lecture 72 Flashcards
Li - pharmacology of opiate drugs
what are the types of alkaloid of opium?
phenathrenes (morphines, codeine, thebaine)
benzylisoquinolines (noscapine, papaverine)
what is an opiate?
naturally occurring opioid that is derived from opium
what genes encode endogenous opioids?
pro-opiomelanocortin
preproenkephalin
prodynorphin
nociceptin/orphanin FQ
what is the function of pro-opiomelanocortin?
produces beta-endorphins which act on the mu opioid receptors
what is the role of preproenkephalin?
produces leu-enkephalin to act on delta-opioid receptors and met-enkephalin to act on mu and delta receptors
what is the role of prodynorphin?
produces dynorphin to act on kappa opioid receptors
what are the type of opioid receptors?
Gi/o
Mu
kappa
delta
nocicpetin/orphanin FQ
what is the function of Gi/o opioid receptors?
inhibit cAMP production
open GIRK potassium channel
close calcium channels
what are the endogenous opioids that correlate to each opioid receptor?
Mu - Endorphin
Kappa - Dynorphin
Delta - Enkephalin
Nociceptin/Orphanin FQ - Nociceptin
what is the role of presynaptic opioid receptors?
inhibit calcium channel (Gi) and decrease NT release
what is the role of postsynaptic opioid receptors?
activate GIRK channel (G-beta-gamma)
cause efflux of potassium to lead to hyperpolarization (less firing)
what are the characteristics associated with beta-endorphins?
produced from pro-opiomelanocortin (POMC)
play a role in runner’s high
what are the therapeutic uses of Mu opioid receptor agonists?
ex. morphine
analgesia (pt-controlled, cancer, pain, palliative, but not as effective for chronic pain)
sedation
antitussive
how does codeine act as an antitussive?
suppresses the cough center in the medulla oblongata
what are the on-target SE of opioids?
respiratory depression (brain stem, pre-botzinger complex in ventrolateral medulla)
constipation (Gi tract)
itching
addiction
urinary retention (due to opioid-induced ADH release)
NV (chemoreceptor trigger zone in medulla)
miosis (oculomotor nerve)
what are the effects of activation of the kappa opioid receptor?
dysphoric (unpleasant) and averse (uncomfortable) effects
what are kappa opioid receptor agonists used for therapeutically?
treatment for addiction by reducing DA release and counterbalancing Mu opioid receptor effects
what is the natural ligand of the delta opioid receptor?
enkephalins (mostly intracellular but externalized after chronic stimuli)
what are the benefits associated with the delta opioid receptor agonism?
reduces anxiety/depression, treats alcoholism, and relieves hyperalgesia and chronic pain
protects against hypoxia, ischemia, and stroke
what is the main SE of delta opioid receptor agonism?
seizures
how do opioid depressants cause DA release?
opioid binds Mu receptor –> Gi signaling inhibits NT release –> less GABA to activate GABA-a –> less inhibition of DA neuron activity –> increase DA release –> increase activation of DA receptors
what are the primary characteristics of morphine?
first-pass hepatic metabolism via CYP3D6 and 3A4
25% bioavailability that is excreted via glomerular filtration
what opioids are prodrugs?
heroin
codeine
tramadol
what opioids do not have active metabolites?
very dangerous
fentanyl and methadone
