Opioids

Question 1

Opioids exert their effect on the brain through which opioid receptors?

Answer 1

Agonist at the following receptors:
1. Mu (μ),
2. Kappa (κ)
3. Delta (δ)
…
(which are all G protein-coupled receptors)

Question 2

What are the effects of opioids exerting their effect on Mu (µ) receptors?

Answer 2

1. Analgesia
2. Euphoria
3. Constipation
4. Respiratory depression
5. Dependence
   ….
   (Dopaminergic cells within ventral tegmental area produce dopamine, which is released into the nucleus accumbens upon stimulation of µ receptors, producing the euphoria and reward that helps drive repeated use)
   (this is the key opioid receptor subtype)

Question 3

What are the effects of opioids exerting their effect on Kappa (κ) receptors?

Answer 3

1. Analgesia
2. Diuresia
3. Dysphoria (a state of unease or generalized dissatisfaction)
   …
   (with repeat opioid exposure, µ receptors in the ventral tegmental area neurons become less responsive to opioid binding and less dopamine is released. This causes causes dysphoria and depressed mood and contributes to drug craving)

Question 4

What are the effects of opioids exerting their effect on Delta (δ) receptors?

Answer 4

1. Analgesia
2. Anxiolysis

Question 5

What is the mechanism of action of methadone?

Answer 5

Full agonist targeting µ receptors
…
(some action against k and δ)

Question 6

What is the half-life of methadone?

Answer 6

15-22 hr

Question 7

What is the mechanism of action of buprenorphine?

Answer 7

1. Partial agonist targeting µ receptors
2. Partial agonist OR functional antagonist targeting κ receptors (possibly with antidepressant effects)
3. Weak δ antagonist

Question 8

What is the half-life of buprenorphine?

Answer 8

24-42 hr (oral administration)

Question 9

What is the mechanism of action of naloxone?

Answer 9

Antagonist targeting all opioid receptors: Mu (μ), Kappa (κ) and Delta (δ)

Question 10

What is the half-life of naloxone?

Answer 10

30-120 minutes
(depending on route)

Question 11

What is the mechanism of action of naltrexone?

Answer 11

Reversible competitive antagonist at Mu (μ) receptor

Question 12

What is the half-life of naltrexone?

Answer 12

4-6 hours
(half-life of the active metabolite is 13 hr)

Question 13

What is the mechanism of action of morphine?

Answer 13

Full agonist targeting Mu (μ) opioid receptors

Question 14

What is the half-life of morphine?

Answer 14

2-3 hours

Question 15

What is the mechanism of action of tramadol?

Answer 15

1. Weak agonist targeting Mu (μ) opioid receptors
2. Serotonin-norepinephrine reuptake inhibitor (SNRI)

Question 16

What is the half-life of tramadol?

Answer 16

1. Weak agonist targeting Mu (μ) opioid receptors
2. Serotonin-norepinephrine reuptake inhibitor (SNRI)