PCOL of Opiate Drugs (Barker) Flashcards
opium contained 2 types of alkaloids
- ___ (most clinically important)
- benzylisoquinolines
___ are only those opioids that are naturally occuring
- phenanthrenes
- opiates
what structure is this
phenanthrene
what structure is this?
benzylisoquinoline
SAR
3 position - ether or ester produces ___ potency (codeine)
6 position - ___ activity (hydromorphone, hydrocodone)
14 position - ___ has increased potency (oxycodone)
N-allyl gives ___ properties (naloxone, naltrexone)
- looks like a long chain
- decreased
- increased
- OH
- antagonist
the human genome contains several genes encoding endogenous opioids
- endogenous peptides
- large precursor proteins are cleaved into more opioid subtypes selective peptides
- degree of redundancy
POMC
- ß-endorphin = ___ receptor
Preproenkephalin
- leu-enkephalin = ___ receptor
- met-enkaphalin = ___ and ___ receptors
preprodynorphin
- dynorphin = ___ receptor
nociceptin/orphanin FQ
mu
delta
mu, delta
kappa
types of opioid receptors
G protein-coupled receptor
- family A - peptide receptors
- G ___ coupled (inhibition of cAMP productioin_
- open ___ channels
- close ___ channels
Mu
- endogenous opioid = ___
Kappa
- endogenous opioid = ___
Delta
- endogenous opioid = ___
Nociceptin, orphanin FQ receptor
- endogenous opioid = ___
Sigma receptors - NOT an opioid receptors
- i/o
- GIRK
- Ca
- endorphin
- dynorphin
- enkephalin
- nociceptin
opioid receptors signal transduction
presynaptic
- inhibit ___ channel (Gi)
- decrease ___ release
postsynaptic
- activate ___ channel (Gßy)
- efflux of K = ___ (more difficult to reach threshold to send action potential)
- Ca
- neurotranmitter
- GIRK
- hyperpolarization
the Mu opioid recceptor
beta-endorphins (endogenous morphine)
- POMC
- component of runners high
therapeutic use
- acute analgesia, not effective for chronic pain
- cancer pain, palliative, patient controlled
- helps manage breakthrough pain
sedation
antitussive - suppress cough center in medulla
opioid induced SE are mostly on-target effects - Mu activation
respiratory depression
- brain stem
constipation
- GI tract
pruritus (itch)
- SE: not allergic reaction, opioid induced ___ release
addiction - nucleus accumbens
urinary retention
- opioid induced ___ release
N/V
- chemoreceptor trigger zone - medulla
miosis - pinpoint pupils
- oculomotor nerve (PAG)
- not mepiridine (has anti-cholinergic effects)
- histamine
- ADH
would you use opioid as an anti-diarrheal?
yes, special formulation to stay out of CNS
Kappa opioid receptor
___ are the natural ligand
activation is ___ and aversive
pontential use for treatment of addition
- reduce ___ release
counterbalance ___ receptor effects
- dynorphins
- dysphoric
- dopamine
- mu
delta opioid receptors
___ are natural ligands
play ___ roles in hypoxia, ischemia, and stroke
- what animals release in hibernation
reduces anxiety, depression, hyperalgesia, and chronic pain
potential treatment for alcoholism
no FDA approved drugs yet
enkephalins
protective
opioid site of action
ventral tegmental area (VTA)
nucleaus accumbens (NAc)
both play a key role in reward
- opiates reduce the release of inhibitory GABA, so ___ production increases
DA
