Test 4: Opioid Agonists specific drugs to know Flashcards
What is the Onset and Peak time of Morphine?
-IV Onset = 20 minutes
-Peak = 30-60 minutes
Variable per patient
What is the distribution of Morphine?
-35% Protein bound
-Vd 2.8 L/kg
-DOA 4-5 hours
LEAST lipophillic of the opioids (very hydrophillic)
-reason why delayed onset and longer DOA.
-Less accumulation in lipid membranes or fatty tissues.
What is the metabolism of Morphine?
-Liver via Phase 2
-Active Metabolites: issue with chronic administration or patients in renal failure (decreased clearance)
What Morphine’s active metabolite, and why is it a concern?
-Morphine-6-glucuronide (M6G)
-More potent than the parent drug in the CNS
-However, M6G is more hydrophillic than parent drug (morphine), which impedes its passage into the CNS. But, with chronic administration or in renal failure patients, M6G can enter the CNS.
-Doesn’t readily cross the BBB, but high plasma levels can increase CNS penetration
-Causes prolonged effect/excessive sedation in renal failure patients
What is the 1/2 life of Morphine in adults and neonates?
-Adults: 3-5 hours
-Neonates: 4-13 hours
Pediatrics have more TBW, so 1/2 life is longer.
-Concern for respiratory depression in kids due to extended DOA and late side effects.
What is the MOA of Morphine?
-Natural opioid agonist
-Causes inhibition of ascending pain pathways
-Alters the perception and response to pain
What are the CNS effects of Morphine?
-Sedation, then analgesia (sedation does NOT mean adequate analgesic coverage)
-Generalized CNS depression
What are the Respiratory effects of Morphine?
-Dose dependent respiratory depression
-Later sign
What are the Cardiovascular effects of Morphine?
-Palpitations
-Hypotension: r/t histamine release and vasodilation
-Bradycardia (should this be tachycardia?)
Large histamine release = dec SVR, dec BP, and inc HR
How does Morphine cause pruritus?
Centrally mediated effect via Mu receptors.
What are the local effects of Histamine release from Morphine?
Local itching, redness, or hives near the site of IV injection.
Is Morphine a common choice for intra-op pain?
No, fentanyls are more common.
-Morphine has a slow onset and slow peak effect
-Also has a large patient variability
-So much more common post op than intra-op.
What are the Onset and Peak times of Hydromorphone?
-IV onset: 15-30 minutes
-Peak: 30-90 minutes
Used at the end of the case, helps create a steady state (can give 0.2 mg q 15-30 minutes to create a steady state)
7-8xs more potent than Morphine. Less hydrophillic = faster onset.
What is the distribution of Hydromorphone?
-20% Protein bound
-Vd = 4 L/kg
-DOA = 4-5 hours
What is the metabolism of Hydromorphone?
-Liver metabolism
-No active metabolites
-Safe for renal patients.
What is the 1/2 life of Hydromorphone?
1-3 hours
What is the usual dose of Hydromorphone?
0.2 - 2 mg
-Risk of tolerance
What is the MOA of Hydromorphone?
Treatment of moderate to severe pain.
-Semisynthetic opioid agonist
-Causes inhibition of ascending pain pathways
-Alters the perception and response to pain
What are the CNS effects of Hydromorphone?
Generalized CNS depression
Can cause N/V
What are the respiratory effects of Hydromorphone?
-Cough suppression via direct action in the medulla
-Respiratory depression
What are the cardiovascular effects of Hydromorphone?
S/Sx can differ depending on patient.
-Palpitations
-Hypotension
-Peripheral vasodilation
-Tachycardia
-Bradycardia
-Flushing
Less anaphylactic profile compared to morphine. No histamine release.
What are the Onset and Peak times of Fentanyl?
-IV Onset = 2-5 minutes
-Peak = 20-30 minutes
Highly lipophillic!
What is the distribution of Fentanyl?
-84% Protein bound
-Vd = 4 L/kg
-DOA = 0.5 - 1 hour
What is the metabolism of Fentanyl?
-First pass uptake in the lungs with temporary accumulation before release into the periphery!! (Unique to fentanyl and its derivatives)
-Liver via N-dealkylation & hydroxylation to inactive metabolites
-Clearance dependent on hepatic blood flow
-Eliminated in urine & bile
-Elimination is prolonged in elderly and neonates.
What is the 1/2 life of Fentanyl?
-2-4 hrs
-single dose actions terminated by redistribution
-continuous infusion actions terminated by elimination
What is the usual dose of Fentanyl?
-Induction = up to 1-2 mcg/kg
-Maintenance = 25-100mcg
What are the Phenylpiperidines?
-Fentanyl
-Alfentanil
-Sufentanil
-Remifentanil
What is the MOA of Fentanyl?
-80 to 100 xs more potent than Morphine
-Synthetic opioid agonist
-Increases the pain threshold
-Inhibits ascending pain pathways
-Phenylpiperidine
What are the CNS effects of Fentanyl?
-Profound dose dependent analgesia & sedation
-Drowsiness
-Confusion
Implicated in N/V
What are the Respiratory effects of Fentanyl?
-Dose dependent depression
-Muscle rigidity/chest wall rigidity (loss of compliance in chest wall)
What are the Cardiovascular effects of Fentanyl?
Overall, pretty stable with CV.
-Bradycardia (transient)
-Hypotension
-Peripheral vasodilation
What are the routes of administration for Fentanyl?
-IV, PCA, Transdermal patch
-Intrathecal & epidural
-Transnasal or Transpulmonary (mucosal absorption)
What are the Onset and Peak times of Remifentanil?
-IV Onset = 1 min
-Peak = 1 min
Moderately lipophillic.
What is the distribution of Remifentanil?
-58% protein bound
-Vd = 0.39 L/kg (smallest Vd)
-DOA = 5-10 minutes
What is the metabolism of Remifentanil?
-Rapidly metabolized in the blood by tissue esterases
-Via hydrolysis catalyzed by general esterase enzymes to a less active compound (Succ metabolism does not influence Remi’s metabolism)
Doses are non-cumulative. Rapid recovery occurs after stopping infusion.
What is the 1/2 life of Remifentanil?
9 minutes (8-20 min)
What is the dose of Remifentanil?
-Comes in a powder that has to be reconstituted.
-If in drip format, start at low dose and see how patient responds.
0.2 - 2 mcg/kg/min.
What is the MOA of Remifentanil?
100-200xs more potent than Morphine
-Synthetic opioid agonist
-Phenylpiperidine with an ester link
-Increases the pain threshold & alters pain perception
-Inhibits ascending pain pathways
What are the CNS effects of Remifentanil?
Occur in <10% of patients.
-Dizziness
- HA
- Agitation
- Fever
Also N/V
What are the CV & Resp effects of Remifentanil?
CV: Dose dependent hypotension & bradycardia
Resp: Depression
Muscle rigidity/truncal rigidity (same as with Fentanyl)
Can you use Remifentanil for post op pain control?
No: Need a plan for management of post-op pain (Blue Box)
Risk for OIH: Opioid Induced Hyperalgesia. Need a longer acting agent on board before a short acting agent is metabolized away.
Can you bolus Remifentanil pre-op or post-op?
No, due to risk of respiratory depression
Why can you NOT give Remifentanil Intrathecally or Epidurally?
-Commercial preparation is as a powder and needs to be reconstituted (1mg, 2mg or 5 mg vials)
-Water-soluble lyophilized (freeze-dried) powder that contains a free base + glycine (transport vehicle)
-Potential for glycine neurotoxicity = DO NOT USE INTRATHECALLY OR EPIDURALLY
What are the Onset and Peak times of Sufentanil?
-IV Onset = 1-3 minutes
-Peak = unknown. Maybe less than 5 minutes?
-Highly lipophillic
What is the distribution of Sufentanil?
-93% Protein bound
-Vd = 2 L/kg
-Dec Vd in elderly
-DOA is dose dependent
What is the metabolism of Sufentanil?
Hepatic via O-demethylation and N-dealkylation.
-1/2 life = 6 hours
What is the dose of Sufentanil?
-Infusion 0.05 – 0.5 mcg/kg/hour
-Bolus 0.1 – 2 mcg/kg (1-2 mcg/kg if used for induction)
-D/C 30-60 min prior to emergence if you want them to breathe on their own.
Can be mixed into Spinal or Epidural.
What is the MOA of Sufentanil?
5-10 xs more potent than Fentanyl (which was 80-100xs more potent than Morphine).
-Synthetic opioid agonist
-Increases the pain threshold
-Inhibits ascending pain pathways
-Phenylpiperidine
List the Phenylpiperidines in order of most to least potent.
Sufentanil > Fentanyl = Remifentanil > Alfentanil
When is Sufentanil used?
Used where profound and often long term anesthesia/analgesia is required.
-Cardiac
-Chronic Pain
-Free tissue transfers (flaps)
What are the CNS effects of Sufentanil?
-Dose dependent sedation & depression
N/V
What are the CV & Resp effects of Sufentanil?
CV: Bradycardia & hypotension
Resp: Dose-dependent respiratory depression (inc incidence of depression in the elderly due to dec Vd).
What is Context-Sensitive Half Time?
The time required for plasma concentrations of a drug to decrease by 50% after discontinuation of an infusion.
-Cannot be predicted by elimination half-life
-Depends on drug distribution
-Explains the duration of action of a drug infusion after the infusion has stopped
Reflects several pharmacokinetic principles
1) As a drug infuses into the body it accumulates in the body’s tissues
-The longer the infusion(context) the more accumulation in the tissues until saturation
-Once the infusion is D/C the stored drug will redistribute back into plasma and maintain the effects
2) Each drug accumulates at a different rate and to a different extent based on its physiochemical properties
3) Drugs are removed from the blood through two major mechanisms
-Distribution – where the drug moves from the blood to the tissues
-Excretion – where the drug is metabolized or excreted unchanged. Does the drug have an active metabolite?
What is the CS 1/2 time of Remifentanil?
Short, stable and wears of very quickly after stopping the infusion.
Remi is pretty static. Turn it off and it’s gone.
-To drop it 50% after 1 hour is 1-2 minutes. To drop it 75% after 1 hour is 7-8 minutes.
-Wears off quickly no matter how long you ran it.
What is the CS 1/2 time of Fentanyl?
Variable, take much longer to wear off and is less predictable.
-Takes a long time for concentration to drop. Why we don’t use fentanyl drips. Plasma concentration stays very high, takes longer to wear off.
What is unique about the CS 1/2 time of Morphine?
Morphine has active metabolite: 10% of metabolized morphine becomes M6G - increasing DOA.
