Opioids II

Question 1

Where are Mu and Kappa Opioid receptors

Answer 1

On primary and secondary afferents in the skin and spinal cord

Question 2

What happens when an agonist binds to a an opioid receptor (Transmissions)

Answer 2

Inhibits pain transmission from skin to brain

Question 3

Where are opioid receptors in the brainstem, what do they do

Answer 3

Rostroventral medulla

Increase diffuse noxious inhibitory control

Question 4

What is the point of diffuse noxious inhibitory circuit?

Answer 4

Inhibits or active pain synapses in the spinal cord

Control the amount of nociceptive information that reaches the brain

Question 5

How do opioids block pain?

Answer 5

Opioid binds to opioid receptors on ON cells in the medulla

Activation of these receptors leads to inhibition of medulla ON cells

Net reduction in nociceptive signals reaching the brain

Question 6

What does dopamine effect?

Answer 6

Motivated Behaviour (Not pleasure)

Question 7

Where is dopamine located

Answer 7

Ventral Tegmental Area (VTA )

Question 8

In the VTA where are mu opioid receptors located

Answer 8

On GABAergic interneurons

Question 9

Mechanism behind how is dopamine released by opioid receptors

Answer 9

GABAergic interneurons tightly control release of dopamine

When opioids bind to mu opioid receptors on these GABAergic interneurons the interneurons are inhibited thus, dopamine is released

Disinhibition: inhibition of the GABAergic interneurons inhibition that is tightly controlling dopamine release

Question 10

What is the difference between nociception and pain

Answer 10

Nociception: Relay of pain signal from periphery to the brain
(Signals)

Pain: Integration of the pain signal with cognitive and emotional context
(Brain processing signals)

Question 11

How do opioid receptors inhibit pain

Answer 11

Decreasing nociception at the level of nociceptors (spinal cord and brain)

Decrease emotional and cognitive aspects of pain (makes pain bother you less)

Question 12

Most opioid agonist bind to which kind of opioid receptor

Answer 12

mu opioid receptors

Question 13

TRV250

Answer 13

Delta opioid agonist

Biased effects that isolate analgesic effects from seizures
(Biased for G-protein pathway)

Question 14

Salvia

Answer 14

Kappa agonists that can cross BBB, have dysphoria and hallucinogenic effects

Question 15

CR845

Answer 15

Kappa agonist that is peripherally restricted, can not cross BBB

Binds to kappa receptors on the skin and inhibits pain while avoiding central nervous system adverse effect

Question 16

What is tolerance, what are the dangers of tolerance and rehab

Answer 16

Decreased response to the effects of drugs, requiring user to use larger doses to achieve the same effect

If a drug user comes off of rehab and tries to take the same high dose they are used to they can overdose as they do not still have the same tolerance they used to

Question 17

Mechanism of tolerance

Answer 17

Agonist binds, g-protein signaling begins, beta-arrestin is recruited
Shuts off signaling (Desensitization)

Receptor+agonist is pulled off of membrane and recycled in the endosome, degraded or recycled back into the membrane

Repeated opioid use –> less receptors on membrane –> reduced agonist effect (tolerance)

Question 18

Physical Barriers for Opioid use

Answer 18

Prevent crushing/chewing of oral tablets for intravenous/intranasal drug use

Question 19

Chemical Barriers for Opioid use

Answer 19

Resist extraction of the opioid by common solvents like water/alcohol

Question 20

Agonist/Antagonist Combinations for preventing Opioid use

Answer 20

Adding an antagonist to interfere with euphoric effects associated with abuse.

Antagonist can be released when oral tablet is tampered with

Question 21

Agonist Replacement Therapy, (use and half-life of replacement agonists)

Answer 21

Blunts the symptoms of withdrawal using other replacement agonists

These agonists have longer half cycles to avoid the repeated high/crash cycle

Allows people to receive treatment without having to worry about withdrawal symptoms

Question 22

Methadone

Answer 22

Full agonist at the mu opioid receptor
Long acting and was the first replacement agonist

Disadvantages is that it is a full agonist so you can still overdose

Question 23

Buprenorphine

Answer 23

Partial agonist at the mu opioid receptor
Replacement agonist with little risk of overdose
Antagonist at the kappa and delta
antagonist at kappa can improve mood

Question 24

What are the two harm reduction treatments?

Answer 24

Supervised consumption sites: Clients bring their own drugs
Provided clean needles and medical supervision

Injectable opioid therapy (iOAT): Clients are prescribed specific doses of opioids (usually hydromorphone), and self administer in iOAT clinics
Monitored for adverse reactions