Opioids Flashcards
What class of opioids is defined by 3 fused benzene rings?
Phenanthrenes
____ is a phenanthrene derivative with two additional ring closures to the 3 benzene rings?
Morphine
____ is structurally the same as morphine, except with an ether substituted for an alcohol.
Codeine
Meperidine falls into the ____ class and was the first ___ opioid.
Phenylpiperidine
Synthetic
____ is the prototype phenylpiperidine. ___ and its congeners are also phenylpiperidines.
Meperidine
Fentanyl
Modification of morphine’s five ring structure resulted in the creation of ____ drugs.
Semisynthetic
Buprenorphine (partial agonist)
Naloxone and naltrexone (antagonists)
Natural agonists:
Morphine and codeine
Semisynthetic agonists:
Heroin and hydromorphone
Synthetic agonists:
Methadone, Fentanyl, Remifentanil, Meperidine, Sufentanil, Tramadol
____ is a semisynthetic partial agonist.
Buprenorphine
____ is a synthetic agonist-antagonist.
Nalbuphine
___ and ___ are semisynthetic antagonists:
Naloxone and Naltrexone
Mu, kappa, and delta opioid receptors are all what type of receptors?
GPCR
What is the “opioid motif”
Tyr - Gly - Gly - Phe - Leu/Met
*found on endogenous agonists
3 effects possible from binding at opioid receptor:
Inhibit adenylyl cyclase –> low cAMP –> decreased conductance of AP
Inhibit influx of Ca by messing up Ca channels
Increase potassium efflux preventing AP
Abrupt w/d of opioid = rebound disinhibition of cAMP causing hyperexcitability symptoms
Opioid Receptors found where in the brain? (5)
Periaqueductal Gray
Area Postrema
Limbic system
Cerebral cortex
Thalamus
brainstem modulates nociceptive transmission via inhibitory pathways of spinal cord
Opioid Receptors found where in spine?
Substantia geletinosa of dorsal horn
Inhibition of substance P release (pre-synaptically), and also blocking the transfer of pain up the cord
Big effects of mu receptor:
What endogenous ligand?
Bradycardia, respiratory depression, euphoria, sedation, miosis, N/v, urinary retention, pruritis, dependence
B-endorphin, endomorphin
Big effects of kappa receptor:
What endogenous ligand?
Less respiratory depression, dysphoria, miosis, diuresis, antishivering, low abuse profile
Dynorphin
T/F: For your next cardiac case you should use only opioids for anesthesia.
Wrongo. Not sufficient as an anesthetic by itself
Big Pharmacokinetics:
Highly lipophilic
Metabolism by liver (except remi)
Excreted by kidneys, secondarily by GI/biliary
Therapeutic Mu effects:
Sedation, Supraspinal analgesia, Spinal analgesia, Anti-tussive
Note: better at treating “second pain” sensations (C-fibers)
Does an opioid produce a differential blockade that we would see in local anesthetics?
No.
DUMB card (Patrick and Abby)
Adverse Effects:
Euphoria, Respiratory depression, Muscle rigidity, Slow gastric emptying, Urinary retention, Pruritis, Depressed cellular immunity, PONV
T/F: Opioids have only a minimal effect on neuromonitoring.
True - minimal effect
How would opioid admin result in increased ICP?
Respiratory depression –> High CO2 –> increased CBF –> inc ICP
we fix this by increasing RR, but outside OR can be issue
How do opioids cause analgesic effect?
Inhibition of ascending transmission of stimuli (from dorsal horn) AND activation of pain control pathways from midbrain (rostral ventromedial medulla)
Tolerance is seen first by a decrease in ___ of the opioid and followed by a decrease in the ___ of the opioid.
Decrease in duration of action, then decrease in effect
___ ___ is potentially life threatening in the post-operative period.
Respiratory depression
morbidly obese and OSA pts inc risk for M&M
Opioids cause a ___ shift on the CO2 response curve
Right shift = less response to hypercapnia
What are risk factors for respiratory depression with opioids (blue box)
High dose opioids
Advanced age
CNS depressants
Renal insufficiency
Morphine
Sleep
Explain the pupillary reflex arc seen with opioids:
Opioid administration causes binding of receptor and depression of GABA
This stimulates the Edinger-Westphal nucleus
This causes the ciliary ganglion to be stimulated by the parasympathetic nervous system
This stimulates the oculomotor nerve and causes miosis (constriction)
Tolerance does not develop to this effect (blue box)
The pupillary reflex arc occurs at ___ doses than respiratory depression and/or analgesia.
Lower doses
Antitussive benefits:
Keeps glottic reflexes intact while increasing tolerance to stimulation
Codeine, Heroin, Hydromorphone
Where is the chemoreceptor trigger zone?
Area postrema of medulla
Floor of 4th ventricle
Opioids are considered to be ___ for people with cardiac compromise.
Safe (blue box)
What opioids release histamine? What are the CV effects of the release?
Morphine, Meperidine, Codeine
HoTN, vasodilation, tachycardia
*can block these effects with H1 or H2 blockers
Of note: agonist-antagonist nalbuphine also releases histamine
___ is the opioid most often associated with muscle rigidity.
Remi (mentions usually with rapid bolus)
Seen as decreased chest wall compliance and hard mask ventilation
___ and ___ are meds that work only on peripheral opioid receptors and therefore are great for GI issues.
Alvimopan and Methylnaltrexone
(probably do not need to know this, just including all meds I see)
___ has the highest rate of immunosuppressant effects.
Morphine
Endocrine:
Increased release of what?
Decreased release of what?
Increased vasopressin release (seems backwards)
Decreased ant pit hormones
Morphine big takeaways:
Natural
Onset 20 mins (longer because least lipophilic)
Active metabolite = Morphine 6 glucuronide
Longer half-life in neonates –> higher TBW %
Releases histamine causing itching and hives
Decrease dose in renal patients
Hydromorphone big takeaways:
Semi-synthetic
7-8x more potent than morphine
Onset 15-30 mins
Safe in renal patients (no active met)
Can be used for cough suppression
Fentanyl big takeaways:
Synthetic
Onset 2-5 mins (highly lipophilic)
Most widely used opioid in anesthesia
First pass uptake in lungs with temporary accumulation before release into periphery
Clearance dependent on hepatic flow (liver dx)
Muscle rigidity
Single dose = redistribution
Continuous infusion = elimination
Remifentanil big takeaways:
Synthetic
Onset 1 min
Rapidly metabolized by tissue esterases
Highest rate of muscle rigidity
Must have plan for post-op pain control(blue box)
Sufentanil big takeaways:
Synthetic
Onset 1-3 mins (most potent)
Used in long term anesthesia/analgesia = cardiac with sternotomy, flap sx
Must d/c 30-60 mins prior to emergence
Which drug is by far the best in terms of context-sensitive half time? The worst?
Best: remi
Worst: fentanyl
Nalbuphine big takeaways:
Synthetic
Agonist-antagonist
Onset 2-3 mins
Kappa agonist, mu antagonist
Avoid in opioid dependent patients
More difficult to reverse than opioid agonists
Releases histamine
Naloxone big takeaways:
Onset 2 mins
DOA only 20-60 mins (important bc we often need to re-dose)
A competitive antagonist at all three receptors
Titrate to 40mcg/mL dose
Can cause pulmonary edema or cardiac arrest = give slow
Does NOT reverse shakiness, tremors, twitches, grand mal seizures, myoclonus of OD
