L19 Flashcards

1
Q

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

A

primary, secondary

skin, spinal chord

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

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

A

inhibits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A

rostroventral medulla

diffuse noxious inhibitory control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

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

A

excitatory
inhibitory
medulla

gate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

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

A

ON

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

•activation of opioid receptors
leads to___ of medulla
ON cells

produces a net__ in nociceptive signals reaching the brain

A

inhibition

reduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

• Dopamine is involved in___ behavior.

A

motivated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Dopamine neurons are located primarily in the

A

ventral tegmental area (VTA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Mu opioid receptors in the VTA are located on

A

inhibitory GABAergic interneurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

So, opioids inhibit inhibition (called____)

leading to dopamine__

A

disinhibition

release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

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)

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

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

and emotional circuits, will always be better analgesics

A

t

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

opioids are good analgesics because

A

they are rewarding (i.e: addictive).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

•most opioid agonists used
for pain are__ agonists

drugs eg
same efficacy/potency?

A

mu

morphine, fentanyl, codeine,
oxycodone
different

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

•delta agonists are being developed for

development initially limited because of

A

chronic migraine

side effects (seizures)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

delta agonist - isolate the analgesic effects from seizures through

A

biased

agonism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

•TRV250

A

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

18
Q

•kappa agonists that penetrate the brain have

not been developed for pain because of

A

dysphoria/hallucinogenic effects (see: Salvia)

19
Q

•peripherally restricted kappa agonists do/do not

cross the blood brain barrier

A

do not

20
Q

drugs bind kappa receptors in the skin

and inhibit pain transmission, while avoiding

A

central nervous system adverse events

21
Q

•CR845,

A

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

22
Q

•Tolerance

A

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

23
Q

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

A

analgesic, euphorigenic, sedative, and respiratory

24
Q

opioid tolerant individual can

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

A

large

25
Q

• 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)

A

• 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)

26
Q

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

A

Physical Dependence
discontinuance
withdrawal

27
Q

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

A

aversive

months

28
Q

t/f: dependence = addiction

A

f

29
Q

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

A

dysfunction

30
Q

physical barriers: Most preventative measures

are about making what difficult.

A

grinding oral tablets and

snorting or injecting (faster onset, bigger high).

31
Q

‣ Chemical Barriers

A

Can be added to resist extraction of the opioid by

common solvents like water/alcohol

32
Q

Agonist/Antagonist Combinations:

A

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).

33
Q

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

A

opioid agonist

cognitive behavioral therapy

34
Q

Agonist replacement therapy:
agonist therapy___ the
symptoms of opioid withdrawal

• replacement agonists have
shorter/longer half-lives, so avoid the
repeated high/crash cycle

A

blunts

longer

35
Q

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

A

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

36
Q

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

A

yes - is a partial agonist

improve

37
Q

suboxone

A

(bupernorphine+naloxone)

38
Q

Supervised consumption sites

A

provide a safe place to take drugs to reduce harm or

poisonings (overdose).

39
Q

Injectable opioid therapy (aka iOAT).

A

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

40
Q

naloxone

A

non-selective competitive opioid

receptor antagonist