Opioid Agonist-Antagonists & Antagonists (Exam II) Flashcards
What is the primary indication for opioid agonist-antagonists?
- Used if unable to tolerate full agonist
Name the four advantages of opioid agonist-antagonists. This will probably be super important
- Analgesia
- Less respiratory depression
- Low dependence potential
- Ceiling effect (prevents ODing)
How potent is Pentazocine?
- 1/5 as potent as Nalorphine (Nalorphine is as potent as morphine)
What receptors does pentazocine bind to?
What type of activity does it exhibit?
- Agonizes κ & δ receptors with weak antagonist activity (partial agonist activity?)
Antagonized by Naloxone
How is pentazocine excreted?
- Glucuronide conjugates in the urine.
Extensive hepatic first pass (20% available post PO)
- Elimination half-time: 2 to 3 hours
Which opioid agonist-antagonist crosses the placental barrier causing fetal depression?
Pentazocine
What is the chronic pain dose of Pentazocine?
What dose and route would be equivalent to morphine 10mg?
- 10 - 30mg IV or 50 mg PO (equivalent to Codeine 60 mgs)
- 20-30mg IM = 10mg morphine (watch for similar analgesia, sedation, and respiratory depressive effects)
How much longer does Pentazocine act when administered epidurally?
Trick question, morphine has a longer duration epidurally :)
Where is butorphanol metabolized?
Excreted?
Elim. Half-Time?
- Liver
- Bile>urine
- 2.5-3.5hrs
What receptors does butorphanol bind to?
- κ = analgesia & anti-shivering
- μ (low, producing antagonism)
- σ (minimal so low dysphoria effects)
Sigma (σ) receptors are associated with what side effect?
Dysphoria
IM 2 to 3 mg of butorphanol is equivalent to _____ mg of morphine.
10
Don’t confuse IM dose of butorphanol (2-3mg) with pentazocine (20-30mg
By what route is butorphanol rapidly and completely absorbed?
Intramuscular
Which receptor has a moderate affinity for butorphanol’s effects to mitigate shivering and produce analgesia?
Kappa
What is Nalbuphine’s Elim. Half-Time?
3-6hrs
What drug is an excellent choice for cardiac catheterization patients?
Why?
- Nalbuphine
- No increase in BP, PA BP, HR or atrial filling pressures!
Big W on this one
What receptors does nalbuphine bind to?
How potent is it?
- μ receptor agonist that is equipotent to morphine.
Dr. Castillo felt it important to state that as an antagonist, Nalbuphine is 1/4th as potent as Nalorphine
Which agonist-antagonist has 50 times greater μ receptor affinity than morphine?
Buprenorphine
What is buprenorphine’s onset?
Duration?
- 30min onset
- 8 hour duration (has prolonged resistance to Naloxone)
What is buprenorphine’s greatest use?
- Opioid use disorder (has low risk of abuse)
Does Buprenorphine have any side effects?
Of course, it’s an opiate. Pretty standard though…
- Drowsiness
- N/V
- Ventilation depression
- Pulmonary edema
- Withdrawals but low risk of abuse.
Which two drugs have resistance to naloxone?
- Buprenorphine and Bremazocine.
Which opioid has high incidence of dysphoria and is therefore not utilized clinically?
Nalorphine (σ receptors)
Nalorphine is equally potent with Morphine
Bremazocine affects ___ receptors and is ___times more potent than morphine
- Kappa (κ)
- 2
This opioid affects δ & µ receptors producing analgesia with no CV effects.
Dezocine
What is the dosing structure of Dezocine?
Onset?
- 0.15 mg/kg IM= Morphine
- 10 to 15 mg IM rapid absorption
- Onset is 15 mins.
What receptor is affected by Meptazinol?
What is it’s weird equivalence dose to morphine?
- mu1 receptors
- 100 mg = 8 mg Morphine
What is Meptazinol’s onset and duration?
How protein bound is it?
rapid onset
- Duration <2hrs
- 25% protein bound
Which of these Opioid Agonist-Antagonists is more potent than Morphine?
Buprenorphine is 50x more potent than Morphine
Nalorphine and Nalbuphine are equipotent to morphine and Meptazinol is less potent than morphine (100mg=8mg)
Which drugs are pure μ-opioid receptor antagonists?
- Naloxone
- Naltrexone
- Nalmefene
These have a high affinity to opioid receptors with no agonist activity
What receptors is naloxone effective on?
- μ, κ, δ (non-selective)
What non-opioid uses does naloxone have?
- ↑ contractility to treat hypovolemic/septic shock
- Antagonism of general anesthesia at high doses.
What is the naloxone IV push dose?
Continuous infusion?
- 1-4 mcg/kg IV
- 5 mcg/kg IV infusion
Your OB patient is having some terrible side effects from her epidural. Can you give naloxone here? If so, how much?
Yes, please make her hate you less.
- 0.25mcg/kg/hr IV
What dose of naloxone is use for shock?
- > 1mg/kg IV
How long does Naloxone last?
- 30 - 45 minutes
Often needs redosing for overdoses.
Naloxone has an elimination half-time of __ to __ minutes and if taken PO, __% is leftover after hepatic 1st pass.
60 to 90min
20% is leftover so it’s best to give IV or IN (why would you even consider PO in an emergency???)
What are the possible side-effects of naloxone?
- Analgesia reversal
- N/V (Admin over 2-3min, rather than as a bolus, decreases N/V occurence.)
- ↑ SNS ( ↑ HR, BP, pulm edema, dysrhythmias, etc.)
What use does naltrexone have?
How long does it last and how is it adminstered?
- EtOH
- Given PO (more effective) lasts for 24 hours.
How does nalmefene’s potency compare to naloxone?
What is it’s dose and max?
Bonus points if you know it’s elim H/T.
- Nalmefene = naloxone
- 15 - 25 mcg IV (max of 1 mcg/kg)
- Elimination half-time is 10.8hrs
What is methylnaltrexone’s use?
- Anti-emetic (antagonizes N/V from opioids)
- Promotes gastric emptying
What is Alvimopan and what is it used for?
How is it metabolized?
Why can’t it be used long term?
- μ-selective PO peripheral opioid antagonist for post-op ileus.
- Gut flora metabolism
- CV problems long term
What are the abuse-resistant opioid formulations?
- Suboxone (buprenorphine + naloxone)
- Embeda (long-release morphine + naltrexone)
- OxyNal (oxycodone + naltrexone)
What opioids-agonists have a significant effect on volatile anesthetics?
What do they do?
- Fentanyl & it’s derivatives decrease the Minimum Alveolar Concentration (MAC) of Iso or Desflurane by 50% or greater.
Fentanyl 3 μg/kg IV 25-30 min prior to incision will have what effect on which volatile gasses?
- 50% MAC reduction for isoflurane and desflurane.
Which opioid partial agonists affect Minimum Alveolar Concentration (MAC)? Is this an increase or decrease? What percent?
All Decrease MAC of Iso and Desflurane
- Pentazocine (11%)
- Butorphanol (8%)
- Nalbuphine (20%)
Where are receptors targeted with opioid neuraxial anesthesia?
- Opioid receptors of the substantia gelatinosa (spinal cord).
Patient cannot have sympathectomy, sensory block, or weakness
What is general rule of dosing for epidural opioids?
- Dose = 5 - 10 x normal
Diffusion of opioids across the _____ ______ results in systemic absorption.
dura mater
Where can opioids be injected during an epidural that results in systemic absorption?
What should be done if this occurs?
- Epidural venous plexus
- Add vasoconstrictor (epi) to the infusion.
What is Cephalad movement (in regards to epidurals)?
Cephalad Movement = the movement of drug/injectate up the spinal cord towards the brain.
What drug attribute decreases cephalad movement?
- Lipid solubility
Regarding lipid solubility in epidural administration, how does fentanyl and sufentanil compare to morphine?
What are their respective peaks?
Fent is 800x>morphine
- peak is 20min
Sufent is 1,600x>morphine
- peak in 6min
________ exhibits much more cephalad movement than __________.
Why is this?
- Morphine ; fentanyl
- Fentanyl and it’s derivatives are much more lipid soluble and thus exhibit less cephalad movement.
What can cause cephalad movement? (besides characteristics of drugs themselves)
Coughing and/or straining
- Drug baracity (Patient’s body position) has no effect on cephalad movement
Drug baricity is the ratio of a drug’s density to the density of cerebrospinal fluid (CSF). Drug baracity can help determine how a drug will spread through the CSF, especially when the patient moves around.
When would epidural CSF levels peak for the following drugs:
- Fentanyl
- Sufentanil
- Morphine
- Fentanyl - 20min
- Sufentanil - 6min
- Morphine - 1-4 hours
When would epidural administered plasma levels peak for the following drugs:
- Fentanyl
- Sufentanil
- Morphine
- Fentanyl - 5-10 min
- Sufentanil - 5 min or less
- Morphine - 10 - 15 min
All of these times are similar to IM route
When would epidural administered intrathecal/cervical CSF levels peak for the following drugs:
- Fentanyl
- Sufentanil
- Morphine
- Fentanyl - minimal to N/A
- Sufentanil - minimal to N/A
- Morphine - 1 - 5 hours due to cephalad movement
What is the most common side effect from neuraxial opioid administration?
Why does this occur?
- Pruritis (esp. OB) in the face, neck, and upper thorax
- Cephalad migration to trigeminal nucleus
What are the treatments for pruritis induced by neuraxial opioids?
- 10mg Propofol
- Naloxone
- Antihistamines
- Gabapentin
Name the list (sorry, this is a lot) of side effects that can occur with neuraxial opioid administration.
- Pruritis (most common, esp. in OB)
- N/V
- Urinary retention D/T interaction at sacral spinal cord that can affect PNS outflow (male>female)
- Respiratory depression (usually occurs within 2hrs of admin but can be delayed as much as 6 to 12 hours!
- Sedation
- CNS excitation –> Skeletal muscle rigidity like seizure activity (scary)
- Herpes simplex labialis viral reactivation (Occurs 2 to 5 days after epidural opioid)
- Neonatal morbidity but negligible in breast milk
Naloxone (0.25 µg/kg/hour IV) is effective in attenuating the side effects (nausea and vomiting, pruritus)
If neuraxial opioids induced a reemergence of a herpes simplex labialis virus, how long would this occur after opioid administration?
- 2 - 5 days
What sign would indicate respiratory depression from neuraxial opioid administration?
What is the treatment?
This will probably be a pretty relevent card.
- ↓LOC from ↑CO₂
- Naloxone 0.25 μg/kg/hr IV
