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Pharmacology > Local Anesthetics > Flashcards

Local Anesthetics Flashcards

1
Q

Local anesthetics

A

reversibly block afferent nerve transmission to produce analgesia WITHOUT loss of consciousness

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2
Q

Afferent

A

sensory neurons

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3
Q

Efferent

A

motor neurons

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4
Q

3 types of blockades

A

Autonomic

Somatic sensory

Somatic motor

block tends to order is this order

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5
Q

Sympathectomy

A

surgical removal of a sympathetic nerve and side effects can result in an autonomic block

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6
Q

Autonomic blockade

A

easiest r/t fiber being on outside the nerve

  • causes vasodilation and decreased BP
  • fluid boluses can be given to get ahead of the block
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7
Q

Somatic sensory blockade

A

block feeling of pain

**what we want to bock

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8
Q

Somatic motor blockade

A

more difficult to block and we don’t necessarily need to bock

*can be useful if surgeon needs a relaxed surgical field

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9
Q

Uses of Local Anesthetics

A

-they are administers near the site of action

  • infiltrated around the nerve;
    1. topically to skin and mucous membranes
    2. injected into blood vessel
    3. injected into the subarachnoid and epidural spaces
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10
Q

Bier Block

A

injecting local anesthetic into the venous system of an upper or lower extremity that has been exsanguinated by compression or gravity and that has been isolated by means of a tourniquet from the central circulation.

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11
Q

Dorsal Nerve Root

A

contains dorsal root ganglia [[cell bodies of AFFERENT (sensory) neurons

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12
Q

Ventral Nerve Root

A

EFFERENT (motor) neuron

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13
Q

Myelinated Nerve Fiber

A

Schwann cell wraps itself around the axon several times [[lipid insulating barrier]]

creating a myelin sheath around the axon

*this increases efficiency [[how fast an AP canspend]]

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14
Q

Unmyelinated Nerve Fiber

A

single Schwann cell surround several axons

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15
Q

Myelinated vs Unmyelinated

A
  • propagation of impulses is similar
  • unmyelinated fibers impulses travel along the length of the fiber in a continuous fashion

-myelinated fibers conduction is ‘salutary’
[[so fast it appears the impulses leap from node of Ranvier (where there is no myelin) to the next

-locals can only work on the node of ranvier
[[need enough local to block 3 nodes –> as the nerve gets bigger the nodes get further apart –> larger nerves are harder to block]]

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16
Q

Membrane

A

-ion channels on membrane guarded by gating mechanism
[[channels are open/ closed depending changing physiological conditions]]

-barrier exists where there is movement of ions along a concentration gradient between intracellular and extracellular space

  • extracellular –> high Na+
  • intracellular –> high K+

K+ sets the resting membrane potential [[-70- -90]]

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17
Q

Nerve Fibers

A

-Diameter of the nerve fiber is proportional to the velocity of an impulse

[[larger the diameter higher the conduction velocity]]

Fibers are classified according to diameter
[[3 types A,B and C fibers]]

Fast and slow pathways

Large fibers have the highest conduction velocity and LOWESR threshold for excitability

[[A- alpha fastest; unmyelinated C-fiber is the slowest]]

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18
Q

A Fibers

A

-myelinated
-1-22 micrometers
- subdivided in 4 types
[[alpha; beta; gamma, delta]]

A- delta Slowest of the A fibers

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19
Q

B Fibers

A
  • myelinated

- 1-3 micrometers

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20
Q

C Fibers

A
  • unmyelinated

- 0.1- 2.5 micrometers

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21
Q

Peripheral Nerve Fibers

A

Largest/ Fastest - Smallest/ Slowest

  • A -alpha fibers; motor and proprioception
  • A -beta fibers; motor, touch, pressure
  • A -delta fibers; pain, temperature, touch [[fast pain]]
  • B-fibers; PREganglionic autonomic
  • C-fibers; dull pain temperature, touch POSTganglionic autonomic [[no myelin]]
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22
Q

Teaching for epidural to a woman in labor

A

“you will feel pressure but no pain’’

why?? hard to block A- alpha and A- beta typically don’t block those fully

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23
Q

Testing nerve block

A

when we block the level of pain [[A- delta fibers]] we also block temperature

*check level of block with cold alcohol swap to. assess their feeling of temperature and pain [[nicer than using a needle]]

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24
Q

Sensitivity to peripheral nerve to LA is determined by what

A

size of myelin

INVERSE relationship

smaller fiber more sensitive
[[why we see an autonomic block first; C and B fibers]]

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25
Q

What is different about sensitivity of peripheral nerves in a lab

A

larger fibers are more sensitive

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26
Q

Why is the sensitivity of peripheral nerves different in the body vs the lab?

A
  • Larger fibers [[A-delta and A-gamma]]are found deeper in the nerve bundle making it harder for the local anesthetic to reach, Smaller fibers B and C more external
  • variable activity in different nerve [[pain fibers fire at higher frequency]]
  • variable ion channel; mechanism
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27
Q

Spread of Local Anesthetic

A

LOCATION!

-Sequence of onset and recovery from a local anesthetic block in a mixed peripheral nerve relied heavily on where it is located
^location is much more important than the sensitivity of the nerve fiber to the LA

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28
Q

Surfaces of peripheral nerves

A

outer surface of peripheral nerve–> mantle; usually more proximal structures

inner surface–> core; these fibers usually serve more distal structures

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29
Q

Clinical sequence of anesthesia with a peripheral nerve block

A

1st sympathetic block [[vasodilation/ warm skin]]

2nd Loss of pain and temperate sensation

3rd loss of proprioception

4th loss of touch and pressure

5th motor blockade
^ to achieve 4 and 5 need a very dense block

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30
Q

How do you test your epidural block before full administration of LA

A

when you inject 5cc of test dose in, go touch feet, if one is warmer than the other you catheter might be teated to one side

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31
Q

Polarity state

A

intracellular space has a relative negative charge compared to the extracellular space

[[this is why Na is impermeable to a resting cell membrane]]

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32
Q

Action Potential

A

a rapid depolarization of the membrane, lasting 1-2 milliseconds

occurs when specific physiological stimulations is received by a nerve receptor

Na+ is responsible for rapid depolarization of cell
K+ responsible for depolarization back to resting membrane potential

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33
Q

How does a nerve blockade work

A
  • block VGNaCC
  • VGNaCC in the CLOSED and INACTIVE state serve as receptors for locals anesthetics
  • LA bind at specific sites on the internal H gate of the channel and physically obstruct the external opening of the channel [[pore block]]
  • LA prevent the passage of Na ions through these channels by binding and stabilizing them in the closed and inactive [[inverse agonist]]

This blocks impulse conduction during the depolarization phase of the AP [[block enough Na gates to never allow the nerve to reach threshold and propagate and AP]]

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34
Q

Resting Nerve sensitivity vs repeatedly stimulated nerve

A

resting nerve is less sensitive to block than a repeatedly stimulated nerve

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35
Q

Frequency or Use dependent Blockage

A
  • LA easily access nerve cell Na Chanels n the activated open state
  • LA easily bind to the receptor in the inactivate closed state

**more often the channel is in this state the more rapidly the block can occur

[[more stimulated more times it will cycle through an action potential of Na channels being activated open, and inactivated closed]]

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36
Q

How do resting nerves receive blockage

A

DIFFUSION!
LA molecule has to diffuse through axonal membrane instead of through the NA channel to reach target

[[more lipid soluble the faster the diffusion]]

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37
Q

Effect of Distance between Nodes of Ranvier

A
  • distance between nodes of ranvier in myelinated fibers contribute to differential nerve block
  • inter-nodal distance increases with fiber length
  • an impulse can make it through 2 blocked nodes but NOT a third
  • blockade of 3 nodes eliminated conduction along a myelinated nerve fiber (A-fiber)
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38
Q

What was the first local anesthetic shown to produce a beneficial differential block

A

Bupivicaine ; sensory block with INCOMPLETE motor block

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39
Q

Differential Nerve Block

A

pain conducting fibers A- delta and C-fibers blocked

A-alpha, beta and gamma NOT completely blocked

**patient feel pressure but NO PAIN

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40
Q

Classification of LA

A

aminoAMIDES

aminoESTERS

if allergic to one usually NOT allergic to the other

metabolism for both are DIFFERENT

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41
Q

Typical LA molecule

A

typically molecules consist of a lipophilic head and intermediate chain conagtinaing either an amide (NH) or ester (COO) and a hydrophilic tail

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42
Q

Amides

A

all amides have an extra I in the name before the Caine part

ex. lidocaine, burpivicaine, etidocaine

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43
Q

Clinical significance to molecular structure

A

class of intermediate chain [[ester vs amide]] affects. biotransformation of molecule

-Ester linkage; 
QUICK METABOLISM 
[[except cocaine]] 
-Amide linkage;
metabolized in liver, complex biotransformation, SLOWER process

Length of intermediate chain
[[increase/ decrease the number of carbons]] determines potency, toxicity and alters metabolism rate and duration of action [[DOA]]

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44
Q

Amide Linkage

A
  • metabolized by liver
  • complex biotransformation
  • metabolism takes longer [[higher risk of toxicity]]
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45
Q

Ester Linkage

A

hydrolysis [[part of phase 1 of metabolism]] is fast by non specific esterase’s in the plasma and tissue

-QUICK METABOLISM
so fast; less risk of toxicity [[once LA diffuses metabolized so quickly]]

cocaine is the exception
[[undergoes significant liver metabolism]]

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46
Q

Cocaine

A

ester LA

exception to the class in regards to metabolism [[undergoes significant liver metabolism]]

Cocaine blocks Na channels in the inactive state

produces pro-sympathetic stimulations by decreasing reuptake of norepinephrine [[more epinephrine at the SA node –> tachycardia]]

used by ENT for its profound vasoconstriction and decreased bleeding

**MONITOR HR and watch got ST changes

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47
Q

Highly Lipid solubility vs water soluble anesthetics

A

Highly lipid soluble anesthetics are;

MORE potent

LONGER duration of action [[DOA]]

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48
Q

Molecular Chain length

A

increase the length of the intermediate chain [[increase the number of carbon atoms]] INCREASE the potency AND toxicity

  • it also alters the metabolism rate and DOA
  • potency and toxicity also increase with the length of the TERMINAL group located on the tertiary amine and aromatic ring
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49
Q

Enantiomers

A

enantiomers of a chiral carbon may vary in terms of;

  • Pharmacokinetics [[absorption, distribution, metabolism, elimination]]
  • pharmacodynamics [[sensitivity, mechanism of effect]]
  • toxicity

ex.
Bupivacaine [[racemic]] vs L- Bupivacaine [[levo-enantiomer]]
**in theory bupivacaiune is less toxic

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50
Q

[[Cm]] Minimum concentration needed to block nerve

A

**conceptual

-nerve fiber diameter influences the minimum concentration needed
[[need to block 3 nodes of ranvier in a myelinated axon, typically that distance is about 1 cm…now nodes are further apart, 3 nodes makes up more distance; will need a higher Cm]]

-To block a motor nerve vs a sensory nerve you will need a higher Cm

-Tissue pH [][ion trapping]]
acidic pH [[all LA arre weak bases]] in tissue LA onset and Cm increases
**increases so much its almost impossible to get effect

-Frequency of nerve stimulation
[[nerves more frequently stimulates easier for LA to bind, lower Cm]]

-Potency of particular LA
[[more potent lower Cm]]

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51
Q

Sustained release LA

A

-prolonged DOA
[[longer analgesia as block wears off]]

  • theoretically decreased toxicity
  • limits opioid use

Types;

  • Liposomes
  • Cyclodextrins
  • Biopolymer
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52
Q

Exparel

A
  • Bupivacaine extended release LIPOSOME injection
  • slow release of bupivacaine block last much longer
  • reduces opioid use
  • its encapsulates bupivacaine in a lysosome
  • over time the it breaks down and releases the bupivacaine

DO NOT MIX or inject ANY other LA at the same site

dose depends on surgical site

[[MAX DOSE; 266mg or 20ml]]

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53
Q

Impact of Nodes of Ranvier

A
  • nodes are the spaces in between myelinated axons where AP can occur
  • LA work on the nodes
  • blockade of 3 nodes [[which is about 1 cm in length]] eliminates conduction along a myelinated nerve fibers
  • an impulse can make it through 2 BLOCKED nodes but NOT a THIRD
  • the THIRD NODE IS important to block to stop conduction
  • distance between the nodes contributes to differential nerve blocks

**internodal distance increases with fiber diameter

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54
Q

Absorption by TYPE of block

A

highest to lowest absorption

  1. intravenous
    [[ex. Bier block]]
  2. tracheal
  3. intercostal
  4. caudal
  5. paracervical
  6. epidural
  7. brachial plexus
  8. subarachnoid space
  9. subcutaneous

[[more vascular the region higher the systemic absorption]]

less of a risk with max dose in SQ vs IV

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55
Q

LA systemic absorption

A

-controlled by physiochemical characteristics [[pKa, pH, lipid solubility]]

-physiologic conditions at the site of injection [[tissue pH, pC02, temperature, patient characteristics]]
^patient characteristics; elderly, pregnant, neonate, infant

-size of vessel
[[smaller vessel less area for absorption

  • volume of solution or vehicle used [[epidural]]
  • concentration of LA

**LA we DO NOT want high absorption

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56
Q

Differential Nerve block

A

Bupivacaiine was the first LA shown to produce a BENEFICIAL differential block [[sensory block with incomplete motor block]]

  • pain conducting fiber A -delta [[fast pain]] and C- fibers [[dull pain]] were blocked
  • A- alpha, beta and gamma fibers not completely blocked

[[patient feel pressure but not pain with surgical stem]]

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57
Q

Ionization of Local Anesthetics

A
  • NONIONIZED form diffuses across the nerve sheath/ membrane
  • once the nonionized form crosses inside the ration of ionized and nonionized form of drug RE-EQUILIBRATES

ex.
mom and fetus, once nonionized drug crosses to fetus the drug then re-equilibrates in both environments
Fetus is more acidic more drug will stay in ionized form and not be able to cross over, when mom re-equilibrates the nonionized in mom will continue to cross over to baby

-after re-equilibration inside the membrane; IONIZED form binds to receptor inside the VGNaC and BLOCKADE

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58
Q

Ionized form > 50% when..

A

Acidic drug in BASIC environment

Basic drug in ACIDIC environment

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59
Q

Non-ionized form >50% when

A

Acidic drug in Acidic environment

Basic drug in basic environment

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60
Q

pKa range of LA

A

7.5- 9

WEAK BASE

-LA are packaged in acacia formulations to improve solubility and stability in the VIAL; often preserve episode

**they are BASIC upon injection

normal body ph 7.4
Body pH will determine how much of drug is in nonionized form

[[ALWAYS have more in IONIZED form, body determines how much more]]

**closer pKa is pH closer to the 50/ 50 ration

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61
Q

LA example of ionization concept

A
  • when pKa = pH drug exists in 50/ 50 from [[half ionized/ half nonionized]]
  • nonionized crosses nerve sheath and axon membrane to get to site of action
  • ionized binds and blocks Na channel

ideal pKa is closes to physiologic pH [[7.4]]

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62
Q

LA onset

A
  • nonionized form crosses membrane
  • pH of local LA [[solution]] and pKa of the drug determine the amount of drug in the nonionized state
  • in area where high/ normal pH values [[high more basic]] rate of absorption is higher
  • lower pH [[under 7.4]] rate of absorption is lower
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63
Q

pKa of drugs

A

Procaine 8.9

Tetracaine 8.5

Bupivicaine 8.1

**Chloroprocaine 8.7

Lidocaine 7.9

Etidocaine 7.7

Mepivacaine 7.6

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64
Q

pKa of Procaine

A

8.9

3% nonionized [[at normal pH]]

onset; SLOW

**topical sprays; onset slow rarely used

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65
Q

pKa of Tetracaine

A

8.5

7% nonionized [[at normal pH]]

onset; SLOW

66
Q

pKa of Bupivicaine

A

8.1

17% nonionized [[at normal pH]]

onset; MODERATE

*if surgeon gives bupivicaine at end of surgery; might need to give fentanyl to help with pain when pt first wakes up bc onset it moderate

67
Q

Most important characteristic determine onset of LA

A

onset pKa!!

68
Q

pKa of Chloroprocaine

A

8.7

2% nonionized [[at normal pH]]

onset; FAST

**exception to rule

give higher concentration [[more molecules and overcome the pKa]]

69
Q

pKa of Lidocaine

A

7.9

24% nonionized [[at normal pH]]

onset; FAST

70
Q

ideal pKa

A

7.4

50/ 50

71
Q

pKa of Etidocaine

A

7.7

33% nonionized [[at normal pH]]

onset; FASt

72
Q

pKa of Mepivacaine

A

7.6

39% nonionized [[at normal pH]]

onset; FAST

**closest to 50/50

73
Q

How can we influence pH/ pKA relationship to speed of onset?

A

-add bicarb to solution right before injection

  • it will increase the onset
  • enhance depth of block
  • increase the spread of the block

**making environment more basic with bicarb gets more drug in the non-ionized form

74
Q

How does infected tissue effect LA

A

infected tissue is acidic

  • LESS drug in nonionized form
  • basic drug in acidic environment [[more ionized]]
75
Q

Ion trapping in pregnancy

A

pH of baby compared to mom is more acidic

nonionized form crosses placenta to baby and then in baby [[more acicid]] more of drug in ionized form and gets ‘trapped’

[[drug re-equilibrates in baby and mom]]

Protein Binding also play a role in ion trapping
[[bupivicaine is very highly protein bound (99%) protein bound keeps it from crossing placenta in great amounts]]

76
Q

What effect does Temperature have on LA onset

A

-lower temp decreased absorption of drug across nerve membrane

**delays onset of block

[[even though cold leg would decrease systemic absorption of LA it also delays onset of block]]

77
Q

Potency

A

*how many molecules we need to effectively block a channel

determined by lipid solubility

more lipid soluble more potent

[[Etiocaine, bupivacaine, tetracaine]]

78
Q

Most potent LA

A

Etidocaine

Bupivacaine

Tetracaine

**very potent –> very lipid soluble

79
Q

What determines potency

A

Lipid solubility

80
Q

Duration of Action [[DOA]]

A

Directly proportional to the amount of time LA is in contact with the nerve fiber
[[how long is my Local drug where I locally put it

  1. Tissue blood Flow [[more blood flow more opportunity for drug to be carried away]]
  2. Addition of Vasoconstriction (epi with lidocaine) [[constrict, decrease blood flow to keep local at site longer]]
  3. Intrinsic vasodilator activity [[Lidocaine can dilate vessels and more blood flow to site; Lidocaine gets carried away by blood flow]]
  4. Lipid solubility [[more will be absorbed and stay in that local tissue]]
  5. Protein Binding [[binds to local proteins with great affinity, its not going anywhere]]
  6. Uptake by lungs [[first pass effect; bupivicaine, lidocaine, prilocaine]]
  7. Metabolism
81
Q

Most important factor to DOA

A

PROETIN BINDING

bupivicaine is very highly protein bound –> LONG DOA

82
Q

What drug can be added to Lidocaine to increase DOA

83
Q

What LA has intrinsic vasodilator activity

84
Q

Benefits of adding vasoconstriction have to LA

A
  1. inhibits systemic absorption of LA
  2. prolonged DOA [[keeps drug at site longer; decreased blood flow]]
  3. detection of intravascular injection ***
    [[if you are in a vessel with you needle and are using incremental dosing and inject 5cc of LA with epi, watch EKG; increased HR, ST changes]]
85
Q

What determines concentration of LA in blood?

A
  1. Concentration of LA administered

2. Tissue Blood flow at site

86
Q

Procaine

A

lipid solubility 1

protein binding 5

duration; short

87
Q

Chloroprocaine

A

lipid solubility 1

protein binding 7

duration; short

88
Q

Lidocaine

A

lipid solubility 4

protein binding 65

duration; moderate

89
Q

What LA under go first pass effect by lungs

A
  • Bupivacaine
  • Lidocaine
  • Prilocaine
90
Q

Mepivacaine

A

lipid solubility 1

protein binding 75

duration; moderate

91
Q

Tetracaine

A

lipid solubility 80

protein binding 95

duration; Long

92
Q

Etidocaine

A

lipid solubility 140

protein binding 95

duration; Long

93
Q

Bupivacaine

A

lipid solubility 30

protein binding 95

duration; long

94
Q

Metabolism of ESTERS

A
  • HYDROLYZED by non-specific esterase enzymes in PLAMA
  • lesser extent liver [[ <5% excrete unchanged in urine]]

-metabolism of ester creates metabolite –> para- aminobenzoic acid (PABA)
[[allergenic but not active]]

**exception cocaine [[significantly metabolized by liver and 10-12% excreted unchanged]]

95
Q

Metabolism of AMIDES

A
  • metabolized by liver
  • microsomal enzymes [[cytochromP450]]

-more complex and SLOWER process
[[increased risk of toxicity]]

96
Q

DOA most influenced by

A

PROTEIN BINDING

97
Q

Onset most influenced by

98
Q

Major reason we want to differentiate between esters and amides

A

metabolism

99
Q

Excreted unchanged is what type of drug

A

more water soluble

leaves body in the same form it enters body

100
Q

Which LA do most people have allergic run to?

A

ESTER

produce metabolite PABA [[para aminobenzoic pic]]

101
Q

Which LA has a slower metabolism/ increased risk of toxicity

102
Q

Potency is determined by

A

Lipid solubility

[[how many Carbon atoms are there; how big is the lipophilic head]]

103
Q

MAX doses of LA

A

Bupivacaine 2.5 mg/kg

Ropivicaine 3mg/kg
* with epi. 3.5mg/kg

Etidocaine 4mg/kg

Lidocaine 4mg/kg
*with epi. 7mg/kg

Mepivacaine 4mg/kg
*with epi. 7mg/kg

Chloroprocaine 12mg/kg

Cocaine 3mg/kg

Tetracaine 3mg/kg

[[max does are additive; switching LA doesn’t increase max dose]]

104
Q

Bupivacaine MAX DOSE

A

2.5mg/kg

highly protein bound [[long DOA]]

105
Q

Ropivicaine MAX DOSE

A

3mg/kg

*with epi –> 3.5mg/kg

106
Q

Etidocaine MAX DOSE

107
Q

Lidocaine MAX DOSE

A

4mg/kg

*with epi–> 7mg/kg

[[same as mepivicaine]]

108
Q

Mepivicaine MAX DOSE

A

4mg/kg

*with epi –> 7mg/kg

[[same as Lidocaine]]

109
Q

Chloroprocaine MAX DOSE

110
Q

Cocaine MAX DOSE

111
Q

Tetracaine MAX DOSE

112
Q

why does epi increase max dose of certain LA

A

epi causes vasoconstriction
[[less vascular absorption]]

*especially Lidocaine that has intrinsic vasodilation

113
Q

CNS [[Local Anesthetic]] Toxicity

A
  • circumoral/ tongue numbness
  • tinnitus
  • vision changes
  • dizziness
  • slurred speech
  • restlessness
  • muscle twitching [[especially face, extremities]] indicated imminent seizure onset

**seizure followed by

  • CNS depression;
  • apnea
  • hypotension
114
Q

why do seizures occur with LA CNS toxicity and how do we treat

A

LA mech of action is to block VGNaC [[stops neuro transmission]]

-we inhibit the channels that maintain the Na balance in cells;

Na imbalance –> seizure

[[inhibiting the inhibitory neurons that maintain a nice balance]]

*treat seizure –> Benzodiazepam, barbiturate, propofol

give 02, maintain airway, help ventilate

115
Q

Why do we like to do our blocks with our patient is awake

A
  • we want to be able to talk to our patient and know what they are feeling [[if they are feeling numbness you might be in vessel; can be detected with incremental dosing]]
  • assess neuro status; if they start having CNS symptoms; cardiac conduction system is next [[get intralipid bc cardiac conduction system is next]]
116
Q

Cocaine CNS Toxicity

A
  • restless
  • tremos
  • seizures
  • euphoria

[[cocaine inhibits VGNaC and the reuptake of epi and norepinephrine in the brain; therefore increasing the levels os epi and norepinephrine in brain]]

117
Q

LA cardiovascular toxicity

A
  • block VGNaC in heart for a long time we interfere with conduction
  • hypotension[[SNS depression]]
  • myocardial depression
  • AV conduction block
  • decreased SVR and CO
  • widened PR interval and. QRS
  • arrhythmias [[Vtach]]
  • possible CV collapse [[more likely to happen with Bupivacaine]]

[[CV toxicity is more resistant than CNS toxicity]]

118
Q

why is lidocaine a good dysthymic drug?

A
  • it doesn’t bind with great affinity to heart [[pops on and off receptor site]]

[[ventricle that’s just constantly firing; lidocaine pops on and off but since it firing so fast lidocaine can slow it down]]

119
Q

Cocaine CV toxicity

A
  • massive sympathetic outflow
  • coronary vasospasm
  • MI
  • dysrhythmias [[Vfib]]

** additional epi and dopa

120
Q

Patients at risk for CV toxicity

A
  • Pregnant lower threshold for toxicity
  • hypoxia

pH abnormalities

-CV modulating drugs [[propofol; anything that has cardiac depressing effects]]

121
Q

LA CV toxicity CV Collapse treatment

A

1st prevent this from happening; incremental dosing!

CPR for a long time
[[bupivacaine half life is 3 hours]]

modified ACLS

intralipid 20% 1.5ml/kg rapid bolus following with an infusion of 0.25ml/kg/min x 10 min
[[will help bupivacaine pop off receptor site]]

122
Q

incremental dosing

A

incremental fractionated dosing [[inject 5cc at a time and wait, watch for EKG changes, talk to patient assess status]]

-aspirate before every injection

**watch EKG

123
Q

Intralipid treatment for CV collapse with LA CV toxicity

A

intralipid 20%

1.5ml/kg rapid bolus immediately

followed by 0.25ml/kg/min x 10 min

124
Q

LA Toxicity in CNS after block resolved

A
  • Transient neurologic syndrom [[TNS]]
  • cauda equina syndrome
  • anterior spiinal artery syndrome
125
Q

Transient neurologic syndrome

A
  • neuro inflammatory process causes pain in the lower back, butt, posterior thighs
  • 6-36 hours after FULL recovery from subarachnoid block

-lasts about a week
will recover but very painful

*risk of tetracaine

126
Q

Cauda equina syndrome

A
  • diffuse lumbosacral injury
  • numbness in lower extremities
  • loss of bowl and bladder control
  • paraplegia

**PERMANENT

lidocaine 5%, Tetracaine and Chloroprocaine have all been implicated

*spinals used to use micro catheters in the subarachnoid space

high concentration low volume via spinal catheter micro- needle

*maybe preservative contributed
[[now spinal vials are preservative free]]

127
Q

What LA were implicated with caudal equine syndrome

A

Lidocaine 5%

Tetracain

Chloroprocaine

128
Q

Whats thought to be the true reason for Cauda Equina Syndrome

A

micro catheter needles that used to be used for spinals [[subarachnoid space]] to administer high concentration low volume in a small volume of CSF very close to nerve root

“little micro Cath laying a nerve root and dumping really concentrated local on it for 12 hours it can be so toxic bc such a high concentration on such a small area”

129
Q

Anterior Spinal Artery Syndrome

A
  • lower extremity paralysis [[may have a sensory deficit]]

- unknown cause

130
Q

Allergic reaction

A

-less than 1% are truly allergic
[[heart racing –> not an allergic reaction some LA have epi]]

-investigate s/s
[[hives, difficulty breathing, hypotension from third spacing]]

some preservatives caused to rxn
[[methylparaben]]

131
Q

Which class of LA is more likely to cause an allergic reaction

A

Esters

-hydrolysis produces metabolite PABA

can still use an amide

132
Q

What drugs can prolong the duration of Ester LA

A

Pseudocholinesterase Inhibitors

133
Q

What drugs can prolong duration of Amide LA

A

Cimetidine and propanolol
[[decrease hepatic blood flow –> decreased metabolism and clearance of Amides bc metabolized by liver]]

  • also cocaine even though its an ester it is metabolized by the liver
134
Q

What’s drugs can increase analgesic effects of LA

A

opioids
[[ent added to bupivacain]]
clonidine

epinephrine
[[added to LA]]

135
Q

How do I choose what LA to use

A

-type of surgery
[[quick surgery wants something with fast onset]]

  • onset
  • potency
  • DOA
  • toxicity
  • site of metabolism
136
Q

Additional uses of Lidocaine

A
  • cough suppressant
  • dysrhythmic
  • prevents ICP and BP elevation during laryngoscope [[very stimulating, want some medicine on board]]
  • prevents reflex bronchospasm that occurs with airway instrument

**lidocaine has intrinsic vasodilation effects

137
Q

Cocaine characteristics

A
  • UNIQUE ester
  • blocks VGNaC

-blocks norepinephrine and dopamine reuptake –> more available
[[unique side effects]]

CNS; euphoria
CV; stimulation, sympathomimetic
[[ST changes]]

metabolized by the liver and plasma esterase [[differently than other esters –> just hydrolysis by plasma esterases]]

used in ENT surgeries because decreased bleeding

138
Q

Procaine characteristics

A

-ester

not used much anymore more [[unfavorable pharmacokinetics]]

SLOW ONSET [[pKa 8.9 –> 97% ionized]]

SHORT DOA

  • used for spinals before lidocaine was developed
  • higher incidence of nausea and CNS side effects
  • ester metabolism produces PABA –> more incidence of hypersensitivity

metabolite that can interred with sulfonamide abx [[give abx prophylatically befoer surgery don’t want a LA that makes it less effective]]

139
Q

Tetracaine characteristics

A

-ester

**not routinely used anymore

  • if used mainly used in spinal and corneal anesthesia
  • NOT popular for epidurals/ spinals
  • LONG DOA [[up to 6 hours if add epi]]
  • *toxicity risk
  • Slow onset [[pKa 8.5]]
  • profound motor block [[not what we want]]
  • higher incidence of Transient Neurologic Syndrome [[TNS]]
140
Q

Chloroprocaine characteristics

A
  • ester
  • very popular in OB anesthesia

-FAST ONSET
-FAST DOA
[[quick on/off]]

-truly an ester in the sense that it gets metabolized very quickly
[[less risk, bigger margin of safety since it is so quickly hydrolyzed; reduces toxicity risk to mom and baby ]]

-epidurals and PNB when short duration is desired [[c-section]]

-implicated with caudal equine syndrome in spinals
being reinvestigated but still considered ‘off- label’ for spinals

-reports of neurologic injury [[but maybe r/t to preservative]]

141
Q

Lidocaine characteristics

A
  • Amide
  • *very popular

-2 actives metabolites
monoethylglycinexylidide
[[80% activity]]

xylidine
[[10% activity]]

routes;
topical 4% –>LTA
[[upper airway for endoscopy; also helps with smooth wakeup]]

regional IV 0.25- 0.5%
[[Bier block –> help with the burn before propofol]]

PNB 1-2%

spinal 1.5-5%
[[1.5% analgesia effect]]
**controversial for spinal use especially continuous –> caudal equina syndromes]]

epidurals 1.5-2%

-RAPID onset

-intermediate duration
[[longer surgeries it can wear off]]

142
Q

Difference between 1% and 2% of a LA

A

1% –> 10mg/ ml
[[less dense than 2%

2% –> 20mg/ ml

**higher concentration giving ore molecules –> denser block

143
Q

Lidocaine metabolites

A

monoethylglycinexylidide
[[80% activity]]

xylidine
[[10% activity]]

144
Q

Mepivacaine

A
  • amide
  • structurally similar to bupivacaine
  • chemically similar to lidocaine
  • LONGER DOA –>less vasodilation [[good when vasoconstrictor is contraindicated]]
  • rapid onset
  • serum E 1/2t about 2 hours
  • slightly more CNS toxicity compared to lidocaine

-NOT effective topically
[[lidocaine is]]

**carries likes to use when she can’t use lidocaine with epi
[[not the same vasodilation as lidocaine–> longer DOA]]

145
Q

Lidocaine with epi would be contraindicated in what surgeries?

A

Finger, toes, nose, hose

*don’t want to use in an area whee there is not good collateral circulation

regular lidocaine has vasodilation
*mepivacaine would be better to use less vasodilation –> longer DOA

146
Q

Prilocaine

A

-Amide

-RAPID metabolism
[[less CNS toxicity than lidocaine]]

-TOXIC metabolite ortho-toludine
[[converts hgb to methgb]]

MAX dose 600 mg
over this you’ll increase risk of toxic metabolite and the conversion of Hgb to methgb

-AVOID IN OB

147
Q

ortho-toluidine

A
  • toxic metabolite produced from prilocaine

- converts Hgb to metHgb

148
Q

Benzocaine

A
  • topical lidocaine preparation

- risk of methemoglobinemia

149
Q

Treatment for Methemoglobinemia

A

methylene blue

1-2mg/kg IV over 5 minutes

150
Q

Etidocaine

A
  • Amide
  • PNB and epidural
  • highly lipid soluble [[potent]]
  • Long DOA [[95% protein bound]]
  • Rapid onset [[pKA 7.7]]

FAST ONSET and LONG DOA

151
Q

Bupivacaine

A
  • Amide
  • used all the time

Longer DOA [[highly protein bound 95%]]
and longer onset [[ pKa 8.1]] compared to lidocaine

popular for differential nerve block
[[block sensory but not motor]]

*great choice for post op pain, labor epidural

spinal 0.5% - 0.75%

epidural 0.0625% - 0.5%

PNB 0.25% - 0.5%

*longer onset keep in mind if injected by surgeon at end of case might not be in effect yet when they wake up, you might need to supplement with some fentanyl

side effects;
very cardiotoxic
[[use 0.5% or lower for epidural and PNB]]

Serum E1/2t is 3.5 hours
[[CV collapse wil be doing CPR for a long time]]

*low incidence of neurons complications with spinals

152
Q

Ropivacaine

A

-Amide

-levo- enantiomer of homolog bupivacaine
[[better toxicity profile; less cardiac toxic]]

  • good differential blockade
  • vasoconstriction
  • 2 active metabolites

serum E1/2t –> 2 hours
[[shorter then bupivacaine in theory CPR would be shorter in CV toxicity]]

-more expensive
[[bupivacaine is very cheap]]

153
Q

Levobupivacaine

A
  • Amide
  • Levo enantiomer of bupivacine
  • less cardiac toxic
  • serum E1/2t 2.6hrs
  • more expensive

**save for cases where larger LA doses required

154
Q

Which LA has geatest CV toxicity risk

A

Bupivacine

very highly protein bound and Serum E1/2t is 3.5 hours
[[CV collapse wil be doing CPR for a long time]]

give lipoprotein!

155
Q

Greater concentration

A

DENSER BLOCK

156
Q

What route can we give closer to max dose

A

EPIDURAL

and we have to redose epidurals bc block regresses

157
Q

What protein is Bupivacaine highly bound to

A

alpha 1 glycoprotein

158
Q

Epidural dosing

A
  • LA has to diffuse across a membrane
    [[epidural dose will be bigger than spinal]]

dose by volume
volume dictated by what level of block is desired

1.25- 1.6 mL/per segment desired
[[more petite 1.25mL; taller 1.6]]

if you are injecting at L2 and want a T6 block; count the segments in between and multiply

*choose concentration based on density of block desired
[[labor vs surgical epidural –> surgical more dense block; higher concentration]]

-administer in incremental dosing
[[inject 5cc and assess; fell toes, talk to them, VS]]

159
Q

Peripheral Nerve Block dosing

A

-volume depends on the block
[[dictated by type of block]]

-choose concentration based on density of block
then figure out max dose

160
Q

Spinal dosing

A

dosed in mg

all are very similar

*small volume high concentration [[2-3 cc]]

Pharmacology (7 decks)

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