OPIOIDS Flashcards
what are opioid drugs, what do they do
narcotic analgesics
reduce pain without producing unconsciousness
main ingredient in opium
morphine
how was heroin made
adding two acetyl groups to morphine, making it more lipid soluble
what are the benefits of heroin + mechanisms of action
reaches the brain faster
more potent than morphine
carrier molecule, acetyl groups cleave off when in brain.
opioid drugs bind to specific receptors in the ____, discovered using ________
brain, radio ligand assays
4 types of opioid receptors
mu, delta, kappa, NOP-R
what type of receptor are opioid receptors
G-protein linked metabotropic receptors
mu receptor has _____ affinity for _____
high, morphine
which areas cause analgesia due to mu receptor (5 areas)
medial thalamus, periaqueductal gray, raphe, locus coeruleus, spinal cord
Brainstem mu receptor binding causes what
cardiovascular/respiratory control, cough control, nausea/vomitting
sensorimotor integration mu receptor locations
thalamus, striatum
NAc Mu receptor effect
feeding, positive reinforcement , pleasurable aspects of fatty/sweet foods.
S (delta receptor) location
forebrain structures
delta receptor roles
olfaction, motor integration, reinforcement and cognitive function and overlap with mu receptors suggest modulation of analgesia.
K-(kappa) receptors location
striatum, amygdala, hypothalamus
kappa receptor role
regulation of pain perception, gut motility, and dysphoria
FQ receptors location + function
wide distribution (cortex, limbic areas, thalamus, raphe nuclei, spinal cord)
Does not bind opioid drugs
lowers pain thresholds
role in feeding, learning, motor function, reward and neuroendocrine regulation
first peptide transmitter that binds to opioid receptors
enkephalin
another endogenous peptide that binds to opioid receptors
endorphins
how are endogenous opioid receptors synthesized
you synthesize them at the cell body, at the nucleus where the DNA and ribosomes are. Usually larger precursor peptides that are cleaved to smaller transmitters
mu receptors are preferentially activated by
endorphins and selectively activated by endorphins
delta receptor preferentially activated by
enkephalins and endorphins
kappa receptor preferentially activated by
dynorphins
Three ways opioids inhibit neural activity
- post synaptic inhibition - receptors activate a G protein that opens k+ channels. hypolarized.
- axoaxonic inhibition - heteroreceptors (presynaptic)- activate G proteins that close Ca2+ channels, reducing transmitter release.
- Presynaptic autoreceptors - reduce release of co-localized NT.
all opioid receptors are coupled to ____ that inhibit ______
GI proteins, adenylyl cyclase-cAMP
Partial agonist of opium
buprenorphine
pure antagonists (2) of opium have high \_\_\_\_, low \_\_\_\_ for receptors
naloxone, naltrexone
high affinity, low efficacy
what do endogenous opioids and opioids do in relation to pain when they bind receptors
inhibit pain signal transduction at multiple sites
spinal cord (spinal analgesia)
opioid interneurons can inhibit. pain projection neurons
do so by activating descending pathways from brain to spine either by
1. inhibit pain projection neurons
2. inhibit excitatory interneurons that synapse on pain projection neurons
opioids activate two descending pain-inhibiting pathways originating in the ___
PAG
what do opioid projections from PAG do
disinhibit raphe (5HT) and locus coeruleus (NE) descending projections that suppress pain signals in the spinal cord
what do low doses of opioids provide
pain relief, constricted pupils, drowsiness, inability to concentrate, dreamy sleep
what do high doses of opioids provide
abnormal state of elation or euphoria
what do highest doses of opioids cause
unconsciousness and death which happens due to suppression of brainstems respiratory centre
how do we therapeutically administer opioids
intra-muscularly, orally (slow absorption not as euphoric)
how do we recreationally administer opioids
more rapid means such as inhalation, snorting, sub-cutaneous, IV
Aversive effects of opioids (4)
dysphoria, anxiety, nausea, restlessness
reduced GI motility hence constiption
IV administration of opioids lead to which risks
infection
collapsed veins
liver/kidney damage
opioids activate ________ and this contributes to
mesolimbic DA pathway, opioid reinforcement
Mu-receptor activation does what in relation to DA
inhibit GABA neurons in VTA, which disinhibit DA neuron firing, increasing DA release
Tolerance of which effects develop quickly, and which develop more slowly
analgesia/pleasurable tolerance = quick
constipation/pupilary dilation = slow
withdrawal of opioid drugs symptoms
depress CNS function, rebound hyperactivity.
opioid antagonist can
precipitate withdrawal symptoms
opioid antagonist in _____ or _____ trigger physical withdrawal
Locus coeruleus or PAG
opioid antagonist in _____ or _____ trigger aversive emotional effects withdrawal
NAc and Amygdala
Methadone is what
opioid agonist, taken orally can help prevent severe withdrawal symptoms
