Opioids

Question 1

What class of opioids is defined by 3 fused benzene rings?

Answer 1

Phenanthrenes

Question 2

____ is a phenanthrene derivative with two additional ring closures to the 3 benzene rings?

Answer 2

Morphine

Question 3

____ is structurally the same as morphine, except with an ether substituted for an alcohol.

Answer 3

Codeine

Question 4

Meperidine falls into the ____ class and was the first ___ opioid.

Answer 4

Phenylpiperidine
Synthetic

Question 5

____ is the prototype phenylpiperidine. ___ and its congeners are also phenylpiperidines.

Answer 5

Meperidine
Fentanyl

Question 6

Modification of morphine’s five ring structure resulted in the creation of ____ drugs.

Answer 6

Semisynthetic
Buprenorphine (partial agonist)
Naloxone and naltrexone (antagonists)

Question 7

Natural agonists:

Answer 7

Morphine and codeine

Question 8

Semisynthetic agonists:

Answer 8

Heroin and hydromorphone

Question 9

Synthetic agonists:

Answer 9

Methadone, Fentanyl, Remifentanil, Meperidine, Sufentanil, Tramadol

Question 10

____ is a semisynthetic partial agonist.

Answer 10

Buprenorphine

Question 11

____ is a synthetic agonist-antagonist.

Answer 11

Nalbuphine

Question 12

___ and ___ are semisynthetic antagonists:

Answer 12

Naloxone and Naltrexone

Question 13

Mu, kappa, and delta opioid receptors are all what type of receptors?

Answer 13

GPCR

Question 14

What is the “opioid motif”

Answer 14

Tyr - Gly - Gly - Phe - Leu/Met
*found on endogenous agonists

Question 15

3 effects possible from binding at opioid receptor:

Answer 15

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

Question 16

Opioid Receptors found where in the brain? (5)

Answer 16

Periaqueductal Gray
Area Postrema
Limbic system
Cerebral cortex
Thalamus
brainstem modulates nociceptive transmission via inhibitory pathways of spinal cord

Question 17

Opioid Receptors found where in spine?

Answer 17

Substantia geletinosa of dorsal horn
Inhibition of substance P release (pre-synaptically), and also blocking the transfer of pain up the cord

Question 18

Big effects of mu receptor:
What endogenous ligand?

Answer 18

Bradycardia, respiratory depression, euphoria, sedation, miosis, N/v, urinary retention, pruritis, dependence

B-endorphin, endomorphin

Question 19

Big effects of kappa receptor:
What endogenous ligand?

Answer 19

Less respiratory depression, dysphoria, miosis, diuresis, antishivering, low abuse profile

Dynorphin

Question 20

T/F: For your next cardiac case you should use only opioids for anesthesia.

Answer 20

Wrongo. Not sufficient as an anesthetic by itself

Question 21

Big Pharmacokinetics:

Answer 21

Highly lipophilic
Metabolism by liver (except remi)
Excreted by kidneys, secondarily by GI/biliary

Question 22

Therapeutic Mu effects:

Answer 22

Sedation, Supraspinal analgesia, Spinal analgesia, Anti-tussive

Note: better at treating “second pain” sensations (C-fibers)

Question 23

Does an opioid produce a differential blockade that we would see in local anesthetics?

Answer 23

No.

DUMB card (Patrick and Abby)

Question 24

Adverse Effects:

Answer 24

Euphoria, Respiratory depression, Muscle rigidity, Slow gastric emptying, Urinary retention, Pruritis, Depressed cellular immunity, PONV

Question 25

T/F: Opioids have only a minimal effect on neuromonitoring.

Answer 25

True - minimal effect

Question 26

How would opioid admin result in increased ICP?

Answer 26

Respiratory depression --> High CO2 --> increased CBF --> inc ICP *we fix this by increasing RR, but outside OR can be issue*

Question 27

How do opioids cause analgesic effect?

Answer 27

Inhibition of ascending transmission of stimuli (from dorsal horn) AND activation of pain control pathways from midbrain (rostral ventromedial medulla)

Question 28

Tolerance is seen first by a decrease in ___ of the opioid and followed by a decrease in the ___ of the opioid.

Answer 28

Decrease in duration of action, then decrease in effect

Question 29

___ ___ is potentially life threatening in the post-operative period.

Answer 29

Respiratory depression *morbidly obese and OSA pts inc risk for M&M*

Question 30

Opioids cause a ___ shift on the CO2 response curve

Answer 30

Right shift = less response to hypercapnia

Question 31

What are risk factors for respiratory depression with opioids (blue box)

Answer 31

High dose opioids Advanced age CNS depressants Renal insufficiency Morphine Sleep

Question 32

Explain the pupillary reflex arc seen with opioids:

Answer 32

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)

Question 33

The pupillary reflex arc occurs at ___ doses than respiratory depression and/or analgesia.

Answer 33

Lower doses

Question 34

Antitussive benefits:

Answer 34

Keeps glottic reflexes intact while increasing tolerance to stimulation *Codeine, Heroin, Hydromorphone*

Question 35

Where is the chemoreceptor trigger zone?

Answer 35

Area postrema of medulla Floor of 4th ventricle

Question 36

Opioids are considered to be ___ for people with cardiac compromise.

Answer 36

Safe (blue box)

Question 37

What opioids release histamine? What are the CV effects of the release?

Answer 37

Morphine, Meperidine, Codeine HoTN, vasodilation, tachycardia *can block these effects with H1 or H2 blockers Of note: agonist-antagonist nalbuphine also releases histamine

Question 38

___ is the opioid most often associated with muscle rigidity.

Answer 38

Remi (mentions usually with rapid bolus) Seen as decreased chest wall compliance and hard mask ventilation

Question 39

___ and ___ are meds that work only on peripheral opioid receptors and therefore are great for GI issues.

Answer 39

Alvimopan and Methylnaltrexone (probably do not need to know this, just including all meds I see)

Question 40

___ has the highest rate of immunosuppressant effects.

Answer 40

Morphine

Question 41

Endocrine: Increased release of what? Decreased release of what?

Answer 41

Increased vasopressin release (seems backwards) Decreased ant pit hormones

Question 42

Morphine big takeaways: Natural

Answer 42

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

Question 43

Hydromorphone big takeaways: Semi-synthetic

Answer 43

7-8x more potent than morphine Onset 15-30 mins Safe in renal patients (no active met) Can be used for cough suppression

Question 44

Fentanyl big takeaways: Synthetic

Answer 44

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

Question 45

Remifentanil big takeaways: Synthetic

Answer 45

Onset 1 min Rapidly metabolized by tissue esterases Highest rate of muscle rigidity *Must have plan for post-op pain control*(blue box)

Question 46

Sufentanil big takeaways: Synthetic

Answer 46

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

Question 47

Which drug is by far the best in terms of context-sensitive half time? The worst?

Answer 47

Best: remi Worst: fentanyl

Question 48

Nalbuphine big takeaways: Synthetic

Answer 48

Agonist-antagonist Onset 2-3 mins Kappa agonist, mu antagonist Avoid in opioid dependent patients More difficult to reverse than opioid agonists Releases histamine

Question 49

Naloxone big takeaways:

Answer 49

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*