Local anesthetics - test 4 Flashcards
(160 cards)
1
Q
What is the first local anesthetic?
A
Cocaine (ester)
2
Q
What was the first use of cocaine?
A
Opthamology (1884)
- cerebral stimulating qualities
- localized vasoconstriction: shrink nasal mucosa
3
Q
What was the first synthetic ester?
A
Procaine - 1905
4
Q
What was the first synthetic amide?
A
Lidocaine - 1943
*gold standard
5
Q
What are the uses for local anesthetics?
A
- treat dysrhythmias
- analgesia: acute and chronic pain
- anesthesia: ans blockade, sensory anesthesia, skeletal muscle paralysis
6
Q
What are the antiarrhythmic drug classes?
A
Class 1: sodium channel blockers
Class 2: beta-blockers
Class 3: potassium-channel blockers
Class 4: calcium-channel blockers
7
Q
What anti-arrhythmic drug class is lidocaine in?
A
Class 1: sodium channel blockers
8
Q
Dose of lidocaine:
A
- 1-2 mg/kg IV = initial bolus over 2-4 minutes
- 1-2 mg/kg/hour = drip - terminated 12-72 hours
9
Q
Intraop infusion dose of lidocaine:
A
1 mg/kg infusion over 1 hour
10
Q
What are considerations of lidocaine?
A
Careful monitoring: cardiac, hepatic, renal dysfunction
11
Q
What plasma lidocaine concentration gives you the effect of analgesia?
A
1-5 mcg/ml
12
Q
What are the dose dependent effects of lidocaine with a plasma lidocaine concentration of 5-10 mcg/ml?
A
- Circum-oral numbness
- Tinnitus
- Skeletal muscle twitching
- Systemic hypotension
- Myocardial depression
13
Q
What are the dose dependent effects of lidocaine with a plasma lidocaine concentration of 10-15 mcg/ml?
A
- Seizures
- Unconsciousness
14
Q
What are the dose dependent effects of lidocaine with a plasma lidocaine concentration of 15-25 mcg/ml?
A
- Apnea
- Coma
15
Q
What plasma lidocaine concentration causes cardiovascular depression?
A
> 25 mcg/ml
16
Q
What is the molecular structure of local anesthetics?
A
- Has a lipophilic portion connected by a hydrocarbon chain to the hydrophilic portion
- Bond between 1 and 2 classifies it as ester or amide
17
Q
Composition of LA will have a pH of _____ and are weak _______.
A
pH of 6; weak bases
18
Q
Procaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration (mg):
pK:
Protein Binding (%):
A
Classification: Ester
Potency: 1
Onset: Slow
Duration after infiltration (min): 45-60
Max single dose for infiltration (mg): 500
pK: 8.9
Protein Binding (%): 6
19
Q
Chloroprocaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
pK:
A
Classification: Ester
Potency: 4
Onset: Rapid
Duration after infiltration (min): 30-45
Max single dose for infiltration (mg): 600
pK: 8.7
20
Q
Tetracaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
pK:
Protein Binding (%):
A
Tetracaine
Classification: Ester
Potency: 16
Onset: Slow
Duration after infiltration (min): 60-180
Max single dose for infiltration (mg): 100 (topical)
pK: 8.5
Protein Binding (%): 76
21
Q
Lidocaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
Toxic Plasma Concentration (mcg/mL)
pK:
Protein Binding (%):
A
Lidocaine
Classification: Amide
Potency: 1
Onset: Rapid
Duration after infiltration (min): 60-120
Max single dose for infiltration (mg): 300
Toxic Plasma Concentration (mcg/mL): >5
pK: 7.9
Protein Binding (%): 70
22
Q
Prilocaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
Toxic Plasma Concentration (mcg/mL)
pK:
Protein Binding (%):
A
Prilocaine
Classification: Amide
Potency: 1
Onset: Slow
Duration after infiltration (min): 60-120
Max single dose for infiltration (mg): 400
Toxic Plasma Concentration (mcg/mL): >5
pK: 7.9
Protein Binding (%): 55
23
Q
Mepivacaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
Toxic Plasma Concentration (mcg/mL)
pK:
Protein Binding (%):
A
Mepivacaine
Classification: Amide
Potency: 1
Onset: Slow
Duration after infiltration (min): 90-180
Max single dose for infiltration (mg): 300
Toxic Plasma Concentration (mcg/mL): >5
pK: 7.6
Protein Binding (%): 77
24
Q
Bupivacaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
Toxic Plasma Concentration (mcg/mL)
pK:
Protein Binding (%):
A
Bupivacaine
Classification: Amide
Potency: 4
Onset: Slow
Duration after infiltration (min): 240-480
Max single dose for infiltration (mg): 175
Toxic Plasma Concentration (mcg/mL): >3
pK: 8.1
Protein Binding (%): 95
25
Levobupivacaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
pK:
Protein Binding (%):
Levobupivacaine
Classification: Amide
Potency: 4
Onset: Slow
Duration after infiltration (min): 240-480
Max single dose for infiltration: 175
pK: 8.1
Protein Binding (%): >97
26
Ropivacaine
Classification:
Potency:
Onset:
Duration after infiltration (min):
Max single dose for infiltration:
Toxic Plasma Concentration (mcg/mL)
pK:
Protein Binding (%):
Ropivacaine
Classification: Amide
Potency: 4
Onset: Slow
Duration after infiltration (min): 240-480
Max single dose for infiltration (mg): 200
Toxic Plasma Concentration (mcg/mL): >4
pK: 8.1
Protein Binding (%): 94
27
Which LA has a potency of 16?
Tetracaine
28
Which LAs have a potency of 4? (4)
- Chloroprocaine
- Bupivacaine
- Levobupivacaine
- Ropivacaine
29
Which LAs have a potency of 1? (4)
- Procaine
- Lidocaine
- Prilocaine
- Mepivacaine
30
Which LA has the highest lipid solubility?
Tetracaine
31
Which LAs have rapid onset?
Chloroprocaine and Lidocaine
32
Which LA has the highest protein binding?
Levobupivacaine (>97%)
33
Which LAs are liposomes?
Lidocaine, tetracaine, and bupivacaine
34
Why are Liposomes used?
- uploads a higher amount of LA into a molecule and have a consistent release of LA into the tissues
- Prolonged duration of action and decreased toxicity
35
Which liposomal LA can last up to 96 hours?
Bupivacaine ER (exparel)
36
What is the MOA of local anesthetics?
- Binds to inactivated closed inner voltage-gated Na+ channels
- Block/inhibit Na+ passage in nerve membranes
- Slows rate of depolarization
- Does not reach threshold, no action potential
37
What are some factors of LAs that affect blockade?
- Lipid solubility or non-ionized/unionized form
- Repetitively stimulated nerve
- Diameter of the nerve
38
What are some other site of action targets for LAs?
- Potassium channels
- Calcium ion channels
- G protein-coupled receptors
39
What component of the local anesthetic is required for a conduction block?
Non-ionized form
40
Larger fibers need ____ higher concentrations of LAs
2x
41
Motor nerve diameter is __x bigger than sensory
2x
42
How many Nodes of Ranvier would preferably be blocked to prevent conduction?
At least 2, preferably 3 (1cm)
43
Which fibers are for pain and temperature?
myelinated A-δ and unmyelinated C fibers
44
Which nerve fibers are the fastest?
Preganglionic B fibers
45
How are pregnant women affected by LAs?
Increased sensitivity and harder to block
46
Are LAs weak acids or bases?
Weak bases with pKa values above physiologic pH
47
Only __% of LAs are in lipid-soluble nonionized form
50%
48
How is onset of action affected if the pKa is closest to physiologic pH?
Most rapid OOA
49
Factors that affect LA absorption:
- Site of injection
- Dosage
- Use of Epi
- Pharmacologic characteristics of the drug
50
What is the primary determinant of potency in LAs?
Lipid solubility
51
What two factors does rate of clearance depend on?
- Cardiac output
- Protein binding
52
How is LAs % bound related to % in plasma?
% bound is inversely related to % in plasma
53
How are Amide LAs metabolized?
Microsomal enzymes in the liver
54
Which amide LA is the most rapidly metabolized?
Prilocaine
55
Which Amide LA has intermediate metabolism?
Lidocaine and Mepivacaine
56
Which amide LAs have the slowest metabolism?
Etidocaine, Bupivacaine and Ropivacaine
57
How are ester LAs metabolized?
Hydrolysis by cholinesterase enzyme in plasma > liver
*except with cocaine
58
What is the metabolite of ester LAs?
para-aminobenzoic acid
59
Which LAs are faster metabolized?
Esters are faster than amides
60
Which LAs have first-pass pulmonary extraction?
- Lidocaine
- Bupivacaine (dose dependent)
- Prilocaine
61
For LAs, how much of the drug is unchanged in the urine?
What about cocaine?
5%
Cocaine = 10-12%
62
True or False: in general, the more lipid soluble the local anesthetic is, the greater its potency
True
63
Which local anesthetic property is most important when it comes to the duration of action?
- Protein binding
- Clearance
64
How does pregnancy affect the metabolism of LAs?
- lower levels of plasma cholinesterases
65
Which LAs have significant transplacental transfer?
Amides, not significant with esters
*ion trapping occurs
66
Bupivacaine protein bound and arterial concentration:
95% - 0.32
67
Lidocaine protein bound and arterial concentration:
70% - 0.73
68
Prilocaine protein bound and arterial concentration
55% - 0.85
69
How is lidocaine metabolized?
What is the metabolite?
Oxidative dealkylation in liver, then hydrolysis
- metabolite = Xylidide
70
Maximum infiltration dose of lidocaine:
300 mgs plain and 500 mgs with epi
71
Lidocaine has prolonged clearance with ____?
pregnancy induced hypertension
72
What is the metabolite of prolocaine and what does it do?
Orthotoluidine - converts hemoglobin to methemoglobin
73
At what dose of prilocaine can methemoglobinemia occur?
What are the s/sx?
>600 mgs
Cyanosis d/t decreased O2 carrying capacity
74
What is the treatment for methemoglobinemia?
Methylene blue
- 1-2 mgs/kg IV over 5 minutes
- Total dose not to exceed 7-8 mg/kg
75
Mepivacaine is similar to lidocaine except....
- longer duration of action
- lacks vasodilator activity
- Prolonged elimination in fetus and newborn; no OB
76
Bupivacaine metabolism:
Aromatic hydroxylation, N-dealkylation, amide hydrolysis and conjugation
77
What is the binding site for bupivacaine?
a1-acid glycoprotein (95%)
78
How is ropivacaine metabolized?
Metabolites?
- Hepatic cytochrome P450 enzymes
- Metabolites can accumulate with uremic patients - lesser system toxicity than bupivacaine
79
What does ropivacaine bind to?
a1-acid glycoprotein
80
How is Dibucaine metabolized?
What is the MOA?
- Liver
- Inhibits activity of normal butyrylcholinesterase by more than 70%
81
Chloroprocaine metabolizes ______ times faster than Procaine.
Pregnancy decreases plasma cholinesterase by ____%
3.5x faster than procaine
40%
82
Which ester LA has the slowest metabolism?
Tetracaine d/t 76% protein bound
83
83
What is unique about benzocaine?
It's a weak acid (pKa 3.5)
84
What is benzocaine used for?
Topical anesthesia of mucous membranes:
- tracheal intubation,
- endoscopy,
- TEE,
- bronchoscopy
85
Benzocaine onset:
Duration:
Dose:
Onset: rapid
Duration: 30-60 minutes
Dose: brief spray (20%) - 200-300 mgs
86
How is cocaine metabolized?
What is it decreased in?
- Metabolism in plasma and liver cholinesterases
- Decreased in pregnancy, neonates, elderly, severe hepatic disease
87
Cocaine peak:
Duration:
Elimination:
Peak: 30-45 minutes
Duration: 60 minutes after peak
Elimination: Urine (24-36 hours)
88
What do you need to caution for when using cocaine?
- Coronary vasospasm
- Vent. dysrhythmias
- HTN
- Tachycardia
- CAD
89
What is the average pKa of local anesthetics?
8
90
What is the function of the alkalinization of LAs?
increases the % of lipid-soluble or non-ionized form
91
Benefits of alkalinization of LA solutions:
- Faster onset of action
- Peripheral and epidural blocks by 3 to 5 minutes
- Enhances the depth
- Increases the speed (Epidural)
92
LA 1's pK is 9.2 and LA 2's pK is 7.5, which of the following are correct statements?
- LA 2 has more ionized component
- LA 1 has more non-ionized component
93
How are LAs affected when mixed with dexmedetomidine?
Increased duration of:
- both motor and sensory blocks
- First analgesic request after spinal anesthesia
94
How are LAs affected when mixed with magnesium?
Increased duration with SAB /c or /s opioids
95
How are LAs affected when mixed with clonidine and ketamine?
Pediatric regional anesthesia prolonged duration
96
How are LAs affected when mixed with dexamethasone?
Increased duration either IV or mixed with LA
97
What are the results of combining chloroprocaine and bupivacaine?
- Produce a rapid onset
- tachyphylaxis
98
What is added to the combination of chloroprocaine and bupivacaine?
8.4% sodium bicarb (1 mL only)
- added to 30 ml of LA
99
The toxic effects of combining LAs are ____
additive
100
Why are vasoconstrictors used with LAs?
The duration of action of a LA is proportional to the time the drug is in contact with the nerve fibers
101
How do the use of vasoconstrictors affect LAs?
- increased neuronal uptake of LA
- a-adrenergic effects may have some degree of analgesia
- No effect on onset rate of LA
- Enhanced cardiac irritability with inhaled anesthetics
- Systemic absorption can lead to HTN
102
How much epinephrine or phenylephrine is given with bupivacaine or lidocaine for a subarachnoid block (SAB)?
- Epi 0.2 mg
- Phenylephrine 2mg
103
Compute 1:500,000 Epi to mcg/mL
1,000,000/ 500,000=2
2 mcg/mL
104
Compute 1:10,000 Epi to mcg/mL
1,000,000/ 10,000 = 100
100 mcg/mL
105
Compute 1:1000 Epi to mcg/mL
1,000,000/ 1000 = 1000
1000 mcg/mL
This is the epinephrine that we find in our crash carts.
106
Local anesthetic strengths:
0.25%
0.5%
1%
2%
4%
- 2.5 mg/mL
- 5 mg/mL
- 10 mg/mL
- 20 mg/mL
- 40 mg/mL
107
Your surgeon injected 20 mLs of Bupivacaine 0.25% with 1:200,000 of Epi. What are the total mgs for Bupivacaine and the total mcgs for Epinephrine?
Bupivacaine:
0.25% = 2.5 mgs/mL
2.5 mgs x 20 mLs = 50 mgs total
Epinephrine:
1:200,000 = 5 mcg/mL
5 mcg x 20 mLs = 100 mcg total
108
Lidocaine Recommended Max Single Dose:
Lidocaine Recommended Max Single Dose with/Epi
Lidocaine Recommended Max Single Dose for Spinal
300 mg
500 mg w/ Epi
100 mg
109
Mepivacaine Recommended Max Single Dose
Mepivacaine Recommended Max Single Dose with/Epi
Mepivacaine Recommended Max Single Dose for Spinal
400 mg
500 mg w/ Epi
100 mg
110
Prilocaine recommended maximum single dose
600 mg
111
Bupivacaine Recommended Max Single Dose
Bupivacaine Recommended Max Single Dose with/Epi
Bupivacaine Recommended Max Single Dose for Spinal
175 mg
225 mg w/ Epi
20 mg
112
112.5 mgs of Bupivacaine with Epi and 250 mgs of Lidocaine with Epi were both given during a plastic surgery case.
What are the percentages of each local anesthetic based on the recommended maximum single dose in mgs?
Max single dose of Bupivacaine with Epi: 225 mg
112.5/225 = 50%
Max single dose of Lidocaine with Epi: 500 mg
250/500 = 50%
113
Where is topical anesthesia applicable?
Mucous membranes of the nose, mouth, tracheobronchial tree, esophagus, or GU tract
114
Which topical anesthetic has localized vasoconstriction, decreases blood loss and improves surgical visualization?
Cocaine
115
Which topical anesthetic is great with surface anesthesia and inhalation does not alter airway resistance, but vasodilation?
Lidocaine
116
Which anesthetics are ineffective as topical anesthetics?
Procaine and chloroprocaine
117
What does a Eutectic Mixture of LA (EMLA) contain?
Dose:
Readiness:
Lidocaine 2.5% and Prilocaine 2.5% = 5% LA
Dose: 1-2 gms/cm2 area
Readiness: 45 minutes OOA
118
118
EMLA should be applied 2 hours before what?
Skin grafting
119
EMLA should be applied 10 minutes before what?
- cautery of genital warts
- venipuncture, LP
- arterial cannulation (nitro)
- myringotomy
120
Considerations for using EMLA:
- caution with methemoglobinemia
- not recommended for skin wounds
- C/I with amide allergies
121
Aside from EMLA, what are other preparations for topical anesthetics?
- Amethocaine (EMLA-like)
- Tetracaine 4% gel
- Lidocaine 7%
- Tetracaine 7%
122
What is local infiltration with LA?
Extravascular placement of LA: subQ injection
123
What tissues is the use of epi contraindicated with LAs?
- Fingers
- Toes
- Ears
- Penis
*not intracutaneously or into tissues at end arteries
123
What LAs are used in an inguinal operative site?
- Lidocaine 1 or 2%
- Ropivacaine 0.25%
- Bupivacaine 0.25%
124
How can you double the duration of local infiltration?
Adding epi 1:200,000
125
How do you achieve a peripheral nerve block?
LA injection into tissues surrounding individual peripheral nerves or nerve plexuses
126
MOA of a peripheral nerve block:
Diffusion from outer mantle to central core of nerve along a concentration gradient
127
S/Sx of a peripheral nerve block:
How does it change when wearing off?
- Proximal affected first then distal
- Proximal comes back first then distal
128
What order does a peripheral nerve block affect the nerves?
Smallest sensory and ANS fibers first, then larger motor and proprioceptive axons
129
What is a peripheral nerve block onset of action dependent on?
Lidocaine OOA?
Bupivacaine OOA?
LA pK
- Lidocaine = 3 minutes
- Bupivacaine = 15 minutes
130
Duration of a peripheral nerve block depends on what?
Dose of local anesthetic
(ex. bupivacaine with epi/fentanyl/clonidine = 12-18 hours)
131
Benefits of continuous infusion blocks:
- improved pain control
- less nausea
- greater satisfaction
- additives are used
132
What are some examples of peripheral nerve blocks?
- interscalene
- axillary
- femoral
- sciatic
133
What is a Bier Block?
IV injection of LA into an extremity isolated from the rest of the systemic circulation with a tourniquet
134
What LAs can be used for a bier block?
- Mepivacaine > lidocaine
- most commonly used is lidocaine
135
What are the steps in a bier block?
- IV start
- Exsanguination
- Double cuff
- LA injection
- IV d/c
136
What is the sequence of blockades for a segmental block in Neuraxial Anesthesia?
1. SNS (Myelinated preganglionic B fibers)
2. Sensory (Myelinated A, B fibers, unmyelinated C fibers)
3. Motor (Myelinated A-δ and unmyelinated C fibers)
137
Neuraxial blockade is the last reference with which assessment parameter?
Leg movement
138
What is a spinal block?
Principal site of action?
Produced by direct injection of LA into subarachnoid
*CSF is confirmation
- Principal site of action is preganglionic fibers
139
With spinal blocks, where is the sensory effect?
SNS effect?
Motor effect?
Sensory = same level of denervation
SNS = 2 spinal segments above sensory
Motor = 2 spinal segments below sensory
140
If the assessed sensory level after SAB is at Thoracic 6 (Tip of Xiphoid Process), what are the:
SNS level
Motor level of the block?
SNS = T4
Motor = T8
141
Most common LAs used for subarachnoid blocks?
- Tetracaine
- Lidocaine
- Bupivacaine
- Ropivacaine
- Levobupivacaine
142
Dosage of subarachnoid block LAs is according to what?
- height of patient (volume of subarachnoid space)
- Segmental level of anesthesia
- Duration of anesthesia desired
143
For SAB, _____ is more important than _______ of drug (%) or the volume (mLs) of the solution injection.
Dose; concentration
144
SAB Dose:
5 ft = _____mL of 0.75% Bupivacaine
+ ______ mL for every inch above…. 2 cc total ( 1½ hours to 2 hours)
1 mL
0.1 mL
For someone who is 5’5”, you will give 1.5 mL of bupivacaine for a SAB.
145
For SAB, the _________ of LA is important in determining the spread of the drug.
Specific gravity
146
What can be added to LA so that its specific gravity can increase?
What can be added to LA so that its specific gravity can decrease?
Glucose added → hyperbaric solution.
Distilled water added → hypobaric solution
147
What is the most common LA used for epidurals?
Lidocaine
*good through tissues and safer
148
Epidrual onset:
15-30 minutes with slow diffusion/delay
149
Can epidurals cross the placental barrier?
Effects on fetus = ?
Yes; 24-48 hours
150
What is the difference between SABs and epidurals?
Epidurals have no differential zone of SNS, sensory and motor blockade - larger doses are required
151
What can you add to both epidural and SABs that are synergistic?
Opioids
152
T/F: Between Lidocaine and Bupivacaine, the former will cross the transplacental barrier more than the latter.
True
153
What is tumescent liposuction?
SQ infiltration of large volumes (5L or more)
Causes taut stretching of overlying blanched skin d/t large volume and vasoconstriction (fat can be aspirated without blood loss and prolongs postop analgesia)
154
What solution is used for tumescent liposuction?
- Diluted lidocaine (0.05% - 0.10%)
- Epi 1:100,000
155
When is the LA plasma peak for tumescent liposuction?
12-14 hours s/p injection
156
Where can tumescent liposuction be given?
Thigh, abdomen, hips, buttocks
157
Recommended dose for tumescent liposuction:
- Regional Anesthesia Lidocaine with Epi: 7 mg/kg
- Highly diluted Lidocaine with Epi Tumescent: 35 to 55 mg/kg
- Theory: 1 gm of SQ can absorb up to 1 mg of Lidocaine
(aka: Tissue Buffering System)
