Lecture 21 - Byram - Local Anesthetics

Question 1

To block nerve transmission, local anesthetics bind to ____

Answer 1

Voltage Gated Sodium Channels

Question 2

Define neuraxial

Answer 2

Spinal or Epidural

Question 3

Local anesthetics for myelinated vs non-myelinated nerves

Answer 3

For myelinated, you must block 3 nodes of ranvier

For non-myelinated, you need to block a longer length/distance (this is a little harder to do)

Question 4

Local anesthetics for core vs mantle fibers

Answer 4

Remember: mantle fibers are on the outside of a peripheral nerve and core fibers are on the inside

1st nerves exposed to local anesthetics = mantle fibers

Block onset is proximal to distal for peripheral nerve blocks

Question 5

What are the 3 types of nerve fibers and which ones are myelinated?

Answer 5

A = myelinated

B = myelinated

C = non-myelinated (thus it’s difficult to block with local anesthetics)

Question 6

How does fiber size affect “block”-ability

Answer 6

Smaller fibers are easier to block than larger fibers

Question 7

What are the top 2 easiest fibers to block with local anesthetics?

Answer 7

B fibers (preganglionic sympathetic) are very small and thus the easiest to block

A-delta fibers are the next easiest to block

Question 8

What is sympathectomy?

Answer 8

Refers to the fact that you will always get sympathetic blockade (because B fibers are the smallest and easiest to block)

Question 9

What two fibers are involved in pain?

Answer 9

A-delta fibers (associated with sharp pain, ex: when you first stub toe)

C-gamma fibers (dull throbbing pain that occurs after the stub)

Question 10

What are the functions of the 4 different A nerve fiber subtypes?

Answer 10

A alpha = motor

A beta = tactile, proprioception

A gamma = muscle tone

A delta = pain and cold temperature

Question 11

For spinal/epidural anesthesia, what types of fibers are the easiest  hardest to block?

Answer 11

Sympathetcomy = easiest

sensory = middle

motor = hardest

Question 12

What are the 3 states/conformations of the voltage gated sodium channel?

Answer 12

Resting = m gate closed, h gate open

Activated/Open = m gate open, h swinging closed

Inactivated = m gate open, h gate closed

Question 13

Where does a local anesthetic bind on the voltage gated sodium channel?

Answer 13

Binds the R site on the inside of the cell (cytoplasmic side)

Thus the anesthetic must cross the lipid bilayer (and be lipophilic)

Question 14

What does frequency dependent blockade refer to?

Answer 14

Is based on fact that R site is more accessible in inactivated and activated states (because H gate isn’t in the way)

In very active nerves, Na+ channels are more in inactivated/activated states and are thus more easily blocked by local anesthetics

Question 15

What are the 2 common structural classes that local anesthetics fall under? What drugs are used for each class?

Answer 15

Amides and esters

Mnemonic: 2 I’s in amides and one I in esters

Question 16

Are local anesthetics acidic or basic?

Answer 16

Weakly basic except for benzocaine

Acidic and basic properties related to pKa and ionization state of tertiary amine

Question 17

Do charged or uncharged forms cross the membrane?

Answer 17

Only uncharged molecules cross the lipid bilayer

*But the charged form more adequately binds (is the active form at the Na+ channel)

Question 18

What are the primary determinants of onset time of local anesthetics? How could you speed up onset?

Answer 18

Primary determinants = pH and pKa

Speed up onset time by adding sodium bicarb (artificially raise pH and have more uncharged form that can cross the bilayer)

Drug with low pKa works faster

Question 19

What is the primary determinant of potency of local anesthetics?

Answer 19

Lipid solubility

More lipophilic = more potent = can give less of the drug (smaller dose)

Question 20

What is the primary determination of duration?

Answer 20

Protein binding (not blood proteins but tissue proteins!)

Binding to tissue proteins creates a depot of local anesthetic that can be distributed to the nerve

More protein bound = lasts longer (Ropivicaine, Bupivicaine)

Question 21

How could you keep local anesthetic near the nerve?

Answer 21

*Note: this applies to drugs that aren’t highly protein bound

Epinephrine to give vasoconstriction

Could also give alpha-2 agonist (epi or dexmedetomidine or clonidine)

Question 22

What is the only anesthetic that can be used intravenously?

Answer 22

Lidocaine

*Low doses are used to treat arrhythmias

Question 23

What are the indications for neuraxial anesthesia?

Answer 23

Surgery for the chest or below

Question 24

At what level does the spinal cord terminate in adults? Infants? What about the dural sac?

Answer 24

Spinal cord – adult: L1-2

Spinal cord – infant: L2-3

Dural Sac: S1-2

Question 25

What is the difference between spinal and epidural?

Answer 25

Spinal is at the level of L3-L5 and the drug is deposited around the cauda equina – everything below is blocked without sparing

Epidural is administered at the nerve roots for any level and blockade occurs bilaterally (concentrated to the areas around the site of injection, with sparing)

Question 26

When do you see respiratory effects to neuraxial anesthesia?

Answer 26

Not seen for thoracic level blockade

See respiratory arrest with high spinal (not due to phrenic nerve but is due to low bp)

Question 27

What factors determines absorption of local anesthetics?

Answer 27

Vascularity of area, drug properties, patient properties, addition of vasoconstrictors

Question 28

What areas have the most –> least absorption?

Answer 28

ICE Acronym: intercostal > caudal > epidural

then brachial plexus followed by sciatic

Question 29

How does renal failure or acidosis affect absorption?

Answer 29

Renal failure is accompanied by low Hb and increased CO (increased blood flow to area = more absorption of local anesthetics)

Acidosis gives more charged molecules which are more easily absorbed by blood

Question 30

What are the sites of elimination for esters vs amides?

Answer 30

Esters = in plasma

Amides = in liver (CYP450)

Question 31

What are the max recommended doses for bupivicaine and lidocaine?

Answer 31

Bupivicaine – adults = 3mg/kg
Bupivicaine – neonates = 2.5 mg/kg

Lidocaine = 5mg/kg
Lidocaine + epi = 7 mg/kg

*Note: bupivicaine is highly protein bound and thus not affected by epi

Question 32

How does respiratory acidosis affect protein binding?

Answer 32

Leads to decreased protein binding, so there’s an increased free fraction of drug delivered to the brain and neurotoxicity can result

Question 33

If slow absorption causes toxicity, which will happen first, neurotoxicity or cardiotoxicity?

Answer 33

Neurotoxicity will occur before cardiotoxicity

Question 34

What is the specific therapy for local anesthetic toxicity?

*ex: for cardiotoxicity

Answer 34

Intralipid

a lipophilic drug that will sequester local anesthetics

Question 35

What types of allergic reactions can occur with local anesthetics?

Answer 35

Type 1 or 4 hypersensitivity

Typically from esters (which are metabolized to PABA)

Question 36

What is PDPH?

Answer 36

Post Dural Puncture Headache

Is common complication of neuraxial anesthesia

Is positional (person feels better standing or sitting vs laying down)