7 - Local Anesthetics Flashcards
Chemical structural components of local anesthetics
Aromatic Moiety
Linker region
Substituted Amine
How are local anesthetics classified?
Based on the linker region
Local Anesthetics - Esters
Cocaine Procaine Benzocaine Proparacaine Tetracaine
Local Anesthetics - Amides
Lidocaine Articaine Bupivacaine Mepivacaine Prilocaine Ropivacaine
Local Anesthetics - Ketone
Dyclonine
Local Anesthetics - Ether
Pramoxine
Tetracaine Duration
30 - 60 min
Procaine Duration
30 - 60 min
Chloroprocaine Duration
30 - 60 min
Cocaine Duration
30 - 60 min
Bupivicaine Duration
2 - 5 hours
Lidocaine Duration
1 - 3 hours
Etidocaine Duration
2 - 4 hours
Mepivicaine Duration
1.5 - 3 hours
Tetrodotoxin
A potent Na+ Channel blocker. Not used as an anesthetic because it is too potent/deadly.
Produced in the liver of a Puffer fish
Saxitoxin
“Shellfish Poisoning”
A potent Na+ Channel blocker, produced by algae which is then ingested by shellfish.
Why administer epinephrine with local anesthetic when injecting?
It’s a damn vasoconstrictor, dude. It prevents the anesthetic from spreading, prolonging its effect, and keeping it from harming the rest of your shit
Advantages/considerations of liposomal administration of the new formulation of Bupivacaine
The reservoir is emptied very slowly, so there is long-lasting effect (48 - 72 hours).
Harder to control the possible toxic effects though
Ways to administer anesthesia
Topical Infiltration (Field Block) Nerve Block Intravenous Regional Spinal Epidural
Steps for Intravenous Regional Anesthesia
Exsanguinate the area with a tourniquet
Inject anesthesia distal to the tourniquet (to block systemic distribution)
Difference between Epidural Anesthesia and Spinal Anesthesia
Epidural = Outside the dura mater Sinal = Penetrate the dura mater (usually at the level of the cauda equina)
Local Anesthetics - Master List of CNS Side Effects
Agitation Convulsions Psychosis Depression Sedation Loss of Consciousness
Local Anesthetics - Master List of Cardiovascular Side Effects
Decreases in myocardial excitability Decreases in conduction rate Decreases in force of contraction Vasodilation (Others may occur when local anesthetics are used with epinephrine)
Local Anesthetics - Master List of Smooth Muscle Side Effects
Relaxation of vascular and bronchial muscles
Local Anesthetics - Master List of Skeletal Muscle Side Effects
Reduced neuromuscular transmission
How many isoforms of voltage-gated sodium channels do humans express?
8 (Though local anesthetics are nonselective)
Which sodium channels are preferentially expressed in peripheral neurons?
Nav1.3
Nav1.7
Nav1.8
Nav1.9
Expression of Nav1.3 in peripheral sensory neurons
Embryogenesis - Normally expressed
Adult - Continued expression in sympathetic neurons
Post-Injury - Upregulated in DRG neurons
Expression of Nav1.7 in peripheral sensory neurons
DRG Neurons - Preferentially expressed
Sympathetic Neurons - Preferentially expressed
Expression of Nav1.8 in peripheral sensory neurons
DRG Neurons - Selectively expressed
Expression of Nav1.9 in peripheral sensory neurons
DRG Neurons - Selectively expressed in small-diameter, nonpeptidergic DRG Neurons
Which sodium channels provide the most information about pain?
Nav1.8
Nav1.9
Inherited Erythromelalgia
Nav1.7 gain-of-function Mutation Episodes of intense pain and erythema Affecting one or both hands Evoked by physical activity or cold No good treatment
Paroxysmal Extreme Pain Disorder
Nav1.7 Mutation Starts very early Affects sympathetic nervous system Can have Harlequin Syndrome Scream when they defecate or get touched in perineum Responds to Carbamazepine
Types of A Fibers
A α
A β
A γ
A δ
Types of C Fibers
Sympathetic
Dorsal Root
B Fibers
Preganglionic Sympathetic
Myelinated
A α Fibers
Afferent to muscles & joints
Efferent from muscles & joints
Myelinated
A β Fibers
Afferent to muscles & joints
Efferent from muscles & joints
Myelinated
A γ Fibers
Efferent to muscle spindles
Myelinated
A δ Fibers
Sensory roots
Afferent peripheral nerves
Myelinated
Sympathetic C Fibers
Postganglionic
Unmyelinated
Dorsal Root C Fibers
Sensory Roots
Afferent peripheral nerves
Unmyelinated
Relationship between diameter of fibers and their susceptibility to local anesthetic
Inverse
The larger a fiber is, the less susceptible it is to local anesthetic
TRP Channels
Sensitive to heat/cold/temperature change
Selectively expressed in pain fibers
Opened by Capsaicin
Provide a back door for selectively targeting fibers
How do we get QX-314 into the cell interiors of pain fibers, when it normally can’t penetrate the plasma membrane?
Administer with Capsaicin. QX-314 goes through the TRPV1 channel to enter the cell, and finally reach its target, the Na+ channel inside
TRP Receptors on Pain Fibers
TRPA1
TRPV1
TRP Receptors on Itch Fibers
TRPV1
H1R
TRPA1
MrgprA3
