OUD 1 - Background, OD, Withdrawal Management Flashcards
What is the mu opioid receptor responsible for? (6)
Responsible for most of the opioid analgesic effect
- Respiratory depression
- Reduced GI motility
- Euphoria
- Physical dependence
- Sedation
What is the delta opioid receptor responsible for? (3)
- Analgesia
- Euphoria
- Phsyical dependence
What is the kappa opioid receptor responsible for? (4)
- Analgesia
- Sedation
- ? Mood
- Does NOT contribute to physical dependence
Define OUD
Primary chronic disease of brain reward, motivation, memory, and related circuitry with a dysfunction in these circuits being reflected in an individual pathologically pursuing reward and/or relief of withdrawal symptoms by substance use and other behaviours
In the DSM-5 there are 2 bits of criteria as follows “patients who are prescribed opioid meds for analgesia may exhibit these two criteria, but would not necessarily be considered to have SUD”. What are the two criteria?
- Tolerance
- Withdrawal
OUD is a long-lasting chronic brain disease. Meaning? (2)
- It does NOT end when the drug is removed from the body or when acute post-drug taking illness dissipates
- Is similar to other chronic diseases such as T2DM and HTN in that it CANNOT be cured but can be treated and managed
Why is OUD associated with increased morbidity and mortality? (2)
- Opioid overdose and trauma is leading cause of death among people using opioids
- Increased rates of HIV, hepatitis, and STDs
Go through the cycle of OUD (3 stages and what part of the brain is involved in each stage)
- Binge/Intoxication - basal ganglia
- Withdrawal/Negative Affect - extended amygdala
- Preoccupation/Anticipation - prefrontal cortex
What is the binge/intoxication stage of addiction?
Individual consumes an intoxicating substance and experiences its rewarding or pleasurable effects
What is withdrawal/negative affect stage of addiction?
Individual experiences a negative emotional state in the absence of the substance
What is the preoccupation/anticipation stage of addiction?
Individual seeks substances again after a period of abstinence
Talk about the 3 stages of addiction. (4 main points to make here)
- The three stages are linked to and feed on each other, but they also involve different brain regions, circuits, and NTs and result in specific kinds of changes in the brain.
- A person may go through this three-stage cycle over the course of weeks or months or progress through it several times in a day.
- There may be variation in how people progress through the cycle and the intensity with which they experience each of the stages.
- The addiction cycle tends to intensify over time, leading to greater physical and psychological harm.
Describe the neurobiology of opioid tolerance starting with when an opioid attaches to the mu receptor and ending at release of dopamine (3 points)
- When an opioid attaches to the mu receptor it triggers a structure in the brain called the mesolimbic (midbrain) reward system in the ventral tegmental area (VTA)
- The VTA system is responsible for the release of dopamine in the nucleus accumbens (NAc) in the basal ganglia
- Release of dopamine in the NAc = pleasure
Describe the neurobiology of opioid tolerance starting with when opioids are taken repeatedly and ending at leading to development of… (5 points)
- When taken repeatedly opioids trigger the brain’s reward system driving a compulsion to take the drug again and again
- Feedback to the prefrontal cortex to the VTA regulates the drive to obtain pleasure (risk vs. rewards)
- Over time, with repeated opioid use, this feedback pathway becomes dysregulated, impairing decision making
- Additionally, opioid receptors in the VTA become less sensitive to opioid stimulation. Dopamine production is reduced and the experience of pleasure/opioid effect is diminished
- Leads to development of opioid tolerance
– Higher and higher doses to achieve same pleasure reward
OUD can also result from changes in the locus coeruleus (LC). What is happening there? (2)
- Neurons in the LC produce noradrenaline and distribute it to other parts of the brain where it stimulates wakefulness, breathing, blood pressure, alertness, etc. (fight or flight)
- When opioids bind to mu receptors in the LC they suppress the release of noradrenaline –> drowsiness, slowed respiration, low blood pressure –> opioid intoxication
