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SRNAPharmacology II > EXAM 3 -Local Anesthetics- COMP > Flashcards

EXAM 3 -Local Anesthetics- COMP Flashcards

1
Q

Comment on desirable characteristics of LA as far as OA, DOA, toxicity degree and reaction

A

Desirable characteristics are:
Very fast onset of action
Long duration of action
NO tachyphylaxis

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2
Q

What was the first Local anesthetics

A

Cocaine

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3
Q

What was the first synthetic ESTER

A

Procaine

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4
Q

Gold standard of local anesthetics? (amide or ester)

A

Lidocaine ; amide

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5
Q

• Local anesthetics and water solubility ? are they acids or bases?

A

Poorly water soluble

They are BASES

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6
Q

When mixed with Hydrochloric acid

A

Become water soluble

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7
Q

Because local anesthetics are poorly water soluble they are supplied as

A

Hydrochloric salts

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8
Q

Local anesthetics since they are supplied as hydrochloric salts become

A

Acidic ph 6.0

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9
Q

How does the fact that they are acidic affect Local anesthetics

A

More painful on injection

Slower onset of action (because they become ionized and only unionized can penetrate)

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10
Q

Benefits of Alkalization of local anesthetic solution

A

Makes onset of action shorter

Less pain when you inject

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11
Q

Some providers may add ________to alkalinized

A

Sodium bicarbonate

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12
Q

What is the Functional unit of peripheral Nerve?

A

Axon

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13
Q

Extension of Centrally located neuron

A

Axon

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14
Q

Function of schwann cells

A

Insulation and Support

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15
Q

In unmyelinated cells, one schwann cell for

A

multiple axons

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16
Q

In LARGER cells, one schwann cell cover___________ with several layers of ______ (lipid)

A

one axon with several layers of MYELIN

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17
Q

Small segment of Axon without myelin

A

Node of Ranvier

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18
Q

What does the Node of ranvier has making it able to generate impulse? how does the impulse travel? what is the term use for that?

A

Contains large number of Sodium channles
Impulse travel from node to node
Saltatory conduction

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19
Q

What is the PRIMARY area where LOCAL anesthetics EXERT THEIR ACTIONS?

A

Node of RANVIER

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20
Q

Which one is more difficult to block with local anesthetics, myelinated or unmyelinated?

A

MYELINATED

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21
Q

Myelinated fibers are _____and conducts impulses _____

A

larger; faster

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22
Q

How many nodes of ranvier must be blocked for prevention of nerve conduction?

A

2-3 Nodes of ranvier

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23
Q

Bundle of axons together is called

A

Fasciculi

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24
Q

What are the 3 layers of the Fasciculi?

A

Endoneurium
Perineurium
Epineurium

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25
Q

Role of epineurium

A

Act as a barrier that Local anesthetics must get through to work.

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26
Q

Resting membrane potential or peripheral nerve? Cause by?

A

-70 to -90 ; ionic imbalance as accomplished by Na-k+ ATPAse

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27
Q

Local anesthetics exert their effects by

A

Blocking the Na+ Channel

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28
Q

Local anesthetics have greater affinity for Na+ channels in _____and _____states. Known as the ________hypothesis (extra)

A

Active
Inactive
Guarded receptor

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29
Q

Some receptors have affinity for both the ionized and UN-ionized form of the local anesthetics? Which form can penetrate the membrane

A

UNIONIZED

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30
Q

MOA of benzocaine______only occur in the ______Form

A

interact with ion channel within the membrane

uncharged form

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31
Q

Define minimum blocking concentration (Cm)

A

The lowest concentration of drugs needed for blocking impulse propagation. think of it like MAC for local anesthetics

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32
Q

Because the ______form of the molecule crosses

the cell membrane, compounds that are more lipophilic have a _____onset of blockade

A

nonionized ; faster onset

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33
Q

Can local anesthetic bind when Na+ in resting state?

A

NO

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34
Q

The more frequently the sodium channel depolarized the

A

the more time for LA have to bind, the faster the drug action will be to block

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35
Q

Effect of : Increased nerve fiber diameter on Cm

A

Increase Cm

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36
Q

Effect of Increased myelination on Cm

A

Increased Cm

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37
Q

Greater distance between nodes of Ranvier on Cm

A

Increased Cm

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38
Q

Summary of factors that increase Cm

A

Increased nerve fiber diameter
Greater distance between node of ranvier
Increased myelination

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39
Q

Effect of “increased tissue pH” on Cm:

A

Decreased Cm

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40
Q

Effect of “ high frequency of nerve stimulator” on Cm

A

Decreased Cm

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41
Q

Effect of “ Pregnancy” on Cm

A

Decreased Cm

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42
Q

Effect of “ elevated tempature” on Cm

A

Decreased Cm

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43
Q

Summary of factors that decrease Cm

A

Increased tissue ph
high frequency of nerve stimulator
Pregnancy
Elevated temperature

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44
Q

Nerve fibers classified based on

A

Diameter and myelination

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45
Q

Conduction faster on

A

Wider diameter and myelination

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46
Q

What are 3 classes of PN fibers?

A

A, B, and C

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47
Q

What are the subtypes of PN A fibers

A

Alpha
Beta
Gamma
Delta

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48
Q

Largest fibers

A

A- Alpha

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49
Q

Fastest conduction velocity

A

A-Alpha (60-120m/s)

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50
Q

Most myelinated

A

A-alpha

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51
Q

A-ALPHA RESPONSIBLE FOR (MP)

A

MOTOR FUNCTION

PROPRIOCEPTION

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52
Q

what is the fiber last blocked by LOCAL anesthetics?

A

A-ALPHA

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53
Q

A-BETA CONDUCTION velocity is

A

30-70m/s

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54
Q

A-BETA responsible for

A

Touch

Pressure

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55
Q

A -GAMMA responsible for

A

Skeletal muscle tone

Reflexes

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56
Q

A- gamma CV

A

15-35 m/s

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57
Q

A- Delta responsible for

A

Pain, temperature and Touch

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58
Q

The fibers constitutes pre-ganglionic autonomic nerves

A

B fibers

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59
Q

Fibers that local anesthetics BLOCK FIRST

A

B fibers

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60
Q

Which are the ONLY UNMYELINATED FIBERS?

A

C fibers

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61
Q

Slowest conduction out of all fibers

A

C fibers (0.5 m/s)

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62
Q

2nd fibers to be BLOCKED is ____ along with _____Fibers

A

C fibers

A-delta fibers

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63
Q

C fibers conduct

A

Pain , temperature, touch and post ganglionic symp neurons

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64
Q

Clinically , sequence of Differential blockade is

A

***Autonomic function BLOCKED FIRST by B fibers
Pain, touch and Temperature by A delta and C fibers)
Motor and proprioception BLOCKED LAST by A-alpha, beta and gamma

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65
Q

Blocked first in differential blockade

A

Autonomic function

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66
Q

Blocked last in differential blockade

A

Motor and proprioception

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67
Q

Best example of differential blockade is

A

Bupivacaine
0.125 % blocks autonomic function some pain and touch BUT NOT motor and proprioception, same with 0.25%
However, 0.5% block them all

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68
Q

NEURONS blocking order

A

Blocking order
1st –> B fibers, autonomic function block
2nd –> A-delta fast pain and temp; C slow pain
3rd –> A-gamma, muscle tone and motor
4th –> A-beta, sensory touch and pressure
5th –> A-alpha, motor and , skeletal muscle

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69
Q

Block throbbing pain and temperature

A

C fibers

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70
Q

Para and sympathetic PREGANGLIONIC Neurons are______ but POST GANGLIONIC neurons are _____

A

B fibers; C fibers

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71
Q

Block SHARP, prickling pain and temperature

A

A-delta

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72
Q

What are the 3 characteristics segments of Local anesthetics?

A 
Aromatic ring (lipophillic)
Intermediate Carbon group (ester or amide) 
Tertiary amine (hydrophillic)
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73
Q

All local anesthetics are (acids/bases)

A

weak bases

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74
Q

***Best determinant of POTENCY for LOCAL anesthetics is

A

Lipid Solubility (Oil water partition is m

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75
Q

The more lipid soluble the agent

Onset of action determines by

A

the more drug enters the axon

Ionization

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76
Q

***The duration of action of local anesthetics is related to

A

PROTEIN BINDING

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77
Q

Linkage characterizes drugs as either

A

Ester or amide

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78
Q

How can you tell ester from amide?

A

Ester “one i”

amide “ two i’s)

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79
Q

Ester are Hydrolized by

A

Plasma cholinesterase (blood)

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80
Q

Hydrolysis of Ester results in which metabolites? and what is it associated with>

A

PABA ( Paraaminobenzoic acid); asscociated with allergic reactions

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81
Q

Amides are metabolized by

A

Liver

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82
Q

Amides allergic reaction are RARE and are due to

A

Methylparaben- structurally similar to PABA

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83
Q

Systemic toxicity ( more likely or less likely with agents)

A

Amide (more likely )

Ester (less likely )

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84
Q

Which one is chemically stable in solution

A

Amide

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85
Q

Onset of action of amide vs ester

A

Amide (mod to fast)

Ester (slow)

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86
Q

pKa of Ester compared to amide

A

Ester 8.5-8.9

Amide close to ph 7.4 which is 7.6 - 8.1

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87
Q

Distribution of local anesthetics is dependent on________and there is _________> what is a major factor?

A

Blood flow
High initial uptake by lung
Redistribution

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88
Q

Relative clinical potency and chloroprocaine; Oil/ water partition

A

1; 1

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89
Q

Relative clinical potency and Mepivacaine; Oil/ water partition

A

2; 1

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90
Q

Relative clinical potency and Lidocaine Oil/ water partition

A

2;4

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91
Q

Relative clinical potency and Tetracaine Oil/ water partition

A

8; 80

92
Q

Relative clinical potency and BUPIVACAINE Oil/ water partition

A

8;30

93
Q

The short duration local anesthetics are

A

PC
Procaine
Chloroprocaine

94
Q

The Intermediation duration local anesthetics are

A

Mepivacaine

Lidocaine

95
Q

The LONG duration of action Local anesthetics are

A

Tetracaine
Etidocaine
Bupivacaine
Ropivacaine

96
Q

The most important determinant of onset of action is

A

IONIZATION

97
Q

Drugs with lower pKa such as _______have SHORTER onset of action

A

AMIDE

98
Q

Speed of onset of local anesthetics related to

A

pKa

99
Q

Decreased tissue pH leads to

A

more ionized local

poorly absorbed in tissue

100
Q

Pt at high risk due to decreased tissue ph are

A

Septic w/ metabolic acidosis

Renal failure patients

101
Q

Agent with the slowest onset of action

A

Procaine

102
Q

2 drugs with SLOW onset of ACTION

A

Procaine

Tetracaine

103
Q

Moderate onset of action : % unionized at physiologic pH of 7.4

A

Bupivacaine

17%

104
Q

Fastest onset of action of LA (CLEM)

A

Chlroprocaine
Lidocaine
Etidocaine
Mepivacaine

105
Q

Lidocaine : % Unionized at physiologic pH of 7.4 ____ph is

A

24%; 7.7

106
Q

Which drug has the HIGHEST % of Unionized at physiologic pH of 7.4?

A

Mepivacaine 39%

pH of 7.6

107
Q

________may reduce the latency of onset and increase the duration of action of local anesthetics

A

• Sodium bicarbonate

108
Q

Drugs that help increasing duration of action

A

Sodium bicarbonate

Dextran

109
Q

theoretically improve the onset &

intensity of block

A

Carbonation

110
Q

• All local anesthetics produce ________ of vascular smooth muscle except____ and___

A

Relaxation

Mepivacaine & Cocaine

111
Q

The vasodilation caused by local anesthetics result in

A

Increase blood flow to the site where it is applied
reduce duration of action
INCREASED potential for systemic toxicity

112
Q

Degree of systemic vasodilation from more to least?

A

Lidocaine > Procaine > Mepivacine (none)

113
Q

Effects of SYSTEMIC TOXICITY depends on

A

TOTAL DOSE GIVEN

114
Q

Area where local anesthetics is applied also affects

A

Speed and extent of systemic absorption/toxicity

115
Q 
***Most to least absorbed  MUST KNOW WELL
IvTIc
CaudPaEpiBP
SubaScif
SuQ
A

Intravenous>Tracheal>Intercostal>
Caudal>Paracervical>Epidural>BrachialPlexus > Subarachnoid/Sciatic/Femoral >
Subcutaneous

116
Q

Why add vasoconstrictors such as EPI to local anesthetics??

A

it Decrease rate of systemic absorption by increasing the concentration of the drug at the site of action resulting in more intense block and less toxicity

117
Q

Epinephrine prolongs the duration of action for local infiltration, peripheral nerve block and epidural administration of 3 drugs >ProLiMe
The other ones yes but no effects on epidural

A

Procaine
Mepivacaine
and lidocaine.

118
Q

Epinephrine proven to be the

A

most effective agent

119
Q

Usual Concentration of Epi for lidocaine

A

1:200,000 or 5mcg/ml

120
Q

Explain why Chrorprocaine has a 2% unionized at physiological pH but still has a fast onset of action

A

because HIGHER concentration administered

121
Q

Plasma half time of procaine and chlorprocaine

A

less than 1 minute

122
Q

What is the most TOXIC ester with limited clinincal use

A

Tetracaine

123
Q

There are no_________cholinesterases meaning drug is eliminated out of the CSF by?

A

Spinal ; diffuse out of the CSF

124
Q

Rate of hydrolysis of Ester from more to least (CPT)

A

Chloroprocaine > Procaine > Tetracaine

125
Q

Drugs that can reduce metabolism of Ester

A

Succinylcholine

because it is also metabolized by plasma cholinesterase which can saturate metabolism

126
Q

Toxicity unlikely with liver disease when given those 2 drugs

A

Procaine and Chlorprocaine

127
Q

Amide are metabolized by the _______and metabolism are affected by

A

Liver;
Hepatic Blood flow
Hepatic enzyme activity

128
Q

Amide metabolism from GREATER To least (PELMeB)

A 
Prilocaine
Etidocaine
Lidocaine
Mepivacaine
Bupivacaine
129
Q

What are the 2 MAJOR factors affecting the clearance of AMIDE local anesthetics?

A

HEPATIC Enzyme activity

Hepatic blood flow

130
Q

For amide, clearance is independent of

A

Potency, lipid solubility, protein binding or chemical structure.

131
Q

Sequence of local anesthetics toxicity
CircLTVS
MURCA

Which is the FIRST SIGN of Toxicity

A
  1. Circumoral numbness (mouth, lip, tongue) FIRST SIGN
  2. Lightheadedness
  3. Tinnitus
  4. Visual Disturbance
  5. Slurring of speech
  6. Muscle twitching
  7. Unconsciousness
  8. Grand mal seizures
  9. Coma
  10. Apnea
132
Q

Lidocaine manifestations at 1-5mcg/ml

A

Analgesia

133
Q

Lidocaine manifestations of toxicity when is there CV collapse

A

> 25mcg/ml

134
Q

Lidocaine manifestations of toxicity when is there Coma/Apnea

A

15-20 mcg/ml

135
Q

Lidocaine manifestations of toxicity when is there Seizures/Unconsciouness

A

10-15mcg/ml

136
Q

MMCTS occurs with 5-10mcg/ml of lidocaine

A 
Muscle twitching
Myocardial depression
CIRCUMORAL /TONGUE NUMBNESS
Tinnitus
Systemic Hypotension
137
Q

What can be aministered to prevent the CNS toxicity of local anesthetics?

A

Midazolam 5-10 minutes prior to LA injection

138
Q

Agents less likely to cause toxicity are (CPL)

A

Chloroprocaine
Prilocaine
Lidocaine

139
Q

Prevention of Toxicity:

A

aspirate syringe before injection (watch for blood or CSF)
Inject small amount 5ml q 30-60 monitor for s/s toxicity
know expected pharmacokinetics of drugs
Continuous monitoring, blood levels may not peak for 30 minutes

140
Q

Acid base disorders that increase risk for toxicity

A

Respiratory and metabolic acidosis

141
Q

Acid base disorders that decrease risk for toxicity

A

Alkalosis

142
Q

At 1st sign of toxicity have patient voluntarily

A

Hyperventilate which will decrease the transfer of agent in to the cell

143
Q

CNS toxicity primary concern is

A

Seizures

144
Q

2 types of neurological disease that can occur

A

Transient neurological sydnrome
Cauda equina

Associated with continous spinal catheters

145
Q

CV toxicity of LA are dose dependent

- Lower concentration_____and ______and higher conentration_____and ______

A

Vasoconstriction, increase SVR

Vasodilation, hypotension

146
Q

Electrophysiology effect of toxicity

A

Decrease automaticity
Prolong conduction time
Increase PR and QRS

147
Q

Selectivity of LA with CARDIOTOXICITY from greatest to lowest? (BEL)

A

Bupivacaine
Etivacaine
Lidocaine

148
Q

Cardiac toxicity associated with BEL are SEVERE AND RESISTANT, use

A

INTRA-LIPID THERAPY

149
Q

For Bupivacaine , use

A

IV lipid emulsion 20%, 100 ml enough to resuscitate from bupivacaine induce arrhythmias

150
Q

Methimobglobinemia what is it?

A

Iron oxidized from ferrous to ferric, cannot bind to or carry O2

151
Q

Treatment of Methymoglobinemia

A

Methylene blue 1-2 mg/kg

152
Q

Lidocaine onset of action

A

< 2min

153
Q

Lidocaine DURATION of action ? Longer with ?

A

30-60 min; Epinephrine

154
Q

Max dose of lidocaine

A

3mg/kg

155
Q

Bupivacaine onset of action is

A

5-10 min

156
Q

Bupivacaine Duration of action is

A

200min ; 540 with epi

157
Q

Bupivacine MAX dose

A

2.5mg/kg

158
Q

Mepivacaine and prilocaine onset of action is

A

3-5 min; 5 min

159
Q

Mepivacaine and prilocaine Duraction of action is

A

45-90 min; 30-90min

160
Q

Max dose of Mepivacaine and prilocaine

A

5-6 mg/kg; 5mg/kg

161
Q

Procaine onset of action is

A

10-20 min

162
Q

Procaine Duration of action is

A

40 min

163
Q

Procaine max dose

A

7mg/kg

164
Q

Ropivacine onset of action is

A

5-15 min

165
Q

Ropivacaine max dose

A

3mg/kg

166
Q

Initial intake of lidocaine in this organ_____

A

LUNG

167
Q

Which will have faster onset of action, drugs with pka close to physiological pH or farther from physiologic pH

A

CLOSEST to physiological pH have a more RAPID onset of action

168
Q

Which is responsible for the Neural blockade?

A

IONIZED

169
Q

Greater vasodilation – ________systemic absorption;_______duraction of action

A

Increased; reduced duration of action

170
Q

Localization of local anesthetic receptor relative to the cell membrane: where is the receptor localized to?

A

Internal membrane surface

171
Q

More chances of Allergic reaction

A

Ester because of PABA

172
Q

Minimum Blocking concentration

A

Lowest concentration of a drug that is needed for blocking impulse propagation

173
Q

Lidocaine and bupivacaine

A

Low pKA

fastest onset of action

174
Q

Concentration use for obstetric NOT FDA approved

A

0.75%

175
Q

LA with EPI

A

Prolonged Duration of action

Decreased Toxicity

176
Q

PRILOCAINE

A

MOST Associated with Methemoglobinemia

177
Q

Chlorprocaine

A

Rapid onset
low potential due to RAPID HYDROLYSIS
Not recommended for spinal

178
Q

Not recommended for spinal

A

Chlorprocaine

179
Q

Procaine

A

First synthetic Anesthetic produce

180
Q

Slow onset and low potency

A

Procaine

181
Q

Limited use due to short duration of action

A

Procaine

182
Q

Toxicity and slow regional onset limit this agent in application such as regional anesthesia

A

Tetracaine

183
Q

Bupivacaine 0.75%

A

Not recommended for pregnant women

184
Q

Bupivacaine 0.75%

A

Not recommended for pregnant women

prolonged asystole

185
Q

Drug of choice for AMI when episodes of vfib and vtach are not easily concerted by defi and epineprhine (persistent afib and vtach)

A

Lidocaine

186
Q

Duration of action of lidocaine

A

Short

187
Q

May cause toxicity at high concentration

A

Lidocaine

188
Q

Lidocaine primary metabolite is

A

Monoethylglyceinexylidide (use to assess hepatic functions to predict morbidity and mortality)

189
Q

Intranasal lidocaine

A

use to assess migraine headache

190
Q

Lidocaine can use to treate

A

Seizure

191
Q

Lidocaine and sodium channels

A

Fast sodium channel blocker

192
Q

Max dose of lidocaine without epi

A

4mg/kg

Total dose not to exceed 300mg

193
Q

Max dose of lidocaine with epi

A

7mg/kg

Total dose not to exceed 500mg

194
Q

Bupivacaine onset, duration and potency

A

onset slow
potency high
duration long

195
Q

Preferred local for Obstetric_____________but IF EMERGENCY C SECTION , _______May be preferred

A

Bupivacaine 0.125 -0.5%; Chloroprocaine

196
Q

Indications for Bupivacaine

A

when long acting needed

Provide sensory analgesia with less motor block

197
Q

Significant advantage of bupivacaine

A

Longer duration

198
Q

Differences amount local anesthetics agents is the duration of block is dependent on

A

Concentration of the anesthetic

199
Q

Contraindications for bupivacaine

A

0.75% NOT BE USED FOR OB (Cardiac arrest, death)

NOT BE USED IN OB PARACERVICAL block due to FETAL bradycardia and death

200
Q

Max single dose of BUPI without epi

A

175mg

201
Q

Max single dose of BUPI with epi

A

225mg

202
Q

Do not repead dose at interval less than ___hours for bupi

A

3 hours

203
Q

Max dose of Bupi in 24 hours

A

400mg

204
Q

If you use the 0.5% solution for bupivacaine without epineprhine used in obstetrics for continuous epidural anesthesia

A

Total dose should be limited to 320mg

205
Q

Onset, potency and duration of Mepivacaine

A

Rapid onset, potency weak, duration of action intermediate

206
Q

This local anesthetic is NOT FOR SPINAL DOSING . However used for?

A

MEPIVACAINE

Epidural and caudal

207
Q

Preferable use in OB patients with hx of HTN or cardiac disease bcause long duration

A

Mepivacaine

208
Q

Less cardiotoxicity and less adverse effects

A

Ropivacaine

209
Q

Onset of action of ropivacaine

A

Moderate

210
Q

Motor block is less intense than bupivacaine

A

Ropivacaine

211
Q

Preferred for procedures where sensory block is desired but intense motor blockade is not required

A

Ropivacaine

212
Q

Long acting lidocaine derivative

A

Etidocaine

213
Q

Used for regional , limited epidural and not used for spinal

A

Etidocaine

214
Q

Cardiotoxic properties similar to bupivacaine

A

Max dose 300mg without epi

400 with 1:200000 epi

215
Q

Onset of action rapid and major drawback is methemoglobin

A

Prilocaine

216
Q

Use in EMLA cream

A

Prilocaine

217
Q

With Prilocaine: Methemoglobin, Due to oxidation of normal hemoglobin by the

A

Prilocaine hepatic derived metabolite O-Toluidine

218
Q

Methomoglobin serum concentrations usually appear

A

8mg/kg or greater max 600mg

219
Q

Chloroprocaine duration of action? onset?potency ?

A

short ; rapid; low

220
Q

Appropriate anesthetic for OP surgery as long as it’s less than 1 hour long

A

Chloroprocaine

221
Q

Chloroprocaine without epi

A

11mg/kg

222
Q

Chloroprocaine with epi

A

14mg/kg to 1000mg

223
Q

Procaine rapid

A

Hydrolysis –> PABA (allergic reactions )

224
Q

Max single dose of Procaine

A

1000mg

225
Q

Tetracaine use for

A

Opthalmic analgesia

226
Q

Prolonged used for not recommended due to

A

Severe Keratitis

Corneal adverse effects

SRNAPharmacology II (32 decks)

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