Barker Pathophysiology of Substance Use Disorder Flashcards
What are the stimulant drugs of abuse?
-Cocaine
-Amphetamine
-Meth
-Bath salts
-Ecstasy
-Nicotine
What are the depressant drugs of abuse?
-Opioids
-Alcohol
-GHB
-Inhalants
What are the psychedelic drugs of abuse?
-LSD
-Psilocybin
-PCP
-Mescaline
-Ketamine
How do you define schedule 1 controlled substances?
-No medical use
-High abuse potential
-Safety not guaranteed
Examples of schedule 1 drugs
-Heroin
-Marijuana
-THC
-LSD
-GHB
-Psilocybin
-MDMA
How do you define schedule 2 controlled substances?
-Medical use
-High abuse potential
-Large risk of dependence
Examples of schedule 2 drugs
-Morphine
-Fentanyl
-Cocaine
-Ritalin
-PCP
-Barbituates
-Oxycodone
-Hydromorphone
How do you define schedule 3 controlled substances?
-Medical use
-Moderate abuse and dependence
Examples of schedule 3 drugs
-Ketamine
-Buprenorphine
-Marinol
How do you define schedule 4 controlled substances?
-Medical use
-Low abuse and dependence
Examples of schedule 4 drugs
Benzodiazepine
How do you define schedule 5 controlled substances?
Lower risk relative to IV
Examples of schedule 5 drugs
-Cough suppressants with small amount of codeine
-Lomotil (antidiarrheal opioid with atropine)
Which substances of abuse act directly on G protein-coupled receptors?
-Opioids
-LSD, mushrooms (psilocybin, psilocin)
-Marijuana, K2, spice
-Gamma hydroxy butyric acid
-Caffeine
Which receptors do opioids act on?
Mu receptors
Which receptors do LSD and mushrooms act on?
Serotonin receptors
Which receptors does marijuana, K2, and spice act on?
Cannabinoid receptors (CB1)
What receptors does gamma hydroxy butyric acid act on?
GABAb
What receptors does caffeine act on?
Adenosine receptors
Which substances of abuse act indirectly on G protein-coupled receptors?
-Cocaine, amphetamine
-MDMA/ecstasy
-Alcohol
Which receptors does cocaine and amphetamine act on?
-Dopamine transporter (dopamine receptors)
-Noradrenaline, serotonin transporters
-Release dopamine, noradrenaline, serotonin -> GPCRs
What receptors does MDMA/ecstasy act on?
Monamine transporters
What receptors does alcohol act on?
-GABA channels, 5HT3, NMDAR, nAchR, KiR3
-Causes release of endogenous opioids
Which substances of abuse act on ion channels?
-Nicotine
-PCP, ketamine
-Benzodiazepines, barbiturates
Which receptors does nicotine act on?
-Ionotropic acetylcholine receptors (Na+)
-Agonist
Which receptors does PCP and ketamine act on?
-Ionotropic NMDA receptors (Ca2+, Na+ - K+
-Antagonist
Which receptors do benzodiazepines and barbiturates act on?
-Ionotropic GABAa receptors (Cl-)
-Positive allosteric modulators
What parts of the brain lead to addiction and craving?
-Frontal cortex
-Nucleus accumbens
-VTA
-Hippocampus
-Substantia nigra
-Striatum
Why does the frontal cortex contribute to addiction?
It is responsible for decision making and impulsivity
Why does the nucleus accumbens contribute to addiction?
It is responsible for pleasure and valuation
Why does the VTA contribute to addiction?
It is the source of dopamine
Why does the hippocampus contribute to addiction?
It is responsible for memory and learning
Why does the striatum contribute to addiction?
It is responsible for reward and value
What is the dopamine hypothesis of addiction?
-“Pleasurable events” release dopamine
-Parkinson patients only develop addiction during treatment
-Dopamine important for assigning value to reward prediction error
-Value provides the drug with an incentive salience
-Salience = state or quality of an item that stands out relative to neighboring items
Limits of the dopamine hypothesis
-Dopamine 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 (decreased liking), enhanced craving
-Dopamine does not encode liking, but involved in making reward predictions and learning from the outcome/error
The glutamate hypothesis of addiction
-Glutamate can increase dopamine activity in NAcc
-Glutamate projection to VTA
-Destruction of this pathway reduces cocaine/morphine reward
-mGluR5 removed in mice show reduced cocaine reward
-NMDA antagonist blocks acquisition of reinforcement learning
-Intra NAcc AMPA injection causes relapse
-Dopamine controls glutamate activity in amygdala
What is long term potentiation?
Persistent increase in synaptic strength following intense stimulation
How does long term potentiation affect addiction?
Rewarding substances cause relative increase in glutamatergic AMPA receptors that causes increases in memory retention
What is the definition of drug abuse?
The use of a drug for a nontherapeutic effect
What is the definition of drug misuse?
-Inappropriate, illegal, or excessive use of a prescription or nonprescription drug
-Taking more/more frequent than prescribed
-Taking it for different indication
-Taking someone else’s medication
What is physical dependence?
-Body needs more drug - tolerance
-Cellular adaptations upon repeated activation of receptors
-Body withdraws without drug
What are the types of withdrawal symptoms?
-Emotional withdrawal symptoms
-Physical withdrawal symptoms
-Dangerous withdrawal symptoms
Emotional withdrawal symptoms
-Anxiety, depression
-Restlessness, insomnia
-Irritability
-Headaches
-Poor concentration
Physical withdrawal symptoms
-Sweating
-Racing heart
-Goose bumps = cold turkey
-Muscle spasms = kicking the habit
-Tremors
-Nausea, vomiting, diarrhea
Dangerous withdrawal symptoms
-Alcohol and tranquilizers
-Grand mal seizures (also tramadol)
-Heart attacks, strokes
-Hallucinations, delirium tremens (DTs)
What is psychological dependence?
-Addiction
-Mental urge to take drug to function
-Compulsive need/craving
-Even absence of withdrawal
What is positive reinforcement?
-Drug is “rewarding” or produces positive reinforcement when the user feels pleasure/satisfaction
-Of value, strengthen behavior to repeat
-Just liking is not enough
What is negative reinforcement?
Reward by escaping negative/painful stimulus or event (NOT same as punishment)
What are the risks of drug binges and multi drug use
-Use of a depressant with a stimulant to numb the crash of the stimulant (Speedball - heroin+coke)
-Risk of overdose (not aware of some signs)
-More difficult to treat overdose
Physiological responses that may lead to fatal overdose
-Respiratory depression associated with opioids and alcohol
-Cardiac arrhythmias, brain hemorrhage, stroke associated with stimulants
-Fatal seizures (also risk during withdrawal)
-Choking on vomit
