Local Anesthesia Flashcards
What is the fundamental difference between local anesthetics and environmental toxins.?
environmental toxins have irreversible effects whereas local anesthetics produce only temporary, and fully reversible, blockade of neuronal activity.
What is the MOA of local anesthetics?
fully reversible neuronal blockade (thought to work on voltage-gated sodium channels involved in the process of neuronal conduction)
Where do local anesthetics function?
nerve axons only
A portion of local anesthetic action is thought to arise from what?
drug is “dissolved” in the neuronal membrane and modulates sodium channel funciton and has surface-charge disruption
Why are action potentials not propogated with administration of local anesthetics?
In the presence of local anesthetic, the critical threshold for spontaneous opening of sodium channels in the immediate vicinity is never reached
True or false: local anesthetics have no effect on the resting membrane potential.
TRUE
List the factors associated with differential blockade.
- Diameter of the nerve bundle (larger diameter nerves require more local anesthetic)
- Position in the nerve bundle (takes longer to impact fibers in the center of the bundle)
- Myelination (“zone of anesthetic” is longer for a myelinated nerve than for a non-myelinated nerve)
- Extent of spontaneous nerve activity (greater blockade in hyperkalemia; less blockade in hypercalcemia)
Which fibers are most affected by local anesthetics?
B- myelinated, larger diameter
C (symp)- nonmyelinated, smallest diameter
C (dorsal root)- nonmyelinated, small diameter
What signals do B and C (symp) fibers carry?
vasomotor, pilomotor, visceromotor
What signals do C (dorsal root) fibers carry?
protopathic
Which fibers are least affected by local anesthetics?
A-alpha
A-beta
myelinated, large
Which signals do A-alpha and A-beta carry?
motor and proprioception
In what states of the Na channel can local anesthetics bind?
activated
inactivated
Why can local anesthetics not bind to the sodium channel in its resting state?
too bulky
In what state of Na channel does the majority of local anesthetic drug binding take place?
inactivated
activated too transient
What is required for passage of a drug across a membrane?
neutral or uncharged state
At what pKa do most local anesthetics act?
8 (weak bases)
What is the pH within nerves?
approximately 7
What is the significance of a pH of 7 inside nerves?
local anesthetics (pKa of 8) get largely ionized and “stuck” within the nerve, which is necessary for sodium channel binding to take place
What happens if extraneural pH changes to 9?
10X more drug (pKa of 8) exists in the neutral state and passes easily across the nerve membrane
What happens if the extraneural pH changes to 7?
10X more drug (pKa of 8) exists in the ionized (charged) form and is trapped in the extraneural state (leads to a less durable nerve block).
What happens if extraneural pH changes to 6 (ex. infalmmation)?
only an extremely low proportion of applied drug can access the nerve and hence the blockade might fail, or at the very least, be extremely weak
Why should you not inject local anesthetic in an inflamed area?
blockade might fail and lead to repeated application until physician has surpassed the maximum recommended dose.
Fibers in the center of a nerve bundle serve what?
distant anatomic locations