Local Anesthetics Flashcards
Neurophysiology
-LAs produce a ____ of sensation in a limited region by ____ impulse conduction in axons of sensory neurons.
-Neurons are ____ cells and are the main ___ of the nervous system.
-The resting membrane potential is generated by ____,____,_____.
-Loss, blocking
-Excitable, signaling units
-N/K/ATPase, K leak channels, Na leak channels
Conduction is faster in… (2)
- in axons with larger diameter
- in myelinated axons
Peptide Biotoxins (MOA)
Block Nav channel from outside
– Saxitoxin (from marine dinoflagellates)
– Tetrodotoxin (from puffer fish)
Local Anesthetics (MOA)
Block Na-channel from cytosolic side
Local anesthetics are ____
What predominates in ECF?
-Weak bases
Protonated, ionized form BH+ predominates in ECF
Unprotonated, non-ionized form B also is present in ECF
(LA) - Non-ionized form has ____
-High lipid solubility
Diffuses through membrane
Protonated in the cytosol to BH+ (pH ICF < pH ECF)
BH+ can’t diffuse back out (“ion trapping”)
- BH+ diffuses into ___ channel
- BH+ binds to sites in channel, ____ channel function
-Affinity for sites is highest in ____ channel
-Open, activated
-Blocking
-Inactivated
Factors influencing the action of LAs
- Membrane depolarization
- pH
- Axon activation
- Differential sensitivity
Membrane depolarization / Axon activation =
Increase block of NaV channel (use-dependent / activity-dependent)
pH,ECF affects fraction of drug in LA (diffusible) form
- Low pH,ECF (inflammation) = Increase fraction in BH+ form = Decrease Rate of Onset
- Addition of NaHCO3 to increase pH of LA solution = Increase fraction in LA form = Increase Rate of Onset
(pain on injection is decreased)
Differential Sensitivity (diameter / myelination vs. sensitivity)
-Small diameter axons are more sensitive to block than large diameter axons
-Unmyelinated axons are more sensitive to block than myelinated axons
Differential Sensitivity
- Aδ and C sensory pain neurons fire at ____ frequencies in situations that cause pain = ____
-Higher frequencies
- = use-dependent block
*May help to explain why pain sensation is blocked before temperature, touch, deep pressure
Local Anesthetic: Duration of Action (ester vs. amide)
Ester LAs metabolized by esterases in plasma/liver
-SHORT DURATION (min)
Amide LAs metabolized in liver by CYPs, then conjugation
-LONGER DURATION (hr)
Amide LAs
-Hepatic disease or decreased hepatic blood flow = _____ duration of action
Increases duration of action
LAs: Duration prolonged by co-administration with vasoconstrictor
-EPI
-Contraindicated in tissues supplied by end arteries to avoid ischemia/necrosis
-Additional benefits: decreased bleeding, increased visualization of surgical field
