L19

Question 1

•mu, delta and kappa opioid
receptors are localized on ___ and ___
afferents in the ___ and __ __

Answer 1

primary, secondary

skin, spinal chord

Question 2

•agonist binding to opioid receptors__ pain transmission from skin to brain

Answer 2

inhibits

Question 3

•opioid receptors are also localized in
the brainstem (__ __)
where they increase __ __ __ __

Answer 3

rostroventral medulla

diffuse noxious inhibitory control

Question 4

diffuse noxious inhibitory circuit comprised of descending__
and__ neurons in the__
that inhibit or activate pain synapses in
the spinal cord

•allows our brain to___ the amount of nociceptive information that reaches the brain

Answer 4

excitatory
inhibitory
medulla

gate

Question 5

•mu and delta opioid receptors
are located on the__ cells in
the medulla

Answer 5

ON

Question 6

•activation of opioid receptors
leads to___ of medulla
ON cells

produces a net__ in nociceptive signals reaching the brain

Answer 6

inhibition

reduction

Question 7

• Dopamine is involved in___ behavior.

Answer 7

motivated

Question 8

Dopamine neurons are located primarily in the

Answer 8

ventral tegmental area (VTA)

Question 9

Mu opioid receptors in the VTA are located on

Answer 9

inhibitory GABAergic interneurons

Question 10

So, opioids inhibit inhibition (called____)

leading to dopamine__

Answer 10

disinhibition

release

Question 11

opiod r inhibit pain by

1) __ nociception at the level of the __, in the __ __, and in the _ _
2) __ the emotional and cognitive aspects of pain (make the pain bother you less)

Answer 11

1) decreasing nociception at the level of the nociceptor, in the spinal cord, and in the brain stem
2) decreasing the emotional and cognitive aspects of pain (make the pain bother you less)

Question 12

t/f: Drugs that target the sensory, as well as cognitive

and emotional circuits, will always be better analgesics

Answer 12

t

Question 13

opioids are good analgesics because

Answer 13

they are rewarding (i.e: addictive).

Question 14

•most opioid agonists used
for pain are__ agonists

drugs eg
same efficacy/potency?

Answer 14

mu

morphine, fentanyl, codeine,
oxycodone
different

Question 15

•delta agonists are being developed for

development initially limited because of

Answer 15

chronic migraine

side effects (seizures)

Question 16

delta agonist - isolate the analgesic effects from seizures through

Answer 16

biased

agonism

Question 17

•TRV250

Answer 17

a delta opioid receptor
biased agonist, currently under
development by Trevena

Question 18

•kappa agonists that penetrate the brain have

not been developed for pain because of

Answer 18

dysphoria/hallucinogenic effects (see: Salvia)

Question 19

•peripherally restricted kappa agonists do/do not

cross the blood brain barrier

Answer 19

do not

Question 20

drugs bind kappa receptors in the skin

and inhibit pain transmission, while avoiding

Answer 20

central nervous system adverse events

Question 21

•CR845,

Answer 21

kappa agonist, analgesic, anti-inflammatory,
and anti-itch properties with little CNS effects,
currently under development by Cara
Therpeutics)

Question 22

•Tolerance

Answer 22

decreased response
to the effects of the drug,
necessitating ever larger doses to achieve the same effect

Question 23

• opioid tolerance develops to the __,__,__,__effects the drugs.

Answer 23

analgesic, euphorigenic, sedative, and respiratory

Question 24

opioid tolerant individual can

take ___ doses (2g) (lethal dose for a drug naive individual is ~30mg)

Answer 24

large

Question 25

• Following agonist binding and G- protein signaling, β-arrestin is recruited to ____signaling (desensitization). •__+___ is pulled off the membrane and recycled in an ___. Is either degraded or recycled back to the membrane. •Repeated opioid use leads to ___ receptors on the membrane → reduced ____ effect (tolerance)

Answer 25

• Following agonist binding and G- protein signaling, β-arrestin is recruited to shut-off signaling (desensitization). •Receptor+agonist is pulled off the membrane and recycled in an endosome. Is either degraded or recycled back to the membrane. •Repeated opioid use leads to less receptors on the membrane → reduced agonist effect (tolerance)

Question 26

__ __ develops following chronic opioid use and is revealed following abrupt____ of drug as___

Answer 26

Physical Dependence discontinuance withdrawal

Question 27

•withdrawal is highly___ and some symptoms can persist for____. May motivate the drug user to make robust efforts to avoid withdrawal

Answer 27

aversive | months

Question 28

t/f: dependence = addiction

Answer 28

f

Question 29

addiction is a brain disease driven by__ in reward, motivation, memory circuitry.

Answer 29

dysfunction

Question 30

physical barriers: Most preventative measures | are about making what difficult.

Answer 30

grinding oral tablets and | snorting or injecting (faster onset, bigger high).

Question 31

‣ Chemical Barriers

Answer 31

Can be added to resist extraction of the opioid by | common solvents like water/alcohol

Question 32

Agonist/Antagonist Combinations:

Answer 32

antagonist can be added to an agonist to interfere with euphoria associated with abuse. The antagonist is only released when oral tablet is tampered with (crushed, injected, etc).

Question 33

•Agonist replacement therapy is treatment approach including maintenance on an __ ___ and __ __ __

Answer 33

opioid agonist | cognitive behavioral therapy

Question 34

Agonist replacement therapy: agonist therapy___ the symptoms of opioid withdrawal • replacement agonists have shorter/longer half-lives, so avoid the repeated high/crash cycle

Answer 34

blunts | longer

Question 35

methadone is a long-acting ___ agonist at the __opioid receptor •disadvantage

Answer 35

full mu it is a full agonist, so overdose still possible

Question 36

•buprenorphine safer than methadone? antagonist activity at kappa may____ mood

Answer 36

yes - is a partial agonist | improve

Question 37

suboxone

Answer 37

(bupernorphine+naloxone)

Question 38

Supervised consumption sites

Answer 38

provide a safe place to take drugs to reduce harm or | poisonings (overdose).

Question 39

Injectable opioid therapy (aka iOAT).

Answer 39

Clients must be referred to program by health care practitioner and must have failed all other addiction treatment. Clients are prescribed specific doses of injectable opioids self adminisiter

Question 40

naloxone

Answer 40

non-selective competitive opioid | receptor antagonist