Opioids II Flashcards
Where are Mu and Kappa Opioid receptors
On primary and secondary afferents in the skin and spinal cord
What happens when an agonist binds to a an opioid receptor (Transmissions)
Inhibits pain transmission from skin to brain
Where are opioid receptors in the brainstem, what do they do
Rostroventral medulla
Increase diffuse noxious inhibitory control
What is the point of diffuse noxious inhibitory circuit?
Inhibits or active pain synapses in the spinal cord
Control the amount of nociceptive information that reaches the brain
How do opioids block pain?
Opioid binds to opioid receptors on ON cells in the medulla
Activation of these receptors leads to inhibition of medulla ON cells
Net reduction in nociceptive signals reaching the brain
What does dopamine effect?
Motivated Behaviour (Not pleasure)
Where is dopamine located
Ventral Tegmental Area (VTA )
In the VTA where are mu opioid receptors located
On GABAergic interneurons
Mechanism behind how is dopamine released by opioid receptors
GABAergic interneurons tightly control release of dopamine
When opioids bind to mu opioid receptors on these GABAergic interneurons the interneurons are inhibited thus, dopamine is released
Disinhibition: inhibition of the GABAergic interneurons inhibition that is tightly controlling dopamine release
What is the difference between nociception and pain
Nociception: Relay of pain signal from periphery to the brain
(Signals)
Pain: Integration of the pain signal with cognitive and emotional context
(Brain processing signals)
How do opioid receptors inhibit pain
Decreasing nociception at the level of nociceptors (spinal cord and brain)
Decrease emotional and cognitive aspects of pain (makes pain bother you less)
Most opioid agonist bind to which kind of opioid receptor
mu opioid receptors
TRV250
Delta opioid agonist
Biased effects that isolate analgesic effects from seizures
(Biased for G-protein pathway)
Salvia
Kappa agonists that can cross BBB, have dysphoria and hallucinogenic effects
CR845
Kappa agonist that is peripherally restricted, can not cross BBB
Binds to kappa receptors on the skin and inhibits pain while avoiding central nervous system adverse effect
What is tolerance, what are the dangers of tolerance and rehab
Decreased response to the effects of drugs, requiring user to use larger doses to achieve the same effect
If a drug user comes off of rehab and tries to take the same high dose they are used to they can overdose as they do not still have the same tolerance they used to
Mechanism of tolerance
Agonist binds, g-protein signaling begins, beta-arrestin is recruited
Shuts off signaling (Desensitization)
Receptor+agonist is pulled off of membrane and recycled in the endosome, degraded or recycled back into the membrane
Repeated opioid use –> less receptors on membrane –> reduced agonist effect (tolerance)
Physical Barriers for Opioid use
Prevent crushing/chewing of oral tablets for intravenous/intranasal drug use
Chemical Barriers for Opioid use
Resist extraction of the opioid by common solvents like water/alcohol
Agonist/Antagonist Combinations for preventing Opioid use
Adding an antagonist to interfere with euphoric effects associated with abuse.
Antagonist can be released when oral tablet is tampered with
Agonist Replacement Therapy, (use and half-life of replacement agonists)
Blunts the symptoms of withdrawal using other replacement agonists
These agonists have longer half cycles to avoid the repeated high/crash cycle
Allows people to receive treatment without having to worry about withdrawal symptoms
Methadone
Full agonist at the mu opioid receptor
Long acting and was the first replacement agonist
Disadvantages is that it is a full agonist so you can still overdose
Buprenorphine
Partial agonist at the mu opioid receptor
Replacement agonist with little risk of overdose
Antagonist at the kappa and delta
antagonist at kappa can improve mood
What are the two harm reduction treatments?
Supervised consumption sites: Clients bring their own drugs
Provided clean needles and medical supervision
Injectable opioid therapy (iOAT): Clients are prescribed specific doses of opioids (usually hydromorphone), and self administer in iOAT clinics
Monitored for adverse reactions
