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Apex > Unit 5 Pharmacology: Local Anesthetics > Flashcards

Unit 5 Pharmacology: Local Anesthetics Flashcards

1
Q

Define conduction velocity

A

How fast an axon transmits the action potential

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2
Q

What 2 things increase conduction velocity?

A

Myelination

Larger fiber diameter

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3
Q

What is saltatory conduction?

A

Myelinated axons allow the electrical current to skip along only the uninsulated regions (the nodes of Ranvier)

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4
Q

What are the 3 major classes of peripheral nerves?

A

A
B
C

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5
Q

How many types of A fibers are there? What are they?

A 
(4)
Alpha
Beta
Gamma
Delta
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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
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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
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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
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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
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10
Q

How many types of B fibers are there? What are they?

A

Just 1

B fibers

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11
Q 
B fibers:
Myelination
Function
Diameter
Velocity
Block onset
A 
Myelination: light
Function: preganglionic ANS fibers
Diameter: 3 um
Velocity: ++
Block onset: First
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12
Q

How many types of C fibers are there? What are they?

A

(2)
Sympathetic
Dorsal root

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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
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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
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15
Q

What is differential blockade?

A

?

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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

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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.

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18
Q

What size nerves typically have a higher Cm?

A

Nerves with a wider diameter

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19
Q

How does tissue pH affect Cm?

A

Cm is reduced by higher tissue pH

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20
Q

How does nerve stimulation affect Cm?

A

Cm is reduced by high frequency nerve stimulation.

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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

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22
Q

Where do local anesthetics bind? How do they bind?

A

Reversibly bind to the alpha subunit of the voltage-gated sodium channel

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23
Q

How many and what type of subunits does the voltage-gated sodium channel contain?

A

1 alpha subunit

2 beta subunits

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24
Q

What subunit forms the entire ion conducting pore in the voltage-gated sodium channel?

A

alpha subunit

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25
Q

Local anesthetics can bind to the voltage-gated sodium channel when it is what position(s)?

A

Active and inactive states

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26
Q

What are the 3 states the sodium channel can exist in?

A

Resting
Active
Inactive

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27
Q

Resting state of the sodium channel:
mV?
Channel open or closed?

A

-70 mV

Channel is closed

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28
Q

Active state of the sodium channel:
mV
Channel open or closed?

A

-70 to +35 mV

Channel opens when threshold potential is reached

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29
Q

Inactive state of the sodium channel:
mV?
Open or closed?

A

+35 to -70 mV

Channel is closed

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30
Q

What occurs during the inactive state of the voltage-gated sodium channel?

A

The inactivation gate plugs the channel until resting membrane potential is re-established.

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31
Q

What is a use-dependent or phasic block?

A

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

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32
Q

What 2 things establish resting membrane potential? What is the net result?

A
  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

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33
Q

What is an action potential?

A

A temporary change in transmembrane potential followed by a return to transmembrane potential

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34
Q

When is an action potential created?

A

When a stimulus opens sodium channels

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35
Q

What is the all or none phenomenon?

A

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

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36
Q

Explain how depolarization is only able to go in one direction

A

The upstream portion of the neuron is in its refractory period (Na+ channels are in the inactive state) and cannot be stimulated.

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37
Q

What restores transmembrane potential to RMP?

A

Potassium conductance is increased and Na/K-ATPase removes all the sodium that entered during depolarization

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38
Q

How do local anesthetics effect depolarization?

A

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.

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39
Q

In the vial are LAs an acid or base?

A

A weak base

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40
Q

How are LAs packaged (formulation) and what kind of pH?

A

Hydrochloride salts in aqueous solution

Low pH to guard against precipitation

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41
Q

Once you inject LA into a patient what happens?

A

It quickly dissociates into an uncharged base (LA) and an ionized conjugate acid (LA+)

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42
Q

What is pKa?

A

The pH where 50% of the drug exists as the unchanged base and 50% of the drug exists as the conjugate acid

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43
Q

What equation can be used to predict the ratio of each moiety of LA?

A

Henderson-Hasselbach equation

pH = pKa + log ( [base] / [conjugate acid] )

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44
Q

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?

A

> 50%

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45
Q

Diffusion of LA into that bloodstream is called?

A

Uptake

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46
Q

What kinds of areas remove LA at a faster rate?

A

Highly vascular areas vs sites with less blood flow

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47
Q

What concept reduces local anesthetic duration while increasing plasma concentration?

A

Uptake

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48
Q

Which part of the LA enters the axoplasm by diffusion?

A

The unchanged base enters via diffusion through the lipid rich axolemma

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49
Q

Once the unchanged base of LA enters the axoplasm how does it change?

A

The ICF is slightly more acidic that the ECF, there is a greater fraction of the ionized conjugate acid inside the cell

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50
Q

What part of the LA binds to the alpha subunit of the voltage-gated sodium channel?

A

Only the ionized conjugate acid

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51
Q

How long does the sodium channel remain in the closed activated state from LA?

A

Until enough of the LA diffuses away

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52
Q

What are the 2 classes of LA?

A

Esters

Amides

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53
Q

What are the 3 key components of a local anesthetic molecule?

A

Benzene ring
Intermediate side chain
Tertiary amine

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54
Q

What medicinal chemistry does the benzene ring hold?

A

Lipophilic - Permits diffusion through the lipid bilayer

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55
Q

What medicinal chemistry does the intermediate chain hold?

A

Determines class - ester or abide
Metabolism
Allergic potential

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56
Q

What medicinal chemistry does the tertiary amine hold?

A

It is hydrophilic
It accepts proton
Makes the molecule a weak base

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57
Q

How to remember which LAs are ester-type

A

Ester was a cyclops - only have one i

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58
Q

List 5 ester-type LAs

A

Benzocaine
Cocaine
Chloroprocaine
Tetracaine

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59
Q

How are ester-type LAs metabolized? Are there any exceptions?

A

Pseudocholinesterase- do deficiency could increase duration of action

Cocaine is also metabolized by the liver

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60
Q

How high is the allergic potential of ester-type LAs?

A

Low

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61
Q

Is there cross sensitivity in the same class of ester-type LAs?

A

Yes

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62
Q

Is there cross sensitivity between ester and amides?

A

No

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63
Q

How to remember amide-type LAs

A

Amide has an i for the extra i in the name (there are 2 i’s)

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64
Q

Name 8 amide-type LAs

A 
Articaine 
Bupivacaine 
Dibucaine
Etidocaine
Levobupivacaine 
Lidocaine
Mepivacaine
Ropivacaine
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65
Q

How are amide-type LAs metabolized? Are there any exceptions?

A

Hepatic carboxylesterase/P450

No

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66
Q

What is the allergic potential of amide-type LAs?

A

Extremely rare

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67
Q

Is there cross sensitivity in the same class with amide-type LAs?

A

No

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68
Q

What probably causes allergic reaction with ester-type LAs (though LAs allergy is rare)

A

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.

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69
Q

What probably causes allergic reaction in the amide class (though LA allergy is rare)

A

Some multi-dose vials contain methylparaben as a preservative, which is similar to PABA

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70
Q

The primary variable that correlates with onset of action of LA is?

The secondary variables that correlate with onset?

A

Primary: pKa

Secondary: dose, concentration

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71
Q

What primary variable correlates the best with potency? What secondary variable?

A

Primary: Lipid solubility
Secondary: intrinsic vasodilation effect

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72
Q

What primary variable correlates the best with LA duration of action? What secondary variables?

A

Primary: protein binding
Secondary: lipid solubility, intrinsic vasodilation effect, addition of vasoconstrictors

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73
Q

How does pKa best correlate with onset of action of LAs?

A

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.

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74
Q

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?

A

The ionized conjugate acid

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75
Q

How does does and concentration effect onset of LA? Examples help to explain

A

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.

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76
Q

How does lipid solubility best correlate with LA potency?

A

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

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77
Q

Agents that are lipophilic tend to be ____ potent and have _____ duration of action.

A

More

Longer

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78
Q

An alkyl group substitution on the amide group and benzene ring does what to lipid solubility?

A

Increases lipid solubility

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79
Q

Stereoselectivity also plays a role in _____ of LAs

A

Potency

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80
Q

How does intrinsic vasodilating ability affect potency of LAs?

A

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

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81
Q

What is the biphasic response on vascular smooth muscle that most LAs have?

A

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

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82
Q

What LA is the exception to the intrinsic vasodilating activity of LAs?

A

Cocaine: it inhibits NE reputable and always causes vasoconstriction

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83
Q

Some texts say there are 2 other LAs (besides cocaine) that do not have intrinsic vasodilating activity:

A

Chloroprocaine

Ropivacaine

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84
Q

Drugs with a greater degree of intrinsic vasodilating effects (lidocaine) under a faster rate of _____

A

Uptake

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85
Q

How does protein biding best correlate with duration of action of LAs?

A

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

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86
Q

How does lipid solubility affect duration of action?

A

Increased lipid solubility correlates with a longer duration of action

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87
Q

How does intrinsic vasodilating activity correlate with duration of action of LA?

A

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
Q

If you put a strong acid or base in water, what will happen?

A

It will dissociate completely

89
Q

If you put a weak acid or base in water what will happen?

A

A fraction will ionize and the remaining fraction will be unionized.

90
Q

Ionization is dependent on which 2 factors?

A
  1. pH of the solution

2. pKa of the drug

91
Q

If a molecule is a weak base and the pH of the solution is > pKa of the drug, what fraction predominates?

A

The unionized fraction

92
Q

If the molecule is a weak acid and the pH of the solution is < the pKa of the drug, which fraction predominates?

A

The unionized fraction

93
Q

If the molecule is a weak base and the pH of the solution is < the pKa of the drug, what fraction predominates?

A

The ionized fraction

94
Q

If the molecule is a weak acid and the pH of the solution is > the pKa of the drug, then what fraction predominates?

A

The ionized fraction

95
Q

Bupivacaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 8.1
Ionization % at 7.4: 83
Protein biding %: 96

96
Q

Levo-bupivacaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 8.1
Ionization % at 7.4: 83
Protein biding %: 98

97
Q

Ropivacaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 8.1
Ionization % at 7.4 : 83
Protein biding %: 94

98
Q

Lidocaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 7.9
Ionization % at 7.4 : 76
Protein biding %: 65

99
Q

Prilocaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 7.9
Ionization % at 7.4 : 76
Protein biding %: 55

100
Q

Mepivacaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 7.6
Ionization % at 7.4 : 61
Protein biding %: 78

101
Q

Procaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 8.9
Ionization % at 7.4 : 97
Protein biding %: 6

102
Q

Chloroprocaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 8.7
Ionization % at 7.4 : 95
Protein biding %: 0

103
Q

Tetracaine:
pka
Ionization % at 7.4
Protein biding %

A

pka: 8.5
Ionization % at 7.4 : 93
Protein biding %: 76

104
Q

With LAs the further pka gets away from physiologic pH, the degree of ionization _______.

A

Increases

105
Q

The closet the pKa of an LA is to the pH of the blood, the _____ the onset.

A

Faster

Exception is chloroprocaine

106
Q

LAs are weak bases that are ionized (charged) at physiologic pH, what is the exception?

A

Benzocaine has a pKa of 3.5, well below physiologic pH

107
Q

Benzocaine is ________ at physiologic pH

A

Non-ionized

108
Q

List 5 factors that influence vascular uptake of LAs:

A 
Site of injection
Tissue blood flow 
Physiochemical properties of LA
Metabolism
Addition of vasoconstrictor
109
Q

What helps influence final plasma concentration?
Total dose
Concentration
Speed of injection

A

Total dose

The same plasma concentration is reached whether 40 mL of 0.25% or 20 mL or 0.5% were used

110
Q

Mnemonic for most vascular & highest Cp block to least vascular & lowest Cp

A

I Think Illogical Imposters Can’t Educate But Fabulous Schools Should

IV, Tracheal, Interpleural, Intercostal, Caudal, Epidural, Brachial plexus, Femoral, Sciatic, SubQ

111
Q

What plasma proteins bind to LAs helping to limit peak plasma concentration?

A

Preferentially bind to alpha1-acid glycoprotein, but will also bind to albumin

112
Q

What organ acts as a reservoir that removes LA from the circulation and limits plasma concentration?

A

The lungs

113
Q

Metabolism decreases plasma LA concentrations, how are the 2 classes of LAs metabolized?

A

Amides and cocaine: P450 enzymes

Esters: pseudocholinesterase

114
Q

How much can the addition of a vasoconstrictor, such as epi or phenylephrine, decrease systemic absorption? What other effect does this have?

A

Decreases systemic absorption by up to 1/3.
Prolongs duration
Effect is greatest with LAs that have significant intrinsic dilating activity

115
Q

Levobupivacaine:
Max dose: mg/kg
Max total dose: mg

A

Max dose: 2 mg/kg

Max total dose: 150 mg

116
Q

Bupivacaine:
Max dose: mg/kg
Max total dose: mg

A

Max dose: 2.5 mg/kg

Max total dose: 175 mg

117
Q

Bupivacaine with Epi:
Max dose: mg/kg
Max total dose: mg

A

Max dose: 3 mg/kg

Max total dose: 200 mg

118
Q

Lidocaine:

Max dose: mg/kg
Max total dose: mg

A

Max dose: 4.5 mg/kg

Max total dose: 300 mg

119
Q

Ropivacaine

Max dose: mg/kg
Max total dose: mg

A

Max dose: 3 mg/kg

Max total dose: 200 mg

120
Q

Mepivacaine

Max dose: mg/kg
Max total dose: mg

A

Max dose: 7 mg/kg

Max total dose: 400 mg

121
Q

Lidocaine with Epi:

Max dose: mg/kg
Max total dose: mg

A

Max dose: 7 mg/kg

Max total dose: 500 mg

122
Q

Prilocaine:

Max dose: mg/kg
Max total dose: mg

A

Max dose: 8 mg/kg

Max total dose: If <70 kg 500mg, if >70 kg 600 mg

123
Q

Procaine:

Max dose: mg/kg
Max total dose: mg

A

Max dose: 7 mg/kg

Max total dose: 350 - 600 mg

124
Q

Chloroprocaine:

Max dose: mg/kg
Max total dose: mg

A

Max dose: 11 mg/kg

Max total dose: 800 mg

125
Q

Chloroprocaine with Epi:

Max dose: mg/kg
Max total dose: mg

A

Max dose: 14 mg/kg

Max total dose: 1000 mg

126
Q

Tetracaine

Max dose: mg/kg
Max total dose: mg

A

Max dose: mg/kg

Max total dose: mg

127
Q

The plasma concentration of LA is a net balance of what 3 things?

A

Vascular uptake to redistribution and metabolism

128
Q

Where do local anesthetic systemic toxicities occur in the body?

A

The heart and brain

129
Q

What is the most common cause of toxic plasma concentrations of LA?

A

Inadvertent IV injection during regional Anethesia

130
Q

What is the most frequent symptoms of LAST? Exception?

A

Seizure

Bupivacaine - cardiac arrest before seizure

131
Q

Is LAST more common with peripheral blocks or epidurals?

A

More common with peripheral blocks

132
Q

What plasma concentration of Lidocaine mcg/mL produces analgesia?

A

1 - 5 mcg/mL

133
Q

The plasma concentration of 5 - 10 mcg/mL produces what CNS and cardiopulmonary effects?

A 
Tinnitus
Numbness of lips and tongue
Skeletal muscle twitching
Restlessness
Vertigo
Blurred vision
Hypotension
Myocardial depression
134
Q

The plasma concentration of 10 - 15 mcg/mL produces what CNS and cardiopulmonary effects?

A

Seizures
Loss of consciousness
No further cardiopulmonary effects

135
Q

The plasma concentration of 15 - 25 mcg/mL produces what CNS and cardiopulmonary effects?

A

Coma

Respiratory arrest

136
Q

The plasma concentration of > 25 mcg/mL produces what CNS and cardiopulmonary effects?

A

No further CNS effects

Cardiovascular collapse

137
Q

What 3 factors increase CNS toxicity of LAs?

A

Hypercarbia
Hyperkalemia
Metabolic acidosis

138
Q

How does hypercarbia increase the risk of CNS toxicity with LAs?

A

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
Q

How does hyperkalemia increase CNS toxicity with LAs?

A

Hyperkalemia raises resting membrane potential, making them more likely to depolarize

140
Q

How does metabolic acidosis increase the risk of CNS toxicity in LAs?

A

Metabolic acidosis decreases the convulsion threshold and favors ion trapping inside the brain

141
Q

How does metabolic acidosis affect the LA fraction of conjugate acid vs uncharged base? Is this significant?

A

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
Q

What 3 factors decrease the risk of CNS toxicity from LAs?

A

Hypocarbia
Hypokalemia
CNS depressants

143
Q

How does hypocarbia decrease the risk of CNS toxicity with LAs?

A

Hypocarbia decreases CBF and reduces drug delivery to the brain, hyperventilation might be helpful

144
Q

How does hypokalemia decrease the risk of CNS toxicity with LAs?

A

Hypokalemia lowers RMP, requiring a larger stimulus to depolarize the nerve

145
Q

How do CNS depressants decrease the risk of CNS toxicity with LAs?

A

CNS depressants such as benzodiazepines and barbiturates raise the seizure threshold

146
Q

What 3 ways do LAs disrupt hemodynamics?

A

Altering the:
cardiac action potential
Myocardial performance
Vascular resistance

147
Q

How do LAs alter the cardiac action potential? (4)

A

Decrease automaticity, conduction velocity, action potential duration, and the effective refractory period

148
Q

How do LAs affect myocardial performance?

A

Depress the myocardium by impairing intracellular calcium regulation

149
Q

How do LAs affect vascular smooth muscle?

A

There is a biphasic effect:
Low concentrations of LAs produce vasoconstriction
Higher doses produce vasodilation and a reduction in SVR

150
Q

What 2 features determine the extent of cardio toxicity with LAs?

A
  1. Affinity for the voltage-gated sodium channel in the active and inactive state
  2. Rate of dissociation from the receptor during diastole
151
Q

Why is cardiac resuscitation so difficult with bupivacaine toxicity?

A

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
Q 
Arrange the order of difficulty of cardiac resuscitation from greatest to least of:
Bupivacaine 
Lidocaine 
Levobupivacaine 
Ropivacaine
A

Bupivacaine > Levobupivacaine > Ropivacaine > Lidocaine

153
Q

The risk of bupivacaine toxicity is increased with? (4)

A

Pregnancy
BB
CCB
Digitalis

154
Q

What is the primary risk of cocaine toxicity? Why?

A

Excessive SNS stimulation.

Cocaine has vasoconstrictive properties, it inhibits NE reuptake into the presynaptic nerve terminal

155
Q

With what 3 drug classes should cocaine use be avoided?

A

MAOIs
TCAs
Sympathomimetics

156
Q

What is the deal with BB in the setting of cocaine overdose?

A

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
Q

What is the best drug of choice for cocaine overdose? What if BB is the only choice in the list?

A

Vasodilator such as Nitroglycerine.

If only BBs are listed, then labetalol or another mixed alpha and beta antagonist

158
Q

What is the dose for cocaine’s use as a vasoconstrictor? Max dose?

A

1.5 - 3.0 mg/kg

Max: 150 - 200 mg

159
Q

What 3 ways can risk of LAST be reduced?

A

using a test dose
Incremental dosing
Periodic aspiration

160
Q

4 major steps in LAST treatment:

A
  1. Manage the airway
  2. Treat seizures
  3. ACLS with specific modifications
  4. Lipid emulsion
161
Q

What 2 things in relation to airway management will worsen LAST?

A

Avoid hypoxia and acidosis

-FiO2 100%

162
Q

If benzodiazepines are ineffective in stopping LAST seizure, what should be given? Why?

A

Small dose of Sux or ND-NMB.

To minimize oxygen consumption, hypoxemia, and acidosis

163
Q

What drug, though has anti-seizure properties, should be avoided? Why?

A

Propofol.

Small doses may abate seizure activity, but larger doses augment myocardial depression

164
Q

What are the specific ACLS modifications for LAST treatment? (3)

A

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
Q

What is the concentration of lipid emulsion?

A

20%

166
Q

What is the bolus dose for lipid emulsion? Infusion rate?

A

Bolus: 1.5 mL/kg (LBW) over 1 minute
Infusion: 0.25 mL/kg/min

167
Q

If symptoms of LAST are slow to resolve, what can be done?

A

Repeat bolus up to 2 more times and increase infusion to 0.5 mL/kg/min

168
Q

How long should the lipid emulsion infused for LAST be continued?

A

Until 10 minutes after achieving hemodynamic stability

169
Q

What is the maximum recommended dose of lipid emulsion?

A

10 mL/kg in the first 30 minutes

170
Q

What is the MOA of lipid emulsion?

A

Lipid sink - an intravascular reservoir that sequesters LA and reduces plasma concentration of LA

171
Q

Lipid emulsion:
Metabolic effect
Inotropic effect
Membrane effect

A

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
Q

Can lipid emulsion be used during pregnancy?

A

Yes.

173
Q

Pancreatitis is a theoretical complication with lipid emulsion, why?

A

Secondary to hyperlipidemia and/or hypermylasemia

174
Q

What happens if a patient completed treated with lipid emulsion and become hemodynamically unstable again?

A

The duration of the LA exceeds that of the lipid emulsion

175
Q

What can be done if ACLS and lipid emulsion therapy fail?

A

Cardiopulmonary bypass

176
Q

What is tumescent anesthesia?

A

Dilute NaCl, lidocaine, epi and bicarb injected into adipose tissue for liposuction

177
Q

What is the most common cause of death with liposuction?

A

Pulmonary embolism

178
Q

What is the maximum dose of lidocaine with epi for tumescent anesthesia?

A

55 mg/kg

vs 7 mg/kg with a max dose of 500 mg normally

179
Q

When does Cp peak with tumescent anesthesia? When is LA completely eliminated

A

Peak: 12 hours
Eliminated: by 36 hours

180
Q

Serum levels of LA with tumescent anesthesia seldom exceed what? Why do we care?

A

1.5 mcg/mL

This is below the threshold for CNS and cardiovascular toxicity

181
Q

MAC may be selected if a small volume of tumescent is used, when is GA recommended?

A

If > 2 - 3 L of tumescent are injected

182
Q

What is the importance about fluid management with tumescent anesthesia?

A

The large amount of fluid can cause intravascular volume expansion -> fluid overload and pulmonary edema

183
Q

When is methemoglobin formed?

A

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
Q

What are the 2 ways methemoglobin decreases oxygen-carrying capacity?

A
  1. HgbMet cant’t bind oxygen molecules

2. HgbMet shifts the oxyhemoglobin dissociation curve to the left, this increases Hgb affinity for O2

185
Q

How does methemoglobin affect a pulse oximeter reading? What should be used to monitor?

A

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
Q

What 4 LAs are most likely to cause methemoglobin?

A

Benzocaine
Cetacaine (contains benzocaine)
Prilocaine
EMLA (prilocaine + lidocaine)

187
Q

What 4 drugs other than LA can cause methemoglobin?

A

Nitroprusside
Nitroglycerine
Sulfonamides
Phenytoin

188
Q

What are the signs and symptoms of methemoglobin?

A 
Hypoxia
Cyanosis
Chocolate colored blood
Tachycardia
Tachypnea
Mental status change
Coma and death
189
Q

What is highly suggestive when cyanosis is present in the presence of normal PaO2?

A

Methemoglobin

190
Q

What is the treatment for methemoglobin? Dose?

A

Methylene Blue

1 - 2 mg/kg over 5 minutes with a max dose of 7 - 8 mg/kg

191
Q

How does methylene blue treat methemoglobin?

A

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
Q

What patients do not possess methemoglobin reductase? How is methemoglobin treated in these patients?

A

Those with glucose-6-phosphate reductase

An exchange transfusion may be required

193
Q

What patient population is at high risk for methemoglobin toxicity? Why?

A

Neonates.

Fetal hemoglobin is relatively deficient in methemoglobin reductase, making it susceptible to oxidation

194
Q

What is in 5% EMLA cream?

A

50/50 combination of 2.5% lidocaine and 2.5% prilocaine

195
Q

What makes EMLA cream absorbable?

A

The melting point of EMLA is lower than either of its constituents

196
Q

How long does it take for EMLA to produce analgesia? When is the max effect?

A

Analgesia achieved within 1 hour.

Max effect after 2 - 3 hours

197
Q

Where can EMLA be applied?

A

Intact skin only.

No MM

198
Q

What can be applied with EMLA simultaneously to hasten absorption?

A

Nitroglycerin

199
Q

Prilocaine is metabolized into what? WHy is this a problem?

A

O-toulidine - oxidizes into methemoglobin

Infants and small children are more likely to become toxic

200
Q 
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
A

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
Q

What effect do epinephrine, dexamethasone, and dextran have as an additive to LAs?

A

Prolong duration of action

202
Q

What effect do clonidine, epinephrine, and opioids (neuraxially) have as an additive on LAs?

A

Provide supplemental analgesia

203
Q

What effect does sodium bicarbonate have as an additive to LAs?

A

Shortens onset time

204
Q

What effect does Hyaluronidase have as an additive to LAs?

A

Improves diffusion through tissues

205
Q

How does epinephrine prolong LA duration of action?

A

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
Q

What LAs does epi do a better job prolonging DOA?

A

LAs of intermediate duration when compared to those of long duration
Lidocaine better than bupivacaine for example

207
Q

How does dexamethasone prolong LA DOA?

A

Correlates with glucocorticoid activity, it acts on the steroid receptor and/or affects systemic uptake of the LA

208
Q

How much can dexamethasone increase DOA of a brachial plexus block?

A

Up to 50%

209
Q

How does dextran prolong LA DOA?

A

By decreasing systemic uptake of LA

210
Q

How does clonidine provide supplemental analgesia as an LA additive? Dose?

A

Analgesia is produced by the alpha-2 agonist in the brain and spinal cord.
100 mcg added to LA

211
Q

How does epinephrine provide supplemental analgesia as an LA additive?

A

Alpha-2 agonism

212
Q

When can opioids be used as an LA additive to provide supplemental analgesia? What occurs when they are used in other blocks? Exception?

A

Spinal and epidurals.
When used in peripheral blocks the results have been mixed.
Chloroprocaine reduces the effectiveness of opioids in the epidural space.

213
Q

How does sodium bicarb shorten onset time of LAs?

A

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
Q

How does Hyaluronidase improve diffusion through tissues as an LA additive?

A

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
Q

Hyaluronidase is commonly used in ophthalmic blocks for what 5 benefits?

A 
Increase speed of onset
Enhance block quality 
Mitigate rise in intraocular pressure
Reduces hematoma size 
Decreases risk of post op strabismus
216
Q

Hyaluronidase has an allergic potential. T/F

A

True

Apex (46 decks)

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