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
2
Q
What was the first Local anesthetics
A
Cocaine
3
Q
What was the first synthetic ESTER
A
Procaine
4
Q
Gold standard of local anesthetics? (amide or ester)
A
Lidocaine ; amide
5
Q
• Local anesthetics and water solubility ? are they acids or bases?
A
Poorly water soluble
They are BASES
6
Q
When mixed with Hydrochloric acid
A
Become water soluble
7
Q
Because local anesthetics are poorly water soluble they are supplied as
A
Hydrochloric salts
8
Q
Local anesthetics since they are supplied as hydrochloric salts become
A
Acidic ph 6.0
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)
10
Q
Benefits of Alkalization of local anesthetic solution
A
Makes onset of action shorter
Less pain when you inject
11
Q
Some providers may add ________to alkalinized
A
Sodium bicarbonate
12
Q
What is the Functional unit of peripheral Nerve?
A
Axon
13
Q
Extension of Centrally located neuron
A
Axon
14
Q
Function of schwann cells
A
Insulation and Support
15
Q
In unmyelinated cells, one schwann cell for
A
multiple axons
16
Q
In LARGER cells, one schwann cell cover___________ with several layers of ______ (lipid)
A
one axon with several layers of MYELIN
17
Q
Small segment of Axon without myelin
A
Node of Ranvier
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
19
Q
What is the PRIMARY area where LOCAL anesthetics EXERT THEIR ACTIONS?
A
Node of RANVIER
20
Q
Which one is more difficult to block with local anesthetics, myelinated or unmyelinated?
A
MYELINATED
21
Q
Myelinated fibers are _____and conducts impulses _____
A
larger; faster
22
Q
How many nodes of ranvier must be blocked for prevention of nerve conduction?
A
2-3 Nodes of ranvier
23
Q
Bundle of axons together is called
A
Fasciculi
24
Q
What are the 3 layers of the Fasciculi?
A
Endoneurium
Perineurium
Epineurium
25
Role of epineurium
Act as a barrier that Local anesthetics must get through to work.
26
Resting membrane potential or peripheral nerve? Cause by?
-70 to -90 ; ionic imbalance as accomplished by Na-k+ ATPAse
27
Local anesthetics exert their effects by
Blocking the Na+ Channel
28
Local anesthetics have greater affinity for Na+ channels in _____and _____states. Known as the ________hypothesis (extra)
Active
Inactive
Guarded receptor
29
Some receptors have affinity for both the ionized and UN-ionized form of the local anesthetics? Which form can penetrate the membrane
UNIONIZED
30
MOA of benzocaine______only occur in the ______Form
interact with ion channel within the membrane
| uncharged form
31
Define minimum blocking concentration (Cm)
The lowest concentration of drugs needed for blocking impulse propagation. think of it like MAC for local anesthetics
32
Because the ______form of the molecule crosses
| the cell membrane, compounds that are more lipophilic have a _____onset of blockade
nonionized ; faster onset
33
Can local anesthetic bind when Na+ in resting state?
NO
34
The more frequently the sodium channel depolarized the
the more time for LA have to bind, the faster the drug action will be to block
35
Effect of : Increased nerve fiber diameter on Cm
Increase Cm
36
Effect of Increased myelination on Cm
Increased Cm
37
Greater distance between nodes of Ranvier on Cm
Increased Cm
38
Summary of factors that increase Cm
Increased nerve fiber diameter
Greater distance between node of ranvier
Increased myelination
39
Effect of "increased tissue pH" on Cm:
Decreased Cm
40
Effect of " high frequency of nerve stimulator" on Cm
Decreased Cm
41
Effect of " Pregnancy" on Cm
Decreased Cm
42
Effect of " elevated tempature" on Cm
Decreased Cm
43
Summary of factors that decrease Cm
Increased tissue ph
high frequency of nerve stimulator
Pregnancy
Elevated temperature
44
Nerve fibers classified based on
Diameter and myelination
45
Conduction faster on
Wider diameter and myelination
46
What are 3 classes of PN fibers?
A, B, and C
47
What are the subtypes of PN A fibers
Alpha
Beta
Gamma
Delta
48
Largest fibers
A- Alpha
49
Fastest conduction velocity
A-Alpha (60-120m/s)
50
Most myelinated
A-alpha
51
A-ALPHA RESPONSIBLE FOR (MP)
MOTOR FUNCTION
| PROPRIOCEPTION
52
what is the fiber last blocked by LOCAL anesthetics?
A-ALPHA
53
A-BETA CONDUCTION velocity is
30-70m/s
54
A-BETA responsible for
Touch
| Pressure
55
A -GAMMA responsible for
Skeletal muscle tone
| Reflexes
56
A- gamma CV
15-35 m/s
57
A- Delta responsible for
Pain, temperature and Touch
58
The fibers constitutes pre-ganglionic autonomic nerves
B fibers
59
Fibers that local anesthetics BLOCK FIRST
B fibers
60
Which are the ONLY UNMYELINATED FIBERS?
C fibers
61
Slowest conduction out of all fibers
C fibers (0.5 m/s)
62
2nd fibers to be BLOCKED is ____ along with _____Fibers
C fibers
| A-delta fibers
63
C fibers conduct
Pain , temperature, touch and post ganglionic symp neurons
64
Clinically , sequence of Differential blockade is
***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
65
Blocked first in differential blockade
Autonomic function
66
Blocked last in differential blockade
Motor and proprioception
67
Best example of differential blockade is
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
68
NEURONS blocking order
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
69
Block throbbing pain and temperature
C fibers
70
Para and sympathetic PREGANGLIONIC Neurons are______ but POST GANGLIONIC neurons are _____
B fibers; C fibers
71
Block SHARP, prickling pain and temperature
A-delta
72
What are the 3 characteristics segments of Local anesthetics?
```
Aromatic ring (lipophillic)
Intermediate Carbon group (ester or amide)
Tertiary amine (hydrophillic)
```
73
All local anesthetics are (acids/bases)
weak bases
74
***Best determinant of POTENCY for LOCAL anesthetics is
Lipid Solubility (Oil water partition is m
75
The more lipid soluble the agent
| Onset of action determines by
the more drug enters the axon
| Ionization
76
***The duration of action of local anesthetics is related to
PROTEIN BINDING
77
Linkage characterizes drugs as either
Ester or amide
78
How can you tell ester from amide?
Ester "one i"
| amide " two i's)
79
Ester are Hydrolized by
Plasma cholinesterase (blood)
80
Hydrolysis of Ester results in which metabolites? and what is it associated with>
PABA ( Paraaminobenzoic acid); asscociated with allergic reactions
81
Amides are metabolized by
Liver
82
Amides allergic reaction are RARE and are due to
Methylparaben- structurally similar to PABA
83
Systemic toxicity ( more likely or less likely with agents)
Amide (more likely )
| Ester (less likely )
84
Which one is chemically stable in solution
Amide
85
Onset of action of amide vs ester
Amide (mod to fast)
| Ester (slow)
86
pKa of Ester compared to amide
Ester 8.5-8.9
| Amide close to ph 7.4 which is 7.6 - 8.1
87
Distribution of local anesthetics is dependent on________and there is _________> what is a major factor?
Blood flow
High initial uptake by lung
Redistribution
88
Relative clinical potency and chloroprocaine; Oil/ water partition
1; 1
89
Relative clinical potency and Mepivacaine; Oil/ water partition
2; 1
90
Relative clinical potency and Lidocaine Oil/ water partition
2;4
91
Relative clinical potency and Tetracaine Oil/ water partition
8; 80
92
Relative clinical potency and BUPIVACAINE Oil/ water partition
8;30
93
The short duration local anesthetics are
PC
Procaine
Chloroprocaine
94
The Intermediation duration local anesthetics are
Mepivacaine
| Lidocaine
95
The LONG duration of action Local anesthetics are
Tetracaine
Etidocaine
Bupivacaine
Ropivacaine
96
The most important determinant of onset of action is
IONIZATION
97
Drugs with lower pKa such as _______have SHORTER onset of action
AMIDE
98
Speed of onset of local anesthetics related to
pKa
99
Decreased tissue pH leads to
more ionized local
| poorly absorbed in tissue
100
Pt at high risk due to decreased tissue ph are
Septic w/ metabolic acidosis
| Renal failure patients
101
Agent with the slowest onset of action
Procaine
102
2 drugs with SLOW onset of ACTION
Procaine
| Tetracaine
103
Moderate onset of action : % unionized at physiologic pH of 7.4
Bupivacaine
| 17%
104
Fastest onset of action of LA (CLEM)
Chlroprocaine
Lidocaine
Etidocaine
Mepivacaine
105
Lidocaine : % Unionized at physiologic pH of 7.4 ____ph is
24%; 7.7
106
Which drug has the HIGHEST % of Unionized at physiologic pH of 7.4?
Mepivacaine 39%
| pH of 7.6
107
________may reduce the latency of onset and increase the duration of action of local anesthetics
• Sodium bicarbonate
108
Drugs that help increasing duration of action
Sodium bicarbonate
| Dextran
109
theoretically improve the onset &
| intensity of block
Carbonation
110
• All local anesthetics produce ________ of vascular smooth muscle except____ and___
Relaxation
| Mepivacaine & Cocaine
111
The vasodilation caused by local anesthetics result in
Increase blood flow to the site where it is applied
reduce duration of action
INCREASED potential for systemic toxicity
112
Degree of systemic vasodilation from more to least?
Lidocaine > Procaine > Mepivacine (none)
113
Effects of SYSTEMIC TOXICITY depends on
TOTAL DOSE GIVEN
114
Area where local anesthetics is applied also affects
Speed and extent of systemic absorption/toxicity
115
```
***Most to least absorbed MUST KNOW WELL
IvTIc
CaudPaEpiBP
SubaScif
SuQ
```
Intravenous>Tracheal>Intercostal>
Caudal>Paracervical>Epidural>BrachialPlexus > Subarachnoid/Sciatic/Femoral >
Subcutaneous
116
Why add vasoconstrictors such as EPI to local anesthetics??
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
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
Procaine
Mepivacaine
and lidocaine.
118
Epinephrine proven to be the
most effective agent
119
Usual Concentration of Epi for lidocaine
1:200,000 or 5mcg/ml
120
Explain why Chrorprocaine has a 2% unionized at physiological pH but still has a fast onset of action
because HIGHER concentration administered
121
Plasma half time of procaine and chlorprocaine
less than 1 minute
122
What is the most TOXIC ester with limited clinincal use
Tetracaine
123
There are no_________cholinesterases meaning drug is eliminated out of the CSF by?
Spinal ; diffuse out of the CSF
124
Rate of hydrolysis of Ester from more to least (CPT)
Chloroprocaine > Procaine > Tetracaine
125
Drugs that can reduce metabolism of Ester
Succinylcholine
| because it is also metabolized by plasma cholinesterase which can saturate metabolism
126
Toxicity unlikely with liver disease when given those 2 drugs
Procaine and Chlorprocaine
127
Amide are metabolized by the _______and metabolism are affected by
Liver;
Hepatic Blood flow
Hepatic enzyme activity
128
Amide metabolism from GREATER To least (PELMeB)
```
Prilocaine
Etidocaine
Lidocaine
Mepivacaine
Bupivacaine
```
129
What are the 2 MAJOR factors affecting the clearance of AMIDE local anesthetics?
HEPATIC Enzyme activity
| Hepatic blood flow
130
For amide, clearance is independent of
Potency, lipid solubility, protein binding or chemical structure.
131
Sequence of local anesthetics toxicity
CircLTVS
MURCA
Which is the FIRST SIGN of Toxicity
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
Lidocaine manifestations at 1-5mcg/ml
Analgesia
133
Lidocaine manifestations of toxicity when is there CV collapse
>25mcg/ml
134
Lidocaine manifestations of toxicity when is there Coma/Apnea
15-20 mcg/ml
135
Lidocaine manifestations of toxicity when is there Seizures/Unconsciouness
10-15mcg/ml
136
MMCTS occurs with 5-10mcg/ml of lidocaine
```
Muscle twitching
Myocardial depression
CIRCUMORAL /TONGUE NUMBNESS
Tinnitus
Systemic Hypotension
```
137
What can be aministered to prevent the CNS toxicity of local anesthetics?
Midazolam 5-10 minutes prior to LA injection
138
Agents less likely to cause toxicity are (CPL)
Chloroprocaine
Prilocaine
Lidocaine
139
Prevention of Toxicity:
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
Acid base disorders that increase risk for toxicity
Respiratory and metabolic acidosis
141
Acid base disorders that decrease risk for toxicity
Alkalosis
142
At 1st sign of toxicity have patient voluntarily
Hyperventilate which will decrease the transfer of agent in to the cell
143
CNS toxicity primary concern is
Seizures
144
2 types of neurological disease that can occur
Transient neurological sydnrome
Cauda equina
Associated with continous spinal catheters
145
CV toxicity of LA are dose dependent
| - Lower concentration_____and ______and higher conentration_____and ______
Vasoconstriction, increase SVR
| Vasodilation, hypotension
146
Electrophysiology effect of toxicity
Decrease automaticity
Prolong conduction time
Increase PR and QRS
147
Selectivity of LA with CARDIOTOXICITY from greatest to lowest? (BEL)
Bupivacaine
Etivacaine
Lidocaine
148
Cardiac toxicity associated with BEL are SEVERE AND RESISTANT, use
INTRA-LIPID THERAPY
149
For Bupivacaine , use
IV lipid emulsion 20%, 100 ml enough to resuscitate from bupivacaine induce arrhythmias
150
Methimobglobinemia what is it?
Iron oxidized from ferrous to ferric, cannot bind to or carry O2
151
Treatment of Methymoglobinemia
Methylene blue 1-2 mg/kg
152
Lidocaine onset of action
< 2min
153
Lidocaine DURATION of action ? Longer with ?
30-60 min; Epinephrine
154
Max dose of lidocaine
3mg/kg
155
Bupivacaine onset of action is
5-10 min
156
Bupivacaine Duration of action is
200min ; 540 with epi
157
Bupivacine MAX dose
2.5mg/kg
158
Mepivacaine and prilocaine onset of action is
3-5 min; 5 min
159
Mepivacaine and prilocaine Duraction of action is
45-90 min; 30-90min
160
Max dose of Mepivacaine and prilocaine
5-6 mg/kg; 5mg/kg
161
Procaine onset of action is
10-20 min
162
Procaine Duration of action is
40 min
163
Procaine max dose
7mg/kg
164
Ropivacine onset of action is
5-15 min
165
Ropivacaine max dose
3mg/kg
166
Initial intake of lidocaine in this organ_____
LUNG
167
Which will have faster onset of action, drugs with pka close to physiological pH or farther from physiologic pH
CLOSEST to physiological pH have a more RAPID onset of action
168
Which is responsible for the Neural blockade?
IONIZED
169
Greater vasodilation -- ________systemic absorption;_______duraction of action
Increased; reduced duration of action
170
Localization of local anesthetic receptor relative to the cell membrane: where is the receptor localized to?
Internal membrane surface
171
More chances of Allergic reaction
Ester because of PABA
172
Minimum Blocking concentration
Lowest concentration of a drug that is needed for blocking impulse propagation
173
Lidocaine and bupivacaine
Low pKA
| fastest onset of action
174
Concentration use for obstetric NOT FDA approved
0.75%
175
LA with EPI
Prolonged Duration of action
| Decreased Toxicity
176
PRILOCAINE
MOST Associated with Methemoglobinemia
177
Chlorprocaine
Rapid onset
low potential due to RAPID HYDROLYSIS
Not recommended for spinal
178
Not recommended for spinal
Chlorprocaine
179
Procaine
First synthetic Anesthetic produce
180
Slow onset and low potency
Procaine
181
Limited use due to short duration of action
Procaine
182
Toxicity and slow regional onset limit this agent in application such as regional anesthesia
Tetracaine
183
Bupivacaine 0.75%
Not recommended for pregnant women
184
Bupivacaine 0.75%
Not recommended for pregnant women
| prolonged asystole
185
Drug of choice for AMI when episodes of vfib and vtach are not easily concerted by defi and epineprhine (persistent afib and vtach)
Lidocaine
186
Duration of action of lidocaine
Short
187
May cause toxicity at high concentration
Lidocaine
188
Lidocaine primary metabolite is
Monoethylglyceinexylidide (use to assess hepatic functions to predict morbidity and mortality)
189
Intranasal lidocaine
use to assess migraine headache
190
Lidocaine can use to treate
Seizure
191
Lidocaine and sodium channels
Fast sodium channel blocker
192
Max dose of lidocaine without epi
4mg/kg
| Total dose not to exceed 300mg
193
Max dose of lidocaine with epi
7mg/kg
| Total dose not to exceed 500mg
194
Bupivacaine onset, duration and potency
onset slow
potency high
duration long
195
Preferred local for Obstetric_____________but IF EMERGENCY C SECTION , _______May be preferred
Bupivacaine 0.125 -0.5%; Chloroprocaine
196
Indications for Bupivacaine
when long acting needed
| Provide sensory analgesia with less motor block
197
Significant advantage of bupivacaine
Longer duration
198
Differences amount local anesthetics agents is the duration of block is dependent on
Concentration of the anesthetic
199
Contraindications for bupivacaine
0.75% NOT BE USED FOR OB (Cardiac arrest, death)
| NOT BE USED IN OB PARACERVICAL block due to FETAL bradycardia and death
200
Max single dose of BUPI without epi
175mg
201
Max single dose of BUPI with epi
225mg
202
Do not repead dose at interval less than ___hours for bupi
3 hours
203
Max dose of Bupi in 24 hours
400mg
204
If you use the 0.5% solution for bupivacaine without epineprhine used in obstetrics for continuous epidural anesthesia
Total dose should be limited to 320mg
205
Onset, potency and duration of Mepivacaine
Rapid onset, potency weak, duration of action intermediate
206
This local anesthetic is NOT FOR SPINAL DOSING . However used for?
MEPIVACAINE
| Epidural and caudal
207
Preferable use in OB patients with hx of HTN or cardiac disease bcause long duration
Mepivacaine
208
Less cardiotoxicity and less adverse effects
Ropivacaine
209
Onset of action of ropivacaine
Moderate
210
Motor block is less intense than bupivacaine
Ropivacaine
211
Preferred for procedures where sensory block is desired but intense motor blockade is not required
Ropivacaine
212
Long acting lidocaine derivative
Etidocaine
213
Used for regional , limited epidural and not used for spinal
Etidocaine
214
Cardiotoxic properties similar to bupivacaine
Max dose 300mg without epi
| 400 with 1:200000 epi
215
Onset of action rapid and major drawback is methemoglobin
Prilocaine
216
Use in EMLA cream
Prilocaine
217
With Prilocaine: Methemoglobin, Due to oxidation of normal hemoglobin by the
Prilocaine hepatic derived metabolite O-Toluidine
218
Methomoglobin serum concentrations usually appear
8mg/kg or greater max 600mg
219
Chloroprocaine duration of action? onset?potency ?
short ; rapid; low
220
Appropriate anesthetic for OP surgery as long as it's less than 1 hour long
Chloroprocaine
221
Chloroprocaine without epi
11mg/kg
222
Chloroprocaine with epi
14mg/kg to 1000mg
223
Procaine rapid
Hydrolysis --> PABA (allergic reactions )
224
Max single dose of Procaine
1000mg
225
Tetracaine use for
Opthalmic analgesia
226
Prolonged used for not recommended due to
Severe Keratitis
| Corneal adverse effects
