Local Anesthetics I (Exam IV) Flashcards
(102 cards)
1
Q
What was the first local anesthetic?
A
Cocaine
S3
2
Q
Is cocaine an ester or amide?
A
Cocaine is an ester.
S3
3
Q
What was cocaine first used for and what was the effect?
A
Ophthalmology (1884)
Local vasoconstriction: shrink nasal mucosa.
S3
4
Q
What was the first synthetic ester developed in 1905?
A
Procaine
S3
5
Q
What was the first synthetic amide developed in 1943?
A
Lidocaine
Gold Standard
S3
6
Q
What are the uses for Local Anesthetics (LAs)?
A
- Treat dysrhythmias
- Analgesia: Acute and chronic pain
- Anesthesia- ANS Blockade, Sensory Anesthesia, Skeletal Muscle Paralysis
S4
7
Q
What antiarrhythmic Drug Class is lidocaine in?
A
Class I: Sodium Channel Blockers
S4
8
Q
MAGA: What is the intra-op infusion dose of lidocaine?
A
1 mg/kg over an hour
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9
Q
What is the IV dose of Lidocaine?
A
- 1 to 2 mg/kg IV (initial bolus) over 2 - 4 min.
- 1 to 2 mg/kg/hour (drip)
S7
10
Q
When should lidocaine be terminated?
A
Terminate within 12 - 72 hours
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11
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 1-5 mcg/ml.
A
Analgesia
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12
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 5-10 mcg/ml.
A
- Circum-oral numbness
- Tinnitus
- Myocardial depression
- Systemic hypotension
- Skeletal muscle twitching
S8
13
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 10-15 mcg/ml.
A
- Seizures
- Unconsciousness
S8
14
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 15-25 mcg/ml.
A
- Apnea
- Coma
S8
15
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is >25 mcg/ml.
A
- Cardiovascular Depression
S8
16
Q
Describe the components that make up the molecular structure of lidocaine.
A
Lipophilic Portion (Aromatic Section)
Hydrocarbon Chain
Hydrophilic (Amino Group)
Bond between the lipophilic portion and the hydrocarbon chain will determine if LA is an ester or an amide.
S9 VERIFY!!!!
17
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.
18
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
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19
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
S10
20
Q
Local anesthetics will typically have a pH of _____ and are weak _______. ?
A
pH of 6; weak bases
A majority of LA are weak bases
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21
Q
Increased potency generally correlates to increased __________.
A
duration
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22
Q
What is the potency, onset, DOA, Max single dose of each LA?
A
23
Q
Which ester is the most potent?
A
Tetracaine
S12
24
Q
Which local anesthetics will exhibit the highest degree of protein binding?
A
- Bupivacaine
- Levobupivacaine
- Ropivacaine
S12
25
Which two local anesthetics will have the most rapid onset?
Chloroprocaine
Lidocaine
## Footnote
S12
26
Which 3 LA will have the highest protein binding?
Levobupivacaine (>97%)
Bupivacaine (95%)
Ropivacaine (94%)
## Footnote
S12
27
Lipid solubility correlates to _______ of the drug.
Which LA has the highest lipid solubility?
- potency
- Tetracaine
## Footnote
S12
28
Lipid solubility
29
pK values closer to a pH of ___________ will have the fastest onset of action.
7.35 - 7.45
## Footnote
S13
30
Which three local anesthetics have pK values closest to 7.35-7.45 ?
- Lidocaine (pK = 7.9)
- Prilocaine (pK = 7.9)
- Mepivacaine (pK = 7.6)
## Footnote
S13
31
Which ester has the greatest degree of lipid solubility?
Tetracaine
## Footnote
S12/13
32
Which amide has the greatest degree of lipid solubility?
Bupivacaine
## Footnote
S12/13
33
How do liposomes and local anesthetics interact?
What is the result?
* Liposomes unload LA's into tissue at a controlled rate.
* Prolonged duration of action & decreased toxicity
## Footnote
S15
34
The FDA released this local anesthetic that contains liposomes and can last up to 96 hours.
Exparel ER (Bupivacaine)
## Footnote
S15
35
What is the mechanism of action of Local Anesthetics?
* Binds to inactivated, closed voltage-gated Na+ channels@ inner gate
* Block/inhibit Na+ passage in nerve membranes
*LA must be non-ionized and lipid-soluble to go through the cell membrane and block the Na+ gated channel from within the cell.*
## Footnote
S16
36
What two things will cause a local anesthetic to not work anymore?
Becoming water-soluble and ionized.
## Footnote
??
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)
## Footnote
S18
38
What happens when you expose LA (a weak base) to an acidic environment?
LA becomes ionized.
When LA becomes ionized, it will not cross cell membrane to block Na+ gated channels.
## Footnote
??
39
What other receptors can be targeted by local anesthetics besides sodium channels?
* Potassium channels
* Calcium Ion Channels
* G protein-coupled receptors
## Footnote
S18 - don't need to truly memorize
40
Minimum Effective Concentration or Cm (LAs) = _________ (Volatile Agents)
MAC
## Footnote
S20
41
What component of the local anesthetic is required for the conduction block?
Non-ionized form (equates with lipid solubility)
## Footnote
??
42
Larger fibers need _____ concentrations of LAs.
higher
## Footnote
S20
43
The diameter of motor nerve is how many times larger than the diameter of the sensory nerve.
2x
## Footnote
S20
44
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)
## Footnote
S20
45
If a LA were given intravascularly, which fibers would be *affected the fastest*?
What signs and symptoms would you see?
**Pre-ganglionic B fibers (SNS)**
Hypotension and tachycardia
## Footnote
S21
46
What fibers are blocked if the patient can't tell if they are being poked by a sharp needle?
* Myelinated A and B fibers
## Footnote
S21
47
What nerve types are typically affected last when administering LA through the epidural/spinal?
What sensations are the last to be affected?
* Myelinated A-δ and unmyelinated C-fibers
* Proprioception and Motor
## Footnote
S21
48
Place in order the fibers that are affected first to last when administering a local anesthetic.
1. Preganglionic B fibers
2. Myelinated A and B fibers
3. Myelinated A-δ and unmyelinated C-fibers
## Footnote
S21
49
Which patient population will have increased sensitivity and be harder to block?
Pregnancy
*Harder or easier?*
## Footnote
S21
50
pKa values closer to physiologic pH result in a _____ rapid onset
more
## Footnote
S22
51
Because the pKA of LA's are 8, less than ______% of the drug is in lipid-soluble nonionized form.
50%
## Footnote
S22
52
If a LA has vasodilator activity, what happens to its potency?
What happens to the duration of action?
LA is less potent
↓ Duration of action
## Footnote
S22
53
Because Lidocaine is a vasodilator, it will have ________ systemic absorption.
greater
## Footnote
S22
54
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
## Footnote
S22
55
Factors that influence the absorption of LA.
* Site of injection
* Dosage
* Epinephrine use
* Pharmacologic characteristics of the drug
## Footnote
S23
56
List the uptake of Local Anesthetics Based on Regional Anesthesia Technique from highest blood concentration to lowest blood conc.
## Footnote
S23
57
________is the **primary** determinant of potency
Lipid solubility
## Footnote
S24
58
The rate of clearance 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.*)
## Footnote
S25
59
Which ester LA will metabolize the fastest?
Chloroprocaine > Procaine d/t the smallest % of protein binding.
## Footnote
S26
60
Which amides will metabolize the slowest?
- Bupivacaine
- Levobupivacaine
- Ropivacaine
## Footnote
S26
61
Why is it important to know the metabolizing rate of LA?
Re-dosing of LA
## Footnote
S27??
62
Where are Amide local anesthetics metabolized?
**Liver** via CYP 450's
## Footnote
S27
63
Which Amide is most rapidly metabolized?
Prilocaine (lowest protein binding)
64
Which Amides exhibit intermediate metabolism?
- Lidocaine
- Mepivacaine
## Footnote
S27
65
Which Amides exhibit the slowest metabolism?
- Bupivacaine
- Ropivacaine
## Footnote
S27
66
How are esters metabolized?
Hydrolyzed by cholinesterases in plasma
## Footnote
S28
67
Cocaine, being an ester, is primarily metabolized via plasma cholinesterases. T/F?
False. Primarily hydrolyzed by liver cholinesterases > plasma cholinesterases. All other esters hydrolyzed by plasma > liver
## Footnote
S28
68
What is the metabolite of esters?
What is the significance of this metabolite?
- ParaAminoBenzoic acid (PABA)
- Common cause of Allergies
## Footnote
S28
69
Is there cross-sensitivity between an amide allergy to an ester allergy?
No
## Footnote
S28
70
Are amides or esters, generally slower at metabolizing?
Amides are slower at metabolism.
(CYP450s instead of plasma cholinesterases)
## Footnote
S28
71
What are the most common LAs that have first-pass pulmonary extraction?
* Lidocaine
* Bupivacaine (dose dependent)
* Prilocaine
## Footnote
S29
72
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.
The poor water solubility of local anesthetics usually limits renal excretion of unchanged drug to less than **5%**
The exception is **cocaine**, of which 10% to 12% of unchanged drug can be recovered in urine.
Water-soluble metabolites of local anesthetics, such as **PABA** resulting from metabolism of ester local anesthetics, are readily excreted in urine.
## Footnote
S29
73
In general, the more lipid soluble the local anesthetic is, the greater the potency. T/F
True
## Footnote
Question slide
74
Which local anesthetic property is most important regarding the duration of action?
**Lipid Solubility** (most important)
| protein binding is more cellular
## Footnote
Question slide
75
Place the three factors below in order of importance for affecting duration of action?
- Protein Binding
- Clearance
- Lipophilicity
1. **Lipid Solubility** (most important)
2. Clearance
3. Protein binding
## Footnote
???
76
How will pregnancy affect
plasma cholinesterase levels?
Lower levels of plasma cholinesterases
*Caution with LA that are esters, bigger impact with normal doses*
*Ester LAs are still given to pregnant women because the effects of the amide LAs are detrimental to the fetus.*
## Footnote
S30
77
What classification of LAs is more likely to cause ion trapping thus affecting fetal health?
Amides
*Ion trapping will lead to LA toxicity in the placenta.*
## Footnote
S30
78
What is ion trapping?
The pH in the fetal environment is more acidic than in maternal circulation.
## Footnote
S30
79
If there is ion trapping in the placenta, what can be given to adjust the pH?
Sodium Bicarb
## Footnote
S30
80
**Bupivacaine**
Protein Bound:
Arterial Concentration:
**Bupivacaine**
Protein Bound: 95%
Arterial Concentration: 0.32
## Footnote
S31
81
**Lidocaine**
Protein Bound :
Arterial Concentration:
**Lidocaine**
Protein Bound: 70%
Arterial Concentration: 0.73
## Footnote
S31
82
**Prilocaine**
Protein Bound:
Arterial Concentration:
**Prilocaine**
Protein Bound: 55%
Arterial Concentration: 0.85
## Footnote
S31
83
What is the major metabolite of lidocaine?
Xylidide
## Footnote
S32
84
What is Lidocaine's max infiltration dose?
- 300 mg solo
- 500 mg with epi
## Footnote
S32
85
Lidocaine will have prolonged clearance with ______
Pregnancy Induced Hypertension
## Footnote
S32
86
What is prilocaine's primary metabolite?
What is the issue with this metabolite?
Metabolite: Orthotoluidine
The metabolite converts Hemoglobin to Methemoglobin, resulting in Methemoglobinemia.
## Footnote
S33
87
What is the result of Methemoglobinemia?
Fe3+ (ferric iron) is not capable of carrying O2
Cyanosis
## Footnote
S33
88
What is the max dose of prilocaine to cause Methemoglobinemia?
600 mgs
## Footnote
S33
89
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)
## Footnote
S33
90
Mepivacaine is similar to Lidocaine except:
* Longer duration of action
* Lacks vasodilator activity
## Footnote
S34
91
Can Mepivacaine be given in pregnant patients?
**No**. Prolonged elimination in fetus
## Footnote
S34
92
What plasma protein does Bupivacaine bind to?
95% bound to α1-Acid glycoprotein
## Footnote
S34
93
Ropivacaine
Metabolism:
Metabolite:
Protein Binding
Ropivacaine
Metabolism: Hepatic cytochrome P450 enzymes
Metabolites: Can accumulate with uremic patients
Lesser system toxicity than Bupivacaine
Protein Binding: α1-acid glycoprotein
## Footnote
S35
94
Dibucaine
Metabolism:
MOA:
Dibucaine
Metabolism: Liver
MOA: inhibits the activity of normal butyrylcholinesterase (plasma cholinesterase) by more than 70%
## Footnote
S35
95
What is procaine's primary metabolite?
PABA
## Footnote
S36
96
Tetracaine metabolism is slower than ______
Procaine
## Footnote
S36
97
Which of the following local anesthetics will have the highest rate of metabolism through hydrolysis?
Procaine
Chloroprocaine
Tetracaine
Chloroprocaine (fastest level of metabolism) > procaine > tetracaine (slowest)
## Footnote
S36
98
What is Benzocaine used for?
**Topical anesthesia of mucous membranes**
Tracheal intubation
Endoscopy,
Transesophageal echocardiography (TEE)
Bronchoscopy
## Footnote
S37
99
Overdose of Benzocaine can lead to ________.
OD of Benzocaine can lead to **Methemoglobinemia**
## Footnote
S37
100
What makes Benzocaine unique?
Weak acid instead of a weak base, like most LA.
pKa = 3.5
## Footnote
S37
101
How is cocaine metabolized?
Who should receive decreased amounts of cocaine?
Metabolized by liver cholinesterase > plasma cholinesterase
Decrease cocaine use in parturients, neonates, the elderly, and severe hepatic disease
## Footnote
S38
102
When should one be cautious when administering cocaine?
Cocaine can cause coronary vasospasm, ventricular dysrhythmias, HTN, tachycardia, and CAD.
## Footnote
S38
