Local Anesthetics I (Exam IV) 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
Even though cocaine is an ester, where is it metabolized?
A
In the liver
5
Q
What was the first synthetic ester developed in 1905?
A
Procaine
6
Q
What was the first synthetic amide developed in 1943?
A
Lidocaine
Gold Standard
7
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
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?
A
- 1 to 2 mg/kg IV (initial bolus) over 2 - 4 min.
- 1 to 2 mg/kg/hour (drip)
11
Q
When should a lidocaine drip be terminated?
A
Terminate within 12 - 72 hours
12
Q
Is lidocaine an amide or ester local anesthetic?
A
Amide
13
Q
What 3 types of careful monitoring is required for lidocaine administration?
A
- Cardiac
- Hepatic
- renal
14
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 1-5 mcg/ml.
A
Analgesia
15
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
16
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 10-15 mcg/ml.
A
- Seizures
- Unconsciousness
17
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 15-25 mcg/ml.
A
- Apnea
- Coma
18
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is >25 mcg/ml.
A
- Cardiovascular Depression
19
Q
Describe the components that make up the molecular structure of local anesthetics.
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.
20
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.
21
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
* an ester has 1 i EX: procaIne
22
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
* An amide has 2 i’s EX: LIdocaIne
23
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
24
Q
Are local anesthetics soluble or insoluble in water?
A
Very insoluble in water
25
The addition of epinephrine does what to local anesthetics?
prolongs duration of action of local aneshetics
26
What does sodium bisulfite do to the local anesthetics?
It makes the local anesthetic more soluble to epinephrine, when mixing them
27
Lidocaine without epi when using as an LA for putting in an IV causes what?
Local vasodilation to the area
28
name the 3 ester LAs
* Procaine
* Chloroprocaine
* tetracaine
29
Name the 6 amide LAs
* Lidocaine
* Prilocaine
* Mepivicaine
* Bupivicaine
* Levobupivicaine
* Ropivicaine
30
The more non-ionized the drug, the more ___, and the ___ it goes through the cell membrane
* Lipid soluble
* faster
31
If the drug is a weak base (Local anesthetic), the PK goes ___ the pH when substractiong to find ionization.
* before
32
What is the major indicator of potency of local anesthetics?
Lipid solubility
33
Which ester is the most potent?
Tetracaine
34
Which amide local anesthetic is the most potent?
- Bupivacaine
35
Which two local anesthetics will have the most rapid onset?
Chloroprocaine
Lidocaine
36
Which 3 LA will have the highest protein binding?
Levobupivacaine (>97%)
Bupivacaine (95%)
Ropivacaine (94%)
37
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)
38
Which ester has the greatest degree of lipid solubility?
Tetracaine (has a lipid solubility of 80, and is the most potent ester)
39
Which amide has the greatest degree of lipid solubility?
Bupivacaine (has a lipid solubility of 28 and is the most potent amide)
40
* How do liposomes and local anesthetics interact?
* What is the result?
* What 3 LA's is it currently being used on?
* Liposomes unload a higher amount of LA's into a molecule and have a constant controlled release of LA into tissues.
* Prolonged duration of action & decreased toxicity
* Lidocaine, tetracaine, and bupivicane
41
The FDA released this local anesthetic that contains liposomes and can last up to 96 hours.
Exparel (Bupivacaine extended release)
42
What is the mechanism of action of Local Anesthetics?
* Binds to and inactivates voltage-gated Na+ channels
* Block/inhibit Na+ passage in nerve membranes because it closes the voltage gated sodium channel from the inside of the cell membrane.
* Causes a very slowed rate of repolarization, threshold is not reached, and no action potential happens
*LA must be non-ionized and lipid-soluble to go through the cell membrane and block the Na+ gated channel from within the cell.*
43
What two things will cause a local anesthetic to not work anymore?
Becoming water-soluble and ionized.
44
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)
45
What are 3 other site of action targets for LA's beside sodium channels?
* Potassium channels
* Calcium ion channels
* GPCRs
46
What component of the local anesthetic is required for a conduction block?
* Non ionized form
* Ionized form
* Both
* None of the above
Non ionized form
47
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.
48
Minimum Effective Concentration or Cm (LAs) = _________ (Volatile Agents)
MAC
49
Larger fibers need _____ concentrations of LAs.
higher
50
The diameter of motor nerve is how many times larger than the diameter of the sensory nerve.
2x
51
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)
52
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
53
What fibers are blocked if the patient can't tell if they are being poked by a sharp needle?
* Myelinated A and B fibers
54
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
55
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
56
Which patient population will have increased sensitivity and be harder to block?
Pregnancy because they have lesser amounts of plasma cholinesterase so we tend to give less to our pregnant patients.
*Harder or easier?*
57
pKa values closer to physiologic pH result in a _____ rapid onset
more
58
Because the pKA of LA's are 8, less than ____% of the drug is in lipid-soluble nonionized form.
50%
59
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
60
Because Lidocaine is a vasodilator, it will have ________ systemic absorption.
greater
61
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
62
What 4 factors influence the absorption of LA.
* Site of injection
* Dosage
* Epinephrine use
* Pharmacologic characteristics of the drug
63
List the uptake of Local Anesthetics Based on Regional Anesthesia Technique from highest blood concentration to lowest blood conc.
| Highest to lowest blood concentration =
* IV
* Tracheal
* Caudal
* Para
64
The rate of clearance is dependent on what two factors?
* Cardiac output
* Protein binding: Lidocaine is cleared the fastest because it is the least protein bound. Ropivicaine is the slowest to nbe cleared because it is the highest protein bound.
Note: % bound is inversely related to % plasma.
(*40% albumin-bound means 60% will float freely in plasma.*)
65
How are ester LA's metabolized?
Hydrolysis ny plasma cholinesterases
66
What is a metabolite of ester LAs?
PABA (para-aminobenzoic acid)
This is the culprit for allergic reactions for ester anesthetics.
67
Which ester LA will metabolize the fastest?
Chloroprocaine > Procaine d/t the smallest % of protein binding.
68
Which amides will metabolize the slowest?
- Bupivacaine
- Levobupivacaine
- Ropivacaine
69
Why is it important to know the metabolizing rate of LA?
Re-dosing of LA
70
Where are Amide local anesthetics metabolized?
Liver via CYP 450's
Because amides are metabolized through the liver, they are slower to metabolize than esters
71
Which Amide is most rapidly metabolized?
Prilocaine (lowest protein binding)
72
Which Amides exhibit intermediate metabolism?
- Lidocaine
- Mepivacaine
73
Which Amides exhibit the slowest metabolism?
- Bupivacaine
- Ropivacaine
74
Is there cross-sensitivity between an amide allergy to an ester allergy?
No
75
What are the most common LAs that have first-pass pulmonary extraction?
* Lidocaine
* Bupivacaine (dose dependent)
* Prilocaine
* This can cause th drug to be inactive once it is released from the lungs into the intravascular system
76
What is the main form of clearance for local anesthetics?
renal
77
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%**
The exception is **cocaine**,
**PABA**
78
In general, the more lipid soluble the local anesthetic is, the greater the potency. T/F
True
79
Which local anesthetic property is most important regarding the duration of action?
* Protein binding
* Lipid solubility
* Metabolism
* Clearance from site of action.
* Protein binding
80
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.*
81
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.*
82
* What is ion trapping?
* What can it cause in the fetus?
* The pH in the fetal environment is more acidic than in maternal circulation.
* Can cause fetal seizures, bradycardia, dysrythmias, and asystole
83
If there is ion trapping in the placenta, what can be given to adjust the pH?
Sodium Bicarb
84
**Bupivacaine**
Protein Bound:
Arterial Concentration:
**Bupivacaine**
Protein Bound: 95% (lesser availalbe to be metabolized, longer duration of action)
Arterial Concentration: 0.32
85
**Lidocaine**
Protein Bound :
Arterial Concentration:
**Lidocaine**
Protein Bound: 70%
Arterial Concentration: 0.73
86
**Prilocaine**
Protein Bound:
Arterial Concentration:
**Prilocaine**
Protein Bound: 55% (more to be metabolized, stays in the system a lesser time, shorter duration of action)
Arterial Concentration: 0.85
87
How is lidocaine metabolized?
Oxidative dealkylination in the liver, then hydrolysis
88
What will affect the metabolism and elimination of lidocaine?
Hepatic disease
89
What is the major metabolite of lidocaine?
Xylidide
90
What is the other use for lidocaine besideas being an amide LA?
anti-dysrhrhmic in ACLS due to being a sodium channel blocker
91
What is Lidocaine's max infiltration dose?
- 300 mg plain
- 500 mg with epi
92
Lidocaine will have prolonged clearance with ______
Pregnancy Induced Hypertension
93
What is prilocaine's primary metabolite?
What is the issue with this metabolite?
Metabolite: Orthotoluidine
The metabolite converts Hemoglobin to Methemoglobin, resulting in Methemoglobinemia.
94
What is the result of Methemoglobinemia?
Fe3+ (ferric iron) is not capable of carrying O2
Cyanosis
95
What is max the dose of prilocaine?
600 mg
96
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 7-8 mg/kg (over 24 hours)
97
Mepivacaine is similar to Lidocaine except:
* Longer duration of action
* Lacks vasodilator activity
98
Can Mepivacaine be given in pregnant patients?
**No**. Prolonged elimination in fetus
99
What plasma protein does Bupivacaine bind to?
95% bound to α1-Acid glycoprotein
100
How is bupivicaine metabolized?
Aromatic hydroxylation, N-dealkylation, amide hydrolysis, and conjugation which is the normal process in the liver
101
* 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
102
* Dibucaine
Metabolism:
* MOA:
* Dibucaine
Metabolism: Liver
* MOA: inhibits the activity of normal butyrylcholinesterase (plasma cholinesterase) by more than 70%
103
*How is procaine metabolized?
* What is procaine's primary metabolite?
* Plasma cholinsterases
* PABA, that is excreted unchanged in the urine
104
* How is chloroprocaine metabolized?
* Pregnancy decreases plasma cholinesterases by what percent?
* Plasma cholinesterase (3.5x faster than procaine)
* 40%
105
Which of the following local anesthetics will have the highest rate of metabolism?
Procaine
Chloroprocaine
Tetracaine
Chloroprocaine (fastest level of metabolism) > procaine > tetracaine (slowest)
106
What is the pKa of Benzocaine and is it a weak acid or base?
* pKa = 3.5
* weak acid
107
What is Benzocaine used for?
Uses: Topical anesthesia of mucous membranes:
* Tracheal intubation,
* Endoscopy, Transesophageal
* echocardiography (TEE),
* Bronchoscopy
* Essentially used to numb the airway for certain procedures
108
* What is the onset of benzocaine?
* Duration
* Dose
* Rapid
* 30-60 minutes
* breif spray (20%) = 200-300mg
109
Overdose of Benzocaine can lead to ________.
OD of Benzocaine can lead to **Methemoglobinemia**
110
A diagnosis of methemoglobinemia was made on a 65 year old male patient weighing 120lbs. What is the maximum dose of methylene blue he can recieve in mg?
436.4mg
111
When is cocaine typically used as a LA?
* ENT procedures
* Awake nasal intubation patients
112
Who should receive decreased amounts of cocaine?
parturients, neonates, the elderly, and severe hepatic disease
113
* What is the peak of cocaine?
* Duration?
* Elimination?
* 30-45 minutes
* 60 minutes after peak (1hour and 30 minutes - 1 hour and 45 minutes)
* Urine from 24-36 hours
114
When should one be cautious when administering cocaine?
Cocaine can cause coronary vasospasm, ventricular dysrhythmias, HTN, tachycardia, and CAD.
