Opioid Agonist antagonist Flashcards
What are all the opiod agonist-antagonists
Pentazocine
Butorphanol
Nalbuphine
Buprenorphine
Nalorphine
Bremazocine
Dezocine
Why use Agonist-Antagonists
Used if unable to tolerate a pure agonist.
Binds to the following receptors:
µ receptors: partial effect (agonist) or no effect (competitive antagonist)
Κ and δ receptors: partial effect (agonist)
Generalized S/E: same as opioid agonists + dysphoric reactions.
Advantages:
analgesia
limited depression of ventilation
Low potential for physical dependence
Ceiling effect prevents additional responses
Pentazocine
Agonist effects on δ and κ receptors with weak antagonist activity
May have withdrawal symptoms
1/5th as potent as Nalorphine
Antagonized by Naloxone
Extensive hepatic first pass (20% available post PO)
Elimination half-time: 2 to 3 hours
Excretion: Glucoronide conjugates = urine
Pentazocine Dose
Moderate Chronic Pain Dose: 10 to 30 mg IV or 50 mgs PO (equivalent to Codeine 60 mgs)
20 to 30 mgs IM: analgesia sedation and depression of ventilation similar to 10 mgs of Morphine
Epidural analgesia: Shorter duration < Morphine
S/E: sedation, diaphoresis, dizziness, dysphoria (high doses), increased HR, BP, PA bp, LVEDP.
Crosses placental barrier fetal depression
Butorphanol receptors
Agonist 20x and antagonist 10x to 30x > Pentazocine
low affinity for µ receptors to produce antagonism
moderate affinity for κ receptors to produce analgesia and anti-shivering effects
minimal affinity for σ receptors so dysphoria is low
2 to 3 mg IM = 10 mg Morphine (depression of ventilation)
Rapidly & completely absorbed with IM.
Butorphanol
Elimination half-time: 2.5 to 3.5 hours
Metabolism: Hepatic
Elimination: Bile > urine
S/E
sedation, nausea, diaphoresis, dysphoria, depression of ventilation, withdrawal symptoms occur
increased BP, PA BP, & C0
Caution: difficult to use with another opioid agonist
Nalbuphine
µ receptors agonist: equally potent to Morphine (10 mg = 10 mg)
Antagonist: 1/4th as potent as Nalorphine
Metabolism: Liver
Elimination half-time: 3 to 6 hours
S/E: sedation, dysphoria, withdrawal symptoms
CV: no increase in BP, PA BP, HR, or atrial filling pressures √√√ cardiac catheterization patients
Buprenorphine
µ receptors agonist affinity is 50x > Morphine
Analgesic potency 0.3 mg IM = 10 mg Morphine
Onset: 30 mins
Duration: 8 hours; prolonged resistance to Naloxone
Uses: Post op, cancer, renal colic, and MI; epidural
S/E: drowsiness, N/V, ventilation depression, pulmonary edema, withdrawal, low risk of abuse.
Nalorphine
Equally potent with Morphine
Not used clinically: high incidence of dysphoria (σ receptors)
Bremazocine
κ receptors 2x potent > Morphine
Naloxone = not effective as reversal (could be other receptors)
Dezocine
δ(delta) & µ: analgesia, no CV
0.15 mg/kg IM= Morphine
10 to 15 mg IM rapid absorption
Onset: 15 mins.
Meptazinol
mu1 receptors
100 mg = 8 mg Morphine
Rapid onset
Duration: < 2 hrs
Protein binding: 25%
Which Opioid Agonist-Antagonist is more potent than Morphine?
Buprenorphine
bremazocine as well
Naloxone, Naltrexone, and Nalmefene
Pure µ opioid receptor antagonists
with no agonist activity
Competitive antagonist
High affinity to opioid receptors
Naloxone
Nonselective antagonist with all 3 opioid receptors
Uses:
opioid-induced depression in post op
neonate* (from mom)
opioid overdose
detect dependence
Hypovolemic/septic shock
Increased myocardial contractility
Antagonism of general anesthesia (high doses)**
Naloxone
Dose
Dose
1 to 4 µg/kg IV
5 µg/kg IV continuous infusion
> 1 mg/kg IV (shock)
Epidural S/E: 0.25 µg/kg/hour IV
Duration: 30 to 45 minutes ***
Metabolism: Liver (glucuronic acid)
Elimination half-time: 60 to 90 minutes
Hepatic first pass: 1/5th PO
S/E: reversal of analgesia*, N/V**, increased SNS (HR, BP, pulmonary edema, cardiac dysrhythmias [v-fib]
Naltrexone
More effective PO
Duration: 24 hours
Uses: alcoholism
Nalmefene
Equipotent to naloxone
Dose: 15 to 25 µg IV (q 2 to 5 mins) 1 µg/kg
Elimination half-time: 10.8 hours
Methylnaltrexone
Highly ionized (quarternary): peripheral
Promotes gastric emptying and antagonizes N/V
No alteration in centrally mediated analgesia
Alvimopan
Newer, µ-selective PO peripheral opioid antagonist
Uses: post op ileus
Metabolism: gut flora
Limitations: long term use CV events
Tamper or Abuse Resistant Opioids
Suboxone (buprenorphine plus naloxone)
Embeda (extended-release morphine plus naltrexone)
OxyNal (oxycodone plus naltrexone)
Side Effects
S/E: histamine release, orthostatic hypotension, N/V
Prolonged exposure to opioids and abrupt withdrawal
Less in short term opioid use
Minimum Alveolar Concentration
Butorphanol: 11% decrease
Nalbuphine: 8% decrease
Pentazocine: 20%
Opioid receptors
Lamina 2 – substantia gelatinosa- soak the dorsal horn to not transmit the impulses
Epidural
Dose is 5 to 10x more
Diffusion of drugs across the dura -> systemic absorption
Highly lipophilic: Fentanyl & sufentanil
Morphine: slower onset, but longer duration, water soluble.
Epidural Uptake
Epidural fat
Epidural venous plexus = systemic absorption
Intervention: Add epinephrine
Diffusion across the dura -> CSF
Lipid solubility
Fentanyl (800x > morphine)
Peak: 20 mins
Sufentanil (1,600x > morphine)
Peak 6 mins
Neuraxial Opioids
Subarachnoid/Spinal/Intrathecal Uptake
Cephalad movement in CSF depends on lipid solubility
Fentanyl & sufentanil < morphine
More in spinal cord < remains in CSF and migrate cephalad
Coughing or straining (not body position: drug baracity)
