Drugs of Abuse, Tolerance and Dependence Flashcards
Differentiate mild from severe substance abuse
Mild: 2-3 symptoms
Severe: 5+ symptoms
Which pathway is activated by all drugs of dependence? What is the end results of activation?
VTA-nucleus accumbens pathway —> dopamine release
VTA= ventral tegmental area
What is responsible for the inhibition of dopamine release from the ventral tegmental area?
GABA-ergic inhibitory interneurons.
Drugs that affect these interneurons can cause dependence
What is cocaine’s MOA?
Cocaine inhibits the dopamine reuptake transporter –> increased dopamine in synaptic cleft
What is the MOA of amphetamines?
Amphetamines inhibits the vesicular monoamine transporter responsible for packing dopamine into the secretory vesicles –> increased dopamine in pre-synaptic clefts –> leakage of dopamine into presynaptic cleft
What aspects of cocaine are altered by route of administration?
Onset, magnitude and duration depend on the route of administration
Users prefer IV administration –> surge
Where is cocaine metabolized?
Liver- by cholinesterases.
Inactive metabolite is detectable in urine for up to 8 days
What is the problem of mixing cocaine and ethanol?
Cocaine in the presence of ethanol is transesterified resulting in cocaethylene, which produces more euphoria and has a longer duration of action.
It is more cardiotoxic than cocaine alone
People who take cocaine are at a higher risk for developing what type diseases?
Autoimmune diseases or connective tissue diseases such as lupus, Goodpasture’s syndrome, SJS
What is the deadly symptom of cocaine?
Cardiac arrhythmias
Name two drugs that may be used for the treatment of acute withdrawal from cocaine
Bromocriptine
Benzodiazepines (mostly lorazepam because it’s less toxic to the liver)
What are the treatment strategies for long term addiction?
No FDA approved pharmacological therapies
Cognitive-Behavioral Therapies- functional analysis and coping skills
Name the 4 most common opiods
Heroin
Morphine
Codeine
Oxycodone
What is the general MOA of opioids?
They cause inhibition of mesolimbic dopamine by acting on mu receptors located on GABAergic interneurons
Do tolerance and dependence occur with heroin use?
Yes, both –> increased in quantities taking
What are the dangerous symptoms associated with heroin overdose?
Respiratory depression and pulmonary edema
Describe the “cross-tolerance” phenomenon of opioids
Development of tolerance to one opioid leads to tolerance of other opioids
Why does heroin last longer than morphine?
Heroin is metabolized to 6-monoacetylmorphine, which is then metabolized further to morphine.
Double the trouble, double the fun.
Is heroin withdrawal life-threatening?
No, although it is profoundly painful
How soon will heroin withdrawal symptoms set in?
12 hours after last dose.
Last between 5-7 days, although some effects can linger
Name 5 withdrawal symptoms specific to opioids
Lacrimation Rhinorrhea Yawning Piloerection/gooseflesh Involuntary movement (kicking the habit!)
What is the treatment for opioid overdose?
Naloxone- mu receptor antagonist
What drug is used for the treatment of opioid addiction/dependence?
Naltrexone- mu opioid receptor antagonist
Name two drugs used for the treatment of opioid withdrawal symptoms/maintenance
Methadone- mu receptor opioid agonist
Buprenorphine- partial mu receptor opioid agonist
What is a contraindication for the use of naltrexone?
Liver failure
Why does naltrexone work for the treatment of opioid addiction?
Because heroin self-administration is no longer rewarding- heroin does not out-compete the antagonistic binding
Why does methadone work for opioid withdrawal?
Because the half-life is so long, that people don’t feel “high” when they take it
Why was suboxone formulated?
Suboxone (buprenorphine/naloxone) was formulated so that if people tried to inject the drug, they would not feel high at all, and the blocking effects of naloxone would lead to withdrawal symptoms
How does THC work?
THC inhibits GABAergic interneurons in the ventral tegmental area leading to increased levels of dopamine in the nucleus accumbens
Name the receptor recently discovered in the MOA of marajuana
CB1
What is the age of onset for Type B alcohol dependence?
<25 (early onset)
Which type of alcohol dependence is more severe?
Type B
What other mental health problems are associated with Type B alcohol dependence?
Personality disorders and criminality
How does alcohol affect GABA?
Increases effects of GABA
How does alcohol affect glutamate?
Inhibits the effects of glutamate
How does alcohol affect the GABAergic and NDMA receptors?
Reduce levels of GABA-ergic receptors
Increase levels of NMDA receptor
Sudden decrease in chronic alcohol consumption leads to overactivation of the NMDA receptor
NMDA sensitization, GABA desensitization
How does alcohol withdrawal lead to sudden death?
NMDA system has been oversensitized (firing like crazy because there is no GABA)
Withdrawal leads to overactivation of NMDA and sudden death
What are the 4 stages of alcohol dependence treatment?
- Identification
- Detox/withdrawal
- Rehab
- Aftercare
Why are benzodiazepines given for alcohol withdrawal symptoms?
They are indirect agonists for GABA receptors
Why is lorazepam often prescribed for the treatment of alcohol withdrawal symptoms?
Because it is not metabolized by the liver, and most alcoholic have a messed up liver
Describe the minor alcohol withdrawal symptoms
Seen: 6-36 hours after the last drink
Hyperarousal, anxiety, GI upset, sweating, palpitations, insomnia, nausea…
Describe the seizure stage of alcohol withdrawal symptoms
6-48 hours after last drink: tonic-clonic seizures –> status epilepticus
Can be life threatening
When do auditory hallucinations occur as a part of alcohol withdrawal?
12-48 hours after the last drink
When does delirium tremens occur?
48-96 hours after last drink. Can last up to 5 days
What are the life-threatening features of delirium tremens?
autonomic instability- fever, tachycardia, hypertension, diaphoresis)…
What are the three drugs approved for the treatment of alcohol dependence?
D-Disulfiram
N- Naltrexone
A- Acamprosate
How does disulfiram work for the treatment of alcohol dependence?
Disulfiram blocks the conversion of acetaldehyde (which gives hangover symptoms) to acetate.
Therefore acetaldehyde builds up and makes you feel sick
Alcohol aversion therapy
What genetic variant do asian people have that slows down the metabolism of acetaldehyde?
ALDH2*2
How does naltrexone work to treat alcohol dependence?
Blocks release of opioid release to nucleus accumbens, decreases alcohol cravings
Which is the best drug available for alcohol treatment? How does it work?
Acamprosate
MOA unknown, but leads to increased balance of neurotransmitters
Which are the two most common hallucinogens?
LSD, mescaline
What is the receptor of LSD?
5HT-2A in the cortex
