Local Anesthetics Flashcards
1
Q
What is the axolemma?
A
cell membrane of
2
Q
What do schwann cells do in unmyelinated nerves?
A
one single schwann cell will cover multiple axons.
3
Q
What do schwann cells do in myelinated nerves?
A
in larger nerves, one schwann cell covers only one axon and has several concentric layers of myelin
4
Q
What are the breaks in the myelin sheath called?
A
Nodes of Ravier
5
Q
What level of nerves/neurons do we block?
A
primarily first order
6
Q
Will unmyelinated or myelinated nerves be blocked faster?
A
unmyelinated
7
Q
Where are VG Na channels located along the axon?
A
at/in the Nodes of Ranvier
8
Q
To block a myelinated axon, how much must be blocked?
A
At least 3 nodes of ranvier in a row
9
Q
What is a fasciculi?
A
bundle of axons
10
Q
How many layers cover a fasciculi?
A
3;
Endoneurium
Perineurium
Epineurium
11
Q
What is the endoneurium?
A
thin delicate collagen that embeds the axon in the fascicule
12
Q
What is the perineurium?
A
layers of flattened cells that binds groups of fascicles together
- bundles of fascicles
13
Q
What is the epineurium?
A
surrounds the perineurium and is composed of connective tissue that holds fascicles together to perform a peripheral nerve
14
Q
Injecting into the perineurium does what?
A
separates the nerves
15
Q
injecting into the perineurium injecting into he endoneurium will be good or bad?
A
direct nerve injury
- needle trauma
- local anesthetic volume will cause pressure
16
Q
injecting into the perineurium injecting into he endoneurium will be good or bad?
A
direct nerve injury
- needle trauma
- local anesthetic volume will cause pressure
17
Q
What is the normal neuron RMP?
A
-70 to -90mV
18
Q
What is the most important pump in the axolemma?
A
Na+/K+ ATPase pump?
2K in
3Na out
19
Q
What is the intracellular K:Na concentration?
A
30:1
20
Q
What does the Nernst equation express?
A
the charge created by the K concentration gradient
21
Q
In the axoplasm, is there excess anions or cations?
A
anions
negatively charged ions
22
Q
What causes a nerve cell depolarization (what ion movement?)
A
VG na channels open, Na rushes INTO the cell
[overrides the K that is maintaining the potential]
23
Q
When do the VG Na channels reach an inactive state?
A
+20mV
24
Q
What phases of the Na channel opening do LA act on?
A
open and inactive
NOT closed
25
What phases of the Na channel opening do LA act on [preferentially]?
open and inactive
NOT closed
26
What confirmation is the Na channel in during repolarization?
inactive
27
Will LA bind to the VG Na channels when in the closed state?
open state?
inactive state?
closed- no
open- yes
inactive- yes
28
Will LA bind to the VG Na channels when in the closed state?
open state?
inactive state?
closed- no
open- yes
inactive- yes
29
LA act on which channels?
Na (preferentially)
K
Ca
G-protein coupled receptors
30
LA prevents movement of what ion and in which direction?
binds to VG Na channel;
| Na cannot rush in, no action potential
31
How to LA affect the action potential?
LA block the transmission of the AP;
do not change the RMP
32
How do LA affect the RMP?
they don't alter the RMP, only AP transmission
33
What is "frequency-dependent blockade"?
resting nerve is less sensitive to LA
a stimulated nerve will be affected more by the LA
34
What is "use-dependent" block?
resting nerve is less sensitive to LA
a stimulated nerve will be affected more by the LA
35
What is "phasic block"?
resting nerve is less sensitive to LA
a stimulated nerve will be affected more by the LA
36
What is the LA MOA?
1. UNionized drug crosses nerve sheath & cell membrane
2. Re-equilibrium drug binds with H+ ion inside the cell (inside the bi-phospholipid layer)
3. drugH binds to open or inactive Na channel producing BLOCK
37
ALL local anesthetics are acids or bases?
WEAK BASE
38
Are big or small nerves easier to block?
small, unmyelinated
39
What will be seen first, before loss of sensation or movement? Why?
vasodilation d/t blockage of small preganglionic (controls SNS) fibers first
40
What type of nerves are harder to block?
big, myelinated
41
What will you see first when a nerve is blocked?
vasodilation/flushing d/t blocking of small preganglionic neurons (SNS)
42
Why do pregnant women complain of nausea after getting a spinal?
vasodilation distal to the block resulting in hypotension =
43
is sensation or motor lost first?
sensation - smaller block = loss of sensation not motor
Be careful d/t unintended injury
44
If motor is blocked, what does that tell us?
preganglionic & sensory nerves should be blocked
45
Who is Karl Koller?
introduced cocaine in 1884
46
Who first began using a drug as a local anesthetic?
Karl Koller
47
When was a drug first used as a local anesthetic?
1884
48
What are the 3 specific portion of the chemical structure of local anesthetics?
```
aromatic ring (makes it lipophilic)
tertiary ring (hydorphilic)
ester OR amide linkage
```
49
Why can local anesthetics get through the axon?
aromatic ring
50
What are 3 characteristics that differentiate ester vs amide local anesthetics?
1. metabolism
2. duration of action
3. allergic potential
51
How to know what kind a local anesthetic is?
ester (one i)
| amide (two i)
52
How are amides metabolized?
by the liver
53
Which type of local anesthetics will have more allergies?
esters
54
What is a metabolite that increases the risk of an allergic reaction?
PABA
para-amino benzoic acid
is made from ester local anesthetics
55
What is a metabolite that increases the risk of an allergic reaction?
PABA
para-amino benzoic acid
is made from ester local anesthetics
56
When does the affect of the LA wear off?
when it goes somewhere else in the body
| more volume can last longer b/c it takes longer to go elsewhere in the body
57
What is C(m)
minimum concentration of LA necessary to produce conduction blockade of a nerve impulse
58
How does the C(m) of sensory fibers differ from the C(m) of motor fibers?
C(m) of motor fibers is approximately TWICE that of sensory fibers
59
Does intrathecal or spinal anesthesia require more local anesthetic?
epidural
60
When injecting an epidural (labor) what is the concentration/volume like?
lower concentration, higher volume
NEVER entering into the dura; hoping to get the nerve roots as they exit
large volume will spread
To allow sensation of contraction & assist
61
Spinal is where?
intrathecal; compromising the dura
injecting onto the nerve
FANTASTIC BLOCK
62
Where does the spinal cord end?
L1-L2?
63
Where does the dural sac end?
sacrum
64
After L1 what is present in the spinal cord?
3 nerves (sacral roots)
65
What is the ligament that attaches the spinal cord to the sacrum?
Coccygeal ligament
66
How will increasing the concentration affect the onset?
increased concentration = faster onset
67
How will increasing the concentration affect the onset?
increased concentration = faster onset
68
Never inject more than __ mL of a drug
5mL
69
ALWAYS ___ before you inject
aspirate
70
Local anesthetics have a strong relationship between potency and ___
lipid solubility
71
What types of local anesthetics are water insoluble?
larger lipid-soluble
72
What type of local anesthetics are highly protein bound?
larger lipid soluble
73
What does lipid solubility of local anesthetics correlate with? (5)
protein binding
increased potency
longer duration of action
tendency for severe cardiac toxicity
74
Potent local anesthetics will produce what?
good, strong, block
BAD if injected into the wrong place
75
What type of local anesthetics (E or A) are lipophilic & protein bound?
AMIDE
76
What kind of local anesthetics have more cardio toxicity?
BUPIVICAINE
77
What kind of protein do local anesthetics bind to preferentially?
alpha1-acid glycoprotein
78
What affects the duration of action of a local anesthetic?
1. lipid solubility
2. protein binding [↑ protein binding = longer DOA]
3. injection site [is it vascular?]
79
For weak bases, closer to what pH means more ionized drug?
7.4
| cannot cross membrane when ionized
80
Local anesthetics with a pKa closer to 7.4 will be slower or faster?
faster; LESS ionized drug
81
What are the 3 local anesthetics that do not cause vasodilation? (or the least)
lidocaine, ropivacaine, cocaine
82
How does vasodilation affect the PK of local anesthetics?
1. decreases the duration of action
| 2. increases plasma concentration [potential toxicity]
83
What determines the plasma level of local anesthetics?
the total dose given,
| not volume or concentration
84
What tissue/location results in the highest blood concentration of local anesthetics?
more vascular..
intravenous
tracheal
caudal
paracervical
85
What tissue/location results in the lowest blood concentration of local anesthetics?
less vascular.. (less to more)
```
subcutaneous
sciatic
brachial
epidural
paracervical
```
86
What are the 2 most common additives to local anesthetics?
1. epinephrine
| 2. sodium bicarbonate
87
What are 6 other less common additives to local anesthetics?
```
clonidine
dexmedetomidine
opioids
ketorolac
dexamethasone
hyaluronidase
```
88
Why is epinephrine added to local anesthetics?
it is a vasoconstrictor that reduces the rate of vascular absorption
89
How does epinephrine change the PK/PD of a local anesthetic? (3)
1. increased duration
2. increased potency
3. decreased risk of toxicity
90
What is the benefit of adding bicarb to the local anesthetic?
1. adding bicarb will increase the pH of the solution, resulting in more unionized drug
2. may result in less pain on injection
91
What is a limitation that can occur when bicarbonate is added to the local anesthetic solution?
precipitation;
do not add with an solution containing epi
92
Which class of local anesthetic is metabolized quicker if absorbed into the systemic circulation?
esters (plasma esterases hydrolyze med)
93
What class of local anesthetic is metabolized slower in the systemic circulation?
amides (metabolized by CYP450 in the liver)
94
How will hepatic disease effect local anesthetics?
it will prolong the metabolism of amides (via CYP450), and patient might have low serum protein levels
95
What patient population might be more sensitive to local anesthetics and why?
1. elderly d/t ↓hepatic or renal function & low serum protein = less protein binding and more free drug
2. pregnant women.
epidural space will be mechanically compressed. Same volume of medication will have a greater spread up or down when injected.
AND
there is some suggestion that progesterone increases sensitivity to local anesthetics
96
What is the plasma half-life of procaine and chloroprocaine?
less than one minute
97
Which local anesthetics have a serum half-life of less than one minute?
procaine & chloroprocaine
98
What is LAST?
Local Anesthetic Systemic Toxicity
99
What is the most common cause of LAST?
the inadvertent injection of local anesthetic intravascularly
100
In LAST, what causes bradycardia?
the blocking of CARDIAC Na channels
101
What is the most serious cardiac sequalae of LAST?
ventricular fibrillation
102
In LAST, what mechanism is thought to be the cause of seizures?
blocking inhibitory neurons in the brain
103
In LAST, which drugs are the least cardiotoxic?
the shortest acting
104
Do more or less potent local anesthetics have higher lipid solubility & protein binding?
more potent agents have higher lipid solubility & protein binding
105
What local anesthetic is the most protein bound?
Bupivacaine
106
When does LAST present?
rapid onset, within 1 minute
107
What are the first s/s of LAST?
```
agitation
tinnitus
circumoral numbness
blurred vision
metallic taste
```
108
What are s/s LAST is progressing?
muscle twitching, unconsciousness, seizures
followed by
CARDIAC & RESPIRATORY arrest
109
What is the FIRST thing you do if you suspect LAST?
CALL FOR HELP
110
What is the SECOND thing you do if you suspect LAST?
manage the airway
111
Incidence of LAST
0.4 in 10,000
112
LAST is most commonly seen in what 3 regional anesthetics?
1. epidural
2. axillary blocks
3. interscalene blocks
113
The brachial plexus is from which nerve roots?
C5-8 - T1
114
Where does the vertebral artery enter the spinal columm?
C7
115
Where does a brachial plexus block target?
C5, C6, C7
116
What 2 anatomical structures cause increased risk of LAST during an epidural placement?
epidural vein & dura
117
What 2 anatomical structures cause increased risk of LAST during an interscalene block?
carotid artery
| internal jugular vein
118
What are 4 strategies to prevent LAST?
| per Dr. Falyar
1. test dosing
2. incremental injection with aspiration
3. use of pharmacologic markers
4. ultrasound
119
What is the treatment for LAST?
1. recognition
2. AIRWAY MANAGEMENT
- Sz suppression with benzo or succinylcholine
- PREVENT hypoxia & ACIDOSIS (will "trap" medication
3. LIPID EMULSION THERAPY
4. VASOPRESSORS
- EPI <1mg/kg
* NOT VASOPRESSIN
120
What is the initial bolus dose of lipid emulsion 20% in a patient <70kg?
bolus 1.5mg/kg over 2-3 minutes
121
What is the initial bolus dose of lipid emulsion 20% in a patient >70kg?
bolus 100mL over 2-3 minutes
122
What is the lipid emulsion 20% infusion dose in a patient <70kg?
~0.25mL/kg/min IBW
123
What is the lipid emulsion 20% infusion dose in a patient >70kg?
200-250mL over 15-20 minutes
124
What if the patient experiencing LAST is still unstable after bolus and infusion?
re-bolus 1 or 2 times.
double infusion rate
**DOSING LIMIT 12ML/KG
125
How long should monitoring continue after LAST event?
at least 4-6 hours after event with cardiac involvement
at least 2 hours after limited CNS event
126
What is the maximum dose of lipid emulsion therapy when treating LAST?
12mL/kg
127
What medication should be AVOIDED when treating LAST, specifically hypotension?
do not give vasopressin
128
Why is it important to make a patient alkalotic when experiencing LAST?
increasing the pH will limit the amount of ionized drug = drug is NOT "trapped" in cells
129
What is the MOA of lipid emulsion therapy in the treatment of LAST?
************
1. "capture" local anesthetic in the blood (lipid sink)
2. increased fatty acid uptake by mitochondria
3. interference of Na channel binding
5. promotion of calcium entry
6. accelerated shunting
130
Allergic reaction is most commonly seen in which type of local anesthetics? Why?
ester local anesthetics
esters are metabolized to/derivatives of para-aminobenzoic acid (PABA), which is a known allergen
131
Is there cross reactivity in local anesthetics?
Yes, among the esters but NOT with the amides
ie. an allergy to an ESTER does not necessarily mean the patient will be allergic to amides
132
An allergic reaction to an amide local anesthetic is most often caused by what?
*preservatives*
133
When is it necessary to ensure the local anesthetic being administered does not contain preservatives?
when doing a spinal or epidural
134
What are 3 preservatives that can sometimes be found in local anesthetic formulations?
1. paraben
2. methylparaben
3. metabisulfite
135
What side effect of local anesthetics alters oxygenation?
methemoglobinemia
136
What is methemoglobinemia?
ferris (Fe2+) form of hemoglobin is converted into ferric (Fe3+) form.
*reduced oxygen carrying capacity = decreased SpO2 that is not responsive to oxygen administration
137
What are 2 local anesthetics most likely to cause methemoglobinemia?
Benzocaine
| Prilocaine
138
Why can Prilocaine cause methemoglobinemia?
metabolite is o-touidine
139
The dosing of prilocaine should not exceed, what?
2.5mg/kg
140
Is local anesthetic based on TBW or IBW?
IBW
141
Prilocaine should be avoided in what 3 patient populations?
children under 6yr
pregnant women
patients taking other oxidizing drugs
142
What is the treatment for methemoglobinemia?
methylene blue 1-2mg/kg over 3-10 minutes
saturation may drop for ~30 seconds upon administration
143
extremely high levels of methemoglobinemia may require __ or __?
dialysis or transfusion
144
What is Cauda Equina Syndrome (CES)?
bowel & bladder dysfunction with lower extremity weakness and sensory impairment related to cord ischemia
- maldistribution of local anesthetic within the intrathecal space
145
What are the risk factors for CES?
cauda equina syndrome
- supranormal doses of local anesthetics
2-chloroprocaine
lidocaine
146
What is Transient Neurologic Symptoms (TNS)?
burning, aching, cramp like pain in the lower back and radiating down the thighs
- for up to 5 days post op
most often associated with intrathecal lidocaine
147
What medication is TNS most associated with?
transient neurological symptoms
lidocaine
148
What are 3 risk factors of TNS?
transient neurological symptoms
1. Lidocaine
2. lithotomy position
- stretch of nerves in addition to the lidocaine?
3. outpatient surgery
149
Who discovered Lidocaine & what year?
Nils Lofgren
| 943
150
What list is lidocaine included on?
the World Health Organization's list of essential medications
151
What is EMLA cream?
1:1 Lidocaine:Procaine mixture
152
What are the 4 patients or locations EMLA is contraindicated in?
1. open skin
2. mucous membrane
3. infants <1 month
4. Hx methemoglobinemia
153
What is a bier block?
| How much medication is used?
2 tourniquets
25-50mL of 0.5%Lidocaine
Onset time 5-10 minutes
tourniquet pain is usually at 20 minutes
154
What types of surgery use bier blocks (2)?
1. closed reduction
| 2. carpal tunnel
155
What are the 2 treatment interventions of LAST?
1. Benzodiazepines
| 2. hyperventilation (raises seizure threshold)
156
The administration of Lidocaine 1.5mg/kg can (3):
1. decrease CBF & ICP
2. block reflex bronchoconstriction on intubation
3. blunt SNS response to intubation
157
What is EXPAREL?
new generation of local anesthetic
| bupivacaine encapsulated in liposomal agent
158
What can exparel be mixed with?
ONLY bupivacaine
159
How long can/does exparel last?
up to 72 hours
160
What is the maximum dose of exparel?
266mg (20mL) - can be diluted up to 0.89mg/mL 1:14
161
What is the minimum size needle exparel can be administered with into the surgical site?
25g
162
Can Exparel and Lidocaine be mixed?
NO!!!
163
What are 3 situations/patients where exparel should NOT be used?
1. obstetrical paracervical block
2. patients < 18yr
3. epidural or intrathecal anesthesia
164
When must exparel be discarded?
after 4 hours
165
What is the incidence of N/V with exparel?
>10%
166
What type of local anesthetic is cocaine?
only naturally occuring
167
What is cocaine made from?
Cocoa plant
168
How does cocaine work?
blocks the monoamine transporter in the adrenergic system
169
What physiological response is created by cocaine?
blocking the reuptake of catecholamines (monoamine transporter block) = more catecholamines = vasoconstriction & SNS stimulation
170
What 3 types of medications should cocaine be used with caution?
1. epinephrine containing medications
2. MOAIs
3. tricyclics
171
What is the maximum dose of cocaine?
5mL of 5% solution
