Local Anesthetics Flashcards
1
Q
Which drug is the prototype for esters?
A
Procaine with a potency ratio of 1
2
Q
What is the potency of Chloroprocaine?
A
4
3
Q
What is the onset of Chloroprocaine?
A
Rapid
4
Q
What is the duration of action of Chloroprocaine?
A
30-45 minutes
5
Q
What is the max safe dose without epi for Chloroprocaine?
A
11 mg/kg
6
Q
What is the max safe dose with epi for Chloroprocaine?
A
14 mg/kg
7
Q
What is the potency ratio for Tetracaine?
A
16
8
Q
What is the onset of Tetracaine?
A
Slow
9
Q
What is the duration of action for Tetracaine?
A
60-180 minutes
10
Q
What is the max safe dose without epi for Tetracaine?
A
1-2 mg/kg
11
Q
What is the max safe dose with epi for Tetracaine?
A
3 mg/kg
12
Q
What is the potency ratio of Lidocaine?
A
1
13
Q
What is the onset of Lidocaine?
A
Rapid
14
Q
What is the duration of action of Lidocaine?
A
60-120 minutes
15
Q
What is the max safe dose of Lidocaine without epi?
A
5 mg/kg
16
Q
What is the max safe dose of Lidocaine with epi?
A
7 mg/kg
17
Q
What is the potency ratio of Ropivacaine?
A
4
18
Q
What is the onset of Ropivacaine?
A
Slow
19
Q
What is the duration of action of ropivacaine?
A
240-480 minutes
20
Q
What is the max safe dose without epi for ropivacaine?
A
2-3 mg/kg
21
Q
What is the max safe dose with epi for ropivacaine?
A
3 mg/kg
22
Q
What is the potency ratio of bupivacaine?
A
4
23
Q
What is the onset of bupivacaine?
A
slow
24
Q
What is the duration of action of bupivacaine?
A
240-480 minutes
25
What is the max safe dose without epi for bupivacaine?
2-3 mg/kg
26
What is the max safe dose with epi for bupivacaine?
3 mg/kg
27
How does lipid solubility affect LA?
Determines their onset of action, more lipid soluble LA will have greater potency and duration of action; there is greater affinity of drug to lipid membranes and therefore greater proximity to sites of action
28
What characteristics of LA affect their duration of action?
protein binding
29
How are esters metabolized?
hydrolyzed by plasma esterases
30
How are amides metabolized?
Primarily hepatic with CYP450
31
How can you tell if a LA is an amide or ester?
Esters have 1 i and amides have 2 i's
32
What is the MOA of LA?
bind to voltage gated Na channels in interior of cell and block depolarizing Na current
33
Will you need more or less LA for a highly stimulated nerve?
Less because more Na channels will be in ready conformation
34
Does more lipid solubility increase or decrease risk for toxicity?
Increases, decreases therapeutic index for hydrophobic drugs
35
Are LA more susceptible to small or large nerve fibers?
Small
36
Are myelinated or unmyelinated fibers easier to block?
Myelinated because the drug pools near axonal membrane
37
In what order to LA inhibit different sensations?
1. pain
2. temperature
3. pressure
4. motor function
38
If you only want to block pain and temperature with a LA, what would you do to achieve that?
Smaller volume or less concentrated
39
What factors determine the plasma concentration of LAs?
- dose of the drug administered
- rate of absorption of the drug
- site injected, vasoactivity of the drug, use of vasoconstrictors
- biotransformation and elimination of the drug from the circulation
- amount bound to protein
40
Where is the primary site of action of LA in the cardiovascular system?
myocardium, LA decrease electrical excitability, conduction rate, and the force of myocardial contraction
41
What other effect do LA cause in the cardiovascular system?
arteriolar dilatation & hypotension
42
What is the relationship between cardiac depressant effects and anesthetic potency in LA?
They parallel each other, bupivacaine which is 4 times more potent than lidocaine is also 4 times more potent in depressing cardiac contractility
43
Can cardiac collapse occur with no warning signs or symptoms of CNS toxicity?
Yes
44
What causes an increased free fraction of bupivacaine in the plasma in pregnant women and newborns?
lower circulating alpha1-acid glycoprotein (AAG)
45
What LAs are preferred in pregnancy and have less risk of cardiac toxicity?
Intermediate duration LAs such as lidocaine and nepivacaine
46
What is the only naturally occurring LA?
cocaine
47
What are the clinically desired actions of cocaine?
Blockade of nerve impulses and local vasoconstriction secondary to inhibition of local NE reuptake
48
Why is cocaine not in popular use now?
High risk for abuse and toxicity
49
What causes the euphoric effects of cocaine?
inhibition of catecholamine uptake, particularly dopamine at CNS synapses
50
What is cocaine currently used for?
Provides topical anesthesia of the upper respiratory tract, where its combined vasoconstrictor and LA properties provide anesthesia and shrinking of mucosa with a single agent
51
Which LA has the most rapid onset and is also metabolized the quickest?
chloroprocaine
52
Is there no placental transfer with chloroprocaine?
no, limited transfer and very useful for emergency c-sections
53
Which ester LA is more slowly metabolized and is considerably more toxic?
Tetracaine
54
How is tetracaine currently used?
for spinal anesthesia when a drug of long duration is needed as well as in various topical anesthetic preparations
55
What is the most widely used and versatile LA?
Lidocaine
56
What are the common concentrations of lidocaine?
1% and 2%
57
What percent lidocaine would you use for IV regional anesthesia?
0.5%
58
What is the other amide LA with pharmologic properties similar to lidocaine?
Mepivacaine
59
What population would you not want to give mepivacaine?
neonates, higher risk for toxicity, so not used in obstetric anesthesia
60
How are the structures of bupivacaine and lidocaine different?
bupivacaine has butylpiperidine
61
Which LA is substantially more cardiotoxic than the others?
bupivacaine
62
Can you ever give bupivacaine IV?
NO, high risk for cardiac toxicity
63
What is generally the treatment for cardiac toxicity caused from bupivacaine?
cardiopulmonary bypass until bupivacaine metabolized out of system
64
What long-acting LA is slightly less potent than bupivacaine and has less risk for cardiac toxicity?
ropivacaine
65
What is the purpose of adding epinephrine to your LA?
decreases blood flow and increases length of block and marker for intravascular injection (if inadvertently inject into vasculature, will see dramatic increase in HR)
66
What are some reasons to add opioids to your LA?
useful for injection in spinal cord because there are opioid receptors present in the substantia gelatinosa, not much clinical use in using opioids peripherally since opioid receptors are absent or weak
67
What is the purpose of using clonidine with your LA?
when administered into the epidural or subarachnoid space, produces dose-dependent analgesia and does not produce depression of ventilation, pruritis, nausea, or vomiting
68
What is the MOA of clonidine?
produces analgesia by activating postsynaptic alpha2 receptors in the substantia gelatinosa of the spinal cord
69
What guides your decision in determining correct LA for your case?
- length of surgery
- speed of onset necessary
- need for post-op pain control
- patient-related factors
70
Your surgeon asks you what would be the max dose of lidocaine with epi for a 50 kg patient?
350 mg
71
The surgeon administers some lidocaine with epi and you see the patient's HR jump from 80 to 120. Would you be concerned about this, and if so what would be your next action?
Not a significant increase in HR so not concerning, the systemic absorption of epi causes a transient increase in HR, if epi injected in vasculature you would a much more dramatic increase in HR
72
Do LA alter the resting membrane potential?
No, they solely prevent the action potential from occurring
73
Which type of LA are more likely to cause allergic reactions?
Esters
74
What causes allergic reactions in certain LA?
PABA (p-aminobenzoic acid-related compounds -->metabolite of ester LA) which is common in many skin products, make-up, lotions, etc.
75
If someone has an allergy to ester LA, can they get amide LA?
YES, no cross-reactivity between esters and amids
76
What factors enhance bupivacaine toxicity?
```
pregnancy
presence of calcium channel blockers
arterial hypoxemia
acidosis
hypercarbia
```
77
What factors influence lidocaine metabolism?
pregnancy-induced hypertension
hepatic disease
reduced liver blood flow
volatile anesthetics
78
What is lidocaine's effect on ventilation response to hypoxia?
Depressed response
79
What are clinical uses of EMLA applications?
Arterial cannulation
Venipuncture
Myringotomy (ear tubes)
Lumbar puncture
80
Which LA produce localized vasoconstriction and anesthesia?
cocaine and lidocaine
81
Which is more cardiotoxic, ropivacaine or bupivacaine?
bupivacaine
82
What are electrophysiological characteristics of lidocaine toxicity?
ECG-PR interval prolongation
83
Does more lipophilic LA benefit from using epi?
no
84
What is EMLA cream composed of?
2.5% lidocaine and 2.5% prilocaine
85
Which LA tend to have a shorter duration of action?
esters
86
The magnitude of systemic absorption of LA is dependent upon:
presence of epi in solution
physiochemical properties of the LA
dose administered into the tissues
vascularity of injection site
87
What does the addition of sodium bicarbonate do to LA?
Speeds onset
88
LA are chemically classified as:
weak bases
89
What effect does fetal acidosis have on local anesthetic accumulation in the body?
Increases anesthetic accumulation
90
The lower the pKa of a LA...
the shorter the onset of action
91
What 3 layers of connective tissue do LA have to diffuse across to affect the nerve?
Endoneurium (surrounds nerve fibers)
Perineurium (surrounds nerve fascicle)
Epineurium (surrounds peripheral nerve)
92
Typically how much of a LA dose will actually hit the nerve?
1-2%
93
Which type of nerves are generally blocked first?
smaller myelinated nerves such as B fibers or A delta fibers (sharp pain and temperature)
94
Which type of nerves are generally blocked last?
small unmyelinated nerves such as C fibers that transmit dull pain
95
Describe detailed MOA of LA
LAs are weak bases that are unionized (lipophilic) and able to cross cell membrane, once they cross cell membrane they pick up H+ to become charged (hydrophilic) and are able to block Na channel from inside of cell
96
What is tonic block?
dose-dependent block of Na channels
97
What is use-dependent block?
relies on the fact that open Na channels are bound more tightly by local anesthetic, so if repeatedly stimulate Na channel it will be in the open conformation more often and LA will be able to better bind to channel
98
What chemical structure gives LA its lipophilic nature?
benzene ring
99
What is the importance of the intermediate chain in LAs?
determines if LA is ester or amide
100
What chemical structure gives LAs its hydrophilic property?
amine group
101
Do acidic environments make LA more or less effective?
Less effective, tissue pH is decreased so when LA is injected into the tissue, more LA is going to become protonated and charged and less will be available to enter cells
102
Which LAs have a metabolite that can cause met Hgb?
Prilocaine with large doses in epidurals and benzocaine in sprays (treated with methylene blue)
103
What are the 8 progressive signs of systemic toxicity?
1. drowsiness
2. paresthesias in the mouth and tongue
3. tinnitus, auditory hallucinations
4. muscular spasm
5. seizures
6. coma
7. respiratory arrest
8. cardiac arrest
104
What are mechanisms of cardiac toxicity in the CNS?
acts at level of medulla to cause hypotension
105
What are mechanisms of cardiac toxicity in the PNS?
Autonomic effects that block sympathetic effects
| Vasomotor effects which lead to vasodilation
106
What are mechanisms of cardiac toxicity in the cardiovascular system?
blocks sodium channels
| Bupivacaine blocks calcium release and reduces mitochondrial activity
107
What is transient neurological syndrome?
pain in the lower extremities that begins within a few hours to 24 hours after spinal anesthesia, resolves by 2-7 days
108
What are some mechanisms to prevent systemic toxicity?
syringe aspiration (when giving a peripheral nerve block or spinal, epidural - make sure not in vein)
test dose
monitors
pre-treat with benzos - helps threshold for seizures
ultrasound
109
What are some treatments for systemic toxicity?
```
NO MORE LA
ABCs
Benzos for seizures
ACLS for cardiac instability
IV lipids
Cardiopulmonary bypass for patients not responding to lipid emulsion or ACLS
```
110
Explain what makes the pharmacokinetics of LA different than most drugs.
LA are injected into tissue and work at injection site and when they are absorbed they are no longer effective, most drugs get injected and have to be absorbed to be effective
