Lecture 9 (Exam 2) - Opioid Agonist/Antagonist & Opioid Antagonists Brooke's Deck Flashcards
What is pentazocine used for and at what dose? (IV, IM, PO)
Moderate chronic pain
IV: 10-30mg
IM: 20-30mg
PO: 50mg
slide 14
What is the PO dose (50mg) of Pentazocine equivalent to?
60mg Codeine
slide 14
What is the IM dose (20-30mg) of Pentazocine equivalent to that produces similar sedation and depression of ventilation?
10mg Morphine
slide 14
Why do we like Pentazocine for epidural analgesia?
Bc it has shorter duration < morphine
slide 14
Pentazocine s/e are similar to morphine’s.
What can it cause at high doses?
What cardiac effects do you see?
Dysphoria ✨
❤️: ⬆in HR, BP, pulmonary artery BP, LVEDP
slide 14
What must you consider when giving Pentazocine to pregnant women?
It crosses the placental barrier and can cause fetal depression. 👶🏻
slide 14
Is Butorphanol (Stadol) more potent than pentazocine? (Agonist and Antagonist effects)
Yes.
Agonist: 20x > (more potent than morphine)
Antagonist: 10-30x >
Butorphanol’s (Stadol) affinity for mu receptors to produce antagonism is ____.
It also has a ____ affinity for sigma, so dysphoria ✨ is low.
Its affinity for Kappa receptors is ______.
Mu: low
sigma: low
kappa: moderate ❄️
slide 15
What is the dose for Butorphanol (stadol) and how many Mg of morphine is this equivalent to?
And why is it given this route?
-2-3mg IM = 10mg morphine (depression of ventilation)
-absorbed immediately
slide 15
Which receptor has moderate affinity for Butorphanol (stadol) to prevent shivering and analgesia?
Kappa receptor! ❄️
slide 15 (he asked this question on a slide)
Butorphanol is metabolized in the liver, eliminated via _____ > urine and its E1/2 is ____ to ____ hours.
bile; 2.5-3.5 hours
slide 16
S/E of Butorphanol (stadol). (❤️, ✨, 💦)
sedation, nausea, diaphoresis 💦, dysphoria ✨, depresses ventilation, W/D can occur
❤️: ⬆ BP, PA BP, CO
slide 16
What can Butorphanol (stadol) cause synergistic effects with?
Other opioid agonists.
slide 16
Castillo wants us to know the least and most of the table (flip card)
Alfentanil:
most - % ionized & protein binding
least - clearance & Vd
Remifentanil:
most- clearance (4000)
Fentanyl:
most - Vd & effect site (brain equilibrium time)
Mu 1: “slow, cold, cant see, cant pee, but happy”
Mu 2: “cant breathe, cant poo & im addicted too”
Kappa: “sad, sleepy, peeing, cant see”
Delta: “ cant breathe, cant pee, cant poo & addicted too” (similar to Mu2)
What are the 7 Opioid Agonist-Antagonists from lecture?
- Pentazocine
- Butorphanol
- Nalbuphine
- Buprenorphine
- Nalorphine
- Bremazocine
- Dezocine
(Slide 11)
When are Opioid Agonist-Antagonists used?
They are used if unable to tolerate a pure agonist.
(Slide 12)
What receptors do Opioid Agonist-Antagonists bind to?
- µ receptors: partial effect (agonist) or no effect (competitive antagonist)
- Κ and δ receptors: partial effect (agonist)
(Slide 12)
What are the generalized side effects of Opioid Agonist-Antagonists?
They are the same as opioid agonists + dysphoric reactions. 😒
(Slide 12)
What are some of the advantages of Opioid Agonist-Antagonists?
Analgesia
Limited depression of ventilation
Low potential for physical dependence
Ceiling effect prevents additional responses
(Slide 12)
Pentazocine
1. What receptors does it bind to?
2. Will you have withdrawal symptoms?
3. It is ____ as potent as Nalorphine.
4. What is it antagonized by?
5. How is it excreted?
- Agonist effects on δ and κ receptors with weak antagonist activity
- Yes
- 1/5th as potent as Nalorphine
- Antagonized by Naloxone
- Glucoronide conjugates = urine
Extensive hepatic first pass (20% available post PO)
Elimination half-time: 2 to 3 hours
(Slide 13)
Why are opioid agonists used?
They are used to control acute or chronic pain.
Some are used for diarrhea & cough.
(Video 00:12)
Opioids bind to opioid receptors in the ____, _____, & ____.
Brain, spinal cord, & GI tract
(Video 00:43)
Nalbuphine, an opioid agonist-antagonist has equipotency with what gold standard drug?
Morphine, so 10 mg of Nalbuphine = 10 mg morphine. (Slide 17)
Which agonist antagonist opioid is good to use in patients with cardiovascular dz?
Nalbuphine. This drug does not cause an increase in BP, pulm pressures, HR, or atrial pressures. (Slide 17)
Nalbuphine is _____ as potent as Nalorphine.
The antagonist effect of Nalbuphine is 1/4th as potent as Nalorphine. (Slide 17)
With EPIDURAL admin of Fentanyl, Sufentanil, and morphine, what are their individual CSF Peak times?
Fentanyl: 20 min
Sufentanil: 6 min
Morphine: 1-4 hours
(slide 35)
With EPIDURAL admin of Fentanyl, Sufentanil, and morphine, what are their individual Plasma Peak times?
Fentanyl: 5-10 min
Sufentanil: < 5 min
Morphine: 10-15 min
All times are similar with IM admins
(slide 35)
Which opioid agonist - antagonist has a long duration and 50 x more affinity with the receptor than morphine?
Buprenorphine. Very high receptor affinity and slow dissociation. Nice long lasting drug but also has a prolonged resistance to Naloxone! (Slide 18)
Buprenorphine dosing: ______ mg IM = 10 mg morphine.
0.3 mg IM, onset in 30 min. Duration 8 hrs. (Slide 18)
Types of pain that Buprenorphine is indicated for?
Moderate to severe pain in the post op period, cancer, renal colic, and MIs. (Slide 18)
Side effects of Buprenorphine?
Pulmonary edema, drowsiness, N/V, depression of ventilation, withdrawal. (Slide 18)
With INTRATHECAL admin of Fentanyl, Sufentanil, and morphine, what are their individual Cervical Level migration expectations?
Fentanyl: minimal
Sufentanil: minimal
Morphine: 1-5 hours cephalad migration can be expected
(slide 35)
Nalorphine is not used as an opioid agonist antagonist because of?
High incidence of dysphoria with sigma receptor activation. (Slide 19)
Bremazocine has a receptor affinity for _____ receptors that is ____ more potent than morphine
Kappa, 2x (slide 19)
______ is similar to Nalbuphine, in that they both do not exhibit cardiovascular effects.
Dezocine (slide 19)
You start an epidural and have since administered an opioid agonist. The pt begins complaining of itching. This is aka ________.
Which pt populations do you expect to this s/e more commonly in?
What is the cause of this?
Treatment?:
pruritis
OB
Cause: cephalad migration to trigeminal nucleus
Rx: Naloxone (will fully reverse the opioid tho*), antihistamines, and gabapentin, and apparently propofol
(slide 36)
Dezocine IM dose?
10 - 15 mg IM, rapidly absorbed or 0.15 mg/kg IM. (Slide 19)
100 mg of Meptazinol is = to ____ mg of morphine.
100mg Meptazinol = 8 mg morphine. (Slide 19)
Meptazinol has a low protein binding of ____ %.
25% (slide 19)
True or False:
- Neuraxial opioids can cause N/V
- Neuraxial opioids cause urinary retention more in females
Bonus: why does urinary retention occur?
True
False; occurs more in males
UR occurs d/t interaction at sacral spinal cord with PNS and peripheral outflow
(slide 36)
So we all opioids make our pts STFU and cause ventilation depression. How long will EARLY s/s of vent depression? How long are DELAYED s/s?
What’s are most reliable s/s of ventilation depression?
Rx (dose)?
Early: within 2 hours
Delayed: 6-12 hours (most likely will be seen with Morphine specifically)
Most reliable s/s: ⬇️ LOC secondary to………………..HYPERCARBIA
Rx: Narcan of 0.25 mcg/kg/hr IV; be sure to monitor EtCO2
(slide 37)
Besides sedation, pruritis, vent depression, N/V, Urinary retention, what else do some opioid agonists (like Fentanyl) cause?
CNS ___________, especially in the _______ causing…, which can make it difficult to _________.
________ activity. We treat this with…
CNS excitation, especially in the thorax causing skeletal muscle rigidity which needs to be considered because his can make it difficult to ventilate**
Seizure activity* - make sure to have benzo’s or propofol PRN
(slide 37)
You’re taking care of Ms. Funkibritches who has a hx of HSV-2, and administer an epidural opioid. What should you warn her about post-op days 2-5?
Herpes simplex viral reactivation secondary to your neuraxial opioid you administered. (She should be resting anyways)
(slide 38)
You’re following up with post-op care for a something y/o mother who underwent a C-section, whom you had administered a neuraxial opioid pre-op. But she’s concerned that she won’t be able to breastfeed her new baby. What should you tell her?
Don’t worry momma. Baby will be fine breastfeeding as neuraxial opioids do not affect the she-brew
(slide 38)
Which has a longer half-time, Naloxone or Nalmefene?
Nalmefene (10.8 hours)
Naloxone’s half-time is 60 to 90 minutes
Slide 25
What is naltrexone typically used for?
Alcoholism
Slide 25
What is the duration of Naltrexone?
24 hours
Slide 25
What is the dose for Nalmefene?
15 to 25 mcg IV (q 2 to 5 minutes)
OR
1 mcg/kg
Slide 25
Nalmefene is equipotent to…
Naloxone
Slide 25
Is Methylnaltrexone ionized or nonionized?
Highly ionized
Slide 26
This opioid antagonist promotes gastric emptying and antagonizes nausea/vomiting
Methylnaltrexone
Slide 26
What is the newer, mu-selective PO peripheral opioid antagonist that is used mainly for post-op ileus?
Alvimopan
Slide 26
Where is Alvimopan metabolized?
Gut Flora
Slide 26
What is a risk of using Alvimopan long term?
Adverse CV Events
Slide 26
What are the three tamper/abuse-resistant opioids discussed in class?
Suboxone
Embeda
OxyNal
Slide 27
Buprenorphine plus naloxone…
Suboxone
Slide 27
Extended release morphine plus naltrexone…
Embeda
Slide 27
Oxycodone plus naltrexone…
OxyNal
Slide 27
what are the 3 pure µ opioid receptor competitive antagonists with no agonist activity discussed?
Naloxone, Naltrexone, and Nalmefene
(slide 22)
For the 3 Opioid Antagonists discussed in class to be considered a “Competitive Antagonists” what 2 things must be present in the body?
- An opioid
- Must have a large enough dose of the antagonist drug to able to outcompete/displace the opioid from the receptor site
(slide 22)
Which Opioid Antagonist is a nonselective antagonist with all 3 opioid receptors?
Naloxone
(slide 23)
Lungs are __________ and affect the drug’s pharmacokinetics’ _____________ phase (i.e. association and dissociation from plasma proteins and diffusion rates)
Reservoirs
Dispositional
(Lung First Pass slide)
Removal of endogenous compounds from the pulmonary arterial blood is known as…
Pulmonary Uptake/Extraction
(Lung first-pass slide)
Define the First Pass Effect
Drugs gets retained/accumulated and removed/cleared/metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action
(Lung First-Pass slide)
What are the uses of Naloxone (Narcan)?
- opioid-induced depression in post op
- neonate* (from mom)
- opioid overdose
- detect dependence (will require more)
- Hypovolemic/septic shock
(It Increased myocardial contractility) - Antagonism of general anesthesia (high doses)**
(slide 23)
What opioid is most known for its Lung first-pass effect in its metabolism?
(HINT): Castillo mentioned this one specifically in lecture
Fentanyl
(Lung first-pass slide; Castillo)
What do we need to remember when giving Naloxone to opioid OD in a pregnant mother?
It crosses the placental barrier and if mom goes into withdrawals so will the fetus.
(slide 23)
What does neuroaxial means?
That does not involve brain, and its and axial component of spinal cord.
Slide 31
Neuraxial opioids are used in _______ and _______ space.
Epidural and subarachnoid space (spinal according to lecture)
Slide 31
Why do we use Neuraxial opioids?
It is used for acute or chronic pain management.
Slide 31
Where does neuraxial opioid work in spine and its receptor?
It works in substantia gelatinosa (lamina II) of spinal cord and work in mu receptor.
Slide 31
What is Naloxone’s:
- Dose:
- Dose during Intra-op:
- Dose during Post-op:
- Dose with continuous IV Infusion (and dose with shock infusion):
- Dose with epidural infusion:
- Dose: 1 to 4 µg/kg IV
- Intra-op: 40-80mcg
- Post-op: 40-80mcg
- 5 µg/kg IV continuous infusion
(> 1 mg/kg IV (shock)) - 0.25 µg/kg/hour IV Epidural
(slide 24 and Slide 2 in additional notes)
Do you see sympathectomy, sensory block, or weakness associated with Neuraxial opioids?
No, It only helps with pain.
Slide 31.
( When we do spinal, we go through our skin, fat, ligamentum flavum and spinous ligament until we reach to epidural space)
Slide 31
What is Naloxone’s:
-Onset:
-Duration:
Metabolism’s
- Elimination 1/2 time:
- 1st pass:
Onset: 1-5min
Duration: 30 min (30-45)
Metabolism: Liver (glucuronic acid)
- E1/2 time: 60-90 min
- Hepatic first pass: 1/5th PO
(Naloxone is absorbed orally, but metabolism during its first pass through the liver renders it only one-fifth as potent as when administered parenterally.)
(slide 24 and Slide 2 in additional notes, Pg. 437)
What are the names that can be referred to subarachnoid space?
intrathecal space and spinal space.
Slide 31
(SAB –>Subarachnoid block is spinal block)
Slide 31
What’s Naloxone’s Side Effects:
- reversal of analgesia*
- N/V** (If given too fast)
- increased SNS (HR, BP, pulmonary edema, cardiac dysrhythmias [v-fib])
(slide 24)
When giving Naloxone, HOW should we give it to help prevent some side effects?
Also, due to its duration of effect, what should we consider?
SLOW (over 2 to 3 minutes)
Since duration is only approx. 30min, may have to do an infusion.
(slide 24, pg. 437)
Why the does given via epidural is 5 to 10x more?
The drug need to cross the dura
(unless we give spinal then we give lower dose)
Slide 32
Drugs give via epidural _____ into dura and may cause _______absorption.
diffuse and systemic absorption
Slide 32
Fentanyl and sufentanil is highly ________.
Lipophilic ( so they diffuse more, so their onset and duration of action is not too long)
Slide 32
Why morphine does not diffuse across dura faster?
Morphine is not as non-ionized fentanyl and sufentanil hence it has slower onset but longer duration of action.
Slide 32
When meds are given via epidural where does the absorption occur?
epidural fat and systemic absorption via epidural venous plexus.
Slide 33
What can you do to prevent the systemic absorption of the medication given via epidural?
Add epinephrine or phenylephrine into our solution.
(this shrinks venous plexus and the medication stays in epidural space longer)
Slide 33
Where do we want our epidural medication to work in spine?
We want meds to diffuse across the dura to CSF
( where we get attachment of mu1, mu2, kappa, and delta occurs in substantial gelatinosa.)
Slide 33
What is the lipid solubility of fentanyl compared to morphine and when does it peak?
800x more lipid soluble than morphine.
Peaks in 20 mins.
Slide 33
What is the lipid solubility of sufentanil compared to morphine and its peak time?
1600x more lipid soluble than morphine in the epidural space.
Peak: 6 mins.
(sufentanil works quickly when we give epidural for moms vs when we give fentanyl to hip surgery patients. Great for moms, they can walk and does not cause sympathectomy. )
Slide 33
Does cephalad movement in CSF occur with subarachnoid/spinal/intrathecal uptake?
Yes, upward movement of CSF occurs depend on lipid solubility of the meds.
Slide 34
Since fentanyl and sufentanil is very lipid soluble will the meds diffuse out of CSF or move up the spinal region?
Fentanyl and sufentanil diffuse out of CSF to spinal region and less medication will have a cephalad movement occur via CSF.
(It will affect HR as T1 and T4 are cardiac accelerators and also affect breathing as C3,C4,C5 and C6 controls diaphragm.)
Slide 34
Does cephalad movement occur with morphine?
Yes, morphine being more water soluble stays in CSF longer and more cephalad movement occurs.
( morphine is less lipid soluble so less movement of meds go to spinal cord.)’
Slide 34
What is possible with an abrupt withdrawal after prolonged exposure to opioids?
(long term, not just 1 operation).
Immunosuppression
Slide 28
Is an opioid allergy more a proven fact or myth?
More so a myth. Only 3 documented cases to date.
People associate the common side effects as “allergies”.
Slide 28
Per Dr. Castillo what is the Minimum Alveolar Concentration needed to be in stage 3 of anesthesia?
100%
Slide 29
What is given that decreases MAC of Iso or Desflurane to 50%?
Opioid Agonists
Fentanyl 3mcg/kg IV 25-30 minutes before surgical incision.
Slide 29
What are the effects on MAC with the following opioid agonists?
Sufentanyl
Alfentanyl
Remifentanyl
Sufentanyl decreases MAC with Enflurane by 70-90%
Alfentanyl can decrease MAC up to 70%
Remifentanyl can have a 50-91% decrease in MAC
Slide 29
Not sure if we need to know this or not for this exam but here ya go:
MAC percentages for the following volitiles
Isoflurane
Sevoflurane
Desflurane
Isoflurane: 1.2%
Sevoflurane: 2%
Desflurane: 6%
Mentioned during slide 29
What are the Patient-Controlled Analgesia doses for:
Morphine
Hydromorphone
Fentanyl
Slide 30
When treating pain, what are the goals of using opioid agonists?
To use short acting opioids
-At the lowest effective dose
-Used for just a few days
Slowly increase their dose as needed!
(Video 00:18)
