Apex- Local Anesthetics Flashcards
1
Q
Local anesthetics inhibit peripheral nerves (speed of onset) in what order?
-A fibers (a,b,d,g); B fibers; C fibers
A
- B
- C
- A gamma
- A delta
- A beta
- A. Alpha
2
Q
Conduction velocity is increased by what 2 things
A
degree of myleination and a wider axon diameter
3
Q
Mylin insulates the axon and allows the electrical current to skip along the uninsulated regions, known as :
What is this process called?
A
Nodes of Ranvier
-saltatory conduction
4
Q
What measure for local anesthetics is analogous to ED50 for IV drugs and MAC for volatile anesthetics?
A
Cm - Minimum effective Concentration
-quantifies the concentretion of a local anesthetic that is required to block conduction
5
Q
What is a good example of a differential blockade and why?
A
Epidural BPV
- in low concentrations it provides analgesia and spares motor function
- as concentration is increased, it anesthetizes resistant nerves that control motor function and proprioception
6
Q
label from top to bottom
A
- Epineurum
- Perineurium
- Endoneurium
- Mylin sheath
- Axon
7
Q
Which type of nerve fibers mediate skeletal muscle tone?
A
A-gamma
8
Q
Which peripheral nerve fibers mediate touch and pressure?
A
A- Beta
(touch and pressure - oh Baby)
9
Q
Local anesthetics can bind to the voltage-gated sodium channel when it is in the
- Resting and active states
- Resting and inactive states
- Active and inactive states
- Active state only
A
- Active and inactive states
10
Q
Local anesthetics preferentially bind to what subunit of the sodium channel
A
alpha subunit
11
Q
The guarded receptor hypothesis states that local anesthetics can’t bind when a receptor is in which state?
A
resting state
12
Q
What 3 states can the sodium channel exist in? (what mV are each)
A
Resting
- -70mV
- Closed (able to be open)
Active:
- -70- +35mV
- When TP is reached, channel opens and NA+ follows it’s concentration gradient (inside to outside)
Inactive:
- +35- -70mV
- Channel is closed
- Inactivation gate plugs the channel until RMP is restablished
- Restoration of RMP converts the channel from the inactive state to the resting state, at which point the nerve can be stimulated again
13
Q
T/F: Local anesthetics have no effect on TP or RMP
A
True!
-When a cricial number of sodium channels are blocked by a local anesthetic, sodium is unable to enter the neuron in sufficent quantity
>cell can’t depolarize
>action potential can’t be propagated
14
Q
What electrolyte regulates RMP vs TP
A
RMP- K
TP- CA
15
Q
What is the RMP and TP in the peripheral nerves?
A
RMP = -70mV
TP = -55mV
16
Q
- Decreased serum K = RMP becomes more (negative postive)
- Increased serum K = RMP becomes more (negative/positive)
A
- decreased serum K = RMP more negative (more K leaking out)
- increased serum K = RMP more positive (less K leaking out)
Think gradients
17
Q
- Decreased serum CA++ - TP becomes more (negative/positive)
- increased serum CA++ - TP becomes more (negative/positive)
A
decreased serum Ca- TP becomes more negative (think you give CA to raise the TP)
-increased serum CA - TP becomes more positive
18
Q
T/F- local anestheetics bind to the alpha-subunit on the outside of the sodium channel
A
false- inside of the sodium channel (when in the active or inactive state)
19
Q
Select the true statement regarding the primary MOA of local anesthetics:
A. The conjugate acid binds to the extracellular portion of the sodium channel
B. The conjugate acid binds to the intracellular portion of the sodium channel
C. The uncharged base binds to the extracellular portion of the sodium channel
D. The unchanged base binds to the intracellular portion of the sodium channel.
A
B. The conjugate acid binds to the intracellular portion of the sodium channel
-local anesthetics are weak bases; when placed into a soultion, they dissociate into an unchanged base and its conjugate acid
-the uncharged base from is required to gain entry into the cell; however, it’s actually the conjugate acid that binds to the sodium channel
20
Q
Are local anesthetics weak acids or weak bases
A
weak bases
21
Q
What happens after you inject a local anesthetic around a nerve?
A
It rapidly dissociates into an uncharged/non-ionized base (LA) and an ionized conjucate acid (LA+)
22
Q
What is the primary determinant of a local anesthetics onset?
A
pKa
23
Q
What is the primary determinant of potency?
A
Lipophilicity
24
Q
What is added to some local anesthetics to reduce the rate of vascular uptake in order to prolong the duration of action?
A
Vasoconstrictors / Epi
25
What is pKa
The pH where 50% of the drug exisits as uncharged/nonionized form and 50% charged/conjugate acid
26
What 3 places can the local anesthetic travel after injected near a peripheral nerve?
1. into the nerve
2. surrounding tissues & bind proteins
3. systemic circulation
27
T/F- local anesthetics are packaged as salts in aqueous solutions
true
28
T/F- the vial soluations are aciditc to help prevent preciptiation
True
29
3 main components of the local anesthetic molecule
1. Benzene ring (lipophilic- permits diffusion thru lipid bilayers)
2. Intermediate side chain (determines class- ester or amide; metabolism, and allergic potential)
3. Tertiary amine (hydrophilic, accepts proton, makes molecule a weak base)
30
What determines the local anesthetics drug glass (ester/amide)
The intermediate side chain
- blue = ester
- orange = amide
31
What is the blue thing and what purpose does it serve
Benzene ring
-lipophilic - permits diffusion thru lipid bi-layers
32
What is the yellow structure
blue vs orange
what purpose does it serve
intermediate side chain
-determines the drug class
blue = ester
orange = amide
-determins how it will be metabolized (ester = esterases, amide = p450)
& allergic potential
33
What structure determins allergic potential
the intermediate chain (yellow)
34
What is the pink structure and what puprose properites does it have (3)
teriary amine
- hydrophillic
- accepts proton
- makes molecule a weak base
35
Which structure makes a molecule a weak base?
The tertiary amine (pink)
36
Two classes of local anesthetics
Esters and Amides
37
Which local anesthetic undergoes both hydrolysis by pseudocholinesterase and P450 metabolism?
Cocaine
38
T/F- a patient with liver disease should receive a reduce dose of single shot amide local anesthetic
False
however, dose should be reduced by 10-50% if repeat injections or a continuous infusion are planned
39
What is the allergic potential of a local anesthetic governed by?
The intermediate chain
40
T/F- true local anesthetic allergy is more likely with an amide compared to an ester
false
ester \> amide
41
Why are esters more likely to cause a true local anesthetic allergy
because of the PABA metabolite
(Para-aminobenzoic acid) - immunogenic molecule capable of causing an allergic reaction
42
Which local anesthetic class has cross-sensitivity within the class
esters
- if allergic to one ester, avoid the rest and give an amide instead
- if allergic to one amide, can use another amide without issue (no PABA)
43
Ester or Amide:
-COO-
Ester
44
Ester or Amide:
-NHCO-
Amide
45
Which characteristics correlate BEST with a local anesthetic duration of action
1. Protein binding
2. Lipid solubility
3. pKa
4. Concentration
**1. Protein binding**
46
Match:
**_onset of action:_**
**_potency:_**
**_duration of action:_**
Primary variables: lipid solubility, protein binding, pka
Secondary variables: intrinsic vasodilating effect, lipid solubility, dose, addition of vasoconstrictors, concentration
_onset of action:_ **pKa**
* dose, concentration
_potency:_ **lipid solubility**
* intrinsic vasodilating effects
_duration of action:_ **protein binding**
* lipid solublity, intrinsic vasodilating effect, addition of vasoconstrictors
47
48
If the pKa of a LA is (close/further) from the pH of the blood, there will be (more/less) molecules available to the penetrate the membrane leading to a (faster/slower) onset of action
_pKa closer to pH:_
* more (lipid soluble, unchanged) molecules to penetrate membrane
* faster onset of action
_pKa further from pH:_
* fewer lipid solubalbe uncharged molecules to penetrate the membrane (more ionized)
* slower onset of action
49
If chloroprocaine has a high pKa why does it have a rapid onset of action?
bc it isn't very potent so a larger doses is needed
\>giving more molecules creates a mass effect that accounts for the rapid onset of action despite a high pKa
50
Which has a faster onset and why:
0.75% bpv or 0.25% bpv
0.75% = faster onset bc more molecules are given
51
What happens when there is an alkyl group substiution on the amide group and benzene ring?
Increased lipid solublity (potency)
52
Why does lidocaine undergo a faster rate of vascular uptake?
because it has a greater degree of intrinsic vasodilating properties
53
If a LA is highly protein bound does it decrease or increase the duration of action?
extends duration of action bc the molecules that bind to the plasma proteins serve as a tissue resovior
54
T/F- a higher degree of lipid solublity correlates with a longer duration of action
true
55
Which local anesthetic doesn't possess any intrinsic vasodilating activity?
Cocaine
-it inhibits NE reuptake and causes vasoconstriction
56
Which substance donates vs accepts a proton (acid vs base)
acid- donates a proton [HA+ \> H+ + A]
base- accepts a proton [B- + H+ \>BH]
57
What happens when you put a strong acid or base in water?
it dissociates completely
58
What happen when you put a weak acid or base in water?
A fraction of it will ionize and the remaining fraction will be unionized
59
What does ionization depend on?
The pH of a solution and the pKa of a drug
60
When a **basic** drug (such as lidocaine) is placed into a relatively more **acidic** enviornment (like the blood), the Hendereson-Hasselbalch equation predicts that the (ionized/unionized) fraction will predominate.
the ionized fraction (conjugate acid)
61
In an (acidic/basic) solution, weak bases are more (ionized/un-ionized) and (water/lipid soluble)
Weak base
_Acidic solution_
* more ionized
* water-soluble
_Basic solution_
* more non-ionized
* lipid-soluble
62
In an (acidic/basic) solution, weak ACIDS are more (ionized/un-ionized) and (water/lipid soluble)
**Weak acid**
**Basic solution**
* more ionized
* water-soluble
**Acidic solution**
* more non-ionized
* lipid-soluble
63
Which local anesthetic does not undergo protein binding?
Chloroprocaine
64
Which 3 locals have a PKA of 8.1
BPV, Levo-BPV, Ropi
65
PKA of lidocaine
What other LA has the same pKa?
7.9
Priolocaine
66
pKa of Mepivacaine
7.6
67
_PkA's of:_
Procaine -
Chloroprocaine-
Tetracaine-
Procaine - 8.9
Chloroprocaine- 8.7
Tetracaine- 8.5
68
Local anesthetic with the highest pKa
Procaine (8.9)
69
What LA is the only one with a pKa well below physiologic pH?
Why?
Benzocaine (3.5pKa)
-it is **non-ionized** at physiologic pH but still possesses anesthetic activity
70
Why are local anesthetics unique in their action?
Because we usually administer them directly to their site of action instead of relying on the bloodstream to do it for us .
71
Lowest protein bound amide- anesthetic
Prilocaine 55%
72
Protein binding of mepivacaine
78%
73
Which LA is only 6% protein bound?
Procaine
74
Which ester-anesthetic is the most protein bound?
Tetracaine- 76%
75
Mneumonic for Most vascular areas for local anesthetic uptake
I Think Illogical Imbiciles Can't Educate but Fabulous Schools Should
I-IV
T-Tracheal
I- Interpleural
I-Intercostal
- Caudal
- Epidural
- Brachial plexus
- Femoral
- Sciatic
- Subq
(spinal)
76
Someone asks you for 100mg of BPV; how much would you draw up if you had :
0. 25% BPV:
0. 5% BPV:
0. 25% - 40 mls (2.5mg x 40mls - 100mg)
0. 5% - 20 mls (5mg x 20mls = 100mg)
77
78
What kinds of proteins do local anesthetics preferentially bind to?
Alpha-1 Acid Glycoprotein
## Footnote
**_Increased in:_**
- surgical stress
- MI
- chronic pain
- RA
- elderly
**_Decreased in:_**
-pregnancy and neonates
79
What acts as a reservoir for local anesthetics that can help remove the LA from the circulation, limiting plasma concentration?
the lungs
80
What does the addition of dexamethasone do?
It extends the duration of a **brachial plexus block**
81
Explain how Exparel works
It's essentially droplets of BPV that are housed in an lipid emulsion that slowly erodes over time, releasing a constant supply of BPV over several days
82
Max dose of Exparel
226mg
83
What local anesthetic is contraindicated for paracervical block in the obstetric population?
Exparel
84
If lidocaine is to be infiltrated at the surgical site, it must be administered a minimum of \_\_\_\_minutes (before/after) exparel injection.
20 minutes BEFORE exparel
-if given after exparel, it can disrupt the liposmal supsension causing the immediate release of BPV (and poss toxicity i would assume?)
85
BPV in any form may not be administered within ____ hours following exparel administration.
96 hours
86
Match the Max doses of LAs
Lidocaine:
Ropi:
BPV:
Mepivacaine:
400mg, 300mg, 200mg, 175mg
Lidocaine: 300mg
Ropi: 200mg
BPV: 175mg
Mepivacaine: 400mg
87
**Max dose mg/kg**
LevoBPV:
BPV:
BPV with Epi:
Ropi:
Lido
Lido with Epi:
Mepivacaine:
Priolocaine:
Procaine:
Chloroprocaine:
Chloroprocaine + Epi:
LevoBPV: 2mg/kg
BPV: 2.5mg/kg
**BPV with Epi: 3mg/kg**
**Ropi: 3mg/kg**
Lido: 4.5mg/kg
**Lido with Epi: 7mg/kg**
**Mepivacaine: 7mg/kg**
Priolocaine: 8mg/kg
Procaine: 7-10mg/kg
Chloroprocaine: 11mg/kg
Chloroprocaine + Epi: 14mg/kg
88
If there is different rate of vascular uptake with different sites, how do clinicians typically determine the max doses?
adults- they will just stay under the total max dose
peds- they will weight base
89
Ropi max dose
mg/kg
total
3mg/kg
200mg
90
Max dose of chloroprocaine
mg/kg
total
11mg/kg
800mg
91
chloroprocaine with epi max
mg/kg
total
14mg/kg
total = 1,000
think it's double lido and epi
92
Cocaine max dose
mg/kg
total
1.5-3mg/kg
150-200mg total
93
What's the most common cause of LAST
inadvertent intravascular injection during regional anesthesia
94
T/F- last is more common with epdiural anesthesia than with peripheral nerve blocks
false
PNB \> epidural
95
with LAST, do CNS or cardaic complications usually present first
CNS
| (except BPV)
96
Treatment of cocaine toxicity
Vasodilator or mixed alpha/beta agonist such as labetalol
97
Lidocaine Cp mcg/ml
CNS vs Cardiopulmonary effects
\>25
15-25
10-15
5-10
1-5
98
3 factors that increase risk of LAST
**_1. Hypercarbia_**
* Increased CBF \> increased drug delivery to the brain
* Decreases protein binding + increases free fx to enter brain
**_2. Hyperkalemia_**
* Raises RMP, making neurons more likely to depolarize
**_3. Metabolic acidosis_**
* Decreases convulsion threshold and favors ion trapping in the brain
\*acidosis increases the free fraction of the ionized portion and decreases unionized - so technically that should decrease the amount that can pass through the BBB, but it's not enough to decrease the risk of CNS toxicity .
99
Why would hyperventilating a patient with suspected LAST be good?
- hypocarbia decreases CBF and reduces drug delivery to the brain
+ can lower serum K, which would lower RMP, requiring a larger stimulus to depolarize the nerve
100
Why would you give a benzo with someone with LAST
to raise the seizure threshold
101
Why does BPV have a higher morbidity with LAST? (2)
1. it has a greater affinity for the voltage-gated sodium channel &
2. a slower rate of dissociation from the receptor during diastole
(so it remains at the receptor for a longer time)
102
Rank difficulty of cardiac resussitation from LAST from most to least difficult:
ropi, levoBPV, BPV, lido
BPV \> LevoBPV \> Ropi \> Lido
103
What 4 things increase the risk of BVP toxicity
1. pregnancy
2. beta blockers
3. calcium channel blockers
4. digitalis
104
What 2 drug classes would see a patient on and be like yo dont give cocaine as your anesthetic to a doc lol
MAOIs and TCA's - both increase the amount of NE and cocaine inhibits reuptake of NE into the presynaptic terminal and would result in excessive SNS stimulation
105
Best drugs to manage HTN in cocaine OD
1. Vasodilator such as nitro
2. Labetaolol (mixed alpha and beta)
- if you give a pure beta blocker, you have unapposed alpha stimulation (from the cocaine) + reduced inotropy (from the beta blocker) setting you up for chf and cardiovascular collapse
106
One mintue folowing an interscalene block, a 62kg patient has a seizure; how much 20% lipid emulsion should you administer?
93mls
(20% lipid emulsion - 1.5ml/kg of lean body mass/1 minute)
107
Steps in treating Last 1-4
**_1. Manage airway_**
* 100% Fio2
* Hypoxia and acidosis will worsen LAST
**_2. Benzos_**
* Raise the seizure threshold
* If ineffective, give a small dose of sux or NDMR to stop muscle contraction
* This minimizes o2 consumption, hypoxemia and acidosis but will not stop seizure activity in the brain
* Avoid propofol (cardiac depression)
**_3. ACLS with specific modifications_**
* Epi can hinder LAST resusitation and also reduces effectiveness of lipid emulsion therapy
* If given, should be given in doses of \< 1mcg/kg
* Avoid vasopressin
* Amio is agent of choice for ventricular dysthryhmias
* avoid lidocaine and procainamide
**_4. Lipid emulsion therapy_**
* 20% 1.5ml/kg (lean body mass) over 1 minute
* Infusion = 0.25ml/kg/min
* Can repeat bolus up to 2 more times and increase gtt to 0.5ml/kg/min
* Continue gtt for 10 mins after acheiving hemodynamic stability
* Max dose is 10ml/kg in the first 30 mins
\*Avoid beta blockers and caclcium channel blockers which will enhance LA induced cardiac disturbances
-if unresponsive to modified ACLS and lipipd emulsion therpay, prepare for Cardiopulmonary bypasss.
108
LAST: what can you do if benzos are ineffective for seizure control
smal ldose of sux or NDMR
- will minimize o2 consumption, hypoxemia, and acidosis
- won't stop seizure activity in the brain
109
why should you be cautious with Epi in LAST
it can hinder resusitation and reduce the effectivenss of lipid emulsion therapy
-if used , keep doses \< 1mcg/kg
110
**_Safe or unsafe in LAST:_**
Propofol
unsafe
111
Safe or unsafe in LAST:
Benzos
112
Safe or unsafe in LAST:
Betablockers
unsafe
113
Safe or unsafe in LAST:
CCBs
unsafe
114
Safe or unsafe in LAST:
Vasopressin
unsafe
115
**_20% lipid emulsion:_**
Bolus dose:
Infusion:
if sx are slow to resolve:
max dose:
_Bolus dose:_ 1.5ml/kg (LBW) over 1 minute
_Infusion:_ 0.25ml/kg/min
_if sx are slow to resolve:_
* can repeat bolus dose up to 2 more times &
* increase rate to 0.5ml/kg/min
_max dose:_
* 10ml/kg in 1st 30 minutes
116
T/F: lipid emulsion therpay is safe in pregnancy
True
117
How long should lipid emulsion therapy be maintained after restoration of hemodynamic stability
10 minutes
118
What is the drug of choice for ventricular dysrhythmias in someone with LAST?
Amio
119
What is the maximum recommended dose for lidocaine during tumescent anesthesia?
- 5mg/kg
- 7mg/kg
- 55mg/kg
- 75mg/kg
**-55mg/kg**
120
the plasma concentration of lidocaine peaks at \_\_\_hrs and is completely eliminated by \_\_\_\_hrs
peak: 12 hours
gone: 36 hours
121
The decision to use MAC or GA is influenced by the amount of tumescent to be injected; GA is recommended if \> _____ L of tumescent is planned.
why?
\>2-3L = General
Bc of risk for fluid shifts
122
Why is fluid management essential in patients getting tumescent ?
bc fluid overload and pulmonary edema may occur as a result of intravascular volume expansion
123
Purpose of large volume tumescent anesthesia during liposuction
purpose of added lidocaine
pupose of added epi
- the large volume injected into the adipose tissue makes it firm and increases the ease of removal
lidocaine- prevents discomfort
epi- minimizes vascular uptake of both the local anesthetic and large volume solution
124
What is the most common cause of death with liposuction?
PE
125
When is methemoglobin formed?
When the iron on the hemeglobin molecule becomes oxidized to it's ferric form (FE+3).
-This reduces oxygen-carrying capacity and shifts the curve to the left
126
What is required to diagnose methemoglobinemia?
A co-oximeter
127
Drugs than can produce methemoglobin
( 3 locals)
(1 sz, 2 dilators, 1 abx)
**_Benzocaine_**
* Cetacaine
**_Prilocaine_**
**_Lidocaine_**
Phenytoin
Nitroprusside, Nitroglycerine
Sulfonamides
128
s/s methemoglobinemia
hypoxia that isn't fixed with increasing FiO2
CCCTT
Chocolate colored blood
Cyanosis
Change in LOC
Tachycardia, tachypneia
129
What is cyanosis in the presecnes of a normal or high PaO2 highly suggestive of ?
methemoglobinemia
130
A significant concentration of methemoglobin can lea to an erroneous SpO2 reading of \_\_\_\_%
85%
131
Treatment and dosing for methemoglobinemia
(max dose)
Methylene blue
1-2mg/kg over 5 minutes
max dose 7-8mg/kg
132
Hepatic metabolizm of _____ yields an oxidizing metabolite **O-Toluidine,** which can lead to \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_-
Prilocaine
methemoglobinemia
133
What does EMLA cream consist of?
50% Prilocaine
50% Lidocaine
\*risk of methemoglobinemia
134
POX emeits 2 constaint light waves
Red- \_\_\_\_nm; absorbed by \_\_\_\_\_\_\_\_
Infrared light- \_\_\_\_\_nm; absorbed by \_\_\_\_\_\_\_\_
**Red - 660**; absorbed by **deoxyhemoglobin**
* Think D/Devel 660
**Infrared light- 940nm**; absorbed by **oxyhemoglobin**
135
136
Patients with what condition should not receive methylene blue
Glucose-6 Phosphate reductase deficiency
G6PR deficiency
- can precipitate hemolytic crisis
137
138
How to treat methemoglobinemia in patietns with a G6PR deficiency (glucose-6-phosphate reductase)
exchange transfusion
(methylene blue can precipitate hemolytic crisis in these people)
139
Why are neonates at a higher risk for methemoglobinemia?
because fetal hemoglobin is deficient in methemoglobin reductase
140
Why can't a pulseox measure methemoglobinemia correctly?
Bc HgbMet absorbs the 660nm and 940nm wavelengths equally.
141
Onset of EMLA cream and max effect
onset = 1 hour
max effect after 2-3 hours
142
What should be applied to EMLA cream after topical application
An occlusive dressing
143
What can be applied simultaneously with EMLA cream to hasten the absorption?
Nitroglycerine
-sounds liek a great idea
144
max dose for what age/weight groups of EMLA cream:
1g max:
2g:
10g:
20g:
(REMEMBER EMLA MAX IS IN **G**)!!
1mg max: **0-3 months or \< 5kg**
2mg: **3-12 months and \> 5kg**
10mg: **1-6 years and \> 10kg**
20mg: **7-12 years and \> 20kg**
145
146
- each additaive prolongs the duration of local anesthetics EXCEPT:
- dexamethasone
- dextran
- epi
- hyaluronidase
- hyaluronidase
- hyaluronic acid is present in the intersistial matrix & basement membrane; it hinders the spread of substances through tissues
- hyaluronidase hydrolyzes hyaluronic acid which then facilitates diffusion of substances in the tissues
147
How does sodium bicarb affect local anesthetics & how is it mixed?
shortens the onset time (debatable)
-mix 1ml of 8.4% sodium bicarb with 10ml of local anesthetic
148
Which local anesthetic reduces the effectiveness of opioids in the epidural space?
Chloroprocaine
149
Someone asks you how does sodium bicarb speed the onset of a local anesthetic
-it increases the number of lipid-soluble molecules, which speeds up the onset of action.
150
Select the BEST local anesthetic to use for a subarachnoid block in the patient who has a sensitivity to BPV
A. Etidocaine
B. Tetracaine
C. Chloroprocaine
D. Lidocaine
B. Tetracaine
-needed to 1. chose and ester and 2. know that chloroprocaine is not used in spinal anesthesa
151
T/F - chloroprocaine is safe for spinal anesthesia
false- neurotoxicity
152
