Exam 2 - Opioid Agonist-Antagonists and Antagonists Flashcards
What are the advantages of using opioid agonist-antagonists?
- Analgesia
- Limited ventilatory depression
- Low potential for physical dependence
- Ceiling effect prevents additional responses
Explain the ceiling effect?
What is pentazocine’s MOA?
Agoinst effects on delta and kappa receptors with weak antagonist activity
Pentazocine is antagonized by ____
____ as potent as nalorphine
Extensive ____
Excreted as ____ in the urine
- naloxone
- 1/5th
- hepatic first pass
- glucoronide conjugates
What is pentazocine used for and at what dose? (IV, IM, PO)
Moderate chronic pain
IV: 10-30mg
IM: 20-30mg
PO: 50mg
Why do we like Pentazocine for epidural analgesia?
Bc it has shorter duration than morphine
Pentazocine s/e are similar to morphine’s.
What can it cause at high doses?
What cardiac effects do you see?
Dysphoria
CV: ⬆in HR, BP, pulmonary artery BP, LVEDP
What must you consider when giving Pentazocine to pregnant women?
It crosses the placental barrier and can cause fetal depression
Is Butorphanol more potent than pentazocine? (Agonist and Antagonist effects)
Yes
Agonist: 20x >
Antagonist: 10-30x >
How does butorphanol produce analgesia and anti-shivering effects?
Moderate affinity for kappa receptors
Dosing for butorphanol?
Equivalent to how many mg of morphine?
- 2-3 mg IM
- 10 mg morphine
It may be difficult to use another ____ in the prescence of butorphanol?
Opioid agonist
What are the generalized side effects of Opioid Agonist-Antagonists?
They are the same as opioid agonists + dysphoric reactions.
Nalbuphine is a ____ receptor agonist and is equally potent to ____
Mu
Morphine
Which agonist antagonist opioid is good to use in patients with cardiovascular dz?
- Nalbuphine
- It does not cause an increase in BP, pulm pressures, HR, or atrial pressures
Buprenorphine is a ____ receptor agoinst with an affinity ____ than morphine
Why can this be a problem?
- Mu
- 50x greater
- Has a prolonged resistance to naloxone
How much buprenorphine is equal to 10 mg of morphine?
0.3 mg IM
Nalorphine is not used as clinically because of?
What is its morphine potency?
- High incidence of dysphoria with sigma receptor activation
- Equivalent potency to morphine
Bremazocine has a receptor affinity for ____ receptors that is ____ more potent than morphine
Can it be reversed by naloxone?
- Kappa
- 2x
- No
Similar to Nalbuphine, in that they both do not exhibit cardiovascular effects.
Dezocine
Dezocine IM dose?
10 - 15 mg IM or 0.15 mg/kg IM
100 mg of Meptazinol is = to ____ mg of morphine
What receptor does it work on?
- 100 mg Meptazinol = 8 mg morphine
- Mu 1
What is the MOA of opioid antagonists?
Pure mu opiod competitive antagonist with no agonist activity
This opioid antagonist is nonselective for all 3 opioid receptors?
Naloxone
What are the uses for naloxone?
- Post op opiod induced depression
- Neonate, from mom
- Opiod OD
- Detecting dependence
- Hypovolemic/septic shock (increases myocardial contractility)
- Antagonizes general anesthesia in high doses
Naloxone dosing
IV:
Continuous infusion:
Shock:
Epidural side effects:
IV: 1-4 mcg/kg
Continuous infusion: 5 mcg/kg
Shock: >1 mg/kg
Epidural side effects: 0.25 mcg/kg/hr
How long does naloxone last?
30-45 mins (may need to redose)
Side effects of naloxone?
- Reversal of analgesia
- N/V
- Increased SNS
What opioid antagonist works better PO?
Uses?
- Naltrexone
- Alcoholism
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
Nalmefene has a half time of?
10.8 hours
Is Methylnaltrexone ionized or nonionized?
Highly ionized
Methylnaltrexone uses?
- Promotes gastirc emptyinh and antagonizes N/V
- No alteration in centrally mediated analgesia
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
Oxycodone plus naltrexone…
OxyNal
Are allergies to opioids true allergies?
- Not really, only 3 documented cases
- S/E are due to histamine release, orthostatic hypotension, N/V
What can prolonged exposure to opioids and abrupt withdrawl cause?
- Immunosuppression
What is given that decreases MAC of Iso or Desflurane to 50%?
Fentanyl 3mcg/kg IV 25-30 minutes before surgical incision
What are the effects on MAC with the following opioid agonists?
Sufentanil
Alfentanil
Remifentanil
Sufentanil decreases MAC with Enflurane by 70-90%
Alfentanil can decrease MAC up to 70%
Remifentanil can have a 50-91% decrease in MAC
Which opiod agonist-antagonists can decrease MAC?
- Butorphanol
- Nalbuphine
- Pentazocine
What are the Patient-Controlled Analgesia doses for:
Morphine
Hydromorphone
Fentanyl
Why is PCA sometimes better than prn dosing?
Benefits of neuraxial opioids?
- No sympathectomy, sensory block, or weakness
What is the dose change for epidurals compared to spinals?
5x-10x the dose, has to diffuse accross the dura
What opioids are given in an epidural and there action? (include peak csf times)
Fentanyl - highly lipophilic (800x more than morphine) - peaks in 20 mins
Sufentanil: highly lipophilic (1600x morphine) - peaks in. 6 mins
Morphine: Slower onset but longer duration - peaks in 1-4 hours
What is the pathway for drugs for epidural uptake?
- Epidural fat → epidural venous plexus → systemic absorption → diffusion across dura → CSF
What can you do to help reduce systemic absoption of epidural opioids?
Add a vasoconstrictor
What contributes to cephalad movement of spinal opioids?
- Lipid solubility
- Coughing or straining
Which drugs tend to have cephalad movements more when given intrathecally?
Morphine > fentanyl and sufentanil
Morphine remains in the CSF more and can migrate upwards, whereas fentanyl crosses into the spinal cord
What are hypobaric and hyperbaric drugs?
Hypobaric drugs float in solution
Hyperbaric drugs are more dense and sink in solution
Positioning affects drug migration due to gravity
Plasma peak of epidural fentanyl, sufentanil, and morphine?
Fentanyl: 5-10 min
Sufentanil: < 5 min
Morphine: 10 - 25 min
Cervical CSF peak levels of fentanyl, sufentanil, and morphine?
Fentanyl: minimal
Sufentanil: minimal
Morphine: 1-5 hours
Most common side effect of neuraxial opiods?
Cause?
Tx?
- Pruritis
- Cephalad migration to trigeminal nucleus
- Tx: naloxone, antihistamines, gabapentin
Who is at high risk for urinary retention d/t neuraxial opioids?
Males, due to interaction at the sacral spinal cord inhibiting PNS outflow
What is the most reliable sign of depression of ventilation d/t neuraxial opiods?
Tx?
- Depressed LOC d/t hypercarbia
- Naloxone 0.25 mcg/kg/hour to decrease side effects
What can be reactivated 2-5 days after epidural opioid administration?
Herpes simplex labialis
