Lecture 6: Opioid and analgesic

Question 1

Definition of opioids

Answer 1

all naturally occurring and synthetic substance that bind to opioid receptor in the brain and periphery

Question 2

Definition of opiates

Answer 2

drugs derived from opium

Question 3

Supraspinal analgesia

Answer 3

suppression of pain by drugs in the brain

Question 4

3 types of opioid receptors

Answer 4

mu, delta, kappa

Question 5

What is a mixed agonist/antagonist opioid?

Answer 5

Has affinity for two or more types of opioid receptors
produce effect in one type and block effect in other type

Question 6

2 types of nociceptors

Answer 6

1. mechanoreceptors: respond to pressure
2. capsaicin receptors: responds to heat acid and inflammation caused by tissue damage

Question 7

How does interneuron in the spinal cord reduce pain?

Answer 7

interneurons are activated by exogenous opiates to release endorphins to suppress nociceptive neurons

Question 8

3 ways of how opiates regulate pain

Answer 8

1. inhibit Ca influx presynaptic, reduce or prevent release of substance P
2. enhance K flow out, hyperpolarize postsynaptic cell, harder to stimulate
3. moderate central perception of pain

Question 9

4 endogenous opioid agonist

Answer 9

1. enkephalins
2. endorphins
3. endomorphins
4. dynorphin

Question 10

Morphine/codeine

Answer 10

morphine way more potent than codeine as an analgesic

Question 11

Heroin

Answer 11

Much faster acting than morphine because more fat soluble transport across BBB easily
more addiction potential

Question 12

Methadone

Answer 12

just as potent as morphine but less sedation
longer lasting than morphine
milder withdrawal

Question 13

Dihydrocodeine

Answer 13

synthetic version of codeine

Question 14

Fentanyl

Answer 14

used in anesthesia
80 times more potent than morphine

Question 15

Hydromorphone

Answer 15

most commonly used opioid
analgesic and antitussive (anti vomit) effects
Mu opioid receptor

Question 16

Meperidine

Answer 16

short-acting
weak agonist
muscarinic and mu opioid effects

Question 17

Pentazocine

Answer 17

mixed agonist antagonist
agonist at kappa
antagonist at mu
less addiction potential

Question 18

Buprenorphine

Answer 18

partial agonist/antagonist
weak agonist at MU
antagonist at Kappa and Delta
less activity than endogenous opiates

Question 19

Naloxone, Nalmefene

Answer 19

opiate antagonist
opiate overdose

Question 20

Naltrexone

Answer 20

used for alcoholism

Question 21

How does opiates lead to addiction?

Answer 21

increase release of dopamine at nucleus accumbens
inhibiting the GABA, lead to less inhibition
increase activity of reward system

Question 22

How does opiates cause withdrawal? (2 reasons)

Answer 22

1. block neurotransmitter release, compensation of receptor number, removal cause hyperactivity because too much receptor
2. acutely block an enzyme, compensation of number of enzyme, removal cause rebound increase in enzyme and its product

Question 23

Main withdrawal symptoms of opiates

Answer 23

dysphoria
drug craving (psychological)

Question 24

Opioid and B-arrestin

Answer 24

originally thought should bias G-protein pathway in GPCR and not activate B-arrestin pathway
however found that respiratory depression and constipation are the same in both WT and B-arrestin knockout animals

Bias activation might not be effective in developing new opioids