Test 4: Opioid Antagonists & Delivery Methods

Question 1

What are the Onset and Peak times for Nalbuphine (Nubain)?

Answer 1

-IV Onset = 2-3 minutes
-Peak = 20 minutes (IV)

Question 2

What is the distribution for Nalbuphine?

Answer 2

-NOT Protein Bound (!)
-Vd = 4.8 L/kg
-DOA = 2-3 hours (possibly 3-6 hours)

Question 3

What are the uses for Nalbuphine (Nubain)?

Answer 3

Agonist-Antagonist.
-moderate to severe pain
-Pre or post op surgical analgesia
-OB analgesia for labor & delivery (does cross placenta)

Question 4

What is the Metabolism of Nalbuphine?

Answer 4

-Hepatic
-Caution in hepatic impairment
-Reduce dose

1/2 life = 2-3 hours

Question 5

What is the dose of Nalbuphine?

Answer 5

Analgesia (for pain):
-10mg/70kg every 3-6hrs
-0.25 - 0.5 mg/kg prn
- Max single dose = 20mg
Can supplement GA with a 0.3-3 mg/kg bolus over 10 minutes.
Not to exceed 160 mg/day

Question 6

What is the MOA of Nalbuphine?

Answer 6

-Synthetic opioid agonist & antagonist
-Kappa = agonist
-Mu = antagonist
- Inhibition of ascending pain pathways
- Alters perception & response to pain

Ceiling effect on resp. depression. can use this if too heavy handed with morphine or dilaudid and pt is having respiratory depression. Can switch to this because of Mu antagonism (not enough to cause pain).

Question 7

What is useful about Nalbuphine?

Answer 7

-Agonist effect at Kappa receptors + antagonist effect at Mu receptors
-Can antagonize respiratory depression of fentanyl or morphine while maintaining analgesia
-Analgesic effects are equal to those of Morphine.
-Difficult to reverse with Naloxone.

Question 8

What are the effects of Nalbuphine?

Answer 8

CNS: generalized depression, fatigue, drowsiness
Resp: No depression with normal doses
CV: No circulatory changes
-Used to antagonize the itching effects of NA morphine

RELEASES HISTAMINE.

Question 9

What are the onset and peak times of Naloxone?

Answer 9

-IV Onset = 2 min
-Peak = 5-15 min

Question 9

What is the distribution of Naloxone?

Answer 9

-Crosses placenta
-DOA 20-60 min
-DOA < most opioid agonists
Repeated doses often needed (opioids can come out of the tissues and cause depressant effects again. May have to redose Narcan).

Question 9

What are the effects of Nalbuphine?

Answer 9

CNS: generalized depression, fatigue, drowsiness
Resp: No depression with normal doses
CV: No circulatory changes
-Used to antagonize the itching effects of NA morphine

RELEASES HISTAMINE.

Question 10

What is the dose of Naloxone?

Answer 10

• 1mcg/kg, repeat as needed
  -Reversal effects are titratable
  -Mix 0.4mg with 9mL NS = 40mcg/mL concentration
  -titrate slowly with anesthesia. Don’t want to reverse analgesia.
  -Street reversal for OD is whole vial (0.4 - 2 mg)

Question 11

What is the Metabolism of Naloxone?

Answer 11

Hepatic via glucoronidation.

1/2 life = 10 hours

Question 12

What is the MOA of Naloxone?

Answer 12

-Semisynthetic opioid antagonist
-Competitive antagonism at mu, kappa & delta receptors
-Reverses analgesia with full doses
-Reverses respiratory depression in smaller doses

Question 13

What are the CNS effects of Naloxone?

Answer 13

-Reverses analgesia
-Inhibits endogenous pain suppression pathways
-SEs = skeletal muscle tremors and diaphoresis due to SNS stimulation

Question 14

What are the Resp effects of Naloxone?

Answer 14

-Reverses depression
-Pulmonary edema (pts with hx of cardiac disease) if given too fast.

Question 15

What are the cardiovascular effects of Naloxone?

Answer 15

-Hyper/hypotension
-Tachycardia, ventricular arrhythmias
-Cardiac arrest

Question 16

What can occur if Naloxone is administered too quickly?

Answer 16

-Pulmonary edema
-Cardiac arrest

Can be due to sudden increases in blood catecholamine levels that predispose patients to Vfib and then cardiac arrest.

Question 16

What are the effects of opioid OD that are NOT reversible with Naloxone (Narcan)?

Answer 16

Shakiness
Tremors
Twitches
Myoclonus
Grand mal seizures

Question 16

Describe administration of Fentanyl via Transdermal Patch.

Answer 16

-Peak plasma concentrations are reached in 18 hours. SQ deposition of drug must be saturated before plasma uptake (not a lot of blood flow in SQ area - takes time to get into system)
-Dose remains stable while patch is on.
-Elimination 1/2 life = 17 hours (because of SQ deposition of drug). Can last up to 72 hours.
-No first phase hepatic metabolism
-No discomfort at site unless adhesive allergy (rotate sites due to local irritation from adhesive)
-25 mcg - 100 mcg/hr for 24-72 hours.
-Minimal patient cooperation required
-Can leave on during surgery but bair hugger vasodilates area, increasing uptake. Don’t put BP cuff on top of patch.
-Not recommended for treatment of post-op pain.

Question 16

Describe Sublingual Absorption of Fentanyl.

Answer 16

-Fentanyl Oralet (transmucosal) – lollipop for peds. Transmucosal absorption
-Similar product available in inc strength for breakthrough cancer pain (buccal transmucosal route)
-Dissolved in a sucrose solution and placed in a lozenge (dissolves into oral mucosa)

Absorbed directly into circulation through the oral mucosa, without passing through the liver.
-Pruritus is a common SE.

Can do nasal spray of fentanyl in adults.
Sufentanil nasal spray abandoned in peds due to inc N/V

Question 16

What is the rate of sublingual absorption of the different opioids?

Answer 16

Minimal:
-Hydromorphone
-Heroin
-Oxycodone

Morphine = 18%

Methadone 34%

Fentanyl 51%

Question 17

What is the most common serious side effect associated with epidural and spinal administration of opioid agonists? (Blue Box!)

Answer 17

Respiratory depression is the most common serious side effect associated with epidural and spinal administration of opioid agonists. (Blue Box!)

Question 18

Is Spinal Use = Epidural Use = IV Use?

Answer 18

No.
-Differ in onset, DOA, & side effects
-Pain will respond differently as well
-Pain unresponsive to systemic meds may respond to neuraxial meds
-🡻some side effects while 🡹 others

Question 19

How do intrathecal opioids work?

Answer 19

-Direct injection of meds into the CSF
-Fast onset at the spinal cord opiate receptors (Substantia gelatinosa): Kappa receptors
-↑ incidence of pruritus: Mild itching of face and chest (esp with morphine)
-↑ incidence of urinary retention: Due to inhibition of sacral parasympathetic outflow
-↑ incidence of PONV: Rostral spread vs vascular uptake

Morphine & Hydromorphone:
-Delayed respiratory depression 2/2 low lipid solubility
-Travel to the midbrain resp centers via the CSF
-Low lipid solubility

Question 19

What is the difference between rostral spread or vascular uptake of intrathecal opioids?

Answer 19

Rostral spread: Mvmt of medication to the head. Gets it to brainstem.

Vascular uptake: Takes it up to CTZ.

Question 20

How do spinal opioids cause urinary retention?

Answer 20

Relaxation of bladder detrusor muscle leads to inability to voluntarily relax the sphincter.

Question 21

How are highly lipid soluble opioids (like Fentanyl) absorbed intrathecally?

Answer 21

-Smaller Vd along the spinal cord, so limited area of analgesia
-This causes a faster clearance from the intrathecal or epidural space, shortening the DOA.
-Higher plasma concentrations.

Question 21

What are spinal opioids good for?

Answer 21

Selective analgesia
-Analgesia in the absence of motor and sympathetic blockade

Question 22

Which is higher, epidural or spinal opioid doses?

Answer 22

Epidural doses are higher than spinal doses.

Spinal: cross the dura and enter CSF and then spinal tissue based on their lipid solubility
Supraspinal: portion of the drug that does not cross the dura but is absorbed into the systemic circulation via epidural vasculature
-Produce plasma levels similar to those of an IM injection

Question 23

Why is analgesia more profound epidurally than systemically?

Answer 23

Clinically, supraspinal and spinal opioid analgesic mechanisms are synergistic.
-This explains why opioids such as fentanyl and sufentanil produce more profound analgesia when delivered epidurally than when delivered systemically, despite the similar blood concentrations measured with both routes of administration.

Question 23

What are the advantages of continuous infusions of opioids?

Answer 23

-Plasma concentrations of opioids can be maintained
-↑ accuracy and consistency
-Hemodynamic stability

Question 23

How do you setup a continuous opioid infusion?

Answer 23

-Loading dose/Induction Dose: Bolus to fill the Vd.
-Then, start infusion rate. Always start low and move up. Maintenance dose keeps Vd filled as the drug is eliminated.
-Can have a long time without stimulation before surgery starts. Not requiring surgical stimulation narcotics. Titrate to needs at the time.
-Adjust dose prn depending on surgical stimulation
-Can dec the overall dose of opioids
-Can prolong emergence if not set up properly. Know how long it’ll take the drug to come off once turned off.

Question 24

What are the devices used for continuous opioid infusions?

Answer 24

1) Manual/gravity via Buretrol: dripping it into fluid. Least safe method. Can open fluids and give 999 bolus on accident.
2) Infusion pump: dial in a dose.
3) Syringe pump: Setting it up within a 60 mL syringe.

Question 25

What are the advantages of continuous opioid infusions (Nagelhout Box 11-4)?

Answer 25

• Hemodynamic stability
• Decreased side effects
• Reduced need for opioid-reversal agents
• Reduced use of vasopressor drugs
• Suppression of cortisol and vasopressin response to cardiopulmonary bypass: stress-free anesthesia
• Reduced total dosage of opioids
• Decreased recovery time

Question 25

Describe administration of Fentanyl via Transdermal Patch.

Answer 25

-Peak plasma concentrations are reached in 18 hours. SQ deposition of drug must be saturated before plasma uptake (not a lot of blood flow in SQ area - takes time to get into system)
-Dose remains stable while patch is on.
-Elimination 1/2 life = 17 hours (because of SQ deposition of drug). Can last up to 72 hours.
-No first phase hepatic metabolism
-No discomfort at site unless adhesive allergy (rotate sites due to local irritation from adhesive)
-25 mcg - 100 mcg/hr for 24-72 hours.
-Minimal patient cooperation required
-Can leave on during surgery but bair hugger vasodilates area, increasing uptake. Don’t put BP cuff on top of patch.
-Not recommended for treatment of post-op pain.