Lecture 21 - Byram - Local Anesthetics Flashcards
To block nerve transmission, local anesthetics bind to ____
Voltage Gated Sodium Channels
Define neuraxial
Spinal or Epidural
Local anesthetics for myelinated vs non-myelinated nerves
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)
Local anesthetics for core vs mantle fibers
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
What are the 3 types of nerve fibers and which ones are myelinated?
A = myelinated
B = myelinated
C = non-myelinated (thus it’s difficult to block with local anesthetics)
How does fiber size affect “block”-ability
Smaller fibers are easier to block than larger fibers
What are the top 2 easiest fibers to block with local anesthetics?
B fibers (preganglionic sympathetic) are very small and thus the easiest to block
A-delta fibers are the next easiest to block
What is sympathectomy?
Refers to the fact that you will always get sympathetic blockade (because B fibers are the smallest and easiest to block)
What two fibers are involved in pain?
A-delta fibers (associated with sharp pain, ex: when you first stub toe)
C-gamma fibers (dull throbbing pain that occurs after the stub)
What are the functions of the 4 different A nerve fiber subtypes?
A alpha = motor
A beta = tactile, proprioception
A gamma = muscle tone
A delta = pain and cold temperature
For spinal/epidural anesthesia, what types of fibers are the easiest hardest to block?
Sympathetcomy = easiest
sensory = middle
motor = hardest
What are the 3 states/conformations of the voltage gated sodium channel?
Resting = m gate closed, h gate open
Activated/Open = m gate open, h swinging closed
Inactivated = m gate open, h gate closed
Where does a local anesthetic bind on the voltage gated sodium channel?
Binds the R site on the inside of the cell (cytoplasmic side)
Thus the anesthetic must cross the lipid bilayer (and be lipophilic)
What does frequency dependent blockade refer to?
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
What are the 2 common structural classes that local anesthetics fall under? What drugs are used for each class?
Amides and esters
Mnemonic: 2 I’s in amides and one I in esters
Are local anesthetics acidic or basic?
Weakly basic except for benzocaine
Acidic and basic properties related to pKa and ionization state of tertiary amine
Do charged or uncharged forms cross the membrane?
Only uncharged molecules cross the lipid bilayer
*But the charged form more adequately binds (is the active form at the Na+ channel)
What are the primary determinants of onset time of local anesthetics? How could you speed up onset?
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
What is the primary determinant of potency of local anesthetics?
Lipid solubility
More lipophilic = more potent = can give less of the drug (smaller dose)
What is the primary determination of duration?
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)
How could you keep local anesthetic near the nerve?
*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)
What is the only anesthetic that can be used intravenously?
Lidocaine
*Low doses are used to treat arrhythmias
What are the indications for neuraxial anesthesia?
Surgery for the chest or below
At what level does the spinal cord terminate in adults? Infants? What about the dural sac?
Spinal cord – adult: L1-2
Spinal cord – infant: L2-3
Dural Sac: S1-2
What is the difference between spinal and epidural?
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)
When do you see respiratory effects to neuraxial anesthesia?
Not seen for thoracic level blockade
See respiratory arrest with high spinal (not due to phrenic nerve but is due to low bp)
What factors determines absorption of local anesthetics?
Vascularity of area, drug properties, patient properties, addition of vasoconstrictors
What areas have the most –> least absorption?
ICE Acronym: intercostal > caudal > epidural
then brachial plexus followed by sciatic
How does renal failure or acidosis affect absorption?
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
What are the sites of elimination for esters vs amides?
Esters = in plasma
Amides = in liver (CYP450)
What are the max recommended doses for bupivicaine and lidocaine?
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
How does respiratory acidosis affect protein binding?
Leads to decreased protein binding, so there’s an increased free fraction of drug delivered to the brain and neurotoxicity can result
If slow absorption causes toxicity, which will happen first, neurotoxicity or cardiotoxicity?
Neurotoxicity will occur before cardiotoxicity
What is the specific therapy for local anesthetic toxicity?
*ex: for cardiotoxicity
Intralipid
a lipophilic drug that will sequester local anesthetics
What types of allergic reactions can occur with local anesthetics?
Type 1 or 4 hypersensitivity
Typically from esters (which are metabolized to PABA)
What is PDPH?
Post Dural Puncture Headache
Is common complication of neuraxial anesthesia
Is positional (person feels better standing or sitting vs laying down)
