Exam 4 - Local Anesthetics Flashcards
(89 cards)
1
Q
What was the first local anesthetic?
What class is it?
A
Cocaine
Ester
2
Q
What was cocaine first used for and what was the effect?
A
Ophthalmology
Local vasoconstriction: shrink nasal mucosa.
3
Q
What was the first synthetic ester developed in 1905?
A
Procaine
4
Q
What was the first synthetic amide developed in 1943?
A
Lidocaine
Gold Standard
5
Q
What are the uses Local Anesthetics (LAs)?
A
- Treat dysrhythmias
- Analgesia: Acute and chronic pain
- Anesthesia- ANS Blockade, Sensory Anesthesia, Skeletal Muscle Paralysis
6
Q
What antiarrhythmic Drug Class is lidocaine in?
A
Class I: Sodium Channel Blockers
7
Q
MAGA: What is the intra-op infusion dose of lidocaine?
A
1 mg/kg over an hour
8
Q
What is the IV bolus and drip dose of Lidocaine?
When should lidocaine be terminated?
A
- 1 to 2 mg/kg IV (initial bolus) over 2 - 4 min.
- 1 to 2 mg/kg/hour (drip)
- terminated 12 - 72 hours
9
Q
What are considerations of lidocaine?
A
Careful monitoring: cardiac, hepatic, renal dysfunction
10
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 1-5 mcg/ml.
A
Analgesia
11
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
12
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 10-15 mcg/ml.
A
- Seizures
- Unconsciousness
13
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 15-25 mcg/ml.
A
- Apnea
- Coma
14
Q
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is >25 mcg/ml.
A
- Cardiovascular Depression
15
Q
How can lidocaine SQ help start IVs?
A
Causes local vasodilation
16
Q
Describe the components that make up the molecular structure of lidocaine.
What about the structure makes a LA an amide or ester?
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
Ester or amide determination is based upon which portion of the molecular structure?
A
Intermediate chain
18
Q
What 2 other drugs are mixed with LA and why?
A
Epinephrine - increases duration of the drug (reduces spread from desired site)
Sodium Bisulfite - increases solubility to epinephrine
19
Q
Composition of LA will have a pH of ____ and are weak _______ ?
A
pH of 6; weak bases
A majority of LA are weak bases
20
Q
What are the ester and amide local anesthetics?
A
Amides (have 2 i’s)
21
Q
What LA have a potency of 1?
A
Procaine, lidocaine, prilocaine, and mepivacaine
22
Q
Which LA will have a potency of 16?
A
Tetracaine
23
Q
Which LAs will have a potency of 4?
A
Chloroprocaine
Bupivacaine
Levobupivacaine
Ropivacaine
24
Q
Which LAs will have 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
What is the general rule between fraction non-ionized and potency?
The higher % non-ionized, the more potent
28
What are Liposomes used for?
* Used to upload a higher amount of LA into a molecule & have a consistent release of LA in the tissues.
* Prolonged duration of action & decreased toxicity
29
FDA released what LA drug that contains liposomes and can last up to 96 hours.
Bupivacaine ER (Exparel)
30
MOA of Local Anesthetics
* Binds to voltage-gated Na+ channels (**must be inactivated and closed**)
* 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.*
31
3 factors affecting LA blockade?
* Lipid solubility or non-ionized form
* Repetitively stimulated nerve (↑ sensitivity)
* Diameter of the nerve (↑ diameter, ↑ LA dose)
32
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.
33
Besides Na+ channels, what are the other sites of action for LA?
* Potassium channels
* Calcium Ion Channels
* G protein-coupled receptors
34
Minimum Effective Concentration or Cm (LAs) = _________ (Volatile Agents)
MAC
35
What component of the local anesthetic is required for the conduction block?
Non-ionized form (equates with lipid solubility) - needs to be able to cross the cell membrane and block Na+ from the inside
36
Larger fibers need _____ concentrations of LAs.
higher
37
The diameter of the motor nerve is how many times larger than the diameter of the sensory nerve.
Twice as large in diameter
38
How many nodes of Ranvier need to be blocked to equate to 1 cm of local anesthesia blockade?
At least 2, preferably 3 Nodes of Ranvier to prevent the conduction (Minimum Effect Concentration)
39
Which nerve fibers are blocked most rapidly?
Pre-ganglionic B fibers (SNS)
40
These pain fibers require equivalent doses of LA?
* Myelinated A-δ and unmyelinated C-fibers
41
Which patient population will have increased sensitivity and require a smaller dose?
Pregnancy
42
Pharmacokinetics of LA
If pKa is close to physiological pH, how does this affect the onset of action?
Rapid onset of action
43
When administering LA, only ______% of the drug is in lipid-soluble nonionized form.
50%
44
If a LA has intrinsic vasodilator activity, what happens to its potency?
What happens to the duration of action?
LA is less potent
↓ Duration of action
| Spreads from intended site
45
Because Lidocaine has vasodilator activity, there is ____ systemic absorption. Resulting in a ____ duration of action.
greater
shorter
46
4 factors that influence the absorption of LA.
* Site of injection
* Dosage
* Epinphrine use (increased DOA)
* Pharmacologic characteristics of the drug
47
List the uptake of Local Anesthetics Based on Regional Anesthesia Technique from highest blood concentration to lowest blood conc.
## Footnote
"I Tried Coffee Plus Espresso, But Shaky Start!"
48
____ is the primary determinant of potency
Lipid solubility
49
The rate of clearance is dependent on what two factors?
* Cardiac output
* Protein binding: % bound is inversely related to % plasma. (*40% albumin-bound means 60% will float freely in plasma.*)
50
Which LA will metabolize the fastest?
Chloroprocaine d/t the 0% of protein binding.
51
Which LA will metabolize the slowest?
Levobupivacaine d/t the highest % of protein binding.
52
Why is it important to know the metabolizing rate of LA.
Re-dosing of LA
53
**Metabolism of Amides.**
Location of Metabolism:
Most rapidly metabolized drug:
Intermediate:
Slow:
Location of Metabolism: Microsomal enzyme (Liver)
Most rapidly metabolized drug: Prilocaine
Intermediate: Lidocaine, Mepivacaine
Slow: Levobupivicaine, Bupivacaine, Ropivacaine
## Footnote
Metabolism is dependent on protein binding! Less protein bound → higher plasma conentration → more metabolized
54
Metabolism of Esters?
Exception?
Hydrolyzed by cholinesterases in plasma, except cocaine which is metabolized by the liver.
55
What is the metabolite of esters?
What is the significance of this metabolite?
ParaAminoBenzoic acid (PABA)
Allergic reactions
56
Is there cross-sensitivity between an amide allergy to an ester allergy?
No
57
Which class of LA has a slower metabolism
Amides are slower at metabolism.
58
What are the most common LAs that have first-pass pulmonary extraction?
* Lidocaine
* Bupivacaine (dose dependent)
* Prilocaine
59
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.
60
In general, the more lipid soluble the local anesthetic is, the greater the potency. T/F
True
61
Which local anesthetic property is most important regarding the duration of action?
**Protein Binding** (most important)
## Footnote
More protein bound → prolonged release from proteins → plasma conc stay elevated longer
62
How does pregnancy affect admistration of local anesthetics?
- Lower levels of plasma cholinesterases = require decreased doses of ester LA
- Amides have significant transfer to the placenta and lead to ion trapping
63
What determines the rate and degree of diffusion of local anesthetics across the placenta?
* Plasma protein binding
* Determines amount of free or unbound drug available in the blood
64
What classification of LAs is more likely to cause ion trapping?
Amides
Esters are hydrolyzed rapidly so they do not readily cross the placenta
*Ion trapping will lead to LA toxicity in the placenta.*
65
Describe ion trapping during pregnancy?
The pH in the fetal environment is more acidic than in maternal circulation (fetal pH 7.3-7.35). LA becomes ionized and trapped in the fetal circulation.
66
If there is ion trapping in the placenta, what can be given to adjust the pH?
Sodium Bicarb
67
**Bupivacaine**
Protein Bound:
Arterial Concentration:
**Bupivacaine**
Protein Bound: 95%
Arterial Concentration: 0.32
68
**Lidocaine**
Protein Bound :
Arterial Concentration:
**Lidocaine**
Protein Bound: 70%
Arterial Concentration: 0.73
69
**Prilocaine**
% Protein Bound
Arterial Concentration
**Prilocaine**
Protein Bound: 55%
Arterial Concentration: 0.85
70
Lidocaine
Metabolite:
What will affect metabolism and elimination:
Lidocaine
Metabolite: Xylidide
What will affect metabolism and elimination: Hepatic disease
71
What is Lidocaine max infiltration dose (plain and w/ epi)?
Maximum infiltration dose:
**300 mg plain**
**500 mg with EPI** (*Rate of distribution is slower with epinephrine, so we can give more lidocaine.*)
72
How will Pregnancy Induced Hypertension affect lidocaine clearance?
Prolong clearance
Systemic vacoconstricion reduces hepatic blood flow
73
Prilocaine metabolite.
What is the issue with this metabolite?
Metabolite: Ortho-toluidine
The metabolite oxidizes Hemoglobin to Methemoglobin, resulting in Methemoglobinemia (doses > 600 mg can cause symptoms)
74
What is the result of Methemoglobinemia?
Cyanosis due to decreased O2 carrying capacity
75
Treatment of Prilocaine induced methemoglobinemia?
Methylene Blue
1 to 2 mg/kg IV over 5 mins (initial dose) - dont exceed 7-8mg/kg
76
Mepivacaine is similar to Lidocaine except:
* Longer duration of action
* Lacks vasodilator activity
* Prolonged elimination in fetus & newborn
* **No Mepivacaine in OB patients**
77
What is bupivacaine bound to?
95% bound to α1-Acid glycoprotein
78
**Ropivacaine**
Metabolized by ____
Metabolites can accumulate with ____ patients
____ system toxicity than Bupivacaine
94% protein bound to ____
Ropivacaine
Metabolism: **P450 enzymes**
Metabolites: Can accumulate with **uremic** patients
**Lesser** system toxicity than Bupivacaine
94% protein bound to **α1-acid glycoprotein**
79
Dibucaine
Metabolism:
Enzyme Inhibition:
Dibucaine
Metabolism: Liver
Enzyme Inhibition: inhibits the activity of normal butyrylcholinesterase (plasma cholinesterase) by more than 70%
*This LA is used to test for atypical plasma cholinesterase.*
80
Procaine Metabolite:
Procaine Metabolite: **PABA** (ester anesthetics), excreted unchanged in the urine
81
Chloroprocaine metabolizes ____ times faster than Procaine.
Pregnancy decreases plasma cholinesterase by ____%
* 3.5x faster than procaine
* 40%
82
Which ester LA has the slowest metabolism?
Tetracaine d/t 76% protein bound
83
Which LA will have the highest rate of metabolism by hydrolysis?
Procaine
Chloroprocaine
Tetracaine
* Chloroprocaine (fastest metabolism, 0% protein bound)
* Procaine (6% protein bound)
* Tetracaine (slowest, 76% protein bound)
84
Benzocaine use:
Uses: Topical anesthesia of mucous membranes:
Tracheal intubation, Endoscopy, Transesophageal echocardiography (TEE), Bronchoscopy
*Benzocaine comes in a spray.*
85
Benzocaine
Onset:
Duration:
Dose: Brief spray (20%) =
Overdose of Benzocaine can lead to ________.
Benzocaine
Onset: Rapid
Duration: 30 to 60 minutes
Dose: Brief spray (20% concentration) = 200 to 300 mgs
OD of Benzocaine can lead to **Methemoglobinemia**
86
What makes Benzocaine unique?
Weak acid instead of a weak base, like most LA.
pKa = 3.5
87
How is cocaine metabolized?
Who should receive decreased amounts of cocaine?
Metabolized by plasma and liver cholinesterase
Decrease cocaine use in parturients, neonates, the elderly, and severe hepatic disease
88
Cocaine
Peak:
Duration:
Elimination:
Cocaine
Peak: 30 to 45 mins
Duration: 60 minutes after peak
Elimination: Urine (24 to 36 hours)
89
Adverse side effects of cocaine.
Cocaine is a stimulant; use it with caution.
Cocaine can cause coronary vasospasm, ventricular dysrhythmias, HTN, tachycardia, and CAD.
