Opioids Flashcards
Which opioid has an atropine-like ring structure creating anticholinergic side effects?
Meperidine
What is the elimination half-life of meperidine? In healthy and renal failure patients?
15 hours for healthy people. Can exceed 35 hours for those with renal failure
Pharmacodynamic differences between synthetic opioids are due to?
Potency, rate of equilibrium between plasma, and site of drug effect
How are semisynthetic opioids changed from natural or synthetic?
modification of the morphine molecule
Which opioids can cause histamine release from Mast cells?
Meperidine, codeine, morphine
Are most opioids weak acids or weak bases?
Weak bases
Bc opioids are mostly weak bases, how does the ionization of the drug change when the physiologic pH is < than the pKa?
When pH < pKa of a weak base, the base (aka drug) will be MORE ionized. Less drug is available to cross membranes.
Bc opioids are mostly weak bases, how does the ionization of the drug change when the physiologic pH is > than the pKa?
When pH > pKa of a weak base, the base (aka drug) will be LESS ionized. Meaning more drug is available to cross membranes.
What are the natural opioids we utilize?
Morphine
What are three endogenous opioid ligands?
Enkephalins
Endorphins
Dynorphins
What are the three opioid receptors?
Mu, Kappa, and Delta
What are the effects of Mu receptor stimulation?
Analgesia
Euphoria
Miosis
Respiratory Depression
Constipation
Bradycardia
Urinary Retention
Risk for dependence/abuse
What are the effects of Kappa receptor stimulation?
Analgesia
DYSphoria
Sedation
Less Respiratory depression***
Diuresis
Miosis
What are the effects of Delta receptor stimulation?
Analgesia
Respiratory Depression
Physical dependence
Constipation
Urinary Retention
How common are true opioid allergies?
Rare. Most are side effects, including localized histamine release (itching), orthostatic hypotension, and nausea & vomiting
How do opioids affect Minimal Alveoli Concentration requirements of volatile anesthetics?
Decreases MAC
Morphine is best for what kind of pain relief?
Moderate - Severe
It is better for continuous dull pain rather than sharp intermittent pain. ex: visceral gut/belly pain
What are the different routes of administration for morphine?
PO, IM, SC, IV, Epidural, IT
Morphine causes which effect first? And then followed by?
Sedation first and then analgesia.
Important to remember that sedation is not an indication of pain control.
Morphine undergoes what kind of metabolism? What is the end product?
Undergoes phase 2 glucuronide conjugation. Forms morphine-6-glucuronide -> an active metabolite
Morphine produces histamine release from tissue _____ cells which can cause _____, _______, and _____.
Mast Cells
Decreased SVR, Hypotension and Tachycardia
What is the consequence of morphine having an active metabolite?
Produces a more prolonged effect, often excessive sedation in renal patients.
What is the Adult Intrathecal (spinal) dosing of morphine?
0.1-0.5mg
Typically 0.2-0.25. Higher doses = pruritis
What is the Pediatric Intrathecal (spinal) dosing of morphine?
0.01mg/kg
What is the Adult Epidural Bolus Dose and frequency of Morphine?
Bolus: 2-6mg every 8-24 hours
What is the Adult Epidural Infusion Dose of Morphine?
0.2-1mg/hr
What is the pediatric epidural dosing for morphine? What is the Max dosing?
0.03-0.05mg/kg
MAX: 0.1mg/kg or 5mg/24hrs)
What is the adult Sedation/Analgesia IV (IM and SC same) dosing for Morphine?
2-20mg every 2-4hours
What is the pediatric Sedation/Analgesia IV dosing for Morphine?
IV usually dosed 0.1mg/kg
Is Hydromorphone natural, synthetic, or semisynthetic?
Semisynthetic
Hydromorphone has a similar pharmacokinetic profile as _______ but is more potent.
Morphine
Why is hydromorphone considered “cleaner” than morphine?
No active metabolites. Can be used in renal / elderly.
What are the routes of admin for hydromorphone?
PO, Rectal, IV
What is the adult IV analgesic dose for hydromorphone?
0.4-2mg IV
What is the pediatric IV analgesic dose for hydromorphone?
0.0005-0.02mg/kg IV
(0.5-20mcg/kg)
Is Meperidine natural, synthetic, or semisynthetic?
Synthetic
Meperidine has a similar structure to what drug? Why is this significant?
Atropine has atropine-like antispasmodic effects (used for shivering)
Meperidine is partially metabolized to?
Normeperidine
Normeperidine has _____ the analgesic effect of Meperidine.
Half
What does Meperidine do to the CNS?
Lowers seizure threshold and induces CNS excitability.
What is the adult post-op shivering dose of Meperidine?
12.5-25mg IV
12.5 usually adequate
A single dose of fentanyl is terminated by?
Redistribution, rather than metabolism and excretion.
Where does fentanyl have significant first-pass uptake?
Lungs with temporary accumulation before release
Fentanyl elimination is prolonged in which patients?
elderly and neonates
Common routes of Fentantl administration?
Transdermal
IV, Epidural, and IT
What is the adult intubation adjunct dose for Fentanyl?
1-3mcg/kg
1mcg/kg most common
What is the adult Intrathecal (spinal) dose for Fentanyl?
10-25mcg
(0.010-0.025mg)
What is the adult epidural dose for Fentanyl? When mixed with a local anesthetic?
10-100mcg, or mixed in local anesthetic 10mcg/ml
For adult sedation/analgesia, what is the loading and maintenance dosing for Fentanyl?
Load: 0.5mcg/kg
Maintenance: 0.01-0.04 mcg/kg/hr
How is Remifentanyl metabolized?
easily and rapidly by blood and tissue plasma esterases
What is the elimination half-life of Remifentanil?
8-20minutes
8 minutes more common!
What is an adverse possible side effect of Remifentanil?
Hyperalgesia
Rank the potency of fentanyl, remifentanil, alfentanil, and sufentanil from highest to lowest
Sufentanil - most potent
Remi and fentanyl are equal in potency but different in duration of action
Alfentanil - least potent
What is the adult induction dose of Remifentanil?
1-3mcg/kg over 1 min
What are the adult general anesthesia adjunct loading, bolus, and maintenance dosing for Remifentanil?
Loading: 0.5-2mcg/kg
Bolus: 0.5-1mcg/kg
Maintenance: 0.05-2mcg/kg/min
What can occur when bolusing Remifentanil?
Significant Bradycardia!
Skeletal Muscle Rigidity (Stiff Chest Syndrome)
can occur with all fast admin of fents
What are sedation doses of remifentanil? both load and maintenance
Load over 30-60s: 0.5-1mcg/kg
Maintenance: 0.025-0.2mcg/kg/min
Remifentanil has increased respiratory depression when given with?
Propofol
How does the potency and half-life of Sufentanil compare to Fentanyl?
Higher potency (10x more potent) and shorter half-life than fentanyl
Does Sufentanil cause the same hyperanalgesia effects as Remifentanil?
No.
Sufentanil can be adminsiterd via?
IV, Epidural, or IT
Under General Anesthesia PRN push doses of Sufentanil can be given, what dose range?
10-50mcg
Depending on the intensity of the procedure under general anesthesia, sufentanil can be administered via infusion. What is the dose range? (hint- large range since it depends in procedure)
Anywhere from 0.3mcg/kg/hr - 2.5mcg/kg/hr
What is the adult load and infusion sedation dosing for Sufentanil?
Load: 0.1-0.5mcg/kg
Infusion: 0.0005-0.01mcg/kg/min
What is the epidural dosing for sufentanil with bupivacaine>
10-15mcg/10mL of 0.125 bupivacaine
What is Methadone primarily used for?
Chronic pain, opioid abstinence syndromes, and heroin addiction
What leads to Methadone’s long half-life?
Extensive protein binding as well as lower intrinsic ability of the liver to metabolize it
What is the adult PO dosing of methadone?
2.5-10mg PO
What is the adult IV, IM, SC dosing for Methadone?
2.5-5mg q8-12hrs
How do you titrate Methadone?
Titrate up q3-5 days
Methadone takes ______ time to reach steady state than other opioids
Longer
Because of the long half-life of methadone, what can occur?
Accumulation
Oxycodone is how much more potent than oral morphine?
twice as potent
Adult PO dosing of oxycodone?
5-15mg immediate release q4-6h
What is the MOA of opioids?
Opioid receptor (mu, kappa, and/or delta) agonists. At pre and post-synaptic sites in the central nervous system (brainstem, spinal cord)
Mu receptors are principally responsible for what kinds of analgesia?
Supraspinal (pain relief mediated by central nervous system (CNS) structures above the spinal cord, primarily in the brainstem, midbrain, and cerebral cortex)
and
Spinal
Respiratory depression is characteristic of which opioid receptor activation?
Mu
Which opioid receptor has less prominent respiratory depression?
Kappa receptor
Hydrocodone has similar potency and duration of action to oral ____?
morphine
Dosing of hydrocodone (PO)
2.5-10mg q4
Morphine 10mg = how much hydrocodone dose
5-10mg
Codeine is a weak opioid compared to others. 10mg Morphine = how much codeine?
morphine 10mg = 120 mg codeine
While it is not used as often anymore for its antitussive effects, what dose of codeine has been shown to be effective?
15mg
Compared to other opioids, codeine is more or less likely to cause respiratory depression?
Less
Adult PO codeine dose? Max daily dose?
15-60mg PO q 4-6
Max 120mg/day
Pediatric PO dosing of codeine? Max doses for ages 2-6 and 6-12?
1-1.5mg/kg/day divided by q4-6hours
Max Dose Age 2-6 = 30mg/day max
Max Dose Age 6-12 = 60mg/day max
What kind of opioid is Buprenorphine?
Synthetic Partial Mu Agonist (agonist - anttagonist)
Does Naloxone reverse buprenorphine?
yes, but difficult due to the high affinity for mu receptor. my need higher or frequent redosing
Because partial opioid agonists (agonist-antagonists) have antagonist properties, what can this do to subsequently administer opioid agonists?
Can reduce their efficacy
What is an advantage to partial opioid agonists?
Ability to produce analgesia with limited respiratory depression
What is the epidural dosing for Buprenorphine? What realm is this usually used for?
300mcg (0.3mg)
Acute pain world (lol) Dr. C’s words
What is the intrathecal dosing of Buprenorphine? When is this a usual adjunct?
150mcg (0.15mg)
C-Sections - good effect
At what dose should Buprenorphine only be given IM
doses greater than 0.3mg /dose
What is the IV / IM dosing and frequency of buprenorphine?
0.3-0.4mg q 6-8 hours
(can repeat initial dose in 30-60 min x1)
Greater doses than 0.3mg should be given IM
the dosing of Buprenorphine is equianalgesia to what IV morphine dose?
10mg IV morphine equianalgesic to 0.3-0.4 IV/IM buprenorphine
Adult dosing of Naloxone for adult opioid overdose? Max dose?
0.2-4mg IV q 2-3min PRN
10mg MAX then have to start infusion
Adult Naloxone dose for reversal of respiratory depression
0.04-0.4mg doses IV 2-3min titrations
Treatment of opioid-induced pruritus with Naloxone dose
0.25mcg/kg/hr
Birth to 5 years or less than 20kg Naloxone dosing?
0.1mg.kg IV q2-3min PRN
