Opioids Flashcards
Opioid receptor subtypes
Mu
Delta
Kappa
ORL-1/NOP
Opioid receptor locations
Mu: brainstem (nTS in medulla oblangata), spinal cord, periphery, GI tract
Delta: cortex, spinal cord
Kappa: cerebral cortex
Mu receptor function
Analgesia
Reward
Cough/respiratory suppression
Constipation
Delta receptor function
Maybe analgesia for chronic pain
Causing seizures
Kappa receptor function
Hallucinations
Aversive
Anxiogenic
Maybe analgesia
Buprenorphine
Partial opioid agonist, safer
Used in opioid agonist therapy
Full opioid agonists
Heroin
Fentanyl
Morphine
Methadone
Oxycodone
Codeine via morphine
Beta-arrestin signaling
- GCPR phosophorylated after activation
- Beta-arrestin binds
- Arrests or redirects further signals, targets receptor to be internalized
- Activates its own pathways
Mu receptor signaling pathways
Gi: analgesia
b-arr: respiratory and GI effects
Codeine/morphine metabolism
Codeine processed by CYP2D6 to morphine
Processed by UGT2B7 into active M6G and inactive M3G
Endogenous opioid peptides
B-endorphins (Mu)
Enkephalins (Delta)
Dynorphin (Kappa)
Endogenous opioid peptide shared sequence
Tyr-Gly-Gly-Phe
Antinocicoception mechanism
Increases diffuse noxious inhibitory control (nocicoceptive gating of pain synapses in spinal cord)
Inhibition of medulla ON cells, reduction of nocicoceptive signaling to brain
Mu receptor dopamine mechanism
Inhibit GABAergic interneurons in VTA, disinhibiting dopamine release in the VTA
TRV250
Delta opioid receptor biased (G-protein path) agonist
In development for chronic migraine
CR845
Peripherally restricted kappa opioid agonist, in development
Preventative treatments for opioid use disorder
Physical barriers: prevent crushing of oral tablets
Chemical barriers: prevent solvent extraction
Agonist/antagonist combination: antagonist released by tampering with tablet, blocks positive effects
Agonist replacement therapy
Maintenance on safer, longer lasting opioid agonist
Avoids debilitating withdrawal and high/crash cycles
Involves CBT, not just drugs
Methadone (full agonist) historically used, OD possible
Buprenorphine, usually as suboxone (+naloxone as anti tampering measure) is safer, partial mu agonist, kappa/delta antagonist
Harm reduction methods (opioid)
Supervised consumption sites: provide supervision and clean needles, anonymous
Injectable opioid therapy (iOAT): requires referral after failure of other treatment, patient prescribed injectable opioids and self administers under supervision
Naloxone (Narcan)
Non selective competitive opioid antagonist
Used to reverse overdose
May need multiple doses, lasts about half an hour
