Opioid Analgesics and Antagonists Flashcards
opium
- effects known for over 5000 years
- chewed or smoked usually
- greeks and romans used opium to produce sleep
- heroin was banned in 1924 given its abuse potential
poppy plant opium comes from
papaver somniferum
- sap from flower pod contains drug
opioids vs opiates
opioids - all naturally occurring and synthetic substances which bind to opioid receptors in brain and periphery. so, anything that binds to opioid receptors.
opiates - drugs derived from opium
analgesia
absence of sense of pain without loss of consciousness
spinal analgesia
suppression of pain by analgesic drugs into the the space around the spinal cord
- at the level of the spinal cord, opiates interfere with the transmission of the pain messages between neurons and therefore prevent them from reaching the brain
supraspinal analgesia
suppression of pain by drugs in the brain itself
- allows a person to know he or she is experiencing a given stimuli/sensation that would be otherwise painful
- reduces pain perception
Opioid receptor subtypes? What class of receptor are they?
µ, ∂, and kappa
- all GPCRs
µ (mu) opioid receptor
(function and endogenous peptide affinities)
function
- supraspinal and spinal analgesia
- sedation
- inhibition of respiration
- slowed gastrointestinal transit
- modulation of hormone and NT release
endorphins> enkephalins>dynorphins
∂ (delta) opioid receptor
(function and endogenous peptide affinities)
supraspinal and spinal analgesia, modulation of hormone and NT release
enkephalins> endorphins>dynorphins
kappa opioid receptor
(function and endogenous peptide affinities)
modest suprapsinal and spinal analgesia, psychotomimetic effects (producing an effect on the mind similar to that of a psychotic state) like dysphoria and depersonalization, slowed GI transit, disorientation, miosis (pupil constriction), and mild resp depression
dynorphins»> endorphins and enkephalins
(dynorphins have a MUCH higher potency)
Number of genes for each of the mu, delta, and kappa receptors
one gene only - thought that differential splicing produces variants within each subcategory (ex. multiple µs)
Established cellular actions of opioids
Opioids have two G protein-coupled actions on neurons
1. close voltage-gated calcium channels on presynaptic nerve terminals which reduces release of glutamate, Ach, NE, 5HT, substance P
(this is how it blocks pain)
2. open K+ channels which inhibits and hyperpolarizes postsynaptic neurons
µ (mu) opioid receptor
(location)
located in:
all pain-control areas of the brain and spinal cord
- periaqueductal gray in midbrain
- spinal trigeminal nucleus
- caudate nucleus
- thalamic nucleus
in respiratory control centres and nucleus accumbens
exogenous ligands of µ OR
morphine and fentanyl
kappa opioid receptor
(location)
- basal ganglia
- nucleus accumbens
- ventral tegmentum
- cortex
- hypothalamus
- PAG
- spinal cord
exogenous ligands of kappa OR
responds to mixed agonist-antagonists like pentazocine and endogenous dynorphin
a mixed agonist-antagonist has affinity for two or more types of opioid receptors and _____
blocks opioid effects on one receptor type while producing opioid effects on a second receptor type
Salvinorin A
pure kappa OR agonist
(compared binding of LSD to salvinorin, LSD binds to a bajiillion things and salvinorin only to kappa OR)
delta opioid receptor
(location)
also found in pain areas of the brain
- PAG
- spinal trigeminal nucleus
- caudate nucleus
- thalamic nucleus
and the nucleus accumbens and libmic system
exact same areas as µ ORs except: present in limbic system and not in respiratory centres
exogenous ligands of delta OR
etorphine
nociceptors
(and two specific types)
general term to describe neurons that carry pain info from skin, muscle to neurons in the spinal cord (detect noxious stimuli)
- mechanoreceptors: respond to pressure
- capsaicin receptors: respond to extremes of heat, to acids, to capsaicin, and to inflammation caused by tissue damage
are inhibited by inhibitory interneurons releasing endorphins
How does that brain interpret pain and send pain-moderating signals
- inhibitory interneurons synapse onto substance-P-releasing-nociceptors and release endorphins to modify pain signal
- the endorphins or other endogenous opioids inhibit release of substance P (or any other NT carrying pain info) onto another neuron that would normally carry the pain signal back to the brain