SS25 Opioid Agonist-Antagonists & Antagonists (Exam 2) 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.
- Analgesia
- Less respiratory depression (better for COPD, Obesity, diff. airway)
- Low dependence potential
- Ceiling effect
Generalized SE of opioid agonist-antagonists.
- same as morphine + dysphoric reactions (ie: fear of impending death)
Sigma (σ) receptors are associated with what side effect?
Dysphoria
What is the ceiling effect?
- prevents additional (ie: OD)
- Drug impacts on body plateaus
- Higher doses do not increase its effects
Which receptors do opioid agonist-antagonists?
- μ - partial agonist effect or no effect (competitive antagonist)
κ & σ - partial agonist effect
What receptors does pentazocine bind to?
What type of activity does it exhibit?
- κ & δ receptor partial agonist activity
- weak antagonistic effects
How potent is Pentazocine?
- 1/5 (20%) as potent as Nalorphine
- Nalorphine equally potent to Morphine
Pentazocine: Pharmacokinetics
- First pass?
- E1/2?
- Excretion?
- Hepatic: HIGH (80%)
- only 20% enters circulation - E1/2: 2 - 3 hrs
- Glucoronide conjugates in the urine
Pentazocine:
- Chronic pain dose IV, IM, & PO?
-Which opioid agonist is the PO dose equal to?
- Which opioid agonist is the IM dose equal?
- IV: 10 - 30mg
- PO: 50 mg (= Codeine 60 mg PO)
- IM: 20-30mg (= 10mg of morphine)
T/F: Epidural analgesia administration of Pentazocine has a shorter duration than Morphine.
- True
Pentazocine SE:
-
increased HR, BP, PAP, LVEDP
-sedation
-diaphoresis
-dysphoria (at high doses) - dizziness
Which opioid agonist-antagonist crosses the placental barrier causing fetal depression?
Pentazocine
What receptors does Butorphanol (Stadol) bind to?
-What responses are elicited?
- κ = (moderate affinity) analgesia & anti-shivering
- μ (low affinity) - low antagonism
- σ (low affinity) - low dysphoria
Potency of Butorphanol
- Agonistic: 20x > Pentazocine
-Antagonistic: 10 - 30 x > Pentazocine
By what route is Butorphanol rapidly and completely absorbed?
- IM
Butorphanol:
PostOp IM dose:
Indications:
- PostOp: 2 - 3 mg IM
- Use: Typically post op pain, anti-shivering, migraines
2 to 3 mg of butorphanol is equivalent to _____ mg of morphine.
- Why is this clinically significant?
- 10 mg
- Ventilation depression
Butorphanol:
- Metabolism?
- E1/2?
- Excretion?
- E1/2: 2.5 -3.5 hrs
- Metabolism: Hepatic
- Excretion: Bile > urine
Butorphanol SE:
- same typical side effects: sedation, nausea, diaphoresis, dysphoria (less frequent), vent depression, wdl symptoms,** increased HR, BP, PAP,CO**
- may difficult to use with other opioid agonist
What drug is an excellent choice for cardiac catheterization patients?
- Why?
- Nalbuphine
- No increase in BP, PAP, HR, or atrial filling pressures
What receptors does Nalbuphine bind to?
- How potent is it?
- μ receptor agonist
- Equally potent to morphine (10 mg = 10 mg)
What’s Nalbuphine antagonistic potency?
- 1/4th as potent as Nalorphine
Nalbuphine:
- Metabolism?
- E1/2?
- SE?
- Liver
- 3 - 6 hrs
- sedation, dysphoria, wdl symptoms
What receptor(s) does Buprenorphine agonizes?
-What is the analgesic potency?
- μ receptor agonist
- Affinity 50x > Morphine
- 0.3 mg IM = 10 mg Morphine
Buprenorphine:
- Onset?
- Duration?
- Onset: 30 mins
- Duration: 8 hrs (slow dissociation from receptors = prolonged resistance to Naloxone)
Buprenorphine SE:
- drowsiness, N/V, low abuse risk, ventilation depression, pulmonary edema
What is buprenorphine’s greatest use?
- Other uses?
- Opioid use disorder (has low risk of abuse)
- Post op, cancer, renal colic (stones), MI, epidurals
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 receptor)
Place the following opioid agonist-antagonist in order of potency to Morphine (low to high).
- Meptazinol
- Pentazocine
- Nalorphine = Nalbuphine = Morphine
- Dezocine
- Bremazocine
- Buprenorphine
Dezocine:
Receptors?
CV effects?
IM dose?
Onset?
- μ δ
- No CV effects
- 10 -15 mg IM rapid absorption
- Onset 15 mins
Meptazinol:
Receptors?
CV effects?
IM dose?
Onset?
- mu 1
- lowest affinity
- Duration = 2 hrs
- Protein binding: 25%
Which drugs are pure μ-opioid receptor antagonists?
- Naloxone
- Naltrexone
- Nalmefene
T/F: All opioid antagonist are competitive
-Why is this?
- True
- High affinity for all opioid receptors
- Bumps the opioid all, binds to receptor, and inhibits activation
What receptors is naloxone effective on?
- Nonselective μ, κ, δ
Naloxone uses (5)
- Neonate (wdl from mom)
- Hypovolemic/ septic (↑ CO)
- Antagonism of general anesthesia at high doses (Physostigmine better)
- PostOp opioid-induced depression ( must be diluted)
- Opioid OD
- Detect dependence (abuser would go into wdls after reversal)
Naloxone:
- Duration of action (DOA)?
- Metabolism?
- E1/2?
- 1st pass?
- SE?
- DOA = 30 - 45 mins
- Metabolism: Liver via glucuronic acid
- E1/2 = 60- 90 mins
- 1st pass= Hepatic 20% PO
- SE: reversal of analgesia, N/V, ↑ SNS, pulm edema, risk for dysrhythmias (ie: VFib) push slow 2 - 3 mins
Naloxone Dosages depends on indication:
- IV push?
- Continuous infusion?
- Shock?
- Epidural side effects?
- IV: 1-4 mcg/kg
- Infusion: 5 mcg/kg b/c DOA
- Shock: > 1 mg/kg
- 0.25 mcg/kg/hr
Which opioid partial agonists have an effect on MAC?
- Pentazocine
- Butorphanol
- Nalbuphine
Naltrexone:
- Use
- Duration
- Most effective route
- Alcoholism
- 24 hr duration
- PO = most effective
Nalmefene:
- Potency compared to naloxone
What is it’s dose, max, & half life?
- Equipotent to naloxone
- 15 - 25 mcg IV q 2 - 5 mins (max of 1 mcg/kg)
- E1/2: 10.8 hrs
Methylnaltrexone:
- Use
- Is it highly ionized or nonionized? How is this clinically significant?
- Promotes gastric emptying and antagonizes N/V
- highly ionized (quaternary): Peripheral pain (CRTZ zone - ↓ N/V )
- No CNS alteration of analgesia
Alvimopan:
- receptor and route?
- use
- metabolized
Long term complications?
- μ-selective PO peripheral opioid antagonist for post-op ileus.
- Metabolism: Gut flora
- Long - term CV events
Which agonist-antagonist has 50 times greater μ receptor affinity than morphine?
Buprenorphine
What are the tamper/abuse-resistant opioid formulations?
- Suboxone (buprenorphine + naloxone)
- Embeda (long-release morphine + naltrexone)
- OxyNal (Oxycodone + Naltrexone)
- Which opioids-agonists have a significant effect on volatiles?
(Think RAFS) - What do they do?
- What do they do?: Decreases anesthetic requirements (↓ MAC)
- Remifentanil: ↓ MAC 50 - 91%
- Alfentanil: ↓ MAC up to 70%
- Fentanyl: ↓ MAC Isoflurane and Desflurane 50%
- Sufentanil: ↓ MAC Enflurane 70 - 90%
Close CV monitoring. Don’t think percentages are important
Per lecture, what dose of Fentanyl affects MAC?
- 3 μg/kg IV 25 - 30 min prior to incision
- Which opioids-agonist-Antagonist effect volatiles?
(Think BNP)
- Butorphanol (11%)
- Nalbuphine (8%)
- Pentazocine (20%)
PCA MORPHINE:
- Bolus
- Basal
- Bolus interval
- 1 - 2 mg
- 0 - 2 mg/hr
- 6 -10 mins
PCA Hydromorphone:
- Bolus
- Basal
- Bolus interval
- 0.2 - 0.4 mg
- 0 - 0.4 mg/hr
- 6 - 10 mins
PCA Fentanyl:
- Bolus
- Basal
- Bolus interval
- 20 - 50 mcg
- 0 - 60 mcg/hr
- 5 - 10 mins
PCA basal rates are not typically recommended for opioid- ____- patients
Naive
Ketamine has analgesic effects with doses greater than _____%.
- 50%
Where are receptors targeted with opioid neuraxial anesthesia (epidural/spinal)?
- Opioid receptors of the substantia gelatinosa (Lamina II).
- Used for acute and chronic pain
- No sympathectomy, sensory block, or weakness/motor block
Epidural space is vascular. How do we confirm we are not in epidural vein?
- Aspirate
Epidural space is a _____ space.
- Potential
How much air can be put into epidural space?
- 3 cc (reabsorbed)
What is general rule of dosing for epidural v spinal opioids?
- Dose = 5 - 10 x more than spinal dose
Diffusion of opioids across the _____ results in systemic absorption.
dura
Epidural uptake includes ___ & ___.
- fat; epidural venous plexus
Goal for epidural uptake:
- Opiate or LA (local anesthetic) to diffuse across dura into CSF, bathe spinal cord, and enter dorsal horn (Lamina II)
Where can opioids be injected during an epidural that results in systemic absorption?
What should be done if this occurs?
- Epidural venous plexus
- Epinephrine + -caine drug (Epi wash) -keeps drug in epidural space
Neo also clinically indicated
What is Cephalad movement (in regards to epidurals)?
Cephalad Movement = the movement of drug up the spinal cord towards the brain
What drug attribute decreases cephalad movement?
- High Lipid solubility
- High to low: Sufentanil»_space;> Fentanyl»_space; Morphine
________ exhibits much more cephalad movement than __________.
Why is this?
- Morphine; Fentanyl/Sufentanil
- Why? Fentanyl & Sufentanil are highly lipid soluble = less cephalad movement towards brain
-Morphine is less lipid-soluble = more cephalad movement via CSF bulk flow
What factors can cause cephalad movement?
- Coughing/ straining (Valsalva)
- Drug baracity
- Body position
What caution must you take using Valsalva maneuver to induce cephalad movement?
- Risk for unintended high spinal → activates cardiac accelerators → cardiac arrest
What is drug baracity?
- Determines how the drug spreads in relation to density
- High density: Hyperbaric = follows gravity and sinks (settles towards dependent area)
- Low density: Hypobaric = rises against gravity and floats towards non-dependent area
- Isobaric: remains at level (ie: Abd. procedures)
What LA baracity would affect the R hip of a patient positioned on the L lateral side?
- Hypobaracity; Needs to float up to right him
When would epidural CSF levels peak for the following drugs:
- Fentanyl
- Sufentanil
- Morphine
- Fentanyl - 20 mins
- Sufentanil - 6 mins
- Morphine - 1 - 4 hrs
Which opioid agonist typically used for walking epidurals in OB?
- Sufentanil
When would epidural administered plasma levels peak for the following drugs:
- Fentanyl
- Sufentanil
- Morphine
- Fentanyl - 5 - 10 mins
- Sufentanil - < 5 mins (crosses dura rapidly)
- Morphine - 10 - 15 min
When would intrathecal/cervical administered CSF levels peak for the following drugs:
- Fentanyl
- Sufentanil
- Morphine
- Fentanyl - minimal
- Sufentanil - minimal
- Morphine - 1 - 5 hours (via CSF bulk flow)
If your patient goes apneic during intrathecal dose, which opioid agonist might have caused this? What part of cord is affected?
- Morphine
- C3 - C5 (phrenic nerve)
Where do we want all spinal anesthetics to go?
- T8 (lower rib cage) per Castillo
What is T1 - T4?
- Cardiac accelerators
Anatomical point of T4?
- Nip line
If given spinal with Lido, what CV effects do you expect to see?
- What can you do pre-op to help prevent this?
- Decrease BP Increase HR
- 500 cc - 1 L bolus
- goal SBP > 140 typically
What is the most common side effect from neuraxial opioid administration?
Why does this occur?
- Pruritus - face, neck, upper chest
- Cephalad migration to trigeminal nucleus
- Prevalent in OB, elderly
What are the treatments for neuraxial- induced pruritus?
(Think PANG)
- Naloxone 0.25 mcg/kg/hr IV)
- Antihistamines
-Gabapentin - Propofol 10 - 20 mg (GABA-a; risk for loss of airway reflexes)
Other SE:
- CNS
- Pulmonary
- GI/GU:
- Viral:
- Fetal:
- CNS: Sedation :) , Skeletal muscle rigidity; sz-like (rare)
- Pulmonary: Resp depression
- GI: N/V
- GU: Urine retention (males; sacral interaction affects PNS outflow)
- Viral: Herpes virus reactivation
- Fetal: Neonatal Morbidity (No breastfeeding for 24 hrs)
What sign would indicate respiratory depression from neuraxial opioid administration?
What is the treatment?
- ↓LOC from ↑CO₂ (hypercarbia)
- Early: w/in 2 hrs; Late: 6 - 12 hrs post
- Naloxone 0.25 μg/kg/hr IV
If neuraxial opioids induced a reemergence of a herpes virus, how long would this occur after opioid administration?
- 2 - 5 days after epidural opioid
Other words for spinal neuraxial opioid block:
- Intrathecal, Subarachnoid
