Opioid Agonist-Antagonists (2) Flashcards
(101 cards)
1
Q
When are opioid agonist-antagonists used?
A
Used if unable to tolerate a pure agonist
2
Q
What receptors do opioid agonist-antagonists bind to?
A
Mu receptors: Partial effect (agonist) not no effect (competitive antagonist)
Kappa/Delta receptors: Partial effect (agonist)
3
Q
What are generalized side effects of opioid agonst-antagonists?
A
Same as opioids + dysphoric reactions (stress/uneasiness)
4
Q
What are advantages of opioid agonist-antagonists?
A
- Analgesia
- Limited depression of ventilation
- Low potential for dependence
- Ceiling effect prevents additional responses
5
Q
What is the ceiling effect for opioid agonist-antagonists?
A
Drugs impact on body plateaus→ taking higher doses does not increase its effect
6
Q
List opioid agonist-antagonists from most potent to least potent when compared to morphine:
A
- Buprenorphine (50x more)
- Butorphanol (4x more)
- Bremazocine (2x more)
- Nalbuphine (equal)
- Nalorphine (equal)
- Dezocine
- Pentazocine (1/5)
- Meptazinol
7
Q
What is the primary MOA of Pentazocine?
A
Agonist effects on delta and kappa
Weak antagonist activity
8
Q
What med antagonizes Pentazocine?
A
Naloxone
9
Q
How is Pentazocine metabolized and excreted?
A
- Extensive hepatic first pass
- Excreted in urine (glucuronide conjugates)
10
Q
Chronic pain dose of Pentazocine:
A
10-30 mg IV or 50mg PO
11
Q
What dose of Pentazocine causes analgesia sedation and depression of ventilation?
A
20-30 mg IM
12
Q
How does epidural duration of action of pentazocine compare to morphine?
A
Shorter duration of action compared to morphine
13
Q
What are side effects of Pentazocine?
A
Sedation
↑HR, BP, PAP, LVEDP
Diaphoresis
Dizziness
14
Q
Does Pentazocine cross placental barrier?
A
Yes, Causes fetal depression
15
Q
How does Butorphanol compare to Pentazocine?
A
Butorphanol 20X agonist effect and 10-30x antagonist effect than Pentazocine
16
Q
Which receptors does Butorphanol have affinity for?
A
Mu receptor → Low affinity
Kappa receptor → Moderate affinity
Sigma receptor → Minimal affinity
17
Q
2-3 mg IM Butorphanol= ____ mg Morphine
A
10
18
Q
T/F: IM Butorphanol has less absorption.
A
False: Butorphanol is rapidly and completely absorbed with IM admin
19
Q
What is the E1/2 time for Butorphanol?
A
2.5-3.5 hrs
20
Q
How is Butorphanol metabolized/eliminated?
A
- Hepatic metabolism
- Eliminated largely in bile
21
Q
What are side effects of Butorphanol?
A
- Sedation
- Nausea
- Diaphoresis
- Withdrawal symptoms
- ↑ BP, PAP, CO
22
Q
_________ stops post op shivering more effectively than other opioids.
A
Butorphanol: Has more kappa effects
23
Q
_________ is useful in the treatment of chronic pain when there is a high risk of physical dependence.
A
Pentazocine
24
Q
It may be difficult to use an opioid agonist affectively as an analgesic in the presence of _____________.
A
Butorphanol
25
Which receptors has a moderate affinity for Butorphanol effects to mitigate shivering and produce analgesia?
Kappa receptor
26
What is the E1/2 time for Nalbuphine?
3-6 hours
27
What is used to reverse the agonist effects of nalbuphine?
Naloxone
28
Which receptors does Nalbuphine act as an agonist? How does the agonist activity compare with morphine?
Mu: equally as potent as morphine
29
How does Nalbuphine antagonist effects compare to Nalorphine?
1/4 as potent as Nalorphine
30
What is E1/2 time for Nalbuphine? Where is it metabolized?
E1/2: 3-6 hrs
Metabolized in the liver
31
What are side effects of Nalbuphine?
* Sedation
* Dysphoria
* Withdrawal symptoms
**** NO increase in BP, PA, HR or atrial filling
32
Which opioid agonist-antagonist would be best to use for cardiac cath patients?
Nalbuphine
33
Which opioid agonist-antagonist has agonist affects 50X more potent than morphine?
Buprenorphine
34
Which receptors does Buprenorphine bind to?
Mu receptors agonist
35
What is the onset for Buprenorphine?
30 min
36
What is the duration of Buprenorphine?
8 hours (prolonged resistance to Naloxone)
37
When is Buprenorphine used?
Post op, cancer, renal colic, and MI; epidural
38
What are side effects of Buprenorphine?
* Drowsiness
* N/V
* Vent depression
* Pulm edema
* Withdrawal
* Low risk for abuse
39
0.3mg IM Buprenorphine is ____X more potent than morphine
50X
40
What is the only clinically used opioid that has higher affinity of the mu receptor than Buprenorphine?
Sufentanil
41
Which opioid agonist-antagonist (not in practice) is equally as potent as morphine but has a high incidence of dysphoria?
Nalorphine
42
Which opioid agonist-antagonist is 2x more potent than morphine by working on the kappa receptors?
Bremazocine
43
Which opioid agonist-antagonist work on delta and mu receptors to provide analgesia with no CV effects?
Dezocine
44
Which receptor does Meptazinol bind to? What is the onset and duration?
Mu1 receptors
Rapid onset
<2 hour duration
Protein binding 25%
45
What is the onset of Dezocine?
15 min
46
Which receptor do opioid antagonists bind to? What are these drugs?
* Pure Mu opioid receptor antagonists
* Naloxone, Naltrexone, Nalmefene
47
What is the MOA of opioid antagonists?
Competitive antagonist: high affinity to opioid receptors (bumps opioid off and binds to receptor but doesnt activate it)
48
Which opioid antagonist is nonselective with all 3 opioid receptors?
Naloxone
49
What are the uses for Naloxone?
* Opioid-induced depression postop
* Neonate depression (from mom)
* Opioid OD
* Detect dependence
* Hypovolemic/septic shock
* Antagonism of GA (high doses)
50
What is the dose for Naloxone? What is the continuous gtt dose?
1- 4 mcg/kg IV
5 mcg/kg IV infusion
51
What is the dose of naloxone for shock? How much Naloxone can be given for epidural side effects?
Shock: >1 mg/kg IV
Epidural side effects: 0.25 mcg/kg/hr IV
52
What is the duration of Naloxone?
30-45min
53
What is the E1/2 time for Naloxone?
60-90 minutes
54
What are side effects of Naloxone?
Reversal of analgesia (intended)
N/V (give slow IVP)
Increase SNS (HR, BP, pulm edema, cardiac dysrhythmias)
55
What route does Naltrexone have the most effect?
PO
56
What is the duration of Naltrexone?
24 hours
57
What is Naltrexone used for?
Alcoholism
58
How does Nalmefene potency compare to Naloxone? What is the dose?
Equipotent
15- 25 mcg IV (every 2-5 min) (1mcg/kg)
59
What is the E1/2 time for Nalmefene?
10.8 hrs
60
What are the clincal uses for Methylnalrexone?
Promotes gastric emptying and antagonizes N/V
61
Methylnaltrexone is highly ionized (quaternary). What does this mean?
Quaternary limits crossing of BBB (better for periphery)
No alteration is centrally mediated analgesia
62
What are uses for Alvimopan?
Post op ileus (increases peristalsis)
63
What is a newer mu selective PO peripheral opioid antagonist?
Alvimopan
64
What are the limitations to the uses of Alvimopan?
Not for long term use (could cause CV events)
65
Metabolism of Alvimopan relies on _____ _______.
Gut flora
66
What is the strategy for making tamper/abuse resistance opioids?
Combining opioid with antagonist (ex: Suboxone, Embeda, Oxynal)
67
What are the components of Suboxone, Embeda, and OxyNal?
Suboxone: Buprenorphine + Naloxone
Embeda: (ER morphine + Naltrexone)
OxyNal: Oxycodone+ Naltrexone
68
Is it common to have opioid allergy?
No, True opioid allergy is rare
Predictable side effects like localized histamine release are misinterpreted as allergies
69
How might opioid therapy potentially alter immunity?
Through Neuroendocrine effects or via direct effects on immune system (with prolonged opioid exposure)
Opioid receptors are present in B and T cells, dendritic cells, neutrophils
70
71
Sufentanil decreases MAC with Enflurane by ___ - ___%
70-90%
72
Alfentanil decreases MAC up to ___%
70%
73
Remifentanil decreases MAC ___ -____%
50-91%
74
Which opioid agonist-antagonist has the highest decrease in MAC when used in combo with volatile anesthetics?
Pentazocine (20% decrease in MAC)
75
Is MAC affected by Opioid agonist-antagonists?
Butorphanol (11% decrease)
Nalbuphine (8% decrease)
76
What are the suggested starting IV regimens of PCA for Morphine, Hydropmorphone, and Fentanyl?
77
Why PCA over PRN drug dosing for pain management?
After achieving effective concentrations, PCA allows patients to self titrate opioid dosing to maintain effective analgesia
No lag time between request for pain med and nurse getting/giving (minimizing time in pain with easy access from PCA)
78
What meds minimize pain perception in the brain through DIC?
Opioids, Alpha 2 agonists ,General anesthetics
79
Which meds work to minimize pain through modulation of afferent signals in the spinal cord?
LA, Opioids, Ketamine, alpha2 agonists
80
Which meds minimize pain transmission by A delta and C fibers?
Local anesthetics
81
Which meds reduce pain by limiting pain transduction by peripheral nociceptors?
LA, NSAIDS
82
Where are opioid receptors in the spinal cord located?
Substantia gelatinosa
83
What does Neuraxial mean?
Below the brain
84
How are neuraxial opioids given?
Either epidural or spinal
85
How is epidural opioid different from spinal/SAB opioids?
* Epidural dose is increased 5-10 times
* Systemic absorption of drug
86
What does the addition of Epi to the solution places into the epidural space do?
Decreases systemic absorption of the opioid--enhances post op analgesia
Add vasoconstrictor (Epi)
87
How the lipid solubility differ between epidural admin of Fentanyl, Morphine, and Sufentanil? what is the peak in the CSF
Sufentanil: Most lipid soluble (1600x >morphine) peak in 6 min
Fentanyl (800x > morphine) peak 20 min
Morphine: slower onset, longer duration. peak 1-4 hrs
88
What is Cephalad movement in CSF and what is this dependent on?
Movement upward (toward the head)
Depends on lipid solubility of drug
89
Which has the most and least cephalad migration: Fent, Morphine. Sufen?
* Fentanyl and Sufentanil: highly lipid soluble are limited in cephalad migration d/t rapid uptake in the spinal cord
* Morphine: less lipid soluble remains in CSF longer and can go to more cephalad locations
90
What can increase movement for CSF?
Coughing or straining
91
Why does the barocity of med matter?
Baracity is the density of the med
Hyperbaric: Med sinks
Hypobaric: Med floats
Isobaric: remains at same level
92
What LA anesthetic baracity would affect right hip of a patient positioned in left lateral position?
Hypobaric LA
93
What are the CSF and plasma peak times as well as cervical levels in epidural fentanyl, Sufentanil, and morphine?
94
What puts patient at high risk for hypotension and bradycardia following spinal anesthesia?
Anesthesia above T5
(T1-T4= cardiac accelerators)
95
Common side effects from neuraxial opioids (dose dependent):
Pruritus (most common in face, neck, upper thorax in OB)
N/V
Urinary retention
Vent depression
Sedation
CNS Excitation
96
What is the cause of Neuraxial opioid pruritus? What is the treatment?
Cephalad migration to trigeminal nucleus (brainstem)
TX: naloxone, Antihistamines, gabapentin
97
What is the most reliable sign of depression of ventilation post Neuraxial opioid admin?
Early: within 2 hours (d/t systemic absorption)
Late: 6-12 hours after (d/t cephalad migration of opioid in CSF to ventral medulla)
Depressed LOC secondary to hypercarbia (late sign)
98
What is the treatment of depressed ventilation after spinal opioid?
Naloxone: 0.25 mcg/kg/hr IV
99
What does CNS excitation S/E from spinal opioid look like?
Tonic skeletal muscle rigidity ike seizure activity
100
What adverse effect can happen 2-5 days after epidural opioid?
Herpes simplex labialis viral reactivity: (likely d/t cephalad migration of opioid CSF and interaction with trigeminal nucleus)
101
Should neuraxial opioids be withheld from women recovering from cesarean delivery d/t concern for neonatal drug exposure in breast milk?
No, Concentration of opioid in breastmilk is negligible after neuraxial opioids
