Opioids Flashcards
What is the difference between an opiate and an opioid?
an opiate is a drug derived from the opium poppy
an opioid encompasses the opiates, but includes any substance that acts on the opioid receptors (can be man-made or endogenous)
What are the 3 receptors opioids bind?
Mu (analgesia, respiratory depression, decreased GI motility, dependence)
kappa (analgesia, sedation, decreased GI motility)
delta (modules mu activity)
What are the encogenous opioids that act on the mu receptors? keppa? delta?
mu - endorphins and endomorphines
kappa = dynorphins
delta = enkephalins
What sort of receptor is the Mu receptor?
a GPCR
What does the mu receptor do when activated? On the presynaptic terminal!
It inhibits a Ca2+ channel and adenylyl cyclase (less cAMP)
Because the Ca2+ channel is inhibited, you have reduced release of glutamate and substance P
thus, the signal isn’t transmitted
In addition to blocking Ca2+ on the presynaptic terminal, what happens in the post synaptic terminal?
postsynaptic inhibition
the receptor activation opens K+ channel, allowing K+ to flow out, causing hyperpolarizaiton and decreased excitability
makes the postsynaptic neuron even less likely to fire
The inhibition of the ascending pain transmission pathway occurs mostly where?
in the dorsal horn, but also in the spinal cord, thalamus and maybe the periphery
What are opioids effect on the descending inhibitory pathway?
It enhances the descending inhibitory pathway, thus further inhibiting the ascending pain pathway
Under normal conditions, an inhibitory interneuron is constitutively releasng GABA onto the efferent presynaptic neuron, thus inhibitin the descending pathway
Opioid receptor activation blocks release of GABA from the inhigitory interneuron, so you get activation of the inhibiting descending pathway
thus, greater inhibition of nociceptive processing in dorsal horn of the spinal cord (Gate theory)
What are some examples of opioid agonists?
they bind the receptor and produce an effect:
morphine, methadone, oxycodone, heroin
How does an antagonist work and what are two examples?
it binds to the receptor but doesn’t have an effect, so it’s usually used to compete for the receptor in opiate addiction
examples include Nalozone and Naltrexone
Why would you maybe want to prescribe a partial agonist and what is an example of one?
It’s less efficacious than a full agonist, but it has lower abuse potential
Buprenorphine is one
It’s often used in tandem with nalozone (combo is subozone)
What is an example of a mixed agonist/antagonist? What is the clinical relevance?
pentazocine
it’s an agonist at kappa and antagonist at Mu
this means if you change someone who is opiate dependant to this, they will enter withdrawal
What are the pros and cons of using opioids orally?
Pro: convenient, longer duration than parenteral routs, better for chronic treatment
Con: high first pass metabolism is limiting, slowe ronset, delayed peak effect
What are the pros and cons of giving opioids IV?
pro: precide and accurate dosin, rapid onset, you can do bolus or continuous and patient can control dose with button
con: increased risk of adverse effects
What are some of the benefits of giving opioids intra-thecally?
longer duration at lower doses than systemic
can avoid some of the brain-mediated adverse effects like respiratory depression
