Exam 2: Local Anesthetics Flashcards
1
Q
Local anesthetics
A
- Local anesthetics (LA) are drugs that reversibly block conduction of electrical impulses along nerve fibers They are a MAJOR component of clinical anesthesia and are increasingly being used to treat chronic and acute pain
2
Q
Nerve anatomy
A
- The axon, and extension of the neuron, is the functional of peripheral nerves
- Major components include axolemma and axoplasm
- Schwann cells surround each axon
- Nerves are considered either myelinated or unmyelinated based on type of axon covering
- Will be blocking axons of 1st order neurons
-
Not all nerves are created the same – how fast they’re affected, for how long they’re affected
- Un/myelinated
3
Q
SCHWANN CELLS
A
- Serve to support and insulate each axon
- Unmyelinated nerves - In smaller nerves, single Schwann cells cover several axons
- LA will get to these first! Bc not as much tissue to get through
- Myelinated nerves - In larger nerves, the Schwann cell covers only one axon and has several concentric layers of myelin
4
Q
Nerve anatomy - nodes of ranvier
A
- Nodes of Ranvier are periodic segments between Schwann cells along the axon that do not contain myelin
- Voltage-gated sodium (Na+) channels are located in these segments and are the primary site of LA action
- Action potentials jump from nerve to nerve, known as saltatory conduction
- To block impulses in myelinated fibers it is necessary for LA to inhibit channels in three successive nodes
- Must block at least 3 nodes to block the AP from going down
5
Q
Nerve anatomy - fasciculi
A
- Bundles of axons are called fasciculi
- Fasciculi are covered with three layers of connective tissue:
- Endoneurium is a thin, delicate collagen that embeds the axon in the fascicule
- Perineurium consists of layers of flattened cells that binds groups of fascicles together
- Epineurium surrounds the perineurium and is composed of connective tissue that holds fascicles together to form a peripheral nerve
- LA must diffuse through these layers to exert their effects
-
Will boil down to how much CT is surrounding that nerve! This is why nerves will look differently
- Nerves come out of spine and converge and diverge
-
Dermatomes are referring to nerve roots
- Vs. Myotomes
- Ex: C5 = endoneurium (ind nerve fibers) and probably perineurium (holding together several fascicles), C5 + C6 held together by epineuereum (bundles of nerves)
- Danger is when you actually inject under the perineurium – pressure/nerve injury/ischemia
6
Q
Nerve conduction physiology
A
- Resting membrane potential of axon
- -70 mV to -90 mV
- Caused by an imbalance axoplasm and extracellular fluid
- Physiologic mechanisms help create this
- Na+ – K+ pump in axolemma
- Intracellular ratio of potassium is 30:1
- Membrane impermeable to other ions (such as Na+)
- Excess of negatively charged ions in axoplasm
- Nernst equation
- Expresses the charge created by K+ concentration gradient
- When an electrical impulse is applied to a nerve, membrane potential is reversed due to influx of Na+
- Overrides K+ directed at maintaining potential
- Once membrane potential reaches 20mV, Na+ in inactive state
- Na+ - K+ pump restores resting membrane potential
- Three Na+ ions leave for each two K+ that enter
- LAs are going to block this! But they don’t alter the RMP!!
7
Q
Local Anesthetic MOA
A
(BASE, you know this bc it’s bound to an acid)
-
Bind to specific sites on the Na+ channel
- Preferential to open and inactive states
- To a lesser extent, also blocks:
- K+ channels
- Ca++ channels
- G protein-coupled receptors
- Block transmission of nerve impulses
- LA do not alter the resting transmembrane potential or threshold potential
- Modulated receptor hypothesis of LA action
- Preference to attach during active or inactive states
- Frequency-Dependent Blockade
- Resting nerve is less sensitive to LA than one repeatedly stimulated
- AKA “use-dependent” or “phasic block”
- Will see quicker block if they’re opening/closing their sodium channels compared to someone at rest ≅ ketamine (works best when someone is already ramped up – give it right at the time of surgical incision)
- ALL local anesthetics are weak bases, not ionized, so it diffuses across.
- Diffusion of an unionized base across the nerve sheath and membrane
- Re-equilibrium between the base and cationic forms in the axoplasm
- Binding of the cation to a receptor inside the sodium channel, resulting in its blockade and inhibition of Na+ conduction.
- Pref when open or inactive state.
8
Q
Differential blockade
A
- Nerves have different sensitivity when exposed to LA
- Small diameter and lack of myelin enhance sensitivity
- Larger nerves conduct impulses faster and are harder to block
- In general, preganglionic are blocked with low concentrations, followed by small C fiber and small A fibers resulting in a loss of pain and temperature.
- Touch and proprioception can still be present but not pain of surgical stimulation
- In an anxious patient any sensation can be seen as LA failure
- LA’s bind to smaller, unmyelinated nerves
-
If you want to know early if your block is working, you’ll see vasodilation, flushed
- Block small, preganglionic nerves 1st – that control SNS tone.
- Those nerves are running in the same channel as the sensory/motor nerves
- Why spinal epidural will see hypotension – 8 oz cup/8 oz container → 8 oz cup in 16 oz container
- Next will see loss of sensation
- Next will lose motor
9
Q
Fiber Type Aa:
fn, diameter, myelination, block onset
A
Aa = alpha
fn: proprioception, motor
“alpha motor neuron”
diameter 6-22 um
myelination - heavy
block onset - last (lots of myelin always takes a long time)
10
Q
Fiber type AB (A beta)
fn, diameter, myelination, block onset
A
- fn: touch, pressure “betta touch”
- diameter 6-22 um
- myelination: heavy
- block onset: intermediate
11
Q
Fiber Type A gamma:
fn
diameter
myelination
block onset
A
- fn: muscle tone “Grandma’s (gamma) got muscle tone!”
- diameter: 3-6 um
- myelination: heavy
- block onset: intermediate (only last one is Aa)
12
Q
Fiber type A Delta:
fn
diameter
myelination
block onset
A
- fn: pain, cold temp, touch
- “Manny was in TRI-delta - pain, cold, touch”
- diameter: 1-5 um
- myelination: heavy
- block onset: intermediate
13
Q
Fiber Type B
fn
diameter
myelination
block onset
A
- fn - preganglionic autonomic vasomotor
- diameter <3 um
- myelination - LIGHT
- block onset - early
14
Q
Fiber Type C Sypathetic
fn
diameter
myelination
block onset
A
- fn - postganglionic (autonomic) vasomotor
- diameter 0.3-1.3 um
- myelination - NONE
- block onset - EARLY
15
Q
Fiber Type C Doral Root
fn
diameter
myelination
block onset
A
- fn - pain, warm and cold temperature, touch
- diameter 0.4 - 1.2
- myelination - NONE
- block onset - EARLY
cold temp is Type A delta fiber, aaaaand Type C Dorsal Root fibers!! Double trouble, that’s why I’m always cold.
16
Q
2 people important to the hx of LA’s
A
- Karl Koller introduced Cocaine as the first LA in 1884
- Halsted recognized its potential for regional and spinal anesthesia
17
Q
LA’s have 3 characteristic segments
A
- An unsaturated, aromatic ring system (lipophilic portion of the molecule)
- A tertiary amine (hydrophilic portion of the molecule)
- Either an ester or an amide linkage binds the aromatic ring to the carbon group.
18
Q
Ester vs. Amide
A
- The ester or amide linkage relevant clinically because of its implications for metabolism, duration and allergic potential
- Esters metab in the plasma by plasma esterase – starts to be metab as soon as it gets into the circ → SHORTER ACTING
- Amide metab by the liver
- Changes in chemical structure affect drug potency, speed of onset, duration of action, and differential block potential
19
Q
Ester LA’s (5)
A
the one that doesn’t have “i’s”
Procaine
Chloroprocaine
Tetracaine
Cocaine
Benzocaine
20
Q
Amide LA’s (6)
A
the ones with “i’s” in them
Lidocaine
Mepivicaine
Prilocaine
Bupivicaine
Ropivicaine
Articaine
21
Q
Clinical Differences between Ester and Amide LA’s: ESTERS
A
- Ester metabolism is catalyzed by plasma and tissue cholinesterase via hydrolysis; occurs throughout the body and is rapid
- although LA allergy is uncommon, esters have a higher potential, and if pts exhibit an allergy to an ester, all esters should be avoided
- ester drugs tend to be shorter acting d/t ready metabolism; tetracaine is the longest acting ester
Aside:
- Breaks down into Paraminobenzoic acid (?)
- Tease out if it’s a true allergy bc HR 110 might have been lido that has Epi in it
- Amide had like 1-2 cases
- Of esters – tetracaine is longest acting, the rest of them at 90 minutes or less
- Amides might last 8+ hrs
22
Q
Clinical Differences between Ester and Amide LA’s: AMIDES
A
- Amides are metabolized in the liver by the CYP1A2 and CYP3A4 and thus a significant blood level may develop with rapid absorption
- Allergy to amides is extremely rare; there is no cross allergy among the amide class or between ester and amide agents
- Amides are longer acting bc they are more lipophilic and protein-bound. They require transport to the liver for metabolism
