Unit 5 Pharmacology: Local Anesthetics Flashcards
(216 cards)
1
Q
Define conduction velocity
A
How fast an axon transmits the action potential
2
Q
What 2 things increase conduction velocity?
A
Myelination
Larger fiber diameter
3
Q
What is saltatory conduction?
A
Myelinated axons allow the electrical current to skip along only the uninsulated regions (the nodes of Ranvier)
4
Q
What are the 3 major classes of peripheral nerves?
A
A
B
C
5
Q
How many types of A fibers are there? What are they?
A
(4) Alpha Beta Gamma Delta
6
Q
A alpha fibers: Myelination Function Diameter Velocity Block onset
A
Myelination: heavy Function: skeletal muscle - motor, proprioception Diameter: 12 - 20 um Velocity: +++++ Block onset: Fourth
7
Q
A beta fibers: Myelination Function Diameter Velocity Block onset
A
Myelination: Heavy Function: Touch, pressure Diameter: 5 - 12 um Velocity: ++++ Block onset: Fourth
8
Q
A gamma fibers: Myelination Function Diameter Velocity Block onset
A
Myelination: medium Function: skeletal muscle - tone Diameter: 3 - 6 um Velocity: +++ Block onset: Third
9
Q
A delta fibers: Myelination Function Diameter Velocity Block onset
A
Myelination: Medium Function: Fast pain, temperature, touch Diameter: 2 - 5 um Velocity: +++ Block onset: Third
10
Q
How many types of B fibers are there? What are they?
A
Just 1
B fibers
11
Q
B fibers: Myelination Function Diameter Velocity Block onset
A
Myelination: light Function: preganglionic ANS fibers Diameter: 3 um Velocity: ++ Block onset: First
12
Q
How many types of C fibers are there? What are they?
A
(2)
Sympathetic
Dorsal root
13
Q
C sympathetic fibers: Myelination Function Diameter Velocity Block onset
A
Myelination: none Function: postganglionic ANS fibers Diameter: 0.3 - 1.3 um Velocity: + Block onset: second
14
Q
C dorsal root fibers: Myelination Function Diameter Velocity Block onset
A
Myelination: none Function: slow pain, temperature, touch Diameter: 0.4 - 1.2 um Velocity: + Block onset: second
15
Q
What is differential blockade?
A
?
16
Q
What is minimum effective concentration (Cm)?
A
A unit of measure that quantifies the concentration of local anesthetic that is required to block conduction. It is analogous of ED50 and MAC
17
Q
A lower Cm means what? Vs a higher Cm?
A
Fibers that are more easily blocked have a lower Cm.
Fibers that are more resistant to local anesthetic blockade have a higher Cm.
18
Q
What size nerves typically have a higher Cm?
A
Nerves with a wider diameter
19
Q
How does tissue pH affect Cm?
A
Cm is reduced by higher tissue pH
20
Q
How does nerve stimulation affect Cm?
A
Cm is reduced by high frequency nerve stimulation.
21
Q
In the clinical setting local anesthetics inhibit peripheral nerves (speed of onset) in what order?
A
B > C > small diameter A > large diameter A
22
Q
Where do local anesthetics bind? How do they bind?
A
Reversibly bind to the alpha subunit of the voltage-gated sodium channel
23
Q
How many and what type of subunits does the voltage-gated sodium channel contain?
A
1 alpha subunit
2 beta subunits
24
Q
What subunit forms the entire ion conducting pore in the voltage-gated sodium channel?
A
alpha subunit
25
Local anesthetics can bind to the voltage-gated sodium channel when it is what position(s)?
Active and inactive states
26
What are the 3 states the sodium channel can exist in?
Resting
Active
Inactive
27
Resting state of the sodium channel:
mV?
Channel open or closed?
-70 mV
| Channel is closed
28
Active state of the sodium channel:
mV
Channel open or closed?
-70 to +35 mV
| Channel opens when threshold potential is reached
29
Inactive state of the sodium channel:
mV?
Open or closed?
+35 to -70 mV
| Channel is closed
30
What occurs during the inactive state of the voltage-gated sodium channel?
The inactivation gate plugs the channel until resting membrane potential is re-established.
31
What is a use-dependent or phasic block?
The more frequently a nerve is depolarized and the voltage-gated sodium channel opens, the more time there is available for local anesthetic binding to occur and the faster the nerve will become blocked
32
What 2 things establish resting membrane potential? What is the net result?
1. The membrane is selectively permeable to K+ (it can leave the cell), but it is impermeable to sodium
2. The Na/K-ATPase extrudes 3 Na+ ions for every 2 K+ ions it brings back into the cell
The net result is a cell interior that is negative with respect to its exterior
33
What is an action potential?
A temporary change in transmembrane potential followed by a return to transmembrane potential
34
When is an action potential created?
When a stimulus opens sodium channels
35
What is the all or none phenomenon?
In order for a neuron to depolarize, sodium must be allowed in the cell, once threshold potential is achieved the cell depolarizers and propagates an action potential, the cell either depolarizes or it doesn’t
36
Explain how depolarization is only able to go in one direction
The upstream portion of the neuron is in its refractory period (Na+ channels are in the inactive state) and cannot be stimulated.
37
What restores transmembrane potential to RMP?
Potassium conductance is increased and Na/K-ATPase removes all the sodium that entered during depolarization
38
How do local anesthetics effect depolarization?
When a critical number of sodium channels are blocked there are not enough open channels for sodium to enter the cell in sufficient quantity, the call can’t depolarize. They do not affect RMP or threshold potential.
39
In the vial are LAs an acid or base?
A weak base
40
How are LAs packaged (formulation) and what kind of pH?
Hydrochloride salts in aqueous solution
| Low pH to guard against precipitation
41
Once you inject LA into a patient what happens?
It quickly dissociates into an uncharged base (LA) and an ionized conjugate acid (LA+)
42
What is pKa?
The pH where 50% of the drug exists as the unchanged base and 50% of the drug exists as the conjugate acid
43
What equation can be used to predict the ratio of each moiety of LA?
Henderson-Hasselbach equation
pH = pKa + log ( [base] / [conjugate acid] )
44
LAs are weak bases with pKa values higher than 7.4 so we can predict that how much of the LA will exist as the ionized conjugated acid?
> 50%
45
Diffusion of LA into that bloodstream is called?
Uptake
46
What kinds of areas remove LA at a faster rate?
Highly vascular areas vs sites with less blood flow
47
What concept reduces local anesthetic duration while increasing plasma concentration?
Uptake
48
Which part of the LA enters the axoplasm by diffusion?
The unchanged base enters via diffusion through the lipid rich axolemma
49
Once the unchanged base of LA enters the axoplasm how does it change?
The ICF is slightly more acidic that the ECF, there is a greater fraction of the ionized conjugate acid inside the cell
50
What part of the LA binds to the alpha subunit of the voltage-gated sodium channel?
Only the ionized conjugate acid
51
How long does the sodium channel remain in the closed activated state from LA?
Until enough of the LA diffuses away
52
What are the 2 classes of LA?
Esters
| Amides
53
What are the 3 key components of a local anesthetic molecule?
Benzene ring
Intermediate side chain
Tertiary amine
54
What medicinal chemistry does the benzene ring hold?
Lipophilic - Permits diffusion through the lipid bilayer
55
What medicinal chemistry does the intermediate chain hold?
Determines class - ester or abide
Metabolism
Allergic potential
56
What medicinal chemistry does the tertiary amine hold?
It is hydrophilic
It accepts proton
Makes the molecule a weak base
57
How to remember which LAs are ester-type
Ester was a cyclops - only have one i
58
List 5 ester-type LAs
Benzocaine
Cocaine
Chloroprocaine
Tetracaine
59
How are ester-type LAs metabolized? Are there any exceptions?
Pseudocholinesterase- do deficiency could increase duration of action
Cocaine is also metabolized by the liver
60
How high is the allergic potential of ester-type LAs?
Low
61
Is there cross sensitivity in the same class of ester-type LAs?
Yes
62
Is there cross sensitivity between ester and amides?
No
63
How to remember amide-type LAs
Amide has an i for the extra i in the name (there are 2 i’s)
64
Name 8 amide-type LAs
```
Articaine
Bupivacaine
Dibucaine
Etidocaine
Levobupivacaine
Lidocaine
Mepivacaine
Ropivacaine
```
65
How are amide-type LAs metabolized? Are there any exceptions?
Hepatic carboxylesterase/P450
No
66
What is the allergic potential of amide-type LAs?
Extremely rare
67
Is there cross sensitivity in the same class with amide-type LAs?
No
68
What probably causes allergic reaction with ester-type LAs (though LAs allergy is rare)
Ester-type LAs are a derivative of para-aminobenzoic acid (PABA), which is an immunogenic molecule capable of causing allergic rx. It is also why cross sensitivity is in this class.
69
What probably causes allergic reaction in the amide class (though LA allergy is rare)
Some multi-dose vials contain methylparaben as a preservative, which is similar to PABA
70
The primary variable that correlates with onset of action of LA is?
The secondary variables that correlate with onset?
Primary: pKa
Secondary: dose, concentration
71
What primary variable correlates the best with potency? What secondary variable?
Primary: Lipid solubility
Secondary: intrinsic vasodilation effect
72
What primary variable correlates the best with LA duration of action? What secondary variables?
Primary: protein binding
Secondary: lipid solubility, intrinsic vasodilation effect, addition of vasoconstrictors
73
How does pKa best correlate with onset of action of LAs?
If the pKa of the LA is closer to pH of the the blood, a larger fraction of molecules will exist as the lipid soluble, uncharged base. More molecules diffusing across the axolemma translates to a faster onset of action.
74
Once the local anesthetic reaches the inside of the neuron, which part of the LA binds to the alpha subunit on the inside of the voltage-gated sodium channel?
The ionized conjugate acid
75
How does does and concentration effect onset of LA? Examples help to explain
Chloroprocaine has a high pKa which suggests a slow onset, however it is not very potent and requires a large dose, this creates a mass effect that explains why it has a rapid onset.
76
How does lipid solubility best correlate with LA potency?
A lipid soluble drug has an easier time diffusing through the epineurium, and more drug inside the nerve means more molecules are available to bind to the receptor
77
Agents that are lipophilic tend to be ____ potent and have _____ duration of action.
More
| Longer
78
An alkyl group substitution on the amide group and benzene ring does what to lipid solubility?
Increases lipid solubility
79
Stereoselectivity also plays a role in _____ of LAs
Potency
80
How does intrinsic vasodilating ability affect potency of LAs?
Absorption into the systemic circulation removes LA from its site of action and contributes to the termination of it’s effect, nearly all LAs have a biphasic response on vascular smooth muscle
81
What is the biphasic response on vascular smooth muscle that most LAs have?
At lower concentrations (below what we use clinically) LAs cause vasoconstriction by inhibiting nitric oxide.
At higher concentrations (what we use clinically) LAs cause vasodilation, some more than others
82
What LA is the exception to the intrinsic vasodilating activity of LAs?
Cocaine: it inhibits NE reputable and always causes vasoconstriction
83
Some texts say there are 2 other LAs (besides cocaine) that do not have intrinsic vasodilating activity:
Chloroprocaine
| Ropivacaine
84
Drugs with a greater degree of intrinsic vasodilating effects (lidocaine) under a faster rate of _____
Uptake
85
How does protein biding best correlate with duration of action of LAs?
After LA injection, some of the molecules penetrate the epineurium, some diffuse away into systemic circulation, and some bind to tissue proteins. Those that bind to plasma proteins serve as a tissue reservoir that extend duration of action
86
How does lipid solubility affect duration of action?
Increased lipid solubility correlates with a longer duration of action
87
How does intrinsic vasodilating activity correlate with duration of action of LA?
A drug with intrinsic vasodilating activity will increase its rate of vascular uptake and shorten its duration of action. Adding a vasoconstrictor such as epi will prolong the duration of these drugs
88
If you put a strong acid or base in water, what will happen?
It will dissociate completely
89
If you put a weak acid or base in water what will happen?
A fraction will ionize and the remaining fraction will be unionized.
90
Ionization is dependent on which 2 factors?
1. pH of the solution
| 2. pKa of the drug
91
If a molecule is a weak base and the pH of the solution is > pKa of the drug, what fraction predominates?
The unionized fraction
92
If the molecule is a weak acid and the pH of the solution is < the pKa of the drug, which fraction predominates?
The unionized fraction
93
If the molecule is a weak base and the pH of the solution is < the pKa of the drug, what fraction predominates?
The ionized fraction
94
If the molecule is a weak acid and the pH of the solution is > the pKa of the drug, then what fraction predominates?
The ionized fraction
95
Bupivacaine:
pka
Ionization % at 7.4
Protein biding %
pka: 8.1
Ionization % at 7.4: 83
Protein biding %: 96
96
Levo-bupivacaine:
pka
Ionization % at 7.4
Protein biding %
pka: 8.1
Ionization % at 7.4: 83
Protein biding %: 98
97
Ropivacaine:
pka
Ionization % at 7.4
Protein biding %
pka: 8.1
Ionization % at 7.4 : 83
Protein biding %: 94
98
Lidocaine:
pka
Ionization % at 7.4
Protein biding %
pka: 7.9
Ionization % at 7.4 : 76
Protein biding %: 65
99
Prilocaine:
pka
Ionization % at 7.4
Protein biding %
pka: 7.9
Ionization % at 7.4 : 76
Protein biding %: 55
100
Mepivacaine:
pka
Ionization % at 7.4
Protein biding %
pka: 7.6
Ionization % at 7.4 : 61
Protein biding %: 78
101
Procaine:
pka
Ionization % at 7.4
Protein biding %
pka: 8.9
Ionization % at 7.4 : 97
Protein biding %: 6
102
Chloroprocaine:
pka
Ionization % at 7.4
Protein biding %
pka: 8.7
Ionization % at 7.4 : 95
Protein biding %: 0
103
Tetracaine:
pka
Ionization % at 7.4
Protein biding %
pka: 8.5
Ionization % at 7.4 : 93
Protein biding %: 76
104
With LAs the further pka gets away from physiologic pH, the degree of ionization _______.
Increases
105
The closet the pKa of an LA is to the pH of the blood, the _____ the onset.
Faster
| Exception is chloroprocaine
106
LAs are weak bases that are ionized (charged) at physiologic pH, what is the exception?
Benzocaine has a pKa of 3.5, well below physiologic pH
107
Benzocaine is ________ at physiologic pH
Non-ionized
108
List 5 factors that influence vascular uptake of LAs:
```
Site of injection
Tissue blood flow
Physiochemical properties of LA
Metabolism
Addition of vasoconstrictor
```
109
What helps influence final plasma concentration?
Total dose
Concentration
Speed of injection
Total dose
| The same plasma concentration is reached whether 40 mL of 0.25% or 20 mL or 0.5% were used
110
Mnemonic for most vascular & highest Cp block to least vascular & lowest Cp
I Think Illogical Imposters Can’t Educate But Fabulous Schools Should
IV, Tracheal, Interpleural, Intercostal, Caudal, Epidural, Brachial plexus, Femoral, Sciatic, SubQ
111
What plasma proteins bind to LAs helping to limit peak plasma concentration?
Preferentially bind to alpha1-acid glycoprotein, but will also bind to albumin
112
What organ acts as a reservoir that removes LA from the circulation and limits plasma concentration?
The lungs
113
Metabolism decreases plasma LA concentrations, how are the 2 classes of LAs metabolized?
Amides and cocaine: P450 enzymes
| Esters: pseudocholinesterase
114
How much can the addition of a vasoconstrictor, such as epi or phenylephrine, decrease systemic absorption? What other effect does this have?
Decreases systemic absorption by up to 1/3.
Prolongs duration
Effect is greatest with LAs that have significant intrinsic dilating activity
115
Levobupivacaine:
Max dose: mg/kg
Max total dose: mg
Max dose: 2 mg/kg
| Max total dose: 150 mg
116
Bupivacaine:
Max dose: mg/kg
Max total dose: mg
Max dose: 2.5 mg/kg
| Max total dose: 175 mg
117
Bupivacaine with Epi:
Max dose: mg/kg
Max total dose: mg
Max dose: 3 mg/kg
| Max total dose: 200 mg
118
Lidocaine:
Max dose: mg/kg
Max total dose: mg
Max dose: 4.5 mg/kg
| Max total dose: 300 mg
119
Ropivacaine
Max dose: mg/kg
Max total dose: mg
Max dose: 3 mg/kg
| Max total dose: 200 mg
120
Mepivacaine
Max dose: mg/kg
Max total dose: mg
Max dose: 7 mg/kg
| Max total dose: 400 mg
121
Lidocaine with Epi:
Max dose: mg/kg
Max total dose: mg
Max dose: 7 mg/kg
| Max total dose: 500 mg
122
Prilocaine:
Max dose: mg/kg
Max total dose: mg
Max dose: 8 mg/kg
| Max total dose: If <70 kg 500mg, if >70 kg 600 mg
123
Procaine:
Max dose: mg/kg
Max total dose: mg
Max dose: 7 mg/kg
| Max total dose: 350 - 600 mg
124
Chloroprocaine:
Max dose: mg/kg
Max total dose: mg
Max dose: 11 mg/kg
| Max total dose: 800 mg
125
Chloroprocaine with Epi:
Max dose: mg/kg
Max total dose: mg
Max dose: 14 mg/kg
| Max total dose: 1000 mg
126
Tetracaine
Max dose: mg/kg
Max total dose: mg
Max dose: mg/kg
| Max total dose: mg
127
The plasma concentration of LA is a net balance of what 3 things?
Vascular uptake to redistribution and metabolism
128
Where do local anesthetic systemic toxicities occur in the body?
The heart and brain
129
What is the most common cause of toxic plasma concentrations of LA?
Inadvertent IV injection during regional Anethesia
130
What is the most frequent symptoms of LAST? Exception?
Seizure
| Bupivacaine - cardiac arrest before seizure
131
Is LAST more common with peripheral blocks or epidurals?
More common with peripheral blocks
132
What plasma concentration of Lidocaine mcg/mL produces analgesia?
1 - 5 mcg/mL
133
The plasma concentration of 5 - 10 mcg/mL produces what CNS and cardiopulmonary effects?
```
Tinnitus
Numbness of lips and tongue
Skeletal muscle twitching
Restlessness
Vertigo
Blurred vision
Hypotension
Myocardial depression
```
134
The plasma concentration of 10 - 15 mcg/mL produces what CNS and cardiopulmonary effects?
Seizures
Loss of consciousness
No further cardiopulmonary effects
135
The plasma concentration of 15 - 25 mcg/mL produces what CNS and cardiopulmonary effects?
Coma
| Respiratory arrest
136
The plasma concentration of > 25 mcg/mL produces what CNS and cardiopulmonary effects?
No further CNS effects
| Cardiovascular collapse
137
What 3 factors increase CNS toxicity of LAs?
Hypercarbia
Hyperkalemia
Metabolic acidosis
138
How does hypercarbia increase the risk of CNS toxicity with LAs?
Hypercarbia increases CBF and drug delivery to the brain.
| It also decreases protein biding and increases the free fraction available to enter the brain.
139
How does hyperkalemia increase CNS toxicity with LAs?
Hyperkalemia raises resting membrane potential, making them more likely to depolarize
140
How does metabolic acidosis increase the risk of CNS toxicity in LAs?
Metabolic acidosis decreases the convulsion threshold and favors ion trapping inside the brain
141
How does metabolic acidosis affect the LA fraction of conjugate acid vs uncharged base? Is this significant?
Acidosis increases the fraction of the conjugate acid and decreases the amount of uncharged base that is available to pass through the BBB, but this is not enough to decrease the risk of CNS toxicity.
142
What 3 factors decrease the risk of CNS toxicity from LAs?
Hypocarbia
Hypokalemia
CNS depressants
143
How does hypocarbia decrease the risk of CNS toxicity with LAs?
Hypocarbia decreases CBF and reduces drug delivery to the brain, hyperventilation might be helpful
144
How does hypokalemia decrease the risk of CNS toxicity with LAs?
Hypokalemia lowers RMP, requiring a larger stimulus to depolarize the nerve
145
How do CNS depressants decrease the risk of CNS toxicity with LAs?
CNS depressants such as benzodiazepines and barbiturates raise the seizure threshold
146
What 3 ways do LAs disrupt hemodynamics?
Altering the:
cardiac action potential
Myocardial performance
Vascular resistance
147
How do LAs alter the cardiac action potential? (4)
Decrease automaticity, conduction velocity, action potential duration, and the effective refractory period
148
How do LAs affect myocardial performance?
Depress the myocardium by impairing intracellular calcium regulation
149
How do LAs affect vascular smooth muscle?
There is a biphasic effect:
Low concentrations of LAs produce vasoconstriction
Higher doses produce vasodilation and a reduction in SVR
150
What 2 features determine the extent of cardio toxicity with LAs?
1. Affinity for the voltage-gated sodium channel in the active and inactive state
2. Rate of dissociation from the receptor during diastole
151
Why is cardiac resuscitation so difficult with bupivacaine toxicity?
When compared to lidocaine, bupivacaine has a greater affinity for the voltage-gated sodium channel and a slower rate of dissociation from this receptor during diastole, so it remains at the receptor for a longer period of time
152
```
Arrange the order of difficulty of cardiac resuscitation from greatest to least of:
Bupivacaine
Lidocaine
Levobupivacaine
Ropivacaine
```
Bupivacaine > Levobupivacaine > Ropivacaine > Lidocaine
153
The risk of bupivacaine toxicity is increased with? (4)
Pregnancy
BB
CCB
Digitalis
154
What is the primary risk of cocaine toxicity? Why?
Excessive SNS stimulation.
| Cocaine has vasoconstrictive properties, it inhibits NE reuptake into the presynaptic nerve terminal
155
With what 3 drug classes should cocaine use be avoided?
MAOIs
TCAs
Sympathomimetics
156
What is the deal with BB in the setting of cocaine overdose?
It is questionable because it allows for unopposed alpha-1 stimulation (increased SVR) and reduced inotropy (beta-1 antagonism), which sets the stage for cardiac collapse
157
What is the best drug of choice for cocaine overdose? What if BB is the only choice in the list?
Vasodilator such as Nitroglycerine.
| If only BBs are listed, then labetalol or another mixed alpha and beta antagonist
158
What is the dose for cocaine’s use as a vasoconstrictor? Max dose?
1.5 - 3.0 mg/kg
Max: 150 - 200 mg
159
What 3 ways can risk of LAST be reduced?
using a test dose
Incremental dosing
Periodic aspiration
160
4 major steps in LAST treatment:
1. Manage the airway
2. Treat seizures
3. ACLS with specific modifications
4. Lipid emulsion
161
What 2 things in relation to airway management will worsen LAST?
Avoid hypoxia and acidosis
| -FiO2 100%
162
If benzodiazepines are ineffective in stopping LAST seizure, what should be given? Why?
Small dose of Sux or ND-NMB.
| To minimize oxygen consumption, hypoxemia, and acidosis
163
What drug, though has anti-seizure properties, should be avoided? Why?
Propofol.
| Small doses may abate seizure activity, but larger doses augment myocardial depression
164
What are the specific ACLS modifications for LAST treatment? (3)
Epi can hinder resuscitation and reduce the effectiveness of lipid emulsion
-if used give in doses < 1 mcg/kg
Avoid vasopressin
To treat ventricular arrhythmias avoid lidocaine and procainamide, use amiodarone
165
What is the concentration of lipid emulsion?
20%
166
What is the bolus dose for lipid emulsion? Infusion rate?
Bolus: 1.5 mL/kg (LBW) over 1 minute
Infusion: 0.25 mL/kg/min
167
If symptoms of LAST are slow to resolve, what can be done?
Repeat bolus up to 2 more times and increase infusion to 0.5 mL/kg/min
168
How long should the lipid emulsion infused for LAST be continued?
Until 10 minutes after achieving hemodynamic stability
169
What is the maximum recommended dose of lipid emulsion?
10 mL/kg in the first 30 minutes
170
What is the MOA of lipid emulsion?
Lipid sink - an intravascular reservoir that sequesters LA and reduces plasma concentration of LA
171
Lipid emulsion:
Metabolic effect
Inotropic effect
Membrane effect
Metabolic effect: enhanced myocardial fatty acid metabolism
Inotropic effect: increased calcium influx and intracellular calcium concentration
Membrane effect: impairs LA binding to voltage-gated sodium channels
172
Can lipid emulsion be used during pregnancy?
Yes.
173
Pancreatitis is a theoretical complication with lipid emulsion, why?
Secondary to hyperlipidemia and/or hypermylasemia
174
What happens if a patient completed treated with lipid emulsion and become hemodynamically unstable again?
The duration of the LA exceeds that of the lipid emulsion
175
What can be done if ACLS and lipid emulsion therapy fail?
Cardiopulmonary bypass
176
What is tumescent anesthesia?
Dilute NaCl, lidocaine, epi and bicarb injected into adipose tissue for liposuction
177
What is the most common cause of death with liposuction?
Pulmonary embolism
178
What is the maximum dose of lidocaine with epi for tumescent anesthesia?
55 mg/kg
| vs 7 mg/kg with a max dose of 500 mg normally
179
When does Cp peak with tumescent anesthesia? When is LA completely eliminated
Peak: 12 hours
Eliminated: by 36 hours
180
Serum levels of LA with tumescent anesthesia seldom exceed what? Why do we care?
1.5 mcg/mL
| This is below the threshold for CNS and cardiovascular toxicity
181
MAC may be selected if a small volume of tumescent is used, when is GA recommended?
If > 2 - 3 L of tumescent are injected
182
What is the importance about fluid management with tumescent anesthesia?
The large amount of fluid can cause intravascular volume expansion -> fluid overload and pulmonary edema
183
When is methemoglobin formed?
The oxygen biding site on the heme portion of Hgb molecule contains an iron molecule in its ferrous form (Fe+2), methemoglobin is formed with the iron molecule becomes oxidized to its ferric form (Fe+3)
184
What are the 2 ways methemoglobin decreases oxygen-carrying capacity?
1. HgbMet cant’t bind oxygen molecules
| 2. HgbMet shifts the oxyhemoglobin dissociation curve to the left, this increases Hgb affinity for O2
185
How does methemoglobin affect a pulse oximeter reading? What should be used to monitor?
HgbMet absorbed 660 nm and 940 nm infrared equally.
Typically a significant concentration of HgbMet will read 85%.
Co-oximeter is required to diagnose HgbMet.
186
What 4 LAs are most likely to cause methemoglobin?
Benzocaine
Cetacaine (contains benzocaine)
Prilocaine
EMLA (prilocaine + lidocaine)
187
What 4 drugs other than LA can cause methemoglobin?
Nitroprusside
Nitroglycerine
Sulfonamides
Phenytoin
188
What are the signs and symptoms of methemoglobin?
```
Hypoxia
Cyanosis
Chocolate colored blood
Tachycardia
Tachypnea
Mental status change
Coma and death
```
189
What is highly suggestive when cyanosis is present in the presence of normal PaO2?
Methemoglobin
190
What is the treatment for methemoglobin? Dose?
Methylene Blue
| 1 - 2 mg/kg over 5 minutes with a max dose of 7 - 8 mg/kg
191
How does methylene blue treat methemoglobin?
Methylene blue is metabolized by methemoglobin reductive to form leucomethylene blue, this metabolite functions as an electron donor, which reduces methemoglobin back to hemoglobin
192
What patients do not possess methemoglobin reductase? How is methemoglobin treated in these patients?
Those with glucose-6-phosphate reductase
| An exchange transfusion may be required
193
What patient population is at high risk for methemoglobin toxicity? Why?
Neonates.
| Fetal hemoglobin is relatively deficient in methemoglobin reductase, making it susceptible to oxidation
194
What is in 5% EMLA cream?
50/50 combination of 2.5% lidocaine and 2.5% prilocaine
195
What makes EMLA cream absorbable?
The melting point of EMLA is lower than either of its constituents
196
How long does it take for EMLA to produce analgesia? When is the max effect?
Analgesia achieved within 1 hour.
| Max effect after 2 - 3 hours
197
Where can EMLA be applied?
Intact skin only.
| No MM
198
What can be applied with EMLA simultaneously to hasten absorption?
Nitroglycerin
199
Prilocaine is metabolized into what? WHy is this a problem?
O-toulidine - oxidizes into methemoglobin
| Infants and small children are more likely to become toxic
200
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EMLA dose recommendations:
0 - 3 months or < 5 kg
3 - 12 months and > 5 kg
1 - 6 years and > 10 kg
7 - 12 years and > 20 kg
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0 - 3 months or < 5 kg: max dose 1 g, max area 10 cm2
3 - 12 months and > 5 kg: max dose 2 g, max area 20 cm2
1 - 6 years and > 10 kg: max dose 10 g, max area 100 cm2
7 - 12 years and > 20 kg: max dose 20 g, max area 200 cm2
201
What effect do epinephrine, dexamethasone, and dextran have as an additive to LAs?
Prolong duration of action
202
What effect do clonidine, epinephrine, and opioids (neuraxially) have as an additive on LAs?
Provide supplemental analgesia
203
What effect does sodium bicarbonate have as an additive to LAs?
Shortens onset time
204
What effect does Hyaluronidase have as an additive to LAs?
Improves diffusion through tissues
205
How does epinephrine prolong LA duration of action?
The alpha-1 agonist effect of epi makes it a potent vasoconstrictor that can decrease systemic uptake of LA, prolong block duration, and enhance quality
206
What LAs does epi do a better job prolonging DOA?
LAs of intermediate duration when compared to those of long duration
Lidocaine better than bupivacaine for example
207
How does dexamethasone prolong LA DOA?
Correlates with glucocorticoid activity, it acts on the steroid receptor and/or affects systemic uptake of the LA
208
How much can dexamethasone increase DOA of a brachial plexus block?
Up to 50%
209
How does dextran prolong LA DOA?
By decreasing systemic uptake of LA
210
How does clonidine provide supplemental analgesia as an LA additive? Dose?
Analgesia is produced by the alpha-2 agonist in the brain and spinal cord.
100 mcg added to LA
211
How does epinephrine provide supplemental analgesia as an LA additive?
Alpha-2 agonism
212
When can opioids be used as an LA additive to provide supplemental analgesia? What occurs when they are used in other blocks? Exception?
Spinal and epidurals.
When used in peripheral blocks the results have been mixed.
Chloroprocaine reduces the effectiveness of opioids in the epidural space.
213
How does sodium bicarb shorten onset time of LAs?
Alkalization increases the number of lipid soluble molecules, which speeds up the onset of action, in clinical practice there is a limit to how much LA solution can be alkalized before it precipitates, so this technique only produces a modest benefit. The increase in nonionized base also increases quality of the block
214
How does Hyaluronidase improve diffusion through tissues as an LA additive?
Hyaluronic acid is present in the interstitial matrix and basement membrane, it hinders the spread of substance through tissue, Hyaluronidase hydrolysis hyaluronic acid, which facilitates diffusion of substance in the tissues.
215
Hyaluronidase is commonly used in ophthalmic blocks for what 5 benefits?
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Increase speed of onset
Enhance block quality
Mitigate rise in intraocular pressure
Reduces hematoma size
Decreases risk of post op strabismus
```
216
Hyaluronidase has an allergic potential. T/F
True
