Local Anesthetics I (Exam IV) Andy's Cards Flashcards
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 uses for Local Anesthetics (LAs)?
A
- Treat dysrhythmias
- Analgesia: Acute and chronic pain
- Anesthesia- ANS Blockade, Sensory Anesthesia, Skeletal Muscle Paralysis
7
Q
What antiarrhythmic Drug Class is lidocaine in?
A
Class I: Sodium Channel Blockers
8
Q
MAGA: What is the intra-op infusion dose of lidocaine?
A
1 mg/kg over an hour
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)
10
Q
When should lidocaine be terminated?
A
Terminate within 12 - 72 hours
11
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 1-5 mcg/ml.
A
Analgesia
12
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
13
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 10-15 mcg/ml.
A
- Seizures
- Unconsciousness
14
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 15-25 mcg/ml.
A
- Apnea
- Coma
15
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is >25 mcg/ml.
A
- Cardiovascular Depression
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.
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
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
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
21
Q
Increased potency generally correlates to increased __________.
A
duration
22
Q
Which ester is the most potent?
A
Tetracaine
23
Q
Which local anesthetics will exhibit the highest degree of protein binding?
A
- Bupivacaine
- Levobupivacaine
- Ropivacaine
24
Q
Which two local anesthetics will have the most rapid onset?
A
Chloroprocaine
Lidocaine
25
Which 3 LA will have the highest protein binding?
Levobupivacaine (>97%)
Bupivacaine (95%)
Ropivacaine (94%)
26
Lipid solubility correlates to _______ of the drug.
Which LA has the highest lipid solubility?
- potency
- Tetracaine
27
pK values closer to a pH of ___________ will have the fastest onset of action.
7.35 - 7.45
28
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)
29
Which ester has the greatest degree of lipid solubility?
Tetracaine
30
Which amide has the greatest degree of lipid solubility?
Bupivacaine
31
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
32
The FDA released this local anesthetic that contains liposomes and can last up to 96 hours.
Exparel ER (Bupivacaine)
33
What is the mechanism of action of Local Anesthetics?
* Binds to voltage-gated Na+ channels
* 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.*
34
What two things will cause a local anesthetic to not work anymore?
Becoming water-soluble and ionized.
35
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)
36
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.
37
What other receptors can be targeted by local anesthetics besides sodium channels?
* Potassium channels
* Calcium Ion Channels
* G protein-coupled receptors
38
Minimum Effective Concentration or Cm (LAs) = _________ (Volatile Agents)
MAC
39
What component of the local anesthetic is required for the conduction block?
Non-ionized form (equates with lipid solubility)
40
Larger fibers need _____ concentrations of LAs.
higher
41
The diameter of motor nerve is how many times larger than the diameter of the sensory nerve.
2x
42
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)
43
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 bradycardia
44
What fibers are blocked if the patient can't tell if they are being poked by a sharp needle?
* Myelinated A and B fibers
45
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
46
Place in order the fibers that are affected first to last when administering a local anesthetic.
1. Preganglionic B fibers
2. A-myelinated fibers and B fibers
3. Myelinated A-δ and unmyelinated C-fibers
47
Which patient population will have increased sensitivity and be harder to block?
Pregnancy
*Harder or easier?*
48
pKa values closer to physiologic pH result in a _____ rapid onset
more
49
Because the pKA of LA's are 8, less than ______% of the drug is in lipid-soluble nonionized form.
50%
50
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
51
Because Lidocaine is a vasodilator, it will have ________ systemic absorption.
greater
52
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
53
Factors that influence the absorption of LA.
* Site of injection
* Dosage
* Epinephrine use
* Pharmacologic characteristics of the drug
54
List the uptake of Local Anesthetics Based on Regional Anesthesia Technique from highest blood concentration to lowest blood conc.
55
________is the primary determinant of potency
Lipid solubility
56
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.*)
57
Which LA will metabolize the fastest?
Chloroprocaine > Procaine d/t the smallest % of protein binding.
58
Which amides will metabolize the slowest?
- Bupivacaine
- Levobupivacaine
- Ropivacaine
59
Why is it important to know the metabolizing rate of LA?
Re-dosing of LA
60
Where are Amide local anesthetics metabolized?
Liver via CYP 450's
61
Which Amide is most rapidly metabolized?
Prilocaine (lowest protein binding)
62
Which Amides exhibit intermediate metabolism?
- Lidocaine
- Mepivacaine
63
Which Amides exhibit the slowest metabolism?
- Bupivacaine
- Ropivacaine
64
How are esters metabolized?
Hydrolyzed by cholinesterases in plasma
65
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
66
What is the metabolite of esters?
What is the significance of this metabolite?
- ParaAminoBenzoic acid (PABA)
- Common cause of Allergies
67
Is there cross-sensitivity between an amide allergy to an ester allergy?
No
68
Are amides or esters, generally slower at metabolizing?
Amides are slower at metabolism.
(CYP450s instead of plasma cholinesterases)
69
What are the most common LAs that have first-pass pulmonary extraction?
* Lidocaine
* Bupivacaine (dose dependent)
* Prilocaine
70
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.
71
In general, the more lipid soluble the local anesthetic is, the greater the potency. T/F
True
72
Which local anesthetic property is most important regarding the duration of action?
**Lipid Solubility** (most important)
73
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
74
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.*
75
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.*
76
What is ion trapping?
The pH in the fetal environment is more acidic than in maternal circulation.
77
If there is ion trapping in the placenta, what can be given to adjust the pH?
Sodium Bicarb
78
**Bupivacaine**
Protein Bound:
Arterial Concentration:
**Bupivacaine**
Protein Bound: 95%
Arterial Concentration: 0.32
79
**Lidocaine**
Protein Bound :
Arterial Concentration:
**Lidocaine**
Protein Bound: 70%
Arterial Concentration: 0.73
80
**Prilocaine**
Protein Bound:
Arterial Concentration:
**Prilocaine**
Protein Bound: 55%
Arterial Concentration: 0.85
81
What is the major metabolite of lidocaine?
Xylidide
82
What is Lidocaine's max infiltration dose?
- 300 mg solo
- 500 mg with epi
83
Lidocaine will have prolonged clearance with ______
Pregnancy Induced Hypertension
84
What is prilocaine's primary metabolite?
What is the issue with this metabolite?
Metabolite: Orthotoluidine
The metabolite converts Hemoglobin to Methemoglobin, resulting in Methemoglobinemia.
85
What is the result of Methemoglobinemia?
Fe3+ (ferric iron) is not capable of carrying O2
Cyanosis
86
What is the max dose of prilocaine?
600 mgs
87
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)
88
Mepivacaine is similar to Lidocaine except:
* Longer duration of action
* Lacks vasodilator activity
89
Can Mepivacaine be given in pregnant patients?
**No**. Prolonged elimination in fetus
90
What plasma protein does Bupivacaine bind to?
95% bound to α1-Acid glycoprotein
91
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
92
Dibucaine
Metabolism:
MOA:
Dibucaine
Metabolism: Liver
MOA: inhibits the activity of normal butyrylcholinesterase (plasma cholinesterase) by more than 70%
93
What is procaine's primary metabolite?
PABA
94
Tetracaine metabolism is slower than ______
Procaine
95
Which of the following local anesthetics will have the highest rate of metabolism?
Procaine
Chloroprocaine
Tetracaine
Chloroprocaine (fastest level of metabolism) > procaine > tetracaine (slowest)
96
What is Benzocaine used for?
Uses: Topical anesthesia of mucous membranes:
97
Overdose of Benzocaine can lead to ________.
OD of Benzocaine can lead to **Methemoglobinemia**
98
What makes Benzocaine unique?
Weak acid instead of a weak base, like most LA.
pKa = 3.5
99
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
100
When should one be cautious when administering cocaine?
Cocaine can cause coronary vasospasm, ventricular dysrhythmias, HTN, tachycardia, and CAD.
