PHRM845-FINAL EXAM Flashcards
Pathophys of SUD
Examples of stimulants
-Cocaine
-Amphetamine
-Meth
-Bath salts (Methamphetamine-like derivative)
-Ecstasy (NMDA)
-Nicotine
Examples of depressants
-Opioids
-Alcohol
-Cannabis
-GHB
-Inhalants
Examples of psychedelics
-LSD
-Psilocybin
-PCP
-Mescaline
-Ketamine
Schedule I
No medical use
High abuse potential
Safety not guaranteed
Examples of schedule I drugs
Marijuana
THC
LSD
GHB
Psilocybin
MDMA
Schedule II
Medical use
High abuse potential
Large risk of dependence
Examples of schedule II
Morphine
Fentanyl
Cocaine
Ritalin
PCP
Barbiturates
Oxycodone
Nabilone
Schedule III
Medical use
Moderate abuse and deprendence
Examples of schedule III
Ketamine
Buprenorphine
Marinol (THC in oil capsule)–delta 9 THC
Schedule IV
Lower risk relative to schedule IV
Examples of schedule IV
-Cough suppressant with small amounts of codeine
-Lomotil (antidiarrheal opioid with atropine)
“Semi legal” highs
Fuel
Glue
New designer drugs (until DEA catches up)
Previously legal, but now illegal drugs
-Spice, K2 (Synthetic THC mimic)
-Bath salts
**Banned, updated by DEA (case by case and blanket ruling)
Cannabis have around ____ different molecules in it
1000
Delta 8 THC is just slightly ___ potent than delta 9.
Both are ___ that activate CB1.
Less
Full agonists
Hemp-derived delta 8 THC is (legal/illegal)
Legal
**Cannabis-derived delta 8 THC is illegal
Hemp has a very ___ % of THC, but at a pharmacological standpoint, they both have the same effect because they are the same molecule.
low
Substances of abuse that act DIRECTLY on GPCR
-Opioids
~Heroin
~Rx meds
**Opioid receptors=mu
-LSD, Mushrooms (Psilocybin, psilocin)
~Serotonin receptor agonist (5HT2A and 5HT2C)
-Marijuana, K2, spice
~Cannabinoid receptors (CB1)
~Whole, endogenous cannabinoid system
~Dampen/bring things up a little (like a dimmer switch)
-Gamma Hydroxy Butyric Acid
~GABA-B (GPCR)
-Caffeine (methylxanthine)
~Adenosine receptors
Substances of abuse that act INDIRECTLY on GPCR
-Cocaine and amphetamine
~DA transporter
~Noradrenaline and serotonin transporters
~Release DA, noradrenaline, serotonin –> GPCR
-MDMA/Ecstasy
~Monoamine transporters (DA and serotonin)
-Alcohol
~GABA channels, 5HT3, NMDA-R, nAch-R, KiR3
~Indirectly causes release of endogenous opioids (GPCR)
Substances of abuse that act on ion channels
-Nicotine
~Ionotropic acetylcholine receptors (Na+)
~Agonist
-PCP, ketamine
~Ionotropic NMDA receptor antagonist
(Ca+, Na+ - K+)
-Benzodiazepines and barbiturates
~Ionotropic GABA-A receptors (Cl-)
~Positive allosteric modulators
What neurotransmitter plays a key role in leading to addiction to drug?
Dopamine
All neuronal pathways that lead to addiction
-Frontal cortex: decision making impulsivity
-Nucleus accumbens: pleasure valuation (where re-enforcement occurs)
-Striatum and Substantia nigra: Rewrd/Value
-Hippocampus: Memory and learning
-Ventral Tegmental Area (VTA): source of dopamine
Stimulants, depressants, and psychedelics all act on the ____ system
mesolimbic
DA hypothesis of addiction
-“Pleasurable events” release DA
-PD pts only develop addiction DURING tx because the meds increase DA neurons
-DA is important for assigning value to reward prediction error.
~Value provides the drug with an incentive salience
~Salience: state or quality of item that stands out relative to neighboring items based on prior experience (ex: red apple)
Limits of DA hypothesis
-DA is NOT required for reward learning
~Dissociation between liking (direct effect) and wanting (motivation) –> you don’t always like what you want
-Tolerance to pleasurable effect (lowers liking), enhanced craving
-DA does not encode liking, but involved in making reward predictions and learning from the outcome/error.
What happens to DA levels when there is NO prediction and a reward occurs?
There is a DA spike after the reward is given
What happens to DA levels when a reward is predicted and it occurs?
There is a DA spike at the time the animal predicts the reward would come…The reward is given later and there is no additional spike that happens at this time.
What happens to DA levels when a reward is predicted, but no reward occurs?
-DA spike when the animal predicts the reward will be given. After a bit of time of the reward not given, the DA levels will drop and this might trigger craving.
Glutamate hypothesis of addiction
-Glu can increase DA activity in NAcc
~Glu projection to VTA
~Destruction of the pathway reduces cocaine/morphine reward
~mGluR5 KO mice show reduced cocaine reward
~NMDA antagonist blocks acquisition of reinforcement learning
~Intra NAcc AMPA (glutamate agonist) injection causes relapse
-DA controls glutamate activity in amygdala
(Emotions–>activity)
How does drug use induce long-term changes in neuronal plasticity?
-Persistent increase in synaptic strength following intense stimulation
-After persistent stimulation, more glutamate receptors will appear on the surface of post-synaptic cell
-Rewarding substances cause relative increase in glutamatergic AMPA receptors
How can cognitive behavioral therapy assist in abstinence?
Retrains memory so that when the drug is given there isn’t much of a response
What is drug abuse?
The use of a drug for a nontherapeutic effect
What is drug misuse?
Inappropriate, illegal, or excessive use of a prescription or nonprescription drug.
~Taking more/more frequently than prescribed
~Taking it for a different indication
~Taking someone else’s medication
Substance use disorder criteria (11 of them)
-What classifies a pt as mild, moderate, or severe?
-What are the 11 criteria?
-Previously substance abuse and substance dependence
-Mild (2-3)
-Moderate (4-5)
-Severe (>6)
- Taking the substance in larger amounts or for longer than you meant to
- Wanting to cut down or stop using the substance, but unable to stop
- Spending a lot of time getting, using, or recovering from use of the substance (preoccupied)
- Cravings and urges to use the substance
- Not managing to do what you should at work, home, or school because of substance use (distracted)
- Continuing to use, even when it causes problems in a relationship
- Giving up important social, occupational, or recreational activities because of substance use
- Using substances again and again, even when it puts you in danger
- Continuing to use even when you know you have a physical or psychological problem that could have been caused or made worse by the substance (against better judgement)
- Needing more of a substance to get the effect you want (tolerance)
- Development of withdrawal symptoms, which can be relieved by taking more of the substance
Physical dependence
-Body needs more of drug to get same feeling–tolerance
~Cellular adaptation upon repeated activation of receptors
-Body withdraws without the drug
Emotional withdrawal symptoms
-Anxiety/depression
-Restlessness/insomnia
-Irritability
-HA
-Poor concentration
Physical withdrawal symptoms
-Sweating
-Racing heart (tachycardia)
-Goose bumps=cold turkey
-Muscle spasms=kicking the habit
-Tremors
-N/V/D
Dangerous withdrawal symptoms
Withdrawing from alcohol and tranquilizers can cause
-Grand mal seizures (also tramadol)
-MI, stroke
-Hallucinations, delirium tremens (DTs)
**Usually clonidine can be used to safely withdraw
Psychological dependence
-ADDICTION
-Mental urge to take drug to function
-Compulsive need/craving
-Even in absence of withdrawal
-Biological basis from memory formation
Drug reward in relation to positive reinforcement
-Drug is “rewarding” or produced positive reinforcement when the user feels pleasure/satisfaction.
~Of value, strengthen behavior to repeat
-Just liking isn’t enough
Drug reward in relation to negative reinforcement
-Just trying to avoid stimulus
-Negative reinforcement: reward by escaping negative/painful stimulus or event (NOT the same as punishment)
Pathways to addiction
Therapeutic use (normal):
-Negative reinforcement–>positive reinforcement–>negative reinforcement
Recreational use (just taking b/c I want to/craving it)
-Positive reinforcement–>Negative reinforcement
Self medication
-Negative reinforcement: just trying to avoid some negative situation
Fatal OD is common with drug abuse-especially ____ abuse
Poly-drug
What are the risks of drug binges and multi drug use?
-Using a stimulant with a depressant to numb the crash of the stimulant (speedball=heroin+cocaine)
-Risk of OD (not aware of some signs)–>more difficult to tx OD
Physiological responses that may lead to fatal OD
-Respiratory depression from opioids and alcohol
-Cardiac arrhythmias, brain hemorrhage, stroke from stimulants
-Fatal seizure from choking on own vomit.
~Also a risk during withdrawal
