Local Anesthetics (4) Flashcards
1
Q
How many classes are there of antiarrhythmic drugs?
A
Class 1: Sodium channel blockers
Class 2: Beta blockers
Class 3: Potassium channel blockers
Class 4: CCB
2
Q
What are the uses for local anesthetics?
A
- Treat dysrhythmias
- Analgesia (acute and chronic)
- Anesthesia (ANS blockade, sensory anesthesia, skeletal muscle paralysis)
3
Q
What was the first local anesthetic?
A
Cocaine
- Ophthalmology (1884)
- local vasoconstriction
- cerebral stimulating
4
Q
What was the first synthetic ester?
A
Procaine (1905)
5
Q
What was the first synthetic amide?
A
Lidocaine (1943)
6
Q
What are all other local anesthetics compared to?
A
Lidocaine
7
Q
What is the dose of lidocaine for initial bolus?
A
1-2 mg/kg IV over 2-4min
8
Q
What is the dose for lidocaine gtt?
A
1-2 mg/kg/hr gtt
Terminated 12-72 hours
9
Q
What is important to monitor when patient is getting IV lidocaine?
A
Cardiac, hepatic, renal dysfunction
10
Q
What effects are associated with 1-5 mcg/mL of lidocaine?
A
Analgesia
11
Q
What effects are associated with 5-10 mcg/mL of lidocaine?
A
- Circum-oral numbness
- Tinnitus
- Skeletal muscle twitching
- Systemic hypotension
- Myocardial depression
12
Q
What effects are associated with 10-15 mcg/mL of lidocaine?
A
- Seizures
- Unconsciousness
13
Q
What effects are associated with 15-25 mcg/mL of lidocaine?
A
- Apnea
- Coma
14
Q
What effects are associated with >25 mcg/mL of lidocaine?
A
Cardiovascular depression
15
Q
What is the molecular structure of local anesthetics?
A
- Lipophilic portion
- Hydrocarbon chain
- Hydrophilic portion
Bond between lipophilic portion and hydrocarbon chain
16
Q
Which bond of LA determines whether it is an ester or amide?
A
Bond between lipophilic (1) and hydrocarbon chain (2)
17
Q
Which part of the LA is the hydrophilic portion?
A
Amino group
18
Q
Which part of the LA structure is the lipophilic portion?
A
Aromatic benzene ring
19
Q
A
bond between hydrocarbon chain on the intermediate chain= middle chain
20
Q
LA are weak ______
A
Bases
poorly soluble in water
usually add epi to make sure the local anesthetics stay longer
21
Q
List ester local anesthetics?
A
- Procaine
- Chloroprocaine
- Tetracaine
22
Q
List amide local anesthetics:
A
- Lidocaine
- Prilocaine
- Mepivacaine
- Bupivacaine
- Levobupivacaine
- Ropivacaine
23
Q
What is the purpose of sodium bisulfide added with LA?
A
Added to LAs when epi is added to prevent breakdown of the vasoconstrictor
Extends shelf life (prevents degradation to precipitate)
24
Q
What is the purpose for adding epi to LA?
A
Prolong the duration of the LA
25
The higher the non ionized component of the LA means more lipid soluble= the higher the ________
potency
26
Non-ionized form help to determine LAs _________ solubility
Lipid
Can cross membrane easily
27
Bupivacaine is more lipid soluble so it is more ________ than lidocaine
POtent
28
What is the major determinant for potency?
Lipid solubility
29
What are 3 liposome forms of LA?
- Lidocaine
- Tetracaine
- Bupivacaine
30
What is the function of liposomes?
Uploads a higher amount of LA into a molecule & have a consistent release of LA in the tissues
(like extended release capsule)
31
What is the benefit for liposomes?
- Prolonged duration of action
- Decreases toxicty
32
What is the MOA of Local anesthetics?
- Binds to and inactivates (Closes) inner voltage gates channels
- inhibit passage of Na in nerve membranes
33
How do LA affect action potential?
- Slows rate of depolarization
- Does not reach threshold
- No action potential propagated
34
What factors can affect local anesthetic blockade?
- Lipid solubility or non-ionized/unionized form
- Repetitively stimulated nerve
- Diameter of the nerve
35
What are other target ion channels for LAs besides Na+?
- Potassium channels
- Calcium Ion Channels
- G protein-coupled receptors
36
Non-ionized form
37
What is the minimum effective concentration (MEC/Cm) for LAs?
- 1 cm blocked (3 nodes of ranvier)
- Larger fibers need higher concentrations of LAs
- Motor 2x bigger diameter than sensory
38
What fibers are the fastest in the propagation of SNS impulse?
Pre-ganglionic B fibers
39
Which fibers control pain/temp (touch, pressure, proprioception, and motor)?
Myelinated A-delta and unmeylinated C fiber
40
__________ increases sensitivity of local anesthetics
Pregnancy (give less)
41
Which pH has the most rapid onset of action for LAs?
pH closest to physiologic pH
42
__________ has greater systemic absorption which makes it potency less
Lidocaine
43
What factors influence LA absorption?
- Site of injection
- Dosage
- Use of Epinephrine
- Pharmacologic characteristics of the drug
44
Which areas of the body are highly vascular and have increased absorption of LA?
45
Using Epi with LA counter acts which effects of LAs?
Vasodilatory effects (enhances/prolongs DOA Of LA)
46
What is the rate of clearance of LA dependent on?
- Cardiac output
- Protein binding
47
Which LA has the fastest clearance between Lido, Mepivacaine, and Bupivacaine?
Lidocaine has faster clearance than mepivacaine and bupivacaine d/t less protein binding of lidocaine
48
Higher protein bound LAs have _______ intravascular clearance
Slower
49
How are amide LAs metabolized?
Microsomal enzymes in the liver
50
Which amides LAs have rapid, intermediate, and slower metabolism?
- Most rapid: Prilocaine
- Intermediate: Lidocaine, Mepivacaine
- Slowest: Etidocaine, Bupivacaine, Ropivacaine
51
How are Ester LAs metabolized?
Hydrolysis by cholinesterase enzyme in the plasma
52
What is a metabolite with metabolism of ester LAs?
Para-aminobenzoic acid (PABA)→ causes allergies
53
________ LAs have slower metabolism than __________ LAs
Amide, Ester
54
Which LAs have pulmonary first pass metabolism?
Lidocaine, bupivacaine (dose dependent), and prilocaine
Inactivated in the lungs
55
True
56
- Clearance (from site of action)
- Protein binding **
57
How are LAs eliminated and cleared?
Renal
- Poor water solubility= unchanged drug in urine (5%)
- PABA through urine
- Cocaine 10-12% unchanged drug
58
What are considerations of local anesthetics with pregnant patients?
- Lower levels of plasma cholinesterases
- Significant transplacental transfer with amides (fetal pH is much lower leads to ion trapping)
59
What happens when the unionized form of LA crosses from mom to fetus?
Unionized form enters acidic environment of fetus and turn ionized and isnt metabolized→ can cause seizures, bradycardia/asystole for the fetus
60
Which LAs have significant protein binding?
61
How is lidocaine metabolised?
Oxidative dealkylation in the liver then hydrolysis
62
What is lidocaine metabolite?
Xylidide
63
What does pregnancy induced hypertension do to clearange of lidocaine?
Prolongs clearance
64
________ disease affects metabolism and elimination of lidocaine
Hepatic
65
What is the max infiltration dose of lidocaine?
300 mg OR
500 mg with epi
66
What is the metabolite of prilocaine?
Orthotoludine
67
What is the MOA of prilocaine metabolite orthotoluidine?
Converts Hemoglobin to Methemoglobin→Methemoglobinemia
68
At what dose is there concern for methemoglobinemia with prilocaine?
>600mg
S/S: cyanosis from decreased O2 carrying capacity
69
What is the treatment of Methemoglobinemia?
TX: Methylene Blue
1 to 2 mgs/kg IV over 5 mins
Total dose not to exceed 7 to 8 mg/kg
70
How does Mepivacaine differ from Lidocaine?
- Longer duration of action
- Lacks vasodilator activity
- Prolonged elimination in fetus & newborn; no OB
71
How is Bupivacaine metabolized?
Aromatic hydroxylation, N-dealkylation, amide hydrolysis and conjugation
72
Which protein does Bupivacaine bind to and what percent it bound?
A1-acid glycoprotein 95%
73
What is Dibucaine used for? What is the MOA?
Used to diagnose succs allergy
MOA: inhibits the activity of normal butyrylcholinesterase (plasma cholinesterase) by more than 70%
Metabolized in liver
74
How is Ropivacaine metabolised?
CYP450
75
Does Ropivacaine metabolize into metabolites?
Can accumulate with uremic patients→Less system toxicity than Bupivacaine
76
How is Chloroprocaine metabolized?
Plasma cholinesterase (3.5x faster)
77
Hydrolysis of LA ranked fasted to slowest:
chloroprocaine > procaine > tetracaine
78
What makes Benzocaine unique structurally from other LAs?
Weak acid (pK 3.5)
79
What are the uses of Benzocaine?
- Topical anesthesia of mucous membranes:
- Tracheal intubation, Endoscopy, Transesophageal echocardiography (TEE), Bronchoscopy
80
What is the onset, duration, and dose of Benzocaine?
Onset: rapid
Duration: 30 to 60 minutes
Dose: Brief spray (20%) = 200 to 300 mgs
81
432mg
82
How is cocaine metabolized? What patients is metabolism decreased in?
- Plasma and liver cholinesterases
- Decreased in: Parturients, Neonates, Elderly, Severe Hepatic Disease
83
Cocaine is a ______ LA
Ester
84
What is the peak, duration, and elimination of cocaine? Caution with which patients?
- Peak: 30 to 45 mins
- Duration: 60 minutes after peak
- Elimination: Urine (24 to 36 hours)
Caution: Coronary vasospasm, ventricular dysrhythmias, HTN, tachycardia, CAD
85
What is the function of alkalinization of LA Solution? What is the benefit?
- Increase percent of lipid soluble (non ionized form) of LAs
Benefits:
Faster onset of action
Peripheral and epidural blocks by 3 to 5 mins.
Enhances the depth
Increase the spread (i.e., epidural)
86
What is used to alkalinize LAs?
8.4% Sodium bicarb (1mL only added to 10mL LA)
87
88
How does mixing dexmedetomidine with LA affect things?
Increased duration of:
* Both motor and sensory blocks
* First analgesic request after spinal anesthesia
89
Magnesium + LA =
Increased duration with subarachnoid block with opioids.
90
Clonidine and Ketamine + LA =
Pediatric regional anesthesia prolonged duration
91
Dexamethasone + LA =
Increased duration either IV or mixed with LA
92
What happens when combining chloroprocaine and bupivacaine?
- Rapid onset
- Tachyphylaxis
93
When local anesthetics are given in combination the toxic effects are ________
additive
94
Why do we use vasoconstrictors (Epi) with LAs?
- Produce vasoconstriction
- Increased neuronal uptake of LA
- α-adrenergic effects may have some degree of analgesia
- No effect on onset rate of LA
- Enhanced cardiac irritability with inhaled anesthetics
- Systemic absorption (HTN/ tachycardia?)
95
How many mcg/mL are in a concentration of 1:200,000?
5mcg/mL
96
Local anesthetics strengths for 0.25%, 0.5%, 1%, 2%, and 4%:
97
Bupivacaine= 50mg total
epi= 100mcg
98
What are uses for LAs?
- Topical
- Local Infiltration
- Peripheral N. Block
- Intravenous
- Epidural
- Spinal
- Tumescent Liposuction
99
Where is topical anesthesia applicable?
- nose
- mouth
- tracheobronchial
- esophagus
- GU tract
100
What LA is the most effective for topical anesthesia?
Cocaine→ localized vasoconstriction and decreases blood loss and improves surgical visualization
101
When is lidocaine used for topical anesthesia?
- Surface anesthesia
- Inhalation does not alter airways resistance
- causes vasodilation
102
Which LAs are not used for topical anesthesia?
- Procaine
- Chloroprocaine
103
What is EMLA?
Eutectic Mixture of LA
104
What is the EMLA composed of?
Cream 2.5% lidocaine and 2.5% prilocaine (5% total LA cream)
105
How long before certain procedures do we need to apply EMLA?
- skin grafting (2 hours)
- Cautery of genital warts (10min)
- Venipuncture, lumbar puncture (10 min)
- Arterial cannulation (Nitroglycerine) (10 min)
- Myringotomy (10 min)
106
What are cautions with EMLA?
- Caution with methemoglobinemia
- Not recommended for skin wounds
- Contraindicated with amide allergies
107
What other preparations are available for topical cream locals?
- Amethocaine (EMLA-like)
- Tetracaine 4% Gel
- Lidocaine 7%
- Tetracaine 7%
108
What type of LA is Epi contraindicated?
Intracutaneously or into tissues at end arteries
(Fingers, toes, ears, nose, and penis
vasoconstriction→ ischemia/necrosis)
109
Where is extravascular placement of LA?
Subcutaneous injection
110
How does subcutaneous LA duration change when epi is added?
Doubled (contraindicated in subq LA of end arteries)
111
How is peripheral nerve block achieved?
LA injection into tissues surrounding individual peripheral nerves or nerve plexuses.
112
What is the MOA of peripheral nerve blocks?
- Diffusion from outer mantle to central core of nerve along a concentration gradient
- Proximal effect first then distal
- Proximal sensation comes back first then distal/ larger motor
113
What is onset of peripheral nerve blocks?
Dependent on local anesthetic pK
lidocaine: 3 min
Bupivacaine: 15 min
114
What is the duration of peripheral nerve blocks?
Depends on dose of LA (Bupivacaine with epi/fentanyl/clonidine = 12 to 18 hrs)
115
What is the benefit of continuous infusion blocks?
- Improved pain control
- Less nausea
- Greater satisfaction
116
Examples of peripheral nerve blocks:
- Interscalene
- Axillary
- Femoral
- Sciatic
117
What is another name for IV regional anesthesia?
Bier block→ IV injection of LA into an extremity isolated from the rest of the systemic circulation with a tourniquet
Sensation and muscle tone dependent on tourniquet
Can use ester or amide: mostly lidocaine
118
What is involved in the bier block?
- IV start
- Exsanguination
- Double cuff
- LA injection
- IV D/C
119
What is the sequence of neuraxial blockade?
1) SNS
2) Sensory
3) Motor
120
Which neurons are first affected with neuraxial anesthesia?
Myelinated Preganglionic B fibers (fastest) (SNS)
121
Which neurons are affected after myelinated preganglionic B fibers?
Myelinated A (medium) and B fibers (faster) THEN Unmyelinated C fibers (small)
122
Neuraxial blockade is the last reference with which assessment parameter?
Leg movement (motor is affected last)
123
How do we confirm we are in the spinal area for subarachnoid block?
CSF confirmation
Preganglionic fibers= principle site of action
124
Sensory effect is on the _________ level of denervation
same
125
Where is the SNS effect of spinal anesthesia block?
2 spinal segments above sensory
126
Where is the motor effect of spinal anesthesia block?
2 spinal segments below sensory
127
1) T4
2) T8
128
What are most common subarachnoid block agents?
- Tetracaine
- Lidocaine
- Bupivacaine
- Ropivacaine
- Levobupivacaine
129
How is subarachnoid block dose calculated?
- Height of patient (volume of subarachnoid space)
- Segmental level of anesthesia desired
- Duration of anesthesia desired
130
________ is more important in subarachnoid blocks than the concentration of drug or the volume of the solution
Dose
(ex: 5ft= 1mL of 0.75% bupivacaine)
+ 0.1mL for every inch above (2mL total)
131
What is important in determining the spread of LA for subarachnoid blocks?
Specific gravity of LA
Hyperbaric (LA sg > CSF) with glucose is additive (spreads down)
Hypobaric with distilled water as additive (LA sg < CSF) (Spreads up)
132
What is the most common epidural anesthetic?
Lidocaine: safe and good diffusion through tissue
133
Why are levobupivacaine and ropivacaine not as safe for epidural anesthesia?
They are highly protein bound so toxic effects last a lot longer (cardiac and CNS toxicity)
134
What is the onset for epidural anesthesia?
- 15-30 minutes (slow diffusion/delay)
- Great with loading dose and then intermittent boluses (usually have continuous gtt)
135
When does epidural pose risk to fetus?
24-48 hours it can go systemic through the veins and cross placental barrier
136
Will bupivacaine or lidocaine have more cross over to the fetus?
Lidocaine crosses more than bupivacaine (lido more rapid onset)
137
_______ are acceptable as additive to both epidural and SAB
opioids (synergistic effect)
138
True
139
What is tumescent liposuction?
- SQ infiltration of large volumes (5L of more) diluted lidocaine solution (0.05-0.1%) and epi
140
What is infiltration of tumescent lipsuction MOA?
- Causes taut stretching and blanching of skin from the large volume of fluid and vasoconstriction
- local anesthesia with bloodless aspirates and prolonged postoperative analgesia
141
When is LA plasma peak after tumescent liposuction?
12-14 hours after injection
142
Where is tumescent liposuction injected?
Thigh, abdomen, hips, butt
143
What is the recommended dose for tumescent?
- Regional Anesthesia Lidocaine with Epi: 7 mg/kg
- Highly diluted Lidocaine with Epi Tumescent: 35 to 55 mg/kg
144
1 gm of SQ tumescent can absorb up to ____mg of Lidocaine
1 (theory)
145
Weak bases=
pK before pH
If weak base (pk 8.0) is put in an acid ph (Blood 7.2)
8.0 – 7.2= +0.8 weak bases are ionized at acid ph
“nicely negative numbers are nonionized”
