Exam 2: Opioids

Question 1

What are opioid antagonists?

Answer 1

Naloxone (narcan) - reverses agnoists, precipitates withdrawal

Naltrexone (trexan)- long acting form

Question 2

What is the difference between natural opioids, semi-synthetics, and fully synthetic?

Answer 2

??

Question 3

What criteria must a compound meet to be an opioid agonist?

Answer 3

1) Exerts effects similar to morphine
2) Acts at opioid receptors
3) Effects blocked by antagonist, naloxone

Question 4

What are the effects of an opioid agonist?

Answer 4

Active Gi
Low cAMP
Decrease Ca2+ influx
Increase K+ efflux

Question 5

What are the pharacokinetic properties of opioids: administration?

Answer 5

1) Synthetics (m/c) oral
2) Syntehtics (M)- parenteral
3) Fentanyl - transdermal

non-therapeutic:

4) Heroin/morphine- parenteral
5) heroin- intranasla
6) opium/heroin- inhalation

Question 6

Kinetics of opioids: distribution?

Answer 6

???

Question 7

Kinetics of Opioids: Biotransformation?

Answer 7

Phase 2 conjugation by liver.

Glucuronide (6 active, 3 inactive)

Question 8

Kinetics of Opioids: Elimination?

Answer 8

???

Question 9

How were opioid receptors discovered?

Answer 9

Smooth muscle bioassay: opioids inhibit contraction caused by electical stimulation, but naloxone brings it back

[3H] Naloxone

Question 10

What are the types of opioid receptors?

Answer 10

1) Mu- reward, cough, emesis, miosis, respiratory, CV, GI suppression
2) Delta - reward, congition, motor, respiratory/GI suppress
3) Kappa- Dysphoria, anxiety
4)Orphan- feed, learn, motor
All analgesia

Question 11

What is the relevance of opioid receptor affinity to opioid potency?

Answer 11

Lower Ki= high affinity = high potency = low ED50

Question 12

How has smooth muscle been used to study the biological effects of opioids? How did this bioassay lead to the discovery of endogenous opioids?

Answer 12

Brain extract blocks contraction of smooth muscle (must be something in brain doing it)
Add naloxone back, inhibits

Question 13

What are the specific synaptic mechanisms by which all opioids affect cellular activity?

Answer 13

A) IPSP (K+ efflux, hyperolarize)
B) Pre inhibition (low transmitter release, reduce Ca2+ influx)
C) autoreceptor activated (decrease transmitter release, reduce Ca2+ influx)

Question 14

What are the acute effects of opioids

Answer 14

sedation, drowsiness, relax, euphoria, constrict pupil (miosis), nausea/vmoit, no cough/respiration, hypothermia, reduced sex drive, analgesia, constipation

Question 15

How do opioids exert analgesic effects to reduce pain?

Answer 15

Spinal/Brain Analgesia = inhibits pain sensation

Limbic/Thalamic/Cortical= inhibit pain perception

Question 16

In all forms of opioids on the table, receptor affinity is…

Answer 16

High or in case of fentanyl and carfentanil, insane

Question 17

What is the only opioid with partial intrinisic efficacy

Answer 17

Buprenorphine

Question 18

What are the symptoms of opioid OD?

Answer 18

Dizzy/confused, tiny pupil, gruggle, snore/choke, blue lips/nails, can’t wake up, slow/no breathing, cold clammy skin, no movement

Question 19

What mechanisms account for opioid OD?

Answer 19

Suppression of medullary center of respiration

Question 20

What interventions can treat opioid OD?

Answer 20

Naloxone vapor

Question 21

What common therapeutic uses of exogenous opioids?

Answer 21

Analgesia
Fentanyl- anesthesia
Cough Suppression
Substance abuse treatment 
reduce intestinal motility

Question 22

How are symptoms of opioid withdrawal related to the acute effects of opioid admin?

Answer 22

They are the opposite.

Acute: constipation, hypothermia, flushing,

Withdrawal: chills, bp, dilation, respiration, pain, depression

Question 23

What cellular mechanism is proposed to underlie tolerance and physical dependence associated with chronic opioid use?

Answer 23

Dynamic tolerance- decrease receptors and increase adenylyl cyclase

cAMP levels adapt to exposure, increase dramatically

Context tolerance too: rat experiment shows more likely to OD

Question 24

What cellular mechanism is proposed to underlie physical dependence associated with chronic opioid use?

Answer 24

Dependence: opposite acute effects, 1-2 weeks, not life threatening

Positive reinforcement: CRAVING, INCREASE RELEASE OF DOPAMINE IN NA

Question 25

How do dopaminergic and GABAergic neurons contribute to positive reinforcement of opioid use?

Answer 25

Koob.
Opioids inhibit GABA in VTA

Disinhibit DA neurons in VTA

Increase DA release in NA

Question 26

By what mechanisms can each drug
contribute to recovery from opioid addiction?
METHADONE

Answer 26

Fully agonist
Oral

Typical opioid, but mild. Reduce withdrawal symptoms/OD risk

Question 27

By what mechanisms can each drug
contribute to recovery from opioid addiction?
BUPRENORPHINE

Answer 27

Partial agonist
Sublingual/Buccal

Typical opioid but mild, reduces risk of OD/withdrawal intensity

Question 28

By what mechanisms can each drug
contribute to recovery from opioid addiction?
CLONIDINE

Answer 28

Noradrenergic alpha autoreceptor agonist

Suppresses physical withdrawal symptoms during week of withdrawal

Reduces release of NE in vesicles, fewer Ca2+ channels open, low cAMP

Question 29

By what mechanisms can each drug
contribute to recovery from opioid addiction?
NALTREXONE

Answer 29

Full antagonist

blocks effects of opioids, precipitates withdrawal in users, blocks life-threatening effects

Question 30

What factors are proposed to account for current epidemic of opioids?

Answer 30

???

Question 31

Suboxone

Answer 31

Buprenorphine and naloxone.

Sublingual

No effect if drug extracted and injected because naloxone blocks effects

Question 32

Morphine becomes heroin by

Answer 32

acetic anhydride, put 2x acetyl groups on it