Week 2: Opioid Agonists & Antagonists Flashcards
Opioids mimic these endogenous peptide opioid receptor ligands
-Endorphins (Mu)
-Dynorphins (Kappa)
-Enkephalins (Delta)
How do opioids work?
As an agonist on opioid receptors at pre and postsynaptic sites in the CNS
Where in the CNS do opioids work
Brainstem
Spinal cord
What are the 3 broad chemical structures of opiods
Natural
Synthetic
Semisynthetic
Substitution of methyl group for hydroxyl group on carbon 3 leads to what opiod
Codeine
Substitution of acetyl groups on carbons 3 and 6 leads to what semisynthetic opioid?
Heroin (Semisynthetic opioid)
Morphine
Natural, semisynthetic, or synthetic opioid?
Natural
Hydromorphone
Natural, semisynthetic, or synthetic opioid?
Semisynthetic
Meperidine
Natural, semisynthetic, or synthetic opioid?
Synthetic
Fentanyl
Natural, semisynthetic, or synthetic opioid?
Synthetic
Remifentanil
Natural, semisynthetic, or synthetic opioid?
Synthetic
Sufentanil
Natural, semisynthetic, or synthetic opioid?
Synthetic
Methadone
Natural, semisynthetic, or synthetic opioid?
Synthetic
Codeine
Natural, semisynthetic, or synthetic opioid?
Natural
Heroin
Natural, semisynthetic, or synthetic opioid?
Semisynthetic
What kind of opioids
-Contain a similar nucleus to morphine
-Pharmacodynamic differences between these drugs include potency, rate of equilibration between plasma and site of drug effect
Natural, synthetic, or semisynthetic opioids
Synthetic opioids
What kind of opioids result from the modification of the morphine molecule?
Natural, semisynthetic, or synthetic opioids?
Semisynthetic opioids
What are mu receptors principally responsible for?
Supraspinal analgesia
Spinal analgesia
Respiratory depression is characteristic of _____ receptor activation
(mu, kappa. delta)
mu
Respiratory depression less prominent with _____ receptor activation
(mu, kappa, delta)
Kappa
Opioids posses similar side effect profiles
True or false
True
Cardiovascular
Opioid side effects
-Bradycardia
-Decreased BP in morphine, meperidine b/c histamine
-Dose-dep. vasodilation
-Minimal effect on BP in healthy pt
-Baroreceptor reflex not affected
-Myocardial contractility not affected
Respiratory
Opioid side effects
-Respiratory depression
-Cough suppression
-Shifts CO2 response curve to right and reduces ventilatory response to CO2
-Decreased RR, increased Vt
-Increased PaCO2 increased ICP
CNS
Opioid side effects
-Sedation
-Euphora, Prolactin release (mu)
-Dysphoria, hallucinations, delirium
(kappa)
-Miosis
GI
Opioid side effects
-N+V
-Decreased peristalsis/gastric
emptying/constipation
-Increased biliary pressure
Musculoskeletal
Opioid side effects
Generalized skeletal muscle rigidity,
“Chest wall” rigidity
(caused by rapid administration of large doses of opioid)
Endocrine/immune
Opioid side effects
-Histamine release (morphine, meperidine, codeine)
-Inhibition of cellular and humoral immune function
-Suppression of natural killer cell function
-Decrease in cortisol
-Increase prolactin, decrease luteinizing hormone, follicle-stimulating hormone, testosterone, estrogen
Cutaneous
Opioid side effects
Pruritus
Release of histamine = flushes skin
Body temp
Opioid side effects
Hypothermia
GU
Opioid side effects
Urinary retention
SSEP
Opioid side effects
Minimal effects on evoked-potentials
Placental transfer
Opioid side effects
Transported across placenta, can lead to depression of neonate
Opioid allergies are commonly claimed but true opioid allergies are rare
True or false
True
Most opioid allergies are side effects that include what?
-Localized histamine release
-Orthostatic hypotension
-N+V
Opioids ________ minimum alveoli concentration (MAC) requirements of volatile anesthetics
increase or decrease
decrease
What opioid is better for continuous, dull pain vs sharp intermittent pain
Morphine
Routes morphine can be administered
IV
IM
SC
Oral
Intrathecal
Epidural
IV morphine causes ______ first, then ______
Sedation, analgesia
Sedation is not an indicator of pain control
True or false
True
Which opioid undergoes phase 2 glucuronide conjugation in the liver to produce an active metabolite?
Morphine
The active metabolite of this opioid produces a more prolonged effect, often excessive sedation, in the renal failure patient
Morphine
Morphine produces a _________ release from tissue mast cells
Histamine
Histamine release from morphine can cause _____, _______, ______
Decreased SVR
Hypotension
Tachycardia
This semisynthetic opioid was derived from morphine in the 1920’s and has a similar pharmacokinetic profile, but is more potent
Hydromorphone
What routes can hydromorphone be administered to
Oral
Rectal
Parenteral
This opioid has no active metabolites and is therefore recommended for renal failure patients, elderly
Hydromorphone
This opioid is structurally similar to atropine and has atropine-like antispasmodic effects
Meperidine
After liver demethylation, this opioid is partially metabolized to an active metabolite
Meperidine
Meperidine’s active metabolite
Normeperidine
Meperidine’s active metabolite, normeperidine, has ______ the analgesic effect, and its elimination half-life is _______ than meperidine
Half, longer
What does normeperidine do to the seizure theshold?
Lowers seizure threshold and induces CNS excitability
Meperidine should be used with caution in what patients?
Renal failure
Cancer patients
Seizure history
The most widely used opioid analgesic in anesthesia
Fentanyl
Fentanyl has a ______ (short, prolonged) duration of action
Short
Fentanyl has a profound dose dependent analgesia
True or false
True
Action of a single dose of fentanyl is terminated by __________
Redistribution
Which opioid undergoes significant first-pass uptake in the lungs, with temporary accumulation before release?
Fentanyl
Fentanyl is metabolized to ________ (active or inactive) metabolites
Inactive
Regarding fentanyl, elimination is prolonged in which two patient populations
Elderly and neonate
Routes fentanyl commonly administered through
IV
Intrathecal
Epidural
Transdermal
This opioid has a rapid onset and an ultra-short duration
Remifentanil
Remifentanil is metabolized by what?
Plasma esterases (blood and tissue esterases)
What is remifentanil’s elimination half life?
8-20 minutes
Hyperalgesia is a side effect of which opioid
Remifentanil
Remifentanil is metabolized to what?
A less active compound
Remifentanil has increased respiratory depression with what drug?
Propofol
You should bolus remifentanil over 1 minute to avoid what?
Bradycardia
Which opioid is very potent, and useful when profound analgesia is needed?
Sufentanil
Sufentanil has a _______ (higher/lower) potency and ________(shorter/longer) half-life than fentanyl
Higher, shorter
Routes sufentanil can be used
IV
Intrathecal
What 3 things is methadone used for primarily?
Chronic pain
Opioid abstinence syndromes
Heroin addiction
Methadone is well absorbed orally, and produces less euphoria
True or false
True
Methadone has ______(high/low) bioavailability and ______ (an, no) active metabolites
high, no
What causes methadone to have a long half-life?
-Extensive protein binding
-Lower intrinsic ability of liver to
metabolize it
What can occur in methadone so that you need to be careful of repeat dosing
Accumulation
Why does it take methadone a longer time to reach steady state than other opioids
A longer half life
Which opioid does “slow on, slow off” refer to?
Methadone
In opioid Agonist-Antagonists, drugs bind to mu-receptors and produce a ____________ response
limited
In opioid Agonist-Antagonists, antagonist properties can reduce___________ of subsequently administered opioid agonists
efficacy
Side effects of opioid Agonist-Antagonists are ___________ (similar/different) to opioid agonists
similar
Advantage of opioid Agonist-Antagonists is to produce analgesia with limited depression of_____________
ventilation
Buprenorphine is what kind of opioid?
Opioid Agonist-Antagonist
Minor changes in chemical structure of opioid agonists can convert it to an opioid ____________
Antagonist
What kind of opioid is naloxone?
Opioid Antagonist
What are the 3 uses of Naloxone?
-Opiate overdose
-Reversal of opiate respiratory depression
-Treatment of opiate-induced pruritus
What accounts for codeine’s analgesic activity?
Approximately 10% of codeine is O-demethylated to morphine
Is codeine likely to cause respiratory depression?
Not as likely to cause respiratory depression as other opioids
Morphine 10mg = ____mg codeine
120 mg
___mg of codeine is effective as antitissive
15 mg
