Opioids

Question 1

Opioid receptor subtypes

Answer 1

Mu
Delta
Kappa
ORL-1/NOP

Question 2

Opioid receptor locations

Answer 2

Mu: brainstem (nTS in medulla oblangata), spinal cord, periphery, GI tract
Delta: cortex, spinal cord
Kappa: cerebral cortex

Question 3

Mu receptor function

Answer 3

Analgesia
Reward
Cough/respiratory suppression
Constipation

Question 4

Delta receptor function

Answer 4

Maybe analgesia for chronic pain
Causing seizures

Question 5

Kappa receptor function

Answer 5

Hallucinations
Aversive
Anxiogenic
Maybe analgesia

Question 6

Buprenorphine

Answer 6

Partial opioid agonist, safer
Used in opioid agonist therapy

Question 7

Full opioid agonists

Answer 7

Heroin
Fentanyl
Morphine
Methadone
Oxycodone
Codeine via morphine

Question 8

Beta-arrestin signaling

Answer 8

1. GCPR phosophorylated after activation
2. Beta-arrestin binds
3. Arrests or redirects further signals, targets receptor to be internalized
4. Activates its own pathways

Question 9

Mu receptor signaling pathways

Answer 9

Gi: analgesia
b-arr: respiratory and GI effects

Question 10

Codeine/morphine metabolism

Answer 10

Codeine processed by CYP2D6 to morphine
Processed by UGT2B7 into active M6G and inactive M3G

Question 11

Endogenous opioid peptides

Answer 11

B-endorphins (Mu)
Enkephalins (Delta)
Dynorphin (Kappa)

Question 12

Endogenous opioid peptide shared sequence

Answer 12

Tyr-Gly-Gly-Phe

Question 13

Antinocicoception mechanism

Answer 13

Increases diffuse noxious inhibitory control (nocicoceptive gating of pain synapses in spinal cord)
Inhibition of medulla ON cells, reduction of nocicoceptive signaling to brain

Question 14

Mu receptor dopamine mechanism

Answer 14

Inhibit GABAergic interneurons in VTA, disinhibiting dopamine release in the VTA

Question 15

TRV250

Answer 15

Delta opioid receptor biased (G-protein path) agonist
In development for chronic migraine

Question 16

CR845

Answer 16

Peripherally restricted kappa opioid agonist, in development

Question 17

Preventative treatments for opioid use disorder

Answer 17

Physical barriers: prevent crushing of oral tablets
Chemical barriers: prevent solvent extraction
Agonist/antagonist combination: antagonist released by tampering with tablet, blocks positive effects

Question 18

Agonist replacement therapy

Answer 18

Maintenance on safer, longer lasting opioid agonist
Avoids debilitating withdrawal and high/crash cycles
Involves CBT, not just drugs
Methadone (full agonist) historically used, OD possible
Buprenorphine, usually as suboxone (+naloxone as anti tampering measure) is safer, partial mu agonist, kappa/delta antagonist

Question 19

Harm reduction methods (opioid)

Answer 19

Supervised consumption sites: provide supervision and clean needles, anonymous
Injectable opioid therapy (iOAT): requires referral after failure of other treatment, patient prescribed injectable opioids and self administers under supervision

Question 20

Naloxone (Narcan)

Answer 20

Non selective competitive opioid antagonist
Used to reverse overdose
May need multiple doses, lasts about half an hour