Test 4: Opioid Antagonists & Delivery Methods Flashcards
What are the Onset and Peak times for Nalbuphine (Nubain)?
-IV Onset = 2-3 minutes
-Peak = 20 minutes (IV)
What is the distribution for Nalbuphine?
-NOT Protein Bound (!)
-Vd = 4.8 L/kg
-DOA = 2-3 hours (possibly 3-6 hours)
What are the uses for Nalbuphine (Nubain)?
Agonist-Antagonist.
-moderate to severe pain
-Pre or post op surgical analgesia
-OB analgesia for labor & delivery (does cross placenta)
What is the Metabolism of Nalbuphine?
-Hepatic
-Caution in hepatic impairment
-Reduce dose
1/2 life = 2-3 hours
What is the dose of Nalbuphine?
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
What is the MOA of Nalbuphine?
-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).
What is useful about Nalbuphine?
-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.
What are the effects of Nalbuphine?
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.
What are the onset and peak times of Naloxone?
-IV Onset = 2 min
-Peak = 5-15 min
What is the distribution of Naloxone?
-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).
What are the effects of Nalbuphine?
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.
What is the dose of Naloxone?
- 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)
What is the Metabolism of Naloxone?
Hepatic via glucoronidation.
1/2 life = 10 hours
What is the MOA of Naloxone?
-Semisynthetic opioid antagonist
-Competitive antagonism at mu, kappa & delta receptors
-Reverses analgesia with full doses
-Reverses respiratory depression in smaller doses
What are the CNS effects of Naloxone?
-Reverses analgesia
-Inhibits endogenous pain suppression pathways
-SEs = skeletal muscle tremors and diaphoresis due to SNS stimulation
What are the Resp effects of Naloxone?
-Reverses depression
-Pulmonary edema (pts with hx of cardiac disease) if given too fast.
What are the cardiovascular effects of Naloxone?
-Hyper/hypotension
-Tachycardia, ventricular arrhythmias
-Cardiac arrest
What can occur if Naloxone is administered too quickly?
-Pulmonary edema
-Cardiac arrest
Can be due to sudden increases in blood catecholamine levels that predispose patients to Vfib and then cardiac arrest.
What are the effects of opioid OD that are NOT reversible with Naloxone (Narcan)?
Shakiness
Tremors
Twitches
Myoclonus
Grand mal seizures
Describe administration of Fentanyl via Transdermal Patch.
-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.
Describe Sublingual Absorption of Fentanyl.
-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
What is the rate of sublingual absorption of the different opioids?
Minimal:
-Hydromorphone
-Heroin
-Oxycodone
Morphine = 18%
Methadone 34%
Fentanyl 51%
What is the most common serious side effect associated with epidural and spinal administration of opioid agonists? (Blue Box!)
Respiratory depression is the most common serious side effect associated with epidural and spinal administration of opioid agonists. (Blue Box!)
Is Spinal Use = Epidural Use = IV Use?
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
