Local Anesthetic Pharmacology Flashcards
1
Q
How have local anesthetics improved over the years?
A
Become less toxic and faster working
2
Q
What is a primary determinant of intrinsic potentcy and duration of LAs?
A
lipid solubilty
3
Q
Do LAs have a greater affinity to lipid membranes?
A
yes
4
Q
Why is it advantageous for LAs to have a greater affinity to lipid membranes?
A
They have a greater proximity to their sites of action
5
Q
The ______ the LA remains in membrane vicinity the _____ likely it will be to effect its action on the ______ channel
A
The LONGER the LA remains in membrane vicinity the MORE likely it will be to effect its action on the NA+ channel
6
Q
What does a greater lipid solubility and duration of action on site do to LA toxicity? Increases or decreases it?
A
INCREASES toxicity
7
Q
What are 2 examples of low lipid solubility LAs?
A
Procaine
Chloroprocaine
8
Q
What are 3 examples of intermediate lipid solubility LAs?
A
Lidocaine
Mepivcacaine
Prilocaine
9
Q
What are 3 examples of high lipid solubility LAs?
A
Bupivacaine
Ropivacaine
Tetracaine
10
Q
______ is related to the the extent to which the LA remains in the vicinity of the nerve
A
DURATION
11
Q
How does the administration of vasoconstrictors prolong the effect of LAs?
A
the vasoconstriction prevents vascular uptake
11
Q
What 3 factors determine how long an LA remains in the vicinity of the nerve?
A
- Lipid solubiilty
- The degree of vascularity of the tissue
- The presence of vasoconstrictors
12
Q
What is the structural classification of cocaine and chlorprocaine?
A
Ester
13
Q
Is the onset of cocaine and chlorprocaine, lidocaine, mepivacaine: slow, moderate or fast?
A
Fast
14
Q
What is the structural classification of lidocaine, mepivacaine, bupivacaine, & ropivacaine?
A
Amide
15
Q
Is the onset of bupivacaine, & ropivacaine: slow, moderate or fast?
A
Moderate
16
Q
Which LA is the longest acting?
A
Bupivocaine
17
Q
Which LA is the shortest acting?
A
chloroprocaine
18
Q
Compare the 1/2 life: Ropiv vs Bupiv
A
Bupiv 1/2 life > Ropiv 1/2 life
19
Q
Are LAs weak acids or weak bases?
A
weak bases
20
Q
What is pKa?
A
the pH at which the ionized and non-ionized forms are present in equal amounts
21
Q
Once equilibrium is reached between the base and the charged forms, which form binds to the LA binding site?
A
charged, ionized
22
Q
The ______ cation is responsible for the neural blockade
A
IONIZED
23
Q
What 2 factors influence time of onset?
A
pKa
diffusibility
24
What 2 factors affects the LAs ability to cross the cell membrane?
molecular weight
liposolubility of the molecule
25
Do LAs have approximately the same molecular weight?
Yes
26
The diffusibility of LAs molecules from the injection site depends on its _______ since LAs have approximately the same weight
HYDROPHLICITY
27
Which LA form is more lipid soluble, ionized or nonionized?
nonionized
28
Which LA form can cross the cell membrane more readily, ionized or nonionized?
nonionized
29
What factor affects the speed of onset?
drug pKa
30
The pKa affects how rapidly the drug ______
IONIZES
31
The concentration of ______ drug available for diffusion across the cell membrane determines blockade
FREE
32
In acidic solutions, molecules of weak bases are in their ionized or unionized state? How does this change in basic solutions?
ionized
unionized
33
In acidic solutions, molecules of weak acids are in their ionized or unionized state? How does this change in basic solutions?
unionized
ionized
34
Ester LAs are hydrolyzed by _____ - an enzyme?
PLASMA CHOLINESTERASE
35
Do esters have a shorter or longer elimination half life?
shorter
36
Are true allergies to LAs commons or rare?
Rare
37
Are allergies more common with ester LAs or amide LAs?
Esters
38
What causes the allergic reaction to ester LAs?
their metabolism to PABA
39
What does PABA stand for?
Para aminobenzoic Acid
40
Can allergic reactions to PABA cause urticaria? Anaphylaxis?
Yes
41
How is PABA formed?
during the metabolism of methlyparaben preservative
42
Order these ester LA metabolism rates from rapid, intermediate, slow: Chloroprocaine, Tetracaine, Procaine?
Chloroprocaine (rapid) > Procaine (Intermediate) > Tetracaine (slow)
43
The varying amide LA metabolism rates is due to which types of enzymes?
microsomal
44
Compared to ester LAs, do amide LAs have a faster or slower metabolism rate?
slower
45
Do amide LAs showcase sustained plasma concetrations?
Yes
46
Which is more likley to cause systemic toxicity, ester or amide LAs? Why?
Amide LAs because their cumulative effect is greater than that of esters
47
Order these amide LA metabolism rates from rapid, intermediate, slow: Lidocaine & Mepivacaine, Prilocaine, Bupivacaine
Prilocaine (rapid) > Lidocaine & Mepivacaine (intermediate), Bupivacaine (rapid)
48
What 3 factors does LA dosing depend on?
- Injection technique
- place of injection
- addition of additives
49
What is max dosing WITHOUT epi in mg of chloroprocaine - for all block sites?
800 mg
50
What is max dosing WITH epi in mg of chloroprocaine - for all block sites?
1000 mg
51
What is max dosing WITHOUT epi in mg of lidocaine - for all block sites?
300 mg
52
What is max dosing WITH epi in mg of lidocaine - for all block sites?
500 mg
53
What is max dosing WITHOUT epi in mg of prilocaine - for all block sites?
600 mg
54
Do you use prilocaine WITH epi?
No
55
What is max dosing WITHOUT epi in mg of mepivacaine - for all block sites?
400 mg
56
What is max dosing WITH epi in mg of mepivacaine - for all block sites?
500 mg
57
What is max dosing WITHOUT epi in mg of bupivacaine - for subq and peripheral block sites?
175 mg
58
What is max dosing WITHOUT epi in mg of bupivacaine - for epidural block sites?
170 mg
59
What is max dosing WITH epi in mg of bupivacaine - for all block sites?
225 mg
60
What is max dosing WITHOUT epi in mg of ropivacaine - for subq and epidural block sites?
200 mg
61
What is max dosing WITHOUT epi in mg of ropivacaine - for peripheral block sites?
250 mg
62
Do you use ropivacaine WITH epi?
No
63
Majority of LA block site onset is fast, which 2 LAs have moderate epidural onset times?
Bupivacaine
Ropivacaine
64
If a patient has low plasma pseudocholinesterase, what can this do to the concentration & effect of chloroprocaine? What could this result in?
- increase the concentration of the LA > prolonged effect
- increased risk for LAST
65
Does chloropracaine have a quick onset?
Yes
66
Is chloropracaine least toxic in epidural?
Yes
67
Does chloropracaine have metabolites? Does this impair subsequent dosing of epidural?
Yes
68
What are the 2 active compounds lidocaine metabolizes to?
MEGX & GX
69
Does lidocaine go through hepatic metabolism?
Yes
70
Does lidocaine have tachyphylaxis - reduced effects at higher doses?
Yes
71
Does adding epinephrine to LA doses prolong duration? What does it cause?
Yes, causes vasoconstriction which inhibits the vasodilation effect - keeps the medication at site of injection longer
72
What condition is seen with subarachnoid injection of lidocaine?
Transient Neurological Symptoms (TNS)
73
What is the post injection onset time of TNS?
4-12 hrs
74
Which LA has a high lipid solubility?
Bupivacaine
75
Is bupivacaine an excellent sensory blockers? Why?
Yes, because it has high lipid solubility
76
Does bupivacaine have high or low frequency of tachyphylaxis?
Low
77
Which dose of bupivacaine has irreversible cardiotoxic effects if injected intravascularly? Is it still on the market?
0.75%, no
78
Match the enantiomer to ropivacaine or bupivacaine: S-enantiomer & R enantiomer?
- Ropivacaine = S-enantiomer
- Bupivacaine = R-enantiomer
79
Is ropivacaine less or more cardiotoxic than bupivacaine? Why?
Less because it has an S-enantiomer
80
Does ropivacaine have less or more motor blockade than bupivacaine? What percent?
Less, 20%
81
Does ropivacaine result in progressive motor blockade?
No
82
What are the 2 reasons for adding epi to LA solution?
- cause vasoconstriction at the site which prolongs drug concentration
- marker for IV injeciton
83
Will the block persist after the A1 adrenergic agonist effect on bloodflow dissapates?
Yes
84
Does epinephrine and other A1 adrenergic agonist increase the intraneural concentration of LAs?
Yes
85
What is the most common dose of epinephrine for an epidural?
1:200,000
86
What is the most common mg dose of epinephrine for a spinal?
0.2 mg
87
Does epi prolong lidocaine and tetracaine?
Yes
88
Does epi prolong lipid soluble agents like bupivacine?
No
89
If 1:200,000 epi is given IV accidentally, can the HR increase? How many beats? What about the BP? By what percent of BBs?
Yes
- HR can increase 30 beats
- BP can increase 10-20% on BBs
90
Should you mix epi in an LA solution for a digital block ( finger, wrist, ankle, etc)?
NO, will cause problematic vasoconstriction
91
Can bicarb increase the pH closer to the pKa of the LA?
Yes
92
Does bicarb affect the speed of onset of ropivacaine?
No
93
What % bicarb is typically added to 10 ml LA solutions? How many mEq/ml is that?
- 8.4%
- 1 mEq/ml
94
What class is clonidine?
A2 adrenergic agonist
95
Clonidine has central _____brain stem & _____ action
Clonidine has central BRAIN STERM & PERIPHERAL action
96
Does clonidine enhance intrathecal and epidural labor analgesia?
Yes
97
Is analgesic effect more potent when clonidine is administered neuraxially with certain LAs? Does it prolong spinal anesthesia?
Yes
98
Individuals on this medication often have clonidine added to their LA?
Those on Subutex
99
What are the 2 most common intrathecal (spinal) opioids?
Fentanyl
Morphine
100
Are fentanyl and sufentanil highly lipid soluble? What is their onset?
Yes, 5-10 mins
101
Is morphine highly lipid soluble? What is spinal its onset?
No, it is hydrophobic. 30-60 min
102
Is hydropmorphone highly lipid soluble? What is spinal its onset?
No, it is hydrophobic. 30-60 min
103
What are the 3 most common epidural opioids?
Fentanyl
Morphine
Sufentanil
104
Do the 3 most common epidural opioids have early systemic uptake?
Yes
105
What is the dermatomal spread for fentanyl and sufentanil - how many?
5-6
106
What is the the epidural onset of fentanyl and sufentanil?
5-10 min
107
What is the the epidural onset of morphine?
1-1.5 hrs
108
Does morphine have an early or late rostral flow?
Late
109
What is rostral flow?
How the anesthetic moves upward in the spinal column toward the head after being injected into the epidural or subarachnoid (intrathecal) space
110
Does adding dexamethasone to LA nerve blocks prolong duration of analgesia?
Yes
111
Is dexamethasone a potent, synthetic corticosteroid? Is it more or less potent than prednisone?
Yes, it is 7x more potent than prednisone
112
Is dexamethasone FDA approved fro perineural administration?
No
