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

Opioid agonists/antagonists - test 2 Flashcards by Allie Biarnesen

What is pentazocine used for and at what dose? (IV, IM, PO)

Moderate chronic pain.
IV: 10-30mg
IM: 20-30mg
PO: 50mg

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What is the PO dose (50mg) of Pentazocine equivalent to?

60mg Codeine

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What is the IM dose (20-30mg) of Pentazocine equivalent to that produces similar sedation and depression of ventilation?

10mg Morphine

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Why do we like Pentazocine for epidural analgesia?

It has shorter duration than morphine

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Pentazocine s/e are similar to morphine’s. What can it cause at high doses? What cardiac effects do you see?

Dysphoria
Cardiac: ⬆in HR, BP, pulmonary artery BP, LVEDP

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What must you consider when giving Pentazocine to pregnant women?

It crosses the placental barrier and can cause fetal depression.

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Is Butorphanol (Stadol) more potent than pentazocine? (Agonist and Antagonist effects)

Yes.
Agonist: 20x > (more potent than morphine)
Antagonist: 10-30x >

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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

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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

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Which receptor has moderate affinity for Butorphanol (stadol) to prevent shivering and analgesia?

Kappa receptor

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Butorphanol is metabolized in the liver, eliminated via _____ > urine and its E1/2 is ____ to ____ hours.

bile; 2.5-3.5 hours

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S/E of Butorphanol (stadol)

sedation, nausea, diaphoresis, dysphoria, depresses ventilation, W/D can occur

Cardiac: ⬆ BP, PA BP, CO

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What can Butorphanol (stadol) cause synergistic effects with?

Other opioid agonists.

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What are the 7 Opioid Agonist-Antagonists from lecture?

Pentazocine
Butorphanol
Nalbuphine
Buprenorphine
Nalorphine
Bremazocine
Dezocine

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When are Opioid Agonist-Antagonists used?

They are used if unable to tolerate a pure agonist.

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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)

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What are the generalized side effects of Opioid Agonist-Antagonists?

They are the same as opioid agonists + dysphoric reactions

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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

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Pentazocine
1. What receptors does it bind to?

Will you have withdrawal symptoms?
It is ____ as potent as Nalorphine.
What is it antagonized by?
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

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Why are opioid agonists used?

They are used to control acute or chronic pain.
Some are used for diarrhea & cough.

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Opioids bind to opioid receptors in the ____, _____, & ____.

Brain, spinal cord, & GI tract

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Nalbuphine, an opioid agonist-antagonist has equipotency with what gold standard drug?

Morphine, so 10 mg of Nalbuphine = 10 mg morphine.

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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.

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Nalbuphine is _____ as potent as Nalorphine.

The antagonist effect of Nalbuphine is 1/4th as potent as Nalorphine.

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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

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

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!

Buprenorphine dosing: ______ mg IM = 10 mg morphine.

0.3 mg IM, onset in 30 min. Duration 8 hrs.

Types of pain that Buprenorphine is indicated for?

Moderate to severe pain in the post op period, cancer, renal colic, and MIs.

Side effects of Buprenorphine?

Pulmonary edema, drowsiness, N/V, depression of ventilation, withdrawal.

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

Nalorphine is not used as an opioid agonist antagonist because of?

High incidence of dysphoria with sigma receptor activation.

Bremazocine has a receptor affinity for _____ receptors that is ____ more potent than morphine

Kappa, 2x

______ is similar to Nalbuphine, in that they both do not exhibit cardiovascular effects.

Dezocine

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), antihistamines, gabapentin, and propofol

Dezocine IM dose?

10 - 15 mg IM, rapidly absorbed or 0.15 mg/kg IM.

100 mg of Meptazinol is = to ____ mg of morphine.

100mg Meptazinol = 8 mg morphine.

Meptazinol has a low protein binding of ____ %.

25%

True or False: - Neuraxial opioids can cause N/V - Neuraxial opioids cause urinary retention more in females - - 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

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

Besides sedation, pruritis, vent depression, N/V, Urinary retention, what else do some opioid agonists (like Fentanyl) cause?

CNS excitation, especially in the thorax causing skeletal muscle rigidity which needs to be considered because this can make it difficult to ventilate** Seizure activity* - make sure to have benzo’s or propofol PRN

A patient who has a hx of HSV-2, and you 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

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?

Baby will be fine breastfeeding as neuraxial opioids do not affect the breast milk

Which has a longer half-time, Naloxone or Nalmefene?

Nalmefene (10.8 hours) Naloxone’s half-time is 60 to 90 minutes

What is naltrexone typically used for?

Alcoholism

What is the duration of Naltrexone?

24 hours

What is the dose for Nalmefene?

15 to 25 mcg IV (q 2 to 5 minutes) OR 1 mcg/kg

Nalmefene is equipotent to…

Naloxone

Is Methylnaltrexone ionized or nonionized?

Highly ionized

This opioid antagonist promotes gastric emptying and antagonizes nausea/vomiting

Methylnaltrexone

What is the newer, mu-selective PO peripheral opioid antagonist that is used mainly for post-op ileus?

Alvimopan

Where is Alvimopan metabolized?

Gut Flora

What is a risk of using Alvimopan long term?

Adverse CV Events

What are the three tamper/abuse-resistant opioids discussed in class?

Suboxone Embeda OxyNal

Buprenorphine plus naloxone…

Suboxone

Extended release morphine plus naltrexone…

Embeda ## Footnote Slide 27

Oxycodone plus naltrexone…

OxyNal

What are the 3 pure µ opioid receptor competitive antagonists with no agonist activity discussed?

Naloxone, Naltrexone, and Nalmefene

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 - a large enough dose of the antagonist drug to outcompete/displace the opioid from the receptor site.

Which Opioid Antagonist is a nonselective antagonist with all 3 opioid receptors?

Naloxone.

Lungs are __________ and affect the drug’s pharmacokinetics’ _____________ phase.

Reservoirs Dispositional.

Removal of endogenous compounds from the pulmonary arterial blood is known as…

Pulmonary Uptake/Extraction.

Define the First Pass Effect.

Drugs get 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.

What are the uses of Naloxone (Narcan)?

- Opioid-induced depression in post-op - neonate, - opioid overdose - detect dependence - hypovolemic/septic shock - antagonism of general anesthesia (high doses)

What opioid is most known for its Lung first-pass effect in its metabolism?

Fentanyl.

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.

What does neuroaxial mean?

That does not involve the brain, and it's an axial component of the spinal cord.

Neuraxial opioids are used in _______ and _______ space.

Epidural and subarachnoid space.

Why do we use Neuraxial opioids?

It is used for acute or chronic pain management.

Where does neuraxial opioid work in the spine and its receptor?

It works in substantia gelatinosa (lamina II) of the spinal cord and works in mu receptor.

What is Naloxone’s dose during Intra-op?

40-80 mcg.

What is Naloxone’s dose during Post-op?

40-80 mcg.

What is Naloxone’s dose with continuous IV Infusion?

5 µg/kg IV continuous infusion.

What is Naloxone’s dose with shock infusion?

> 1 mg/kg IV.

What is Naloxone’s dose with epidural infusion?

0.25 µg/kg/hour IV Epidural.

Do you see sympathectomy, sensory block, or weakness associated with Neuraxial opioids?

No, it only helps with pain.

What is Naloxone’s onset time?

1-5 min.

What is Naloxone’s duration?

30 min (30-45).

What is Naloxone’s elimination half-life?

60-90 min.

What is Naloxone’s hepatic first pass effect?

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.)

What are the names that can be referred to subarachnoid space?

Intrathecal space and spinal space

What are Naloxone’s side effects?

- Reversal of analgesia, - N/V (if given too fast), - increased SNS (HR, BP, pulmonary edema, cardiac dysrhythmias).

When giving Naloxone, how should we administer it to help prevent some side effects? Due to it's duration of effect, what should we consider?

SLOW (over 2 to 3 minutes). Since duration is only approx. 30 min, may have to do an infusion

Why is the dose given via epidural 5 to 10x more?

The drug needs to cross the dura (unless we give spinal then we give lower dose)

Drugs given via epidural _____ into dura and may cause _______ absorption.

Diffuse and systemic absorption.

Fentanyl and sufentanil are highly ________.

Lipophilic (they diffuse more, so their onset and duration of action is not too long)

Why does morphine not diffuse across dura faster?

Morphine is not as non-ionized as fentanyl and sufentanil, hence it has a slower onset but longer duration of action.

When meds are given via epidural, where does the absorption occur?

Epidural fat and systemic absorption via epidural venous plexus.

What can you do to prevent the systemic absorption of the medication given via epidural?

Add epinephrine or phenylephrine into our solution (this shrinks the venous plexus and the medication stays in epidural space longer)

Where do we want our epidural medication to work in the 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

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.

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.

Does cephalad movement in CSF occur with subarachnoid/spinal/intrathecal uptake?

Yes, upward movement of CSF occurs depending on the lipid solubility of the meds.

Since fentanyl and sufentanil are very lipid soluble, will the meds diffuse out of CSF or move up the spinal region?

Fentanyl and sufentanil diffuse out of CSF to the 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 through C3-C5)

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)

What is possible with an abrupt withdrawal after prolonged exposure to opioids?

Immunosuppression.

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"

Per Dr. Castillo, what is the Minimum Alveolar Concentration needed to be in stage 3 of anesthesia?

100%.

What is given that decreases MAC of Iso or Desflurane to 50%?

Opioid Agonists, specifically Fentanyl 3mcg/kg IV 25-30 minutes before surgical incision. ## Footnote ]

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.

What are the MAC percentages for the following volatiles: Isoflurane, Sevoflurane, Desflurane?

- Isoflurane: 1.2%, - Sevoflurane: 2%, - Desflurane: 6%.

When treating pain, what are the goals of using opioid agonists?

To use short acting opioids at the lowest effective dose for just a few days, slowly increasing their dose as needed.