Lecture 18 - Opioids II Flashcards
dopamine is involved in:
motivated behaviour
where are dopamine neurons located?
primarily in the ventral tegmental area (VTA)
mu opioid receptors in the VTA are located on:
inhibitory GABAergic interneurons
do mu opioid agonists lead to increased or decreased dopamine release?
increased dopamine release (inhibits inhibitory GABAergic interneurons)
how do opioid receptors inhibit pain?
1) decreasing nociception at the level of the nociceptor, in the spinal cord, and in the brain stem
2) decreasing the emotional and cognitive aspects of pain (make pain bother you less)
which are better analgesics: drugs that target the sensory aspects of pain, or drugs that target the cognitive/emotional aspects of pain?
sensory
what is the problem with trying to develop good non-addictive analgesics?
opioids are good analgesics because they are rewarding
decreased response to the effects of the drug, necessitating even larger doses to achieve the same effect
tolerance
how large a dose can an opioid tolerant person take?
2g (lethal dose for a drug naive individual is ~30mg)
how does opioid desensitization work?
following agonist binding and G-protein signalling, beta-arrestin is recruited to shut-off signalling
when the receptor agonist complex is pulled off the membrane and recycled in an endosome, then it is either:
degraded or recycled back to the membrane
repeated opioid use leads to:
less opioid receptors on the membrane –> reduced agonist effect (tolerance)
develops following chronic opioid use and is revealed following abrupt discontinuance of drug as withdrawl
physical dependence
acute opioid withdrawl includes:
- rhinorrhea (runny nose)
- lacrimation (tearing eyes)
- chills
- muscle aches
- diarrhea
- yawning
- anxiety
aversion to withdrawl symptoms can drive the transition to:
addiction
true or false: drug addiction is the same thing as drug dependence
false
a brain disease driven by dysfunction in reward, motivation, and memory circuitry
addiction
what are the five major characteristics of addiction?
- inability to abstain consistently
- impairment of behaviour control
- drug craving
- diminished recognition of significant problems with ones behaviours and interpersonal relationships
- dysfunctional emotional response
what type of disease is substance use disorder?
a biopsychosocial disease
can increase your likelihood of developing an addiction and can promote continued drug use
biological factors
risky drug use is highly correlated with:
- socioeconomic status (poverty)
- homelessness
- social isolation
- early life trauma
interventions in drug addiction need to target:
both psychosocial and biological factors
the rise in opioid overdoses in Canada was initially blamed on:
reckless prescribing of supposedly ‘safer’ opioids like oxycodone
what are the three waves of the opioid crisis?
1) early 2000s - prescription opioid drugs (oxycodone)
2) early 2010s - cheap heroin from Mexico
3) 2020s - fentanyl-tainted illicit drugs
go review slide 538
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a talk-based psychosocial intervention administered by a licensed psychologist; aims to develop non-drug coping strategies to triggers
cognitive behavioural therapy
individuals are rewarded (money) for evidence of positive behavioural change
contigency management interventions/ motivational incentives
involves organizations such as Alcoholics Anonymous and Narcotics Anonymous
counseling/therapeutic communities
- connects people seeking treatment to a community of non-users
- de-stigmatizes drug use
- can connect users with medical interventions
- free
these are all positive aspects of:
Narcotics Anonymous/Alcoholics Anonymous
- no medical interventions
- religious undertones can be off-putting for some
- abstinence only
these are all negative aspects of:
Narcotics Anonymous/Alcoholics Anonymous
a comprehensive treatment approach including maintenance on an opioid agonist and cognitive behavioural therapy
agonist replacement therapy
agonist therapy blunts the symptoms of:
opioid withdrawl
since replacement agonists have longer half-lives, you avoid the:
repeated high/crash cycle
- reduced drug cravings
- better participation in addiction treatment since withdrawl symptoms aren’t a distraction
- improved social function
- reduction in infectious disease/death associated with illicit drug use
these are all postivie aspects of:
agonist replacement therapy
a drug which acts as a partial agonist at the mu opioid receptor, and an antagonist at the kappa and delta opioid receptor
buprenorphine
how does buprenorphine affect mood?
antagonist at kappa receptor improves mood
buprenorphine is marketed as:
suboxone (buprenorphine + naloxone)
interventions or services that are offered to minimize the harms of illicit drug use
harm reduction
what are some examples of harm reduction?
needle exchange, naloxone kits, safe consumption sites, and safe supply
provide a safe place to take drugs to reduce harm or poisonings (overdoses)
supervised consumption sites (SCS)
do clients have to bring their own drugs to supervised consumption sites (SCS)?
yes (they are provided clean needles and medical supervision)
do you need a referral to access supervised consumption sites (SCS)?
no, anyone can access them and can remain anonymous
refers to a legal and regulated supply of drugs that have traditionally been acceptable through the illicit drug market
safe supply
drugs in “safe supply” include:
opioids, cocaine, methamphetamine, MDMA, and LSD
- strong evidence that these interventions reduce morbidity and mortality associated with opioid use
- provide access to information and resources for additional treatment
these are all positive aspects of:
harm reduction (SCS/iOAT - injectable opioid agonist therapy)
- normalizes risky drug use
- moral argument for providing drugs to people with addiction (are they getting better?)
- “not in my backyard” (NIMBY) related to the location of SCS/iOAT clinics (need to be found across communities in order to be effective)
these are all negative aspects of:
harm reduction (SCS/iOAT)
a non-selective competitive opioid receptor antagonist which is available to the public as an intramuscular injection or nasal spray, works within minutes and lasts about half an hour
acute intoxication treatment
what is an example of acute intoxication treatment?
naloxone
