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 (than morphine) does Pentazocine act when administered epidurally?
Trick question, morphine has a longer duration epidurally :)
What are some of pentazocine’s S/E?
sedation (duh), diaphoresis, dizziness, dysphoria in high doses (b/c δ receptor activation).
- Also increased HR, BP, LVEDP, and Pulm. Art Pressure
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!
u in Nalbuphine for µ receptor
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
u in Buprenorphine for µ receptor
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.
It is typically used to treat opioid use disorders
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
o in NalOrphine for σ receptor. Get it? sigma looks kin of like a o. No? Ok then.
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
D in dezocine for δ receptor
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
M in meptazino for Mu receptor (specifically µ1)
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
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
- Causes no alteration in centrally mediated analgesia
It is highly ionized quaternary which makes it difficult to cross BBB
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
- Butorphanol (11%)
- Nalbuphine (8%)
- Pentazocine (20%)
Regarding PCAs, basal infusions are typically recommended for which type of patients?
Opioid-naive
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 (spinal dose?)
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
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.
What local anesthetic baracity would affect the left hip of a patient positioned at the left lateral position?
Hyperbaric so that the anesthetic sinks to the appropriate hip.
Hypobaric floats, Isobaric holds in place, hyperbaric sinks
Baracity=density relationship to the location of administration
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 (careful of drug synergism/re-sedation)
- 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!, especially with morphine)
- 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
Order the agonist/antagonists in order from least to most potent.
Exact potency not needed, just least potent to most potent (compared to morphine)
- Meptazinol (approx 1/12th potency)
- Pentazocine (1/5th potency)
- Nalbuphine and Naloprphine (equipotent to morphine)
- Bremazocine (2x potency)
- Dezocine (approx 7x potency)
- Butorphanol (20-30x potency)
- Buprenorphine (50x potency)
Stupid mnemonc for you: My PEt Nessie BREaks Down Before BUrPing (I’m obviously really tired)
What portions of the spinal cord are considered the cardiac accelerators?
T1-T4 (we don’t want our epidural drugs going past T4)
