injected into epidural space

Question 6

Spinal

Answer 6

Injected into CSF in lumbar region

Question 7

Local anesthetic structure

Answer 7

Has:
Aromatic group
Linker (ester or amide)
Amino group to accept proton

Question 8

How to tell if local anesthetic is ester or amide?

Answer 8

All amides have ‘i’ before the caine.

Question 9

Molecular target of LA?

Answer 9

Vg Na channel, they bind within the pore

Question 10

What contributes to adverse effects of local anesthetics?

Answer 10

Lack of specificity for types of Na channels.

Question 11

Which form (protonated vs unprotonated) has a higher affinity for Na binding site?

Answer 11

Protonated, because can enter from aqueous environments.

Question 12

Are most LAs acid or base?

Answer 12

Weak base (pKa between 7.5 and 9)

Question 13

Henderson Hasselbalch eq

Answer 13

pH + log (proton/unproton) = pKa

Question 14

If pH is lower than 7.4, the effect of an LA is…(greater or weaker)?

Answer 14

Weaker, less is protonated.

Question 15

Two routes to LA binding site?

Answer 15

Intracellular moving into pore through cytoplasm.
Membrane delimited (moving from membrane to pore).

Question 16

What is use-dependent inhibition?

Answer 16

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.

Question 17

Is access to channel from membrane use-dependent?

Answer 17

No. So even inactive neurons can be inhibited by this route.

Question 18

Barriers to therapeutic binding site?

Answer 18

Drug must pass between a series of liquid/aqueous phases.

Epineurium, perineurium, endoneurium, cell membrane

Question 19

Potency is determined by?

Answer 19

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.

Question 20

Do highly hydrophobic drugs block fast or slow?

Answer 20

Slow, because lower concentrations are used.

Question 21

Most sensitive fibers to LA? Why?

Answer 21

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.

Question 22

Effect of LA on vessels?

Answer 22

Normally vasodilators because they inhibit sympathetic postgangionic fibers.

Question 23

Problem with vasodilation with local anesthetics?

Answer 23

Flushes drug away into systemic circulation.

Question 24

Solution to vasodilation?

Answer 24

Vasoconstriction w/ epinephrine.

Question 25

Problem with ester LAs?

Answer 25

Metabolized to PABA in plasma, which can cause hypersensitivity reaction in some patients. Vasoconstrict, chance of problem is reduced.

Question 26

How are amides metabolized?

Answer 26

Metabolized partly by CYP450 in liver. Terminated by systemic distribution, so greater risk of systemic adverse effects.

Question 27

For which class of LA is chance of systemic side effects greater?

Answer 27

Amides

Question 28

What patients should avoid amide LAs?

Answer 28

Hepatic disease

Question 29

CNS effects of LA

Answer 29

Sedation, seizures, LOC

Question 30

Cardiac effects

Answer 30

Occur at higher doses than CNS symptoms. Arrythmias (av block, ventricular arrest),

Question 31

Cocaine

Answer 31

Naturally occurring, vasoconstrictor, prevents monoamine reuptake. Mainly used on mucous membranes.

Question 32

Procaine

Answer 32

Devoid of abuse potential. Low potency, slow onset, short duration. Can't use topically, only infiltration.

Question 33

Tetracaine

Answer 33

Slow onset, but more potent and longer lasting. Used mainly for spinal block and topically.

Question 34

Benzocaine

Answer 34

Unique structure that lacks an ionizable group. Poor aqueous solubility, strictly used for surface anesthesia.

Question 35

Lidocaine

Answer 35

Amide, commonly used, rapid onset, moderately hydrophobic. Elimination is flow-limited, so caution w/liver disease.

Question 36

Prilocaine

Answer 36

Only a weak vasodilator, epi not usually required. Large Vd. Rapid systemic elimination. Can cause methemoglobinemia.

Question 37

Bupivacaine

Answer 37

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.

Question 38

Ropivacane

Answer 38

Derived from the r enantiomer of bupivacane. Less cardiotoxic.