Jose: Chapt. 26 Local Anesthetics Flashcards
1
Q
What are the chemical characteristics that make up most local anesthetic drugs?
A
Esters or amides of simple benzene derivatives.
2
Q
Subgroups within local anesthetics are based on what characteristics?
A
Chemical Characteristics: Esters or amides of simple benzene derivatives…and their Duration on Action.
3
Q
Commonly used local anesthetics are _____ _____ with at least ____ ionizable ______ function.
A
Weak bases; 1; amine.
4
Q
Amine functional groups of most local anesthetics can become charged through _________.
A
Gain of a proton (H+)
5
Q
The degree of ionization is a function of ______?
A
The pKa of the drug and pH of the medium.
6
Q
The degree of ionization of a drug is dependent on?
A
the pH of the tissue
7
Q
The pH of infected tissue tends to be more?
A
Acidic
8
Q
The pKa of most local anesthetics is between?
A
8.0 - 9.0
9
Q
Which LA is an exception to the pKa of most LA’s?
A
Benzocaine
10
Q
______ - acting LA’s are readily absorbed into the blood from the injection site after administration.
A
Shorter
11
Q
The duration of action of most LA’s is limited, unless __________.
A
Blood flow to the area is reduced.
12
Q
What is usually administered with LA’s to improve their duration of action?
A
vasoconstrictors, usually an alpha-agonist simpathomimetic.
13
Q
Why is cocaine an exception to the addition of vasoconstrictors with LA’s?
A
Because it already has intrinsic sympathomimetic action due to its inhibition of NE reuptake into nerve terminals.
14
Q
Longer-acting LA’s are less dependent on coadministration of vasoconstrictors? (T/F)
A
True
15
Q
What are some long-acting agents that don’t require coadministration of vasoconstrictors?
A
Bupivacaine, ropivacaine, tetracain
16
Q
What is “surface activity?”
A
Ability to reach superficial nerves when LA is applied to surface of mucousa membranes.
17
Q
Surface activity is a special property of which LA’s?
A
cocaine and benzocaine: only available topical
Lidocaine and tetracaine
18
Q
Where is metabolism of ester LA carried out?
A
By plasma cholinesterases (pseudocholinesterases)
19
Q
List the speed of metabolism for the ester LA’s.
A
Procaine: Very Rapid (T1/2: 1-2min)
Cocaine: Slower than Procaine
Tetracaine: Very Slow
20
Q
Where are the amide LA’s metabolized?
A
Liver, in part by CYP 450 isozymes
21
Q
What is the half-life of lidocaine?
A
Approx 1.5 hr
22
Q
What is the half-life of prilocaine?
A
Approx 1.5 hr.
23
Q
Which are the two longest-acting amide LA’s?
A
Bupivacaine and Ropivacaine
24
Q
What is the half-life of Bupivacaine?
A
3.5 hr
25
What is the half-life of Ropivacaine?
4.2 hr
26
How does liver dysfunction effect elimination half-life?
May increase elimination half-life of amide LA's; and increase risk of toxicity.
27
What does acidificaiton of the urine do to LA's?
promotes ionization
28
The _____ form of LA's are more rapidly excreated than the ______ forms.
charged; non-ionized
29
What is the MOA of LA's?
block voltage-dependent sodium channels and reduce the influx of sodium ions; preventing depolarization fo the membrane and blocking conduction of the AP.
30
How do LA's prevent AP?
By blocking voltage gated sodium channels, preventing depolarization and blocking conduction of AP.
31
How do LA's gain access to their receptors?
From cytoplasm or the membrane
32
How do drug molecules reach the cytoplasm?
By crossing the lipid membrane
33
Which type of LA's reach effective intracellular concentrations more rapidly, and why?
Lipidsoluble (non-ionized, uncharged); because drug molecules must cross the lipid membrane to reach the cytoplasm.
34
Which form of the drug is more effective at blocking, once inside the axon?
Ionized (charged)
35
Why are both the ionized and unionized forms of LA's important?
Ionized (charged): Better at causing an effect; more effective at blocking while inside the axon.
Nonionized (uncharged): Better at reaching the receptor site; more lipid soluble forms reach effective intracellular concentrations more rapidly because they must cross the lipid membrane to reach the cytoplasm.
36
37
The affinity of the receptor site within the sodium channel is a function of what?
the state of the channel, whether it is resting, open or inactive.
38
\_\_\_\_\_ fibers are usually blocked before \_\_\_\_\_\_fibers.
Rapidly firing; Slowly firing
39
How do the ions K+ and Ca2+ effect LA activity?
High extracellular [K+] may enhance LA activity.
High [Ca2+] may antagonize LA activity.
40
Differential sensitivity of various types of nerve fibers to LA's is dependent on?
Fiber diameter, myelination, physiologic firing rate, and atomic location.
41
Which fibers are blocked more easily?
smaller, myelinated fibers.
42
What is the firing rate for activated pain fibers?
rapidly
43
Why is pain sensation selectively blocked by LA's?
because activated pain fibers fire rapidly
44
Which fibers are blocked sooner and why; peripheral or core nerve fibers?
Periphery, thick nerve bundle are blocked sooner than those in the core because they are exposed earlier to higher concentrations of the anesthetic.
45
Most local anesthetics have ______ \_\_\_\_\_\_ effects on skeletal muscle neuromuscular transmission.
Weak Blocking Effects
46
Cocaine has significant LA action on membranes?
False.
The mood elevation induced by cocaine reflects actions on dopamine or other amine-mediated synaptic transmission in the CNS rather than a local anesthetic action on membranes.
47
LA's are commonly used for minor surgery in combination with vasoconstrictors? T/F
True. Often used with Epinephrine.
48
The onset of LA action may be accelerated by the addition of what?
Sodium Bicarbonate, wich enhances intracellular acces of these weakly basic compounds.
49
How does Sodium Bicarb effect onset of action?
Accelerates onset by enhancing intracellular access of LA's, which are weakly basic.
50
Which LA has the fastest onset of action?
Articaine
51
How are LA's used in spinal anesthesia?
to produce autonomic blockade in ischemic conditions.
52
53
How are slow epidural LA infusions administered?
At low concentrations for postoperative analgesia, in the same way as epidural opioid infusions.
54
Repeated epidural injection in anesthetic doses may lead to \_\_\_\_\_\_\_?
Tachyphylaxis
55
(T/F) Intravenous LA's may NEVER be used in the perioperative period?
False.
IV LA's may be used in perioperative period for reducing pain.
56
What addiitonal forms of LA's are sometimes used adjuctively in neuropathic pain states?
Oral or parenteral
57
What does the picture display?
Schematic diagram of the sodium channel in an excitable membrane (eg, an axon) and the pathways by which a local anesthetic molecule (Drug) may reach its receptor. Sodium ions are not able to pass through the channel when the drug is bound to the receptor.
The local anesthetic diffuses within the membrane in its uncharged form. In the aqueous extracellular and intracellular spaces, the charged form (Drug+) is also present.
58
Susceptibility to Block: Fiber Type A; Alpha?
Function?
Diameter (µm)?
Myelination?
Conduciton Velocity (m/s)?
Sensitivity to Block?
Fiber Type:
Type A; Alpha
Function: Proprioception, motor
Diameter: 12–20µm
Myelination: Heavy
Conduction Velocity (m/s): 70–120
Sensitivity to Block: +
Delta Pain, temperature 2–5 Heavy 12–30 ++
59
List the Type A nerve fibers.
Alpha, Beta, Gamma, Delta
60
List the Type C nerve fibers.
Dorsal root and sympathetic
61
Susceptibilityh to block: Fiber Type A: Beta.
Function?
Diameter (µm)?
Myelination?
Conduction Velocity (m/s)?
Sensitivity to Block?
Fiber Type A: Beta
Function: Touch, pressure
Diameter: 5–12
Myelination: Heavy
Conduction Velocity: 30–70
Sensitivity to Block: ++
Gamma Muscle spindles 3–6 Heavy 15–30 ++
Delta Pain, temperature 2–5 Heavy 12–30 ++
62
Susceptibility to block: Fiber Type Gamma.
Funciton?
Diameter (µm)?
Myelination?
```
Conduction Velocity (m/s)
Sensitivity to Block?
```
Fiber Type Gamma
Funciton: Muscle spindles
Diameter: 3–6
Myelination: Heavy
Conduction Velocity: 15–30
Sensitivity to Block: ++
Delta Pain, temperature 2–5 Heavy 12–30 ++
63
Susceptivilty to Block: Fiber Type Delta
Function?
Diameter (µm)?
Myelination?
Conduction Velocity (m/s)
Sensitivity?
Fiber Type Delta.
Function: Pain, temperature
Diameter: 2–5
Myelination: Heavy
Conduction: 12–30
Sensitivity: +++
64
Susceptibility to Block: Fiber Type B
Function?
Diameter (µm)?
Myelination?
Conduction Velocity (m/s)
Sensitivity to Block?
Fiber Type B
Function: Preganglionic, autonomic
Diameter: \<3
Myelination: Light
Conduction: 3–15
Sensitivity: ++++
65
Susceptibility to Block: Type C: Dorsal Root.
Funciton?
Diameter (µm)?
Myelination?
Conduction Velocity (m/s)
Sensitivity to Block?
Fiber Type C: Dorsal Root
Function: Pain
Diameter: 0.4 - 1.2
Myelination: None
Conduction Velocity: 0.5 - 2.3
Sensitivity: ++++
66
Susceptibility to Block: Fiber Type: Sympathetic
Function?
Diameter (µm)?
Myelination?
Conduction Velocity (m/s)?
Sensitivity to Block?
Fiber Type: Sympathetic
Function: Postganglionic
Diameter: 0.3 - 1.3
Myelination: None
Conduction Velocity: 0.7 - 2.3
Sensitivity: ++++
67
Where do most important toxic effects of LA occur?
in the CNS
68
What are some toxic effects of LA?
Central effects, light-headedness or sedation, restlessness, nystagmus, and tonic-clonic convulsions
69
What follows severe convulsions associated with CNS toxicity and LA's?
Severe convulsions may be followed by coma with respiratory and cardiovascular depression.
70
All LA's are vasodilators, except \_\_\_\_.
Cocaine
71
What cardiac effects are associated with high plasma levels of LA's?
Patients with preexisting cardiovascular disease may develop heart block and other disturbances of cardiac electrical function at high plasma levels of local anesthetics
72
Bupiviacaine is what kind of mixture?
Racemic mixture of 2 isomers
73
What cardiotoxic effects may be exhibited with Bupivacaine?
Severe cardiotoxicity, including arrhythmias and hypotension.
74
What is the (S) isomer of Bupivacaine? Is it more or less cardiotoxic?
Levobupivacaine; less
75
Cardiotoxicity has also been reported for ________ when used for peripheral nerve block.
Ropivacaine
76
The ability of _______ to block NE reuptake and the drugs vaso-\_\_\_\_\_ actions contribute to cardiovascular toxicity.
Cocaine; constricting
77
What are the cardiovascular toxic effects of cocaine abuse?
Severe hypertension with cerebral hemorrhage, cardiac arrhythmias, and MI.
78
What is Prilocaine metabolized to?
Products that include o-toluidine
79
Why is o-toluidine toxic?
it is capable of converting hemoglobin to methemoglobin
80
81
Which type of LA's are metabolized to products that cause antibody formation?
Ester-type LA's
82
Allergic reactions to LA's is frequent? (T/F)
False
83
How can LA allergic reactions be prevented?
By using an agent from the amide sublass.
84
What is the toxic effect of high concentrations of LA's?
Local neurotoxic action (especially in the spinal cord) that includes histologic damage and permanet impairment function.
85
How is severe LA toxicity treated?
Symptomatically, there are no antidotes.
86
Convulsions related to LA toxicity are usually managed using what?
IV diazepam or a short-acting barbituate such as thiopental. Hyperventalation with O2 is helpful.
87
What drugs are occasionally used to control violent convulsive activity?
Neuromuscular blocking drugs
88
How do you treat cardiovascular toxicity of Bupivacaine overdose?
It is difficult to treat and has caused fatalities in young adults; IV administration of lipid has been reported beneficial.
89
Characteristic properties of local anesthetics include all of the following EXCEPT
(A) An increase in membrane refractory period
(B) Blockade of voltage-dependent sodium channels
(C) Effects on vascular tone
(D) Preferential binding to resting channels
(E) Slowing of axonal impulse conduction
Local anesthetics bind preferentially to sodium channels in the open and inactivated states. Recovery from drug-induced block is 10–1000 times slower than recovery of channels from normal inactivation. Resting channels have a lower affinity for local anesthetics. The answer is D.
90
The pKa of lidocaine is 7.7. In infected tissue, which can be acidic, for example, at pH 6.7, the percentage of the drug in the nonionized form will be
(A) 1%
(B) 10%
(C) 50%
(D) 90%
(E) 99%
Because the drug is a weak base, it is more ionized (protonated) at pH values lower than its pKa. Because the pH given is 1 log unit lower (more acid) than the pKa, the ratio of ionized to nonionized drug will be approximately 90:10. The answer is B. (Recall from Chapter 1 that at a pH equal to pKa, the ratio is 1:1; at 1 log unit difference, the ratio is approximately 90:10; at 2 log units difference, 99:1; and so on.)
91
Which statement about the speed of onset of nerve blockade with local anesthetics is correct?
(A) Faster in hypercalcemia
(B) Faster in myelinated fibers
(C) Faster in tissues that are infected
(D) Slower in hyperkalemia
(E) Slower in the periphery of a nerve bundle than in the
center of a bundle
Myelinated nerve fibers are blocked by local anesthetics more readily than unmyelinated ones. See the Skill Keeper answer for an explanation of the effects of hypocalcemia and hyperkalemia on nerve blockade by local anesthetics. The answer is B.
92
The most important effect of inadvertent intravenous administration of a large dose of lidocaine is
(A) Bronchoconstriction
(B) Methemoglobinemia
(C) Renal failure
(D) Seizures
(E) Tachycardia
Of the effects listed, the most important in local anesthetic overdose (of both amide and ester types) concern the CNS. Such effects can include sedation or restlessness, nystagmus, coma, respiratory depression, and seizures. Intravenous diazepam is commonly used for seizures caused by local anesthetics. Methemoglobinemia is caused by a prilocaine metabolite. The answer is D.
93
All of the following factors influence the action of local anesthetics EXCEPT
(A) Acetylcholinesterase activity in the region of the injection site
(B) Blood flow through the tissue in which the injection is made
(C) Dose of local anesthetic injected
(D) The use of vasoconstrictors
(E) Tissue pH
Local anesthetics are poor substrates for acetylcholinesterase, and the activity of this enzyme does not play a part in terminating the actions of local anesthetics. Ester-type local anesthetics are hydrolyzed by plasma (and tissue) pseudocholinesterases. Persons with genetically based defects in pseudocholinesterase activity are unusually sensitive to procaine and other esters. The answer is A.
94
You have a vial containing 10 mL of a 2% solution of lidocaine. How much lidocaine is present in 1 mL?
(A) 2 mg
(B) 5 mg
(C) 10 mg
(D) 20 mg
(E) 50 mg
The fact that you have 10 mL of the solution of lidocaine is irrelevant. A 2% solution of any drug contains 2 g/100 mL. The amount of lidocaine in 1 mL of a 2% solution is thus 0.02 g, or 20 mg. The answer is D.
95
Which statement about the toxicity of local anesthetics is correct?
(A) Bupivacaine is the safest local anesthetic to use in patients at risk for cardiac arrhythmias.
(B) In overdosage, hyperventilation (with oxygen) is helpful to correct acidosis and lower extracellular potassium
(C) Intravenous injection of local anesthetics may stimulate ectopic cardiac pacemaker activity
(D) Most local anesthetics cause vasoconstriction
(E) Serious cardiovascular reactions are more likely to occur with tetracaine than with bupivacaine
Acidosis resulting from tissue hypoxia favors local anesthetic toxicity because these drugs bind more avidly (or dissociate more slowly) from the sodium channel binding site when they are in the charged state. (Note that onset of therapeutic effect may be slower because charged local anesthetics penetrate the membrane less rapidly; see text.) Hyperkalemia depolarizes the membrane, which also favors local anesthetic binding. Oxygenation reduces both acidosis and hyperkalemia. Bupivacaine may cause severe cardiotoxicity including arrhythmias. The answer is B.
96
8. A vasoconstrictor added to a solution of lidocaine for a peripheral nerve block will
(A) Decrease the risk of a seizure
(B) Increase the duration of anesthetic action of the local anesthetic
(C) Both A and B
(D) Neither A nor B
Epinephrine increases the duration of a nerve block when it is administered with short- and medium-duration local anesthetics. As a result of the vasoconstriction that prolongs the duration of this block, less local anesthetic is required, so the risk of toxicity (eg, a seizure) is reduced. The answer is C.
97
A child requires multiple minor surgical procedures involving the nasopharynx. Which drug has high surface local anesthetic activity and intrinsic vasoconstrictor actions that reduce bleeding in mucous membranes?
(A) Bupivacaine
(B) Cocaine
(C) Lidocaine
(D) Mepivacaine
(E) Tetracaine
Cocaine is the only local anesthetic with intrinsic vasoconstrictor activity owing to its action to block the reuptake of norepinephrine released from sympathetic nerve endings (Chapter 9). Cocaine also has significant surface local anesthetic activity and is favored for head, neck, and pharyngeal surgery. The answer is B.
98
Prilocaine is relatively contraindicated in patients with cardiovascular or pulmonary disease because the drug
(A) Acts as an agonist at β adrenoceptors in the heart and the lung
(B) Causes decompensation through formation of methemoglobin
(C) Inhibits cyclooxygenase in cardiac and pulmonary cells
(D) Is a potent bronchoconstrictor
(E) None of the above
Large doses of prilocaine may cause accumulation of o-toluidine, a metabolite that converts hemoglobin to methemoglobin. Patients may become cyanotic with blood “chocolate colored.” High blood levels of methemoglobin have resulted in decompensation in patients who have cardiac or pulmonary diseases. The answer is B.
99
Drugs used for LA: Sublass:
List the Amides.
Articaine
Bupivacaine
Levobupivacaine
Lidocaine
Mepivacaine
Prilocaine
Ropivacaine
"I" before "caine"
100
Drugs used for LA: Sublass:
List the Esters
Benzocaine
Cocaine
Procaine
Tetracaine
101
What is the MOA of Amide LA's
Block Na+ channels slows, then prevents action potential propogation.
102
What is the Pharmacokinetics of Amide LA's?
Hepatic metabolism via CYP450 in part.
103
What are the half-lives of Amide LA's?
Lidocaine and Prilocaine: \< 2hrs
All others: 3-4 hrs
104
What is the Clinical Application of Amide LA's?
Analgesia via topical use, or injection (perineural, epidural, subarachnoid)
Rarely used IV.
105
Amide LA's are used IV. (T/F)
False. Amide LA's are rarely used IV
106
Toxiciteis of Amide LA's.
CNS: Excitatory, seizures
CV: Vasodilation, hypotension, arrhythmias (bupivacaine)
107
Which amide LA has a toxic effect that results in Arrhythmias?
Bupivacaine
108
What is the MOA of Ester LA's?
Same as Amide LA's (Blockade of Na+ channels slows, then prevents action potential propogation); plus, cocaine has intrinsic sympathomimetic actions.
109
What is the Pharmacokinetic action of Ester LA's?
Rapid metabolism via plasma esterases; they have a short half-life.
110
What is the Clinical Application of Ester LA's?
Analgesia, topical only for cocaine and benzocaine
111
What are the Toxic Effects of Ester LA's?
CNS: Excitatory, seizures
CV: Vasodilation (EXCEPTION: Cocaine Vasoconstricts), HypOtension, Arrhythmias.
When abused, cocaine causes HTN, Sz, and arrhythmias.
112
Why are Sodium, Potassium and Calcium significant in the use of Local Anesthetics and Cardiac Toxicity?
Sodium channel blockers bind more readily to open (activated) or inactivated sodium channels. Hyperkalemia depolarizes the resting sodium membrane potential, so more sodium channels are in the inactive state. Conversely, hypercalcemia tends to hyperpolarize the resting potential and reduce the block of sodium.
113
