CHAPTER 22 | Local Anesthetics Flashcards
The Na-K-ATPase pump pumps _____ in and _____ out
2 K+ in and 3 Na+ out
The key target of local anesthetics is:
voltage-gated sodium channel
The binding is intracellular and is mediated by what interaction?
Hydrophobic interactions
What mechanism keeps cell membranes at a resting potential?
Na-K-ATPase pump
Individual nerve fibers within each fascicle are surrounded by this layer which is a LOOSE connective tissue containing GLIAL cells, fibroblasts, and blood capillaries
Endoneurium
A dense layer of collagenous connective tissue called that surrounds EACH FASCICLE:
Perineurium
Encases GROUPS OF FASCICLE into a cylindrical sheath:
Epineurium
True or false:
Myelin sheaths shield nerve fibers from local anesthetics, thus making them less sensitive to local anesthetics?
FALSE
Local anesthetics bind at the nodes between myelin segments, making myelinated fibers MORE sensitive to Local Anesthetics
- Myelin improves the electrical insulation of nerve fibers and permits more rapid impulse transmission via SALTATORY CONDUCTION
Sequence of nerve fibers in the differential block:
B –> C –> A
A FIBERS are large diameter
myelinated fibers which are primarily for:
Motor and Sensory functions
C FIBERS are small-diameter nonmyelinated which are primarily for:
Pain, Temperature, and Autonomic functions
What is the basic chemical structure of local anesthetics?
1) Benzene ring
2) Link
3) Amine
True or false:
Local anesthetics are weak acids and become uncharged by giving a proton away on the amine part.
FALSE
Local anesthetics are weak BASES and become CHARGED by ACCEPTING a proton on the amine part
TRUE or FALSE
The resting membrane potential, approximately −70 to −90 mV in neurons is derived predominantly from a difference in the intracellular and extracellular concentrations of potassium and sodium ions
FALSE
The resting membrane potential is -60 to -70 mV
TRUE or FALSE
The spike in membrane potential peaks around +50 mV, at which point the influx of sodium is replaced with an efflux of potassium, causing a reversal of membrane potential, or repolarization.
TRUE
+50 mV is the spike to push Na in and push K out => REPOLARIZATION
TRUE of voltage-gated sodium channel EXCEPT:
A. Each voltage-gated sodium channel is a complex made up of one principal α-subunit and one or more auxiliary β- subunits
B. B -subunit is a single-polypeptide transmembrane protein that contains most of the key components of the channel function
C It has four homologous α-helical domains (D1 to D4) that form the channel pore and control ion selectivity, voltage-sensing regions that regulate gating function and inactivation, and phosphorylation sites for modulation by protein kinases
D. A triad of highly hydrophobic amino acids (isoleucine, phenylalanine, and methionine [IFM]) appears to be an important structural determinant of fast activation
B . B -subunit is a single-polypeptide transmembrane protein that contains most of the key components of the channel function
The a-subunit contains MOST of the key components of the channel function.
The variant of Voltage-gated Na channel involved in Hyperkalemic periodic
paralysis:
Voltage-gated Na channel 1.4
Nine isoforms of voltage-gated sodium channels (NaV 1.1 to NaV 1.9)
have been identified; each relates to a unique α-subunit subtype.
NaV 1.4 is expressed in skeletal muscles and primarily affected in Hyperkalemic periodic paralysis
The variant of Voltage-gated Na channel involved in Brugada syndrome, a long
QT syndrome.
Voltage-gated Na channel 1.5
Nine isoforms of voltage-gated sodium channels (NaV 1.1 to NaV 1.9)
have been identified; each relates to a unique α-subunit subtype.
NaV 1.5 is expressed in cardiac muscles and embryonic neurons. It is primarily affected in Brugada Syndrome
True of the LIPID MEMBRANE bilayer EXCEPT:
A. The natural “local anesthetic” tetrodotoxin (TTX) binds at the external
surface of the sodium channel and actively interact with the clinically used local anesthetics
B. The neutral base (N) is more LIPID SOLUBLE preferentially partitions into the lipophilic membrane interior, and easily passes through the membrane.
C. The charged form (NH+) is more WATER SOLUBLE and binds to the sodium
channel at the negatively charged membrane surface
D. The N form can cause membrane expansion and closure of the sodium
channel.
E. The NH+ form will directly inhibit the sodium channel by binding with a local
anesthetic receptor.
A. Tetrodotoxin (TTX) binds at the external
surface of the sodium channel and actively interact with the clinically used local anesthetics.
- The natural “local anesthetic” tetrodotoxin (TTX) binds at the external surface of the sodium channel and has NO INTERACTION with the clinically used local anesthetics
This THEORY proposes that local anesthetics bind to the open or the inactivated channels more avidly than the resting channels.
Modulated-receptor Theory
Refers to the reduction in the number of sodium channels for a given drug
concentration present in the open state at equilibrium.
TONIC BLOCKADE
This theory assumes that the intrinsic binding affinity remains essentially CONSTANT regardless of a channel’s conformation
Guarded-receptor Theory