Local Anesthetics Flashcards
1
Q
Local anesthetics produce _____ of impulses along the central and peripheral nerve pathways
A
reversible conduction blockade
2
Q
1st Local Anesthetic
1st Synthetic Local (Ester)
1st Amide Local
A
1st Local Anesthetic Cocaine 1884
1st Synthetic Local (Ester) Procaine 1905
1s Amide Local Lidocaine 1943
3
Q
Chemical structure:
Lipophilic and hydrophilic portion separated by
A
hydrocarbon
4
Q
In the chemical structure, the lipophilic portion is the….
What is it necessary for?
A
Benzene Ring
Necessary for activity
5
Q
What is the chemical structure for esters and amides
A
ester C-O-C
amide NH-C
6
Q
Where does ion trapping happen?
A
within the cell
7
Q
What is the pH extracellulary?
What is the pH intercellular?
A
extracellular 7.4
intracellular 7.0
8
Q
What are the S and R enantiomers?
A
S = LEFT (Sinister) R = RIGHT (Rectus)
9
Q
Racemic mixtures have what type enantiomer?
A
BOTH
10
Q
Pure Isomers only have 1 enantiomer, which enantiomer? and which LAs?
A
Ropivacaine and Levobupivacaine (ONLY 2!)
Both are S enantiomers
11
Q
What is the benefit of S enantiomers?
A
Less cardio and neurotoxic
“this is why we give ropi in kids”
12
Q
What is the MOA for LAs?
A
Inhibit Na+ ions passage through ion-selective Na+ channels
13
Q
What does the inhibition of Na ions do?
A
Slows rate of depolarization
Threshold potential not reached
No action potential propogated
14
Q
What does the inhibition of Na ions NOT alter
A
Resting membrane potential
Threshold potential
15
Q
Local anesthetics bind to the (alpha or beta) subunits of the voltage gated sodium channel
A
Alpha (there are 2 alpha subunits in the Nm receptor)
16
Q
When can LAs bind?
A
in the active and inactive states (CANNOT bind during the resting phase)
(the more frequently the nerve is depolarized, the voltage gated Na channel opens - the more time for LA binding to occur)
Nerves with more activity have faster blockade!
17
Q
Where does the LA bind to on the alpha subunit?
A
internal (this is a weak binding)
18
Q
What are other sites of action for LAs?
A
Voltage-dependent potassium ion channels
(Much lower affinity)
Calcium ion currents (L-type)
G protein-coupled receptors
19
Q
What is minimum concentration (Cm)?
A
minimum concentration to produce conduction blockade
Analogous to MAC
20
Q
What are factors that increase or decrease (Cm)
A
Increases: larger diameter
Decreases: higher frequency, higher pH
21
Q
T/F: the Cm for motor is twice the amount for sensory
A
True (Possible explanation for sensory block with no motor)
22
Q
How many Nodes of Ranvier must be blocked?
A
2, preferably 3
23
Q
What is the order of blockade?
A
B Fibers (preganglionic sympathetic efferent) C Fibers A delta (post ganglionic, afferent) A gamma A beta A alpha
24
Q
Which nerves are unmylinated?
A
C fibers
25
Which nerves travel faster?
mylinated
26
What is the function of A alpha fibers
motor, proprioception
27
What is the function of A beta fibers
touch, pressure
28
What is the function of A gamma fibers
muscle tone
29
What is the function of A delta fibers
Pain (fast), cold temp, touch
30
What is the function of B fibers
Preganglionic (efferent), autonomic
31
What is the function of C fibers
Postganglionic (afferent)
| Pain (slow), warm temp, touch
32
What is the order of a differential blockade?
ATP-TP-MVP
```
Autonomic
Temperature
Pain
Touch
Pressure
Motor
Vibration
Proprioception
```
33
What is a differential blockade?
Blockade of some fibers but not others
May block, B fibers, C fibers, and small and medium A fibers
May not block Large A fibers
34
You may have a sympathectomy from a differential block. What is a sympathectomy?
Loss of sensation for pain, and temp
| May still have proprioception and motor
35
LAs are _____, with a pKa of ____, and pH values of ____
weak bases
7. 6-8.9
3. 9-6.5
36
Acid+base =
more ionized
37
What form does the LA need to be to in order to cross the lipid bylayer
un-ionized
38
Do LA with pka nearest to physiologic pH have a faster or slower onset?
FASTER
39
All LAs are weak bases with one exception, which is:
What is the pka?
Benzocaine
pKa – 3.5
Does not ionize based on pH
40
What is the MOA of benzocaine?
unknown
41
Lidocaine pka is 7.9, when placed in an environment with a pH of 7.9, what does this mean?
What happens in a ph of 7.6, 7.4, 7.2
50% ionized, 50% unionized
As you decrease pH, it becomes more and more ionized (REMEMBER, its the un-ionized portion that crosses lipid bilayer)
42
What happenes when you inject lidocaine into a septic patient?
there will be more ionized portion of the drug and be less effective
43
What does adding bicarb to LA do?
Higher pH is closer to pKa of about 8
More un-ionized to cross
Faster onset by 3-5 minutes
Also higher pH thought to lessen sting of local infiltration
44
How are LA’s distributed?
```
1st large uptake to lungs
2nd distribution to high perfused tissue
(heart, brain, kidneys)
3rd distribution to low perfused tissue
(muscle and fat)
```
45
Are esters or amides are widely distributed?
Amides
46
What is placental transfer influenced by?
Which drugs are highly protein bound?
Influenced by protein binding
(proteins too large to cross)
Bupivacaine and Ropivacaine highly bound
Lidocaine not as much
47
Explain fetal ion trapping
Once un-ionized local crosses placenta and hits low fetal pH more drug is ionized and can’t cross back
Build up of trapped local in fetal circulation leads to toxicity in fetus
48
What is potency related to?
Lipid solubility
| More lipid soluble means easier to cross lipid by-layer
49
What is onset related to?
State of Ionization – most important
| Lipid Solubility
50
What is duration of action related to?
Protein Binding
| Lipid Solubility
51
How are amides metabolized?
Mainly HEPATIC metabolism
| Minimal renal excretion of unchanged drug
52
What are the fast, intermediate, slow amides with regard to metabolism and clearance
Fastest
- Prilocaine
Intermediate
- Lidocaine and Mepivicaine
Slow
- Etidocaine, Bupivacaine, Ropivacaine
53
How are esters metabolized?
Rapid hydrolysis
- Cholinesterases (pseudocholinesterase)
- Mostly plasma, lesser liver
54
What are the rapid, intermediate, slow esters with regards to metabolism and clearance?
Rapid
- Chloroprocaine
Intermediate
- Procaine
Slow
- Tetracaine (tetracaine is longest acting ester)
55
For esters, what is the one exception to hydrolysis?
Cocaine - significant metabolism by the liver
56
What is PABA and what can happen?
```
Metabolites of esters mostly inactive
Paraaminobenzoic acid (PABA)
```
PABA - allergic
57
What common local injection site contains little to no cholinesterase enzyme?
CSF
Must wait until drug goes into systemic circulation for hydrolysis
58
In what states are plasma cholinesterase (pseudocholinesterase) inhibited in?
```
Deficiency
Liver disease
Increased BUN
Parturients
Chemotherapy patients
```
59
What can be added to LAs for vasoconstriction?
Epinephrine, phenylephrine, norepinephrine
| epi superior
60
What is the epi dose?
1:200,000
| or 5mcg/ml
61
What do the vasoconstrictions do?
```
Limits systemic absorption
Maintains drug concentration around nerves
Can prolong Lidocaine by 1/3
No effect to onset
Helps to decrease toxicity
```
62
Which 2 local anesthetics have no vasodilator activity?
Cocaine
Ropivacaine
(also Lidocaine according to Nagelhout)
(Chloroprocaine according to APEX)
63
What is the risk of adding opioids to spinals and epidural LAs
Risk for respiratory depression and oxygen desaturation
64
```
Clonidine:
Is a preservative free _____
Enhances ______ anesthesia
When used in combination with opioids is ___
Epidural dose:
Spinal dose:
```
```
alpha 2 agonist
Neuraxial
Additive
Epidural 150 mcg or 2mcg/kg
Spinal 15-45 mcg
(PROLONGS block)
```
(APEX - increases analgesia properties via alpha 2 agonism)
65
What is the pH of 2% lido?
| What is the pH of 2% lido with epi?
6. 5
| 4. 5 with epi
66
What benefit does mixing locals have?
Combos
Faster onset
Longer Duration
Lido/Bupivicaine
Cholorprocaine/Bupivicaine
67
Mixing locals has what type of effect?
additive and not synergistic!!
68
T/F: allergic reactions to LAs are common?
FALSE
Rare - <1% allergic reaction
Most are adverse responses to excess plasma concentration
Allergic reaction to preservative free amides is so low its not even reportable
69
Esters are more likely to cause allergic reaction d/t?
PABA
70
What is the other thing that make people allergic to LAs
the preservative (Methylparaben)
71
Is there a cross sensitivity to LAs?
NOOO
72
After LA injection you notice hypotension with syncope or tachycardia, what probably happened?
Likely IV injection
73
What is LA toxicity dependent on?
Dependent of total amount of drug
NOT volume or Concentration
Ex.
40mL of 1% or 80mL of 0.5%
Both 400 mg
74
```
Lidocaine
Max dose:
Max dose with epi:
Plain mg/kg:
With epi mg/kg:
```
Max dose: 300
Max dose with epi: 500
Plain mg/kg: 4.5
With epi mg/kg: 7
75
```
Ropiviciaine:
Max dose:
Max dose with epi:
Plain mg/kg:
With epi mg/kg:
```
Max dose: 200
Max dose with epi: (not listed)
Plain mg/kg: 2.5
With epi mg/kg: 2.5
76
```
Bupiviaine:
Max dose:
Max dose with epi:
Plain mg/kg:
With epi mg/kg:
```
Max dose: 175
Max dose with epi: 225
Plain mg/kg: 2.5
With epi mg/kg: 3
77
What is the progression of plasma levels and CNS effects?
```
Vertigo
Tinnitus
Ominous feelings
Circumoral numbness
Garrulousness
Tremors
Myoclonic jerks
Convulsions
Coma
Cardiovascular collapse
```
78
What is the blood flow of LA to tissues (fastest to slowest)
```
IV
Tracheal
Intercostal
Caudal
Paracervical
Epidural
Brachial Plexus
Subarachnoid
Subcutaneous
(In time I can please everyone but Suzi and Sally)
```
79
What is transient neurologic symptoms (TNS)?
Moderate to severe pain
| Lower back, buttocks, and posterior thighs
80
What is TNS most common with?
Highest risk after intrathecal lidocaine
81
What is cuada equine syndrome
Diffuse injury across lumbosacral plexus
- Various degrees of sensory anesthesia
- Bowel and bladder sphincter dysfunction
- Paraplegia
82
What are big red flags to doing a caudal block?
Sacral dimple and hairy nevi
83
What is anterior spinal artery syndrome
Lower extremity paresis and variable sensory deficit
84
Cardiotoxicity is more or less resistant than CNS
more
85
Why can you see profound hypotension with cardiotoxicity?
Relaxation of arteriolar vascular smooth muscle
| Direct myocardial Depression
86
In what anesthetic might you see cardiotoxicity BEFORE CNS effects?
Bupivacaine
Order of CV toxicity according to APEX
Bupi > Levobupiva > Ropiva > Lidocaine
87
What is the initial treatment of LAST?
Airway management
- 100% O2
Seizure suppression
- Benzodiazepines
- AVOID propofol if cardiovascular instability
- Alert for possible cardiopulmonary bypass
88
What is the next treatment for LAST?
Management of arrhythmias
- BLS and ACLS
- AVOID vasopressin, calcium channel blockers, betablockers, or local anesthetic
- REDUCE epi to <1 mcg/kg
89
Explain Lipid Emulsion Therapy (20%) for LAST
1. 5 mL/kg (lean body mass) IV over 1 minute
0. 25 mL/kg/min
Repeat Bolus once or twice for persistant cardiovascular collapse
Double infusion rate to 0.5 mL/kg/min if BP remains low
Continue infusion for at least 10 min after circulatory stability
Upper limit: Approximately 10 mL/kg lipid emulsion over first 30 minutes
90
Methamoglobinemia is related to which LAs?
Prilocaine >8 mg/kg, Benzocaine, Cetacaine, Lidocaine
Also Nitroglycerin, Phenytoin, and Sulfonamides
91
What is the treatment of methamoglobinemia?
Methylene Blue 1-2mg/kg IV over 5 minutes
| Do not exceed 7.8 mg/kg
92
What are the low potency/short duration LAs?
Procaine
| Chloroprocaine
93
What are the intermediate potency/duration LAs?
Lidocaine
94
What are the long acting/long duration LAs?
Bupivacaine, Ropivacaine, Tetracaine
95
What are the Fast Onset LAs?
Cloroprocaine & Lidocaine
96
What are the slow onset LAs?
Bupicacaine, Ropivacaine, Tetracaine, Procaine
* the further away the pKa from physiologic (pH 7.4) the slower the onset
Bupivacaine 8.1
Ropivacaine 8.1
Tetracaine 8.5
Procaine 8.9
97
Factors that increase neurotoxicity
Hypercarbia, Hyperkalemia, Hypoxemia, Acidosis
98
Factors that decrease neurotoxicity
Hypocarbia, hypokalemia, CNS depressants
