Local Anesthetics Flashcards
Local anesthetics reversibly block afferent nerve transmission to produce analgesia and anesthesia without loss of consciousness. What are the 3 ways in order easiest to hardest.
- Autonomic blockade
- Somatic sensory blockade
- Somatic motor blockade
LAs administered near the site of action.
How are Local Anesthetics used
- They are infiltrated around the nerve,
- applied topically to the skin and mucous membranes, or
- injected into blood vessels that are first exsanguinated in order to provide intravenous regional anesthesia
- They are also injected into the subarachnoid and epidural spaces for diffusion to desired levels in the spinal column
Myelinated Nerve Fiber:
Unmyelinated Nerve Fiber:
A Schwann-cell wraps itself around the axon several times, enveloping the axon in a myelin sheath
A single Schwann cell surrounds several axons
Importance of Myelination.
Myelinated vs Unmyelinated Fibers
Conduction:
Propagation of impulses is similar in both
Unmyelinated fibers: impulses travel along the length of the fiber in a continuous fashion
Myelinated fibers, conduction is “saltatory”so fast (50X) that it appears as if impulses leap from one node of Ranvier (no myelin) to the next
Membrane:
Ion Channels are guarded by a gating mechanism. How does this mechanism operate
opens or closes depending on changing physiologic conditions
The membrane forms a barrier across which there is movement of ions along a concentration gradient between the intracellular and extracellular spaces
The membrane forms a barrier across which there is movement of ions along a concentration gradient between the intracellular and extracellular spaces
EXTRAcellular contains a high concentration of SODIUM and low concentration of potassium; reverse for intracellular
Nerve Fibers:
The velocity an impulse travels is proportional to
The diameter of the fiber: the larger the diameter, the higher the conduction velocity
How are fibers classified
Fibers classified according to diameter, three types: Primary afferent axons
A, B and C fibers
Describe A fibers
(myelinated) 1 to 22 microns Subdivided into: α β γ δ in order of decreasing size
Describe B fibers
(myelinated) 1 to 3 micrometers
Describe C fibers
(unmyelinated fibers) 0.1 to 2.5 micrometers
A-alpha fibers:
MP
motor & proprioception
A-beta fibers:
MTP
motor, touch, pressure
A- gamma fibers:
M
motor/muscle tone (muscle spindle)
A-delta fibers:
PTT
fast pain pain, temperature,touch
B-fibers:
PREganglionic autonomic
C- fibers:
Slow/ dull pain, temperature, touch, POSTganglionic autonomic– NO MYELIN
Nerve Fibers fast and slow pathways.
What is the Slowest of the A fibers?
Slowest nerve fiber?
Myelinated A-delta fibers (slowest of the A fibers)
Unmyelinated C fibers (much slower)
Conduction depends on?
Large fibers have the highest conduction velocity and the lowest threshold for excitability
Clinically…. The sensitivity of a peripheral nerve to LA is inversely related to size. That is why you see autonomic blockade first, sensory second and motor last.
In motor neuron, due to the space between the nodes are larger you’ll need more anesthetic to cover a larger area.
Difference between clinical observation and research theories
anatomic issues (larger nerves found deeper in nerve bundles – harder for the LA to reach) variable activity in different nerves (pain fibers fire at higher frequency)….i.e. frequency dependent blockade variable ion channel mechanisms
Difference between clinical observation and research theories
anatomic issues
(larger nerves found deeper in nerve bundles – harder for the LA to reach)
variable activity in different nerves (pain fibers fire at higher frequency)….i.e. frequency dependent blockade
variable ion channel mechanisms
Autonomic nerves are outside of the bundle of nerve fibers and are readily and easily blocked first
Activity also affects blockade. Autonomic are consistently firing over motor.
Frequency dependent blockade.
Outer surface of a peripheral nerve is known as the
mantle (usually more proximal structures)
Inner surface known as
core (these fibers usually serve more distal structures)
THE SEQUENCE OF ONSET AND RECOVERY FROM A LOCAL ANESTHETIC BLOCK IN A MIXED PERIPHERAL NERVE RELIES HEAVILY ON WHERE IT IS LOCATED
Autonomic block is seen first
Can be helpful in assessment.
Clinical sequence of anesthesia:
1st- Autonomic sympathetic block (vasodilatation, warm skin)
2nd – Loss pain and temperature sensation
3rd – Loss of proprioception
4th - Loss of touch and pressure
5th – Motor blockade
Nerve Blockade is caused by prevention of voltage dependent increase in Na Conductance
Local anesthetic will bind to a local voltage gated Na+ channel in the nerve membrane ultimate promoting action potential propagation.
They bind in the inactivated closed state
(resting, active, inactive- frequency dependent blockade). The more the channel changes states the easier it is to block.
Local anesthetics bind at specific sites on the internal H gate of the channel & physically obstruct the external openings of the channels
Local anesthetics bind at specific sites on the internal H gate of the channel & physically obstruct the external openings of the channels
Where do LAs bind on a channel ?
Local anesthetics bind at specific sites on the internal H gate of the channel & physically obstruct the external openings of the channels
Acting as a pore blocker
What does Local anesthetics prevent?
Local anesthetics prevent passage of sodium ions through these channels by binding and stabilizing them in the inactivated-closed conformational state.
Essentially acting as an inverse agonist holding in the inactivated close state.
Local anesthetics- blocks impulse conduction during which phase of the action potential
depolarization phase so it does not reach threshold there preventing action potential
- What state do Local Anesthetics easily ACCESS nerve cell Na channels
In what state LA’s easily bind to the receptor
- in the “activated-open”
2. in the “inactivated-closed” state
The more frequently the nerve is in this state, (i.e. cycled through an action potential) the more rapidly blockade occurs
Frequency or Use Dependent Blockade
Resting nerve less sensitive to block than a repetitively stimulated nerve. How are resting nerves blocked
Lipid solubility determines (i.e. it has to diffuse through the axonal membrane instead of through the Na channel to reach its target)
PKa is important.
What contributes to differential nerve block
Distance between Nodes of Ranvier in myelinated fibers contributes to differential nerve block
The internodal distance increases with fiber diameter
An impulse can make it through two blocked nodes but not a third
What happens with the Blockade of three nodes (1cm)
eliminates conduction along a myelinated nerve fiber (A fibers)
Differential Nerve Block with bupivacaine
Bupivacaine was the first local anesthetic shown to produce a beneficial differential block: Sensory block with incomplete motor block
Bupivacine promotes Sensory block with incomplete motor block
What fibers are blocked and what fibers are spared
Pain conducting fibers (A delta, C fibers) blocked
A alpha, beta, & gamma fibers not completely blocked
Patients feel pressure but not pain with surgical stimulation
Local anesthetics are classified chemically
As aminoamides or aminoesters
The typical molecule consists of a lipophilic head (an aromatic ring), an intermediate chain containing either an amide (NH) or an ester (COO-) and a hydrophilic tail (a tertiary amine).
