Lecture 6: Opioid and analgesic Flashcards
Definition of opioids
all naturally occurring and synthetic substance that bind to opioid receptor in the brain and periphery
Definition of opiates
drugs derived from opium
Supraspinal analgesia
suppression of pain by drugs in the brain
3 types of opioid receptors
mu, delta, kappa
What is a mixed agonist/antagonist opioid?
Has affinity for two or more types of opioid receptors
produce effect in one type and block effect in other type
2 types of nociceptors
- mechanoreceptors: respond to pressure
- capsaicin receptors: responds to heat acid and inflammation caused by tissue damage
How does interneuron in the spinal cord reduce pain?
interneurons are activated by exogenous opiates to release endorphins to suppress nociceptive neurons
3 ways of how opiates regulate pain
- inhibit Ca influx presynaptic, reduce or prevent release of substance P
- enhance K flow out, hyperpolarize postsynaptic cell, harder to stimulate
- moderate central perception of pain
4 endogenous opioid agonist
- enkephalins
- endorphins
- endomorphins
- dynorphin
Morphine/codeine
morphine way more potent than codeine as an analgesic
Heroin
Much faster acting than morphine because more fat soluble transport across BBB easily
more addiction potential
Methadone
just as potent as morphine but less sedation
longer lasting than morphine
milder withdrawal
Dihydrocodeine
synthetic version of codeine
Fentanyl
used in anesthesia
80 times more potent than morphine
Hydromorphone
most commonly used opioid
analgesic and antitussive (anti vomit) effects
Mu opioid receptor
Meperidine
short-acting
weak agonist
muscarinic and mu opioid effects
Pentazocine
mixed agonist antagonist
agonist at kappa
antagonist at mu
less addiction potential
Buprenorphine
partial agonist/antagonist
weak agonist at MU
antagonist at Kappa and Delta
less activity than endogenous opiates
Naloxone, Nalmefene
opiate antagonist
opiate overdose
Naltrexone
used for alcoholism
How does opiates lead to addiction?
increase release of dopamine at nucleus accumbens
inhibiting the GABA, lead to less inhibition
increase activity of reward system
How does opiates cause withdrawal? (2 reasons)
- block neurotransmitter release, compensation of receptor number, removal cause hyperactivity because too much receptor
- acutely block an enzyme, compensation of number of enzyme, removal cause rebound increase in enzyme and its product
Main withdrawal symptoms of opiates
dysphoria
drug craving (psychological)
Opioid and B-arrestin
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
