Ch11: Opioids

Question 1

Where are opioids in the brain?

Answer 1

Basal ganglia, amygdala, periaqueductal gray (associated with sensation of pain)

Question 2

How does the brain eliminate opioids?

Answer 2

Active transport mechanism. Brain has low levels of opioids compared to other body tissues because brain eliminates opioids by active transport mechanism.

Question 3

Four types of opioid receptors

Answer 3

1) Mu (u)
2) Kappa ((k)
3) Delta
4) ORL1

Sigma is not a receptor for opioid molecules

Question 4

What do opioid receptors do?

Answer 4

• They are G-protein-coupled receptors that release second messengers
• Activate potassium (K+) channels in the membrane & inhibit calcium (Ca) channels

Question 5

What happens when all 4 opioid receptors are activated?

Answer 5

• Activation of all 4 cause inhibition at post-synaptic membranes
• On presynaptic neurons, they inhibit the release of neurotransmitters (e.g., glutamate, GABA, norepinephrine)
• Inhibit production of cAMP, which inhibits membrane excitability and transmitter release

Question 6

Partial agonist

Answer 6

Opioids that terminate the activity of more potent agonist drugs and at the same time have a milder effect on their own.

E.g., nalorphine, pentazocine, cyclazocine

Nalorphine has a weak effect on the receptor, but binds strongly to it. Those with the weakest attraction at the receptor have the greatest effect on the receptor.
Acts as an antagonist (bc it blocks the morphine), but is also an agonist (bc it stimulates the receptor in a mild way).

Question 7

Opioid antagonist

Answer 7

Displaces any other opioid from the receptor but has almost no agonist effect of its own. Used to treat opioid OD because it will immediately terminate the action of all agonists.

E.g., Naloxone - pure antagonist at mu, kappa, and delta receptors

Question 8

Sites of action in the CNS

Answer 8

1) Analgesic effects

2) Reinforcement
- The extent to which an opioid acts as a mu agonist is positively correlated with its reinforcing effect and its abuse potential.
- In ventral tegmental area in animals.

2) Vital life functions

3) Dependence
- In the periventricular gray
- Does not directly involve mesolimbic reward system

Question 9

Which 3 important centres in the brainstem do mu-agonist opioids depress?

Answer 9

1) Respiratory centre
- Causes slow, shallow breathing
- Death from opioid OD is a result of respiratory depression

2) Vomiting centre

3) Cough centre
- Suppression of cough centre is why opioids have been included in cough medicines

Question 10

Effects of opioids on the body

Answer 10

• Nausea and vomiting, caused by chemoreceptor trigger zone
• Constricts pupils of the eyes
• Dilation of peripheral blood vessels (some low blood pressure)

Question 11

Effects of opioids on sleep

Answer 11

• Do not increase sleep

- Acute administration causes insomnia