Opioid agonist-antagonists Flashcards
Advantages of opioid agonist-antagonists include
- Analgesia
- Limited depression of ventilation (still some but limited)
- low potential for physical dependence
- ceiling effect prevents additional responses
Phenomena where a drug’s impact on the body plateaus
Ceiling effect
Pentazocine as agonistic effects on which receptors?
delta(δ) and kappa (k) receptors
Pentazocine potency compared to Nalorphine
1/5th as potent as nalorphine
“gold standard” for comparing opioid agonist-antagonists
Nalorphine (equivalent to morphine)
Pentazocine is antagonized by
Naloxone (narcan)
How much is Pentazocine affected by 1st pass metabolism
highly, 20% available post PO
Pentazocine excretion
Glucuronide conjugates via urine
Pentazocine chronic pain dose
10-30mg IV, or 50mg PO (equivalent to 60mg codeine)
A common CV side effect from opioid agonist-antagonists is
decreased BP and increased HR as compensatory mechanism
Butorphanol agonist effect is ______ and antagonist effect is ____ to ____ compared to Pentazocine
agonist 20x and antagonist 10-30x higher than Pentazocine
(stronger than morphine)
Butorphanol has a _____ affinity for μ receptors, _____ affinity for k receptors, and _______ affinity for σ receptors
μ= low (antagonism)
k=moderate (analgesia and anti-shivering)
σ= minimal (low dysphoria)
E1/2 time of Butorphanol is
2.5-3.5hrs
Metabolism and Elimination of Butorphanol
Metab= liver
excretion = Bile/fecal > urine
Which receptor has a moderate affinity for Butorphanol’s effects to mitigate shivering and produce analgesia?
k- kappa receptors
Nalbuphine agonistic effect compared to morphine
equally potent
Nalbuphine antagonist effect compared to Nalorphine
1/4th as potent as Nalorphine
E1/2time of Nalbuphine
3-6hrs
A benefit of Nalbuphine that is different than the others
No increase in HR/BP, good for cardiac patients
Buprenorphine potency compared to morphine
μ receptor agonists 50x higher than morphine
(0.3mg IM = 10mg morphine)
DOA of Buprenorphine
8hrs
Because of its long duration of action, Buprenorphine has a _____ resistance to naloxone
prolonged/high resistance to naloxone
Which opioid agonist-antagonist is equally potent to morphine but causes higher amounts of dysphoria, so it is not commonly used?
Nalorphine
Meptazinol protein binding amount
25%
Naloxone, Naltrexone, and Nalmefene are considered
μ-opioid receptor antagonists, no agonist activity
competitive antagonists -> high affinity to opioid receptors
Naloxone uses
- opioid-induced depression in post-op
- neonate* (from mom)
- opioid overdose
- detect dependence
- Hypovolemic/septic shock (inc. myocardial contract.)
- Antagonism of general anesthesia (high doses)
Naloxone doses
- 1-4 mcg/kg IV
- 5 mcg/kg continuous infusion
- > 1mg/kg IV for shock
- epidural s/e= 0.25mcg/kg/hr IV
Naloxone DOA
30-45min, will likely require redosing
A dangerous s/e to Naloxone
cardiac dysrhythmias (v-fib), recommend to give slowly to avoid
Naltrexone is more effective when given _____
PO
Naltrexone DOA
24hrs
Naltrexone is primarily used for
alcoholism
Nalmefene is _______ potent compared to naloxone
equipotent
Nalmefene dose
15-25mcg IV q2-5min til 1mcg/kg
Nalmefene E1/2time
10.8hrs
Methylnaltrexone is highly ionized and quarternary, meaning it
does not cross BBB, effects only peripherally
Methylnaltrexone is used to
promote gastric emptying and antagonizes N/V; no alteration in centrally mediated analgesia
Alvimopan is primarily used for
newer μ-selected PO opioid antagonist, used for post-op ileus
metabolized by gut flora
limited in long term use s/t CV events
Suboxone is a combination of _____ and ______
buprenorphine and naloxone
Embeda is a combination of ______ and ______
extended-release morphine and naltrexone
OxyNal is a combination of _____ and _____
oxycodone and naltrexone
Fentanyl decreases MAC of Iso and Desflurane by how much
50%
PCA dosing of morphine
basal= 0-2mg/hr, bolus= 1-2mg, interval= 6-10min
PCA dosing of hydromorphone
basal=0-0.4mg/hr, bolus= 0.2-0.4mg, interval 6-10min
PCA dosing of fentanyl
basal = 0-60mcg/hr, bolus= 20-50mcg, interval= 5-10min
Neuraxial analgesia targets
opioid receptors in Lamina 2 (substantia gelatinosa) of spinal cord
The 2 types of neuraxial analgesia includes
epidural and spinal/intrathecal/subarachnoid block (SAB)
epidural dosing is _____ compared to spinal
5-10x higher
In what analgesia does the drug diffuse across the dura
epidural
which neuraxial used opioids are highly lipophilic
fentanyl and sufentanil
which neuraxial used opioids are highly hydrophilic
morphine (slower onset, longer duration)
Epidural uptake can occur via
- epidural fat
- epidural venous plexus
Which epidural uptake can cause systemic effects?
uptake via epidural venous plexus
which is a method used to reduce venous uptake in epidurals
use of vasoconstrictor in conjunction
which vasoconstrictors can be used in epidurals
Epi (primary), phenylephrine
Lipid solubility of fentanyl compared to morphine
800x more lipophilic than morphine
lipid solubility of sufentanil compared to morphine
1600x more lipophilic than morphine
_________ is when neuraxial opioids migrate upward
Cephalad movement
Which spinal level are cardiac accelerator fibers located
T1-T4
Which spinal level dermatome is at the nipple line
T4
Which spinal level dermatome is the xiphoid
T6-8
Which spinal level dermatome is the umbilical region
T10
Which opioid when given spinally is more likely have cephalad migration
morphine (mixes with CSF d/t its hydrophilic property)
What causes an increase in cephalad movement
coughing and straining (valsalva)
What is baracity?
whether the drug sinks or floats
Hyperbaric drugs ____
sink
Hypobaric drugs _____
float
What local anesthetic baracity would affect the right hip of a patient positioned in the left lateral position?
hypobaric
Opioid epidural admin/CSF peak times
fentanyl= 20min
sufentanil= 6min
morphine= 1-4hrs
Opioid epidural admin/plasma peak
fentanyl= 5-10min, similar to IM
sufentanil= <5min, similar to IM
morphine= 10-15min, similar to IM
Opioid intrathecal/CSF/cervical levels
fentanyl= minimal
sufentanil= minimal
morphine= 1-5hrs
Neuraxial anesthesia can cause pruritis if it reaches the ________
trigeminal nucleus in brainstem
Treatment of pruritis due to neuraxial analgesia
Naloxone, antihistamines, gabapentin, propofol 10-20mg IV
S/e of neuraxial analgesia include
- ventilatory depression
- “neuropathic” Pruritis
- N/V
- urinary retention in men
- sedation
- CNS excitation (tonic skeletal muscle rigidity like seizure activity)
- herpes simplex labialis viral reactivation 2-5days after epidural opioid
- neonatal morbidity
Women are instructed not to breastfeed for how long after given neuraxial analgesia
24hrs
