Lecture 17 - Opioids I

Question 1

dried latex obtained from a poppy

Answer 1

opium

Question 2

any drug derived from opium

Answer 2

opiates

Question 3

any drug that binds to an opioid receptor (includes opiates, as well as synthetic opioid agonists)

Answer 3

opioid

Question 4

used by law enforcement to refer to illegal use of opioids for non-medical purposes

Answer 4

narcotics

Question 5

opioid receptors are:

Answer 5

inhibitory GPCRs (Gi)

Question 6

activation of opioid receptors leads to:

Answer 6

neuronal inactivation and reduced neurotransmitter release

Question 7

what are the four types of opioid receptors?

Answer 7

• mu
• kappa
• delta
• ORL1

Question 8

why do the different opioid receptors produce different effects when activated?

Answer 8

differences due to receptor distribution (different neurons, different brain circuits), and ligand specificity (drugs are selective for different opioid receptors)

Question 9

where is ORL1 expressed?

Answer 9

widely expressed in the CNS

Question 10

the last opioid receptor discovered (based on sequence homology), poorly studied, and may be involved in fear processing

Answer 10

ORL1

Question 11

what are the effects of mu opioid agonists?

Answer 11

• analgesia
• reward
• antitussive
• respiratory depression
• constipation

Question 12

morphine, codeine, and heroin are all:

Answer 12

full mu opioid agonists

Question 13

what are the effects of mu opioid antagonists?

Answer 13

• aversive
• prevent reward
• block overdose

Question 14

naloxone is a:

Answer 14

mu opioid antagonist

Question 15

what are the effects of delta opioid agonists?

Answer 15

• not rewarding
• no analgesia except in chronic pain and migraines
• some are seizure inducing

Question 16

what are the effects of delta opioid antagonists?

Answer 16

no obvious effects

Question 17

what are the effects of kappa opioid agonists?

Answer 17

• hallucinogenic
• anxiogenic
• analgesic and antipuretic

Question 18

salvia is a(n):

Answer 18

kappa opioid agonist

Question 19

what are the effects of kappa opioid antagonists?

Answer 19

potential antidepressant/anxiolytic

Question 20

a partial agonist at the mu opioid receptor; has mild to moderate analgesic efficacy, but a safe therapeutic index

Answer 20

buprenorphine

Question 21

which is a more potent opioid agonist: fentanyl or morphine?

Answer 21

fentanyl

Question 22

true or false: opioid ligands can have multiple effects on more than one opioid receptor

Answer 22

true

Question 23

drug which acts as a partial agonist at the mu opioid receptor and an antagonist at the delta/kappa opioid receptor

Answer 23

buprenorphine

Question 24

buprenorphine is a common treatment for:

Answer 24

pain and opioid addiction (opioid agonist therapy)

Question 25

delta agonists are being developed to treat:

Answer 25

chronic migraine

Question 26

at first, the development of delta agonists was restricted due to the risk of triggering seizures, but later on it was found that you can isolate the analgesic effects of delta agonists from seizures through:

Answer 26

biased agonism

Question 27

what is TRV250?

Answer 27

a delta opioid receptor biased agonist

Question 28

what are the two major pathways that can be triggered by activity at the delta opioid receptor?

Answer 28

G protein pathway and beta-arrestin pathway

Question 29

arrests G protein signalling that leads to tolerance following chronic opioid use, and activates its own intracellular signalling pathways that contributes to some of the drug effects

Answer 29

beta-arrestin

Question 30

what are beta-arrestins?

Answer 30

a family of intracellular proteins important for regulating signal transduction at GPCRs

Question 31

following receptor activation and G-protein cleavage, the GPCR is ______, which signals ______

Answer 31

phosphorylated, beta-arrestin to bind

Question 32

beta-arresting binding blocks ______, redirects ______, and targets ______

Answer 32

further G-protein signalling, signalling to alternative pathways, receptors for internalization

Question 33

selectivity for different receptor subtypes

Answer 33

receptor selectivity

Question 34

selectivity for different signalling pathways coupled to the same receptor

Answer 34

functional selectivity

Question 35

do all opioids lead to beta-arrestin recruitment?

Answer 35

no

Question 36

for the delta opioid receptor, which pathways blocks migraines and which pathways drives seizures?

Answer 36

G-protein signalling pathway blocks migraines, and the beta-arrestin signalling pathway drives seizures

Question 37

kappa agonists that penetrate the brain have not been developed for pain because of:

Answer 37

dysphoria/hallucinogenic effects

Question 38

peripherally restricted kappa agonists do not cross the:

Answer 38

blood brain barrier

Question 39

these drugs bind kappa receptors in the skin and inhibit pain transmission, while avoiding adverse events in the CNS

Answer 39

kappa opioid agonists

Question 40

a kappa opioid agonist which acts as a potent analgesic, anti-inflammatory, and has anti-itch properties with little CNS effects

Answer 40

nalfurafine

Question 41

where are kappa opioid receptors located?

Answer 41

on the terminals of dopamine neurons in the striatum

Question 42

kappa receptors are upregulated in disorders associated with:

Answer 42

dysphoria (depression, chronic pain, and addiction)

Question 43

a kappa antagonist which has completed phase 2 clinical trials with promising results for major depressive disorder

Answer 43

aticaprant

Question 44

most mu agonist opioids are ______ when taken orally

Answer 44

well absorbed

Question 45

when ingested, morphine undergoes:

Answer 45

extensive first-pass metabolism

Question 46

is codeine more or less impacted by first-pass metabolism than morphine?

Answer 46

less, since it is a prodrug that is metabolized into morphine by liver enzymes

Question 47

opioid agonists are widely distributed through body tissues, with highest concentrations in:

Answer 47

highly perfused body tissues (brain, lungs, liver, kidney, spleen)

Question 48

distribution of opioid agonists depends on:

Answer 48

route of administration

Question 49

true or false: opioid agonists can cross placental barriers, and exert effects on fetus that can result in both respiratory depression and physical dependence in neonates

Answer 49

true

Question 50

morphine is metabolized by:

Answer 50

phase II glucuronidation

Question 51

morphine is metabolized into:

Answer 51

morphine-3-glucuronide and morphine-6-glucuronide

Question 52

the most important glucuronidation enzyme is:

Answer 52

UGT2B7

Question 53

morphine-6-glucuronide is an:

Answer 53

active metabolite (can prolong morphine effects)

Question 54

codeine is metabolized into morphine by:

Answer 54

CYP2D6

Question 55

genetic polymorphisms of CYP2D6 are linked to:

Answer 55

variation in analgesic and adverse responses among patients (particularly for codeine)

Question 56

polar metabolites, including glucuronide conjugates of opioid analgesics, are excreted mainly in the:

Answer 56

urine