Pain Management and Local Anesthetics - Quiz 4 Flashcards
1
Q
How is meperidine classified?
A
Synthetic opioid agonist at mu and kappa receptors
2
Q
Meperidine is structurally related to
A
the fentanyls and atropine
3
Q
Why has Meperidine fallen out of favor?
A
From all the side effects, particularly neuro
4
Q
How is meperidine metabolized
A
Extensive hepatic metabolism (90%)
5
Q
Meperidine is broken down into 2 different metabolites, what is the first metabolite?
A
Initial demethylation to normeperidine
- Active metabolite
- Becomes a problem in ppl with renal dysfunction
- Seizure, confusion, agitation
6
Q
Meperidine is broken down into 2 different metabolites, what is the second metabolite?
A
Second breakdown to meperidinic acid
7
Q
How are the 2 metabolites from meperidine excreted?
A
Primarily excreted by the kidneys
8
Q
What is the elimination half time of meperidine
A
3-5 hours
9
Q
What percentage of meperidine is bound to protein
A
60%
10
Q
How potent is meperidines first metabolite, normeperidine
A
One half the analgesic properties of meperidine
11
Q
How long is the elimination half time of normeperidine
A
Elimination half-time is 15 hours
12
Q
How long is the elimination half time of normeperidine in patients with renal failure?
A
> 35 hours
13
Q
Normeperidine produces CNS stimulation, what is some of the toxic side effects?
A
Seizures, myoclonus, agitation, hallucinations
14
Q
What are the cardiac side effects of meperidine?
A
- Interferes with compensatory SNS reflexes
- therapeutic doses is associated with orthostatic hypotension
- May increase heart rate (reflection of its atropine like qualities)
15
Q
What are the respiratory side effects of meperidine?
A
respiratory depression
16
Q
Meperidine taken with an SSRI can cause what?
A
Serotonin Syndrome
17
Q
Serotonin syndrome has a low risk of occurrence, but when it does, what is the main symptoms you will see?
A
First you will see accelerated HTN
then tachycardia, diaphoresis, hyperreflexia
18
Q
What does meperidine cause post up? and at what dosage?
A
Post-op shivering
12.5-25 mg
19
Q
Will one time dose of meperidine build up an active metabolite?
A
no
20
Q
When doing medication equivalents, what is everything based off of?
A
Morphine
21
Q
What is the MOA of methadone?
A
Mu agonist with NMDA antagonism
22
Q
How is methadone eliminated?
A
renal and fecal
23
Q
What is significant about the variable half life of methadone?
A
has the ability to last 8-60 hours, difficult to pull equivalence to other medications, can build up and accumulate – increase resp depression and death
24
Q
What is significant about the EKG and methadone?
A
QT prolongation, which can lead to tornadoes
25
Why were opioid agonist, antagonist created?
Created in response to overage of resp depression and deaths from pure opiate agonist
26
Where do opioid agonist-antagonist work?
at the Mu receptor
27
Does the agonist/antagonist opioids have more or less affinity?
Affinity is LESS than a pure agonist
28
What happens if you increase the dose of an opioid agonist/antagonist?
You reach a ceiling effect, increasing the dose does not produce an additional response
29
Opioid agonist/antagonist produce analgesia with little effect on what?
with limited depression of ventilation
30
Agonist /antagonist drugs should be reserved for patients who
cannot tolerate pure agonist.
31
Cross tolerance can happen between
all opioids
32
What is cross tolerance
You can switch opioid medication but you will still have a tolerance to its medication equivalence. Just a new agonist is hitting the receptor.
33
Can tolerance occur without dependacne?
yes
34
Can dependance occur without tolerance?
no, this is addiction
35
When are you considered opioid tolerant?
if you are using more than 60 mg morphine or equivalent per week
36
What is one way to combat cross tolerance to opioids?
to add adjunct medication – Tylenol, lyrica, Neurontin, clonidine
37
Minor changes in the structure of an opioid agonist convert the drug into an opioid antagonist, Naloxone is the N-alkyl derivative of
oxymorphone
38
Opioid antagonist are which type of antagonism?
Competitive antagonism – fighting for mu receptors (hopefully antagonist kicks off agonist)
39
After displacement from the Mu receptor, does binding of the pure antagonist activate the mu receptor?
No
40
Do opioid antagonist have a high or low affinity for the receptor
high affinity
41
Naloxone is a ________ antagonist, having effects at all 3 receptors (gamma, kappa, mu)
nonselective
42
What is naloxone used for?
Treatment of Opioid-induced depression of ventilation post-op and overdoses
43
How fast does naloxone produce reversal effects in IV vs nasal spray?
IV - under 1 minute
| Nasal spray - under 2 minutes
44
What is the duration of action of naloxone and what does this mean?
30-45 minutes? may need to re-dose, opioid effects of opioid will last longer than naloxone
45
How is naloxone metabolized?
hepatic ally
46
What are the side effects of naloxone?
Very CV stimulating - tachycardia, HTN
N/V
47
Why do you need to be careful when reversing a potential overdose on someone who is a chronic opioid user?
risk of putting them into withdrawal. What is worse? - withdrawal symptoms or overdose (can we put them on a vent for now?) both can be fatal
48
Where are the neuraxil opioid receptors located that allow placement of opioids in epidural or subarachnoid space?
opioid receptors (mu) are present in the substantia gelatinosa of the spinal cord
49
What happens if you inject a highly lipophilic medication into a epidural space?
Its going to move right out of epidural tissue into general circulation, just as if you gave it IM/IV
50
CSF concentration of fentanyl will peak ___ minutes after epidural administration of fentanyl.
20
51
Epidural administration of opioid produces blood/plasma concentrations that are ______ to IM administration of drug at equivalent dose.
similar
52
Why would you add Epi to a neuraxail opioid epidural?
causes vasoconstriction, making blood vessels smaller, makes it more difficult for lipophilic meds to move out of area
53
When giving an epidural, what moves the medication of the intended spot?
blood flow
54
What happens if you inject into a highly vascular area?
you are going to have a much short duration in that location because its going to get swept up by blood flow faster than if you put it SQ (low vascular, highly fatty)
55
Movement of intrathecal opioid is dependent on bulk flow of
CSF
56
in intrathecal neuraxial opioids, what can affect movement in CSF?
coughing or straining
57
What is the main side effect of neuraxial opioids?
Puritus! - ITCHING doesn’t necessarily mean they are having allergic reaction (is there depression of ventilation?)
Other s.e. are N/V, urinary retention, response depression
58
What is an unusual side effect of neuraxial opioids?
Viral reactivation - reactivation of latent and viral infection (shingle, chicken pox, TB)
59
What class is ketoralac?
NSAID
60
What is the black box warning on ketoralac?
5 days - max use of toradol before have to be seen by provider. Increased risk of GI bleed
61
When using ketoralac, which COX system helps prevent GI upset?
COX1 is inhibiting the prostaglandin production work to maintain mucus layer around stomach and GI tract that is protective. When that goes away,, increased risk for GI bleed.
62
What are the side effects of ketoralac?
ARF - common cause
GI bleed - reduced COX 1
CHF - cause you to hold onto fluids
platelet malfunction - antiplatlet effect
63
What is a specific COX2 inhibitor that should lower risk of GI upset, GI bleed?
Celebrex
Give this pre-op, esp. when NPO and becoming dehydrated – possibly safer
64
What is the onset and duration of Acetaminophen
Onset 15 min
| Duration 4-6 hours
65
What is the main concern about taking too much Acetaminophen?
Hepatotoxicity
66
What is the treatment for Tylenol overdose?
N-acelycistine
67
what is the MOA of Tylenol?
Questionable mechanism
68
What is the max mg each dose of tylonal can have?
325 mg
69
What is the recommend maximum daily dose of Tylenol?
3gram (used to be 4g)
70
What is the MOA of tramadol (ultram)
mu agonist, weak SNRI
71
Does tramadol have an active metabolite?
No
72
What is a major side effect of tramadol?
lowers the seizure threshold. Even someone who has never had seizures before can get them.
73
Local anesthetics do what to nerve fibers?
reversibly block the conduction of electrical impulses along nerve fibers.
74
Do LA cause any nerve damage?
no evidence of structural damage to nerve fibers.
75
What will change the onset of action of LA's
pKa and chemical structure
76
What will change the duration of action of a LA?
lipophalicity
77
What is a saltatory conduction?
jumping electrical conduction down a nerve, accelerating with each jump
78
What are Schwann cells?
any of the cells in the peripheral nervous system that produce the myelin sheath around neuronal axons
79
What does unmyelinated mean?
Action potential travels as continuous waves (not jumping) in a "push" pattern
80
What does myelinated mean?
Action potentials “jump” or propagate by saltatory conduction. (+Na)
81
What is Nodes of Ranvier?
the gap in the myelin sheath of a nerve, between adjacent Schwann cells
82
What is the site of action for local anesthetics
Na channels
83
What is the Resting membrane potential of a peripheral nerve
-70mV
84
When a chemical, mechanical, or electrical impulse is applied to a resting nerve, the membrane potential is reversed due to
intracellular movement of Na+.
85
The Na,K, ATpase pump works in what ratio
3:2 ratio, 3 Na in - 2K out
86
Describe A Alpha fibers
Largest in diameter (15-20µm)
The most heavily myelinated
Fastest conduction velocity of all the fibers
Motor function and proprioception
87
Describe A Beta fibers
Diameter (4-15µm)
Second fastest conduction velocity
Motor function, touch and pressure sensation
88
Describe A Gamma fibers
Diameter (4-15µm)
| Muscle spindles and reflex
89
Describe A Delta fibers
Diameter (3-4µm) – smaller the diameter – pumps up conduction
Slower conduction velocity than other A fibers
Pain and temperature sensation
90
Describe B fibers
Diameter (4µm)
Slower conduction velocity and less myelination than A fibers.
Preganglionic autonomic nerves
91
Describe C fibers
Diameter (1-2µm)
Slowest speed of conduction
Conduct pain and temperature impulses
The only fibers that are unmyelinated
92
Is motor function sensitive to the effects of LAs?
No - person can still move, just don’t want them to feel
93
Where is the first place the LA will act?
1st effect will be at B fibers (autonomic effects) – change in signal transmission from blockade of Na channels
94
Why are higher doses of LA needed in order to blunt motor function?
not as susceptible to effect of local anesthetic
95
For LAs where is the receptor site?
INSIDE the nerve fiber
96
To bind to its receptor site, the LA has to be
IONIZED
97
Once inside the cell the ionized portion more avidly binds the
sodium channel inside the cell
98
Our bodies have a neutral pH, why did we create weak basis
so they maintain stability and liopphilicity when injected into neutral body environment
99
You have to have a weak base injected into a neutral pH to stay ______ to move inside nerve terminal where it is more ______ - becomes ionized through the Henderson Hasselback equation, too bind to receptor.
lipophilic
acidic
100
EVERY local anesthetic is made up of 3 compounds, what are they?
An unsaturated aromatic ring system
An intermediate carbon group
A tertiary amine
101
What do we get from the intermediate group?
where you get amid vs ester
102
How do you tell apart the esters vs the amides?
the amides all have i's in the first part
```
Lidocaine
Mepivacaine
Prilocaine
Bupivacaine
Levobupivacaine
Ropivacaine
Etidocaine
```
the esters do not
Procaine
Chloroprocaine
Tetracaine
Cocaine
103
Onset of action: Lipid solubility-major determinant is amount of LA that is in
the non ionized state
104
Onset of action: pKa is the pH of the LA at which the amount of
ionized and non-ionized drug is equal
105
LA with a pKa closet to physiologic pH will have a higher concentration of non-ionized form that can
readily pass thru the nerve cell membrane.
106
Ion trapping results from changes in pH in relationship to the agent’s
pKa
107
What is the pharmacokinetics of LAs all they way through the body
When we inject, it goes into the nerve terminal, picked up by blood flow to move it to the site of action, metabolized by liver and renally excreted
108
Highly or poorly lipid soluble LA have a longer duration of action, because they are less likely to be cleared by blood flow
highly lipid soluble (gets sequestered in lipid depot) (less likely to be taken away by blood stream)
109
If the pKa is slightly above 7.5, what does that mean?
they are weak bases
110
Intracostal will have a shorter duration of action that SQ, why?
the intercostal area is more vascular than SQ, more blood flow
111
the addition of epi to a LA is a vasoconstrictor and increases the duration of action by roughly how long?
increase duration of action by 25% roughly
112
What are some advantages of adding epi to LAs
```
Decreases vascular absorption
Increases nerve cell uptake
Enhances the quality of analgesia
Prolongs the duration of action
Limits toxic side effects
```
113
All LAs except for ________ have natural dilatory effects (works against us). It shortens its own duration of action, that’s why we give epi.
Cocaine
114
Highly perfused organs are responsible for initial uptake, what are they?
Brain, lung, liver, kidney, and heart
115
Esters are predominately metabolized by
pseudocholinesterase
116
Procaine and benzocaine are metabolized to
p-aminobenzoic acid (PABA) ~ associated with allergic reactions
117
What pts are at risk for a toxic reaction when taking esters?
Pts with genetically abnormal pseudocholinesterase
118
How are Amides metabolized?
Metabolized by microsomal P-450 enzymes in liver
119
Which metabolism is faster, esters or Amides?
esters
120
The metabolites of what 2 LA's can cause Methemoglobinemia
Prilocaine and benzocaine
121
Hight concentrations of Methemoglobinemia will show what S/S?
Brownish gray cyanosis
Tachypnea
Metabolic acidosis
```
Severe S/S
Tissue hypoxia
Headache
Irritability
Loss of consciousness
```
122
What is the treatment for Methemoglobinemia
Spontaneous recovery in 2-3 hours
Immediate reversal with methylene blue IV if having true CV ischemia
123
Why would you add sodium bicarb to a LA?
will bring it back to a more neutral or basic area to improve its non ionized form
124
What happens if you have Inadvertent intravascular injection of an LA
Local anesthetic systemic toxicity (LAST)
Instead of local reaction, can get cardio and CNS effects
125
Explain the symptoms have CV toxicity from low to high
HTN, tachycardia
Bradycardia/hypotension
up to Asystole
126
Explain the symptoms have cerebral toxicity from low to high
acting abnormal
confusion, dizziness, tinnitus, metallic taste
up to seizures
127
Which LA has very commonly makes people "speak gibberish" and act strange
Lidocaine
128
CV toxicity in LA administrations have what in regards to outcomes?
Very grave clinical outcomes
129
Why do all LA depress myocardial automaticity
the are Na channel blockers
130
Which LA has a very common occurrence of CV toxicity?
Bupivacaine
131
What is the treatment if LAs get into systemic circulation?
Use and intralipid solution (10-30%)
propofol does NOT work!!!
132
What are the Transient Neurologic Symptoms from spinals?
Tingling, burning aching in lower extremities and backside
133
Which LA has a high incidence of TNS with spinal anesthesia?
Lidocaine has 13% incidence (this is high)
bupivicaine #2
134
are TNS sysmtoms permanent?
no but can last up to 10 days
135
higher risk of allergic reactions come from esters or amides?
esters
136
What 2 LA mixtures is EMLA cream made up of?
Mixture of lidocaine and prilocaine
137
Where is the site of action of EMLA cream
acts at little nerve endings at site of application
138
How long does EMLA cream take to work?
1 hr
139
Where should you NOT put topical anesthesia unless being supervised for a specific case?
nose, mouth - absorbed more rapidly into vena cava
140
Topical cocaine cause
vasoconstriction
