Local Anesthetics I (Exam IV) Flashcards
(90 cards)
1
Q
What was the first local anesthetic?
A
Cocaine
2
Q
Is cocaine an ester or amide?
A
Cocaine is an ester.
3
Q
What was cocaine first used for and what was the effect?
A
Ophthalmology (1884)
Local vasoconstriction: shrink nasal mucosa.
4
Q
What was the first synthetic ester developed in 1905?
A
Procaine
5
Q
What was the first synthetic amide developed in 1943?
A
Lidocaine
Gold Standard
6
Q
What are the general uses for Local Anesthetics (LAs)?
A
- Treat dysrhythmias
- Analgesia: Acute and chronic pain
7
Q
What are the anesthesia uses for LAs?
A
- ANS Blockade
- Sensory Anesthesia
- Skeletal Muscle Paralysis
8
Q
What antiarrhythmic Drug Class is lidocaine in?
A
Class I: Sodium Channel Blockers
9
Q
MAGA: What is the intra-op infusion dose of lidocaine?
A
1 mg/kg over an hour
10
Q
What is the IV dose of Lidocaine? (Bolus and drip)
A
- 1 to 2 mg/kg IV (initial bolus) over 2 - 4 min.
- 1 to 2 mg/kg/hour (drip)
11
Q
When should an IV lidocaine gtt be terminated?
A
within 12 - 72 hours
12
Q
What patients should be carefully monitored when giving lidocaine?
A
Heart, liver, kidney patients
13
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 1-5 mcg/ml.
A
Analgesia
14
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 5-10 mcg/ml.
A
- Circum-oral numbness
- Tinnitus
- Skeletal muscle twitching
- Systemic hypotension
- Myocardial depression
15
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 10-15 mcg/ml.
A
Seizures
Unconsciousness
16
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 15-25 mcg/ml.
A
Apnea
Coma
17
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is >25 mcg/ml.
A
- Cardiovascular Depression
18
Q
Describe the components that make up the molecular structure of local anesthetics
A
(1) Lipophilic Portion (aromatic) connected by a (2) Hydrocarbon chain to the (3) Hydrophilic portion (amino)
19
Q
What structural component of a LA determines if it is an ester or an amide?
A
Bond between the lipophilic portion and the hydrocarbon chain will determine if LA is an ester or an amide.
(intermediate chain/hydrocarbon chain)
20
Q
What type of local anesthetic would you anticipate from the figure below?
A
Ester due to the ester bond between the aromatic and the intermediate chain
21
Q
What type of local anesthetic would you anticipate from the figure below?
A
Amide due to the amide bond between the aromatic and the intermediate chain
22
Q
Local anesthetics will typically have a pH of _____ and are _____. ?
A
pH of 6; weak bases
A majority of LA are weak bases
pH 6 (HCL salt)
23
Q
Why is epi added to lidocaine?
A
Epi: The vasoconstriction from the epi causes lidocaine to stay at the side therefore prolonging the duration of action
24
Q
Why is sodium bisulfite added to lidocaine with epi?
A
It acts as a preservative to stabalize epi.
25
As a general rule, the ______ the nonionized component the better the lipid solubility and higher the potency.
Higher
## Footnote
This isnt always the case Ex. Lidocaine and bupivicaine dont follow this rule.
26
Which LA is the most potent? What is the potency?
Tetracaine (16)
## Footnote
Memory trick for the potency. Tetra is four. 4 X 4 =16
27
Which local anesthetic exhibits the highest degree of protein binding? What % is bound?
**Levobupivacaine (>97%)**
28
Which two local anesthetics will have the most rapid onset?
**Chloroprocaine (fastest)
Lidocaine**
29
Lipid solubility correlates to _______ of the drug.
Which LA has the highest lipid solubility?
- potency
- Tetracaine
30
Which ester has the greatest degree of lipid solubility? What is the lipid solubility of this drug?
Tetracaine (80)
31
Which amide has the greatest degree of lipid solubility?
Bupivacaine (28)
32
How do liposomes and local anesthetics interact?
What is the result?
**Liposomes upload higher amount of LA into a molecule and have consistent release of LA in the tissue.**
**Prolonged duration of action & decreased toxicity**
33
The FDA released this local anesthetic that contains liposomes and can last up to 96 hours.
Exparel ER (Bupivacaine)
34
What is the mechanism of action of Local Anesthetics?
1. Goes from outside to inside through the cell membrane (this is why lipid solubility is important)
2. Once inside, it blocks/inhibits the **INNER** voltage gated Na+ channel
35
What happens after the inner VG Na channel has been blocked via LAs?
doesnt reach threshold, no action potential.
36
What two things will cause a local anesthetic to not work anymore?
Becoming water-soluble and ionized.
37
What factors affect the degree of blockade seen from local anesthetics?
* Lipid solubility or non-ionized form
* Repetitively stimulated nerve (↑ sensitivity)
* Diameter of the nerve (↑ diameter, ↑ LA need)
38
What other receptors can be targeted by local anesthetics besides sodium channels?
* Potassium channels
* Calcium Ion Channels
* G protein-coupled receptors
39
Minimum Effective Concentration or Cm (LAs) = _________
MAC (Volatiles)
40
What component of the local anesthetic is required for the conduction block?
Non-ionized form (equates with lipid solubility)
41
Larger fibers need _____ concentrations of LAs.
higher
42
The diameter of a _____ nerve is _____ times larger than the diameter of the _____ nerve.
Motor
**2x**
Sensory
43
How many nodes of Ranvier need to be blocked to equate to 1 cm of local anesthesia?
At least 2, preferably 3 Nodes of Ranvier to prevent the conduction (Minimum Effect Concentration)
44
If a LA were given intravascularly, which fibers would be affected the fastest?
**Pre-ganglionic B fibers (SNS)**
45
When looking at pain/temp, what fibers does that use?
What sensation is the last to be affected?
* Myelinated A-delta & A-beta and unmyelinated C-fibers
* Motor
46
Place in order the fibers that are affected first to last when administering a local anesthetic.
1. Preganglionic B fibers (SNS)
2. Myelinated A-delta & A-beta and unmyelinated C-fibers (Sensory)
3. Myelinated A-alpha (Motor)
47
pKa values closer to physiologic pH result in a _____ rapid onset
more
48
If a LA has vasodilator activity, what happens to its potency?
What happens to the duration of action?
**Less potent**
↓ **Duration of action**
49
Because Lidocaine has vasodilator activity, there is (greater/less) _______ systemic absorption. Resulting in a (shorter/longer) ________ duration of action at the site of injection.
- greater
- shorter
50
Factors that influence the absorption of LA.
1. Site of injection
2. Dosage
3. Epinephrine use
4. Pharmacologic characteristics of the drug
51
List the uptake of Local Anesthetics Based on Regional Anesthesia Technique from highest blood concentration to lowest blood conc. (8)
52
________is the primary determinant of potency
**Lipid solubility**
53
The rate of clearance of LAs is dependent on what two factors?
* Cardiac output
* Protein binding:
Note: % bound is inversely related to % plasma.
(*40% albumin-bound means 60% will float freely in plasma.*)
54
When looking at Lidocaine, Bupivicaine and mepivacaine. Which one will have the longest duration of action?
- Bupivacaine (95% protein bound)
55
How are Amide local anesthetics metabolized?
Liver via CYP 450's
56
Place these amide LAs in order of most rapidly metabolized to slowest. Lidocaine, Bupivacaine and Prilocaine.
1. **Prilocaine (55% protein bound)**
2. Lidocaine (70% protein bound)
3. Bupivacaine (95% protein bound)
57
How are esters metabolized?
Hydrolyzed by cholinesterases in plasma
58
Cocaine, being an ester, is primarily metabolized via plasma cholinesterases. T/F?
False. Primarily hydrolyzed by liver cholinesterases > plasma cholinesterases.
59
What is the metabolite of esters?
What is the significance of this metabolite?
**Para-AminoBenzoic acid (PABA)**
- Common cause of Allergies
60
Are amides or esters, generally slower at metabolizing?
Amides are slower at metabolism.
(CYP450s instead of plasma cholinesterases)
61
What are the most common LAs that have first-pass pulmonary extraction?
* Lidocaine
* Bupivacaine (dose dependent)
* Prilocaine
62
What happens to the drug during first-pass pulmonary extraction?
It is metabolized and becomes inactive
63
The poor water solubility of local anesthetics usually limits renal excretion of unchanged drug to less than ______%
The exception is ______, of which 10% to 12% of unchanged drug can be recovered in urine.
Water-soluble metabolites of local anesthetics, such as _______ resulting from metabolism of ester local anesthetics, are readily excreted in urine.
5%
cocaine
PABA
64
In general, the more lipid soluble the local anesthetic is, the greater the potency. T/F
True
## Footnote
Holy shit, he keeps repeating this which is why there are 1700 of the same card. Sorry!
65
Which local anesthetic property is most important regarding the duration of action?
A. Protein binding
B. Lipid solubility
C. Metabolism
D. Clearance
A
Higher protein binding = longer DOA
66
How will pregnancy affect
plasma cholinesterase levels?
Lower levels of plasma cholinesterases
67
What do we worry about when giving LAs during pregnancy? Is this specific to amides or esters?
Ion trapping if we give Amides, leading to LA toxicity in the placenta and fetus
## Footnote
(Not significant with esters)
68
Why does ion trapping occur?
The pH in the fetal environment is more acidic than in maternal circulation.
69
If there is ion trapping in the placenta, what can be given to adjust the pH?
**Sodium Bicarb**
70
**Bupivacaine**
Protein Bound:
Arterial Concentration:
**Bupivacaine**
Protein Bound: 95%
**Arterial Concentration: 0.32**
71
**Lidocaine**
Protein Bound :
Arterial Concentration:
**Lidocaine**
Protein Bound: 70%
Arterial Concentration: 0.73
72
**Prilocaine**
Protein Bound:
Arterial Concentration:
**Prilocaine**
Protein Bound: 55%
Arterial Concentration: 0.85
73
_____ is metabolized via oxidative dealkylation in the liver, then hydrolysis. It also has the metabolite, Xylidide.
Lidocaine
74
What is Lidocaine's max infiltration dose? (solo & w epi)
**300 mg solo**
**500 mg with epi**
75
Lidocaine will have prolonged clearance with ______
Pregnancy Induced Hypertension
76
What is prilocaine's primary metabolite?
What is the issue with this metabolite?
Metabolite: Orthotoluidine
The metabolite converts Hemoglobin to Methemoglobin, resulting in Methemoglobinemia.
77
What is the result of Methemoglobinemia?
Cyanosis d/t decreased O2 carrying capacity
78
What is the max dose of prilocaine?
600 mgs
79
What is the treatment for methemoglobinemia secondary to prilocaine overdose?
Methylene Blue
- 1 to 2 mg/kg IV over 5 mins (initial dose)
- Total dose not to exceed 8 mg/kg (over 24 hours)
80
Mepivacaine is similar to Lidocaine except:
* Longer duration of action
**Lacks vasodilator activity**
81
Can Mepivacaine be given in pregnant patients?
**No**. Prolonged elimination in fetus
82
What plasma protein does Bupivacaine and Ropivacaine bind to? what %?
**α1-Acid glycoprotein**
Bupivacaine - 95%
Ropivacaine - 94%
83
______ **inhibits the activity of normal butyrylcholinesterase (plasma cholinesterase) by more than 70%**
Dibucaine
84
Between Tetracaine and Procaine, which one has a slower metabolism?
Tetracaine
85
Put these in order from fastest rate of metabolism to slowest.
Procaine
Chloroprocaine
Tetracaine
Hydrolysis: Chloroprocaine (fastest) > procaine > tetracaine (slowest)
## Footnote
(He says this could be a matching question!!) Easy memory trick, they are in alphabetical order, C P T
86
What is Benzocaine used for?
Uses: Topical anesthesia of mucous membranes:
87
What do we need to worry about in terms of dosing with Benzocaine?
**A brief 1 second spray (20%) = 200-300mgs**
**Methemoglobinemia**
88
What makes Benzocaine unique?
Weak acid instead of a weak base, like most LA.
pKa = 3.5
89
Who should receive decreased amounts of cocaine?
1. Parturients
2. Neonates
3. Elderly
4. Severe hepatic disease
90
Administration of cocaine can cause what five things that we should be cautious about when giving it.
**1. Coronary vasospasm
2. Ventricular dysrhythmias
3. HTN
4. Tachycardia
5. CAD.**
