2-18 Drug Tolerance / Abuse / Dependence Flashcards
What are the top 3 ILLICT drugs used among persons 12 and older?
Marijuana
Psychotherapeutics
Cocaine
Name 7 categories of drugs of abuse (and provide some examples):
Which drug is the most addictive?
Psychomotor stimulants (cocaine, amphetamines)
Opiates and Opioids (heroin-MOST ADDICTIVE, morphine, codeine, oxycodone, hydromorphine)
Cannabinoids (marijuana)
Alcohol
Sedatives (barbiturates, benzodiazepines)
Nicotine
Hallucinogens (LSD, mescaline “club drugs”
DSM-V criteria for Substance Use Disorder include the following symptoms (7), within ______ (#) months:
Which symptom is the marker of physiological dependence?
How many symptoms would indicate…
“Mild” substance use disorder?
“Moderate” substance use disorder?
“Severe” substance use disorder?
DSM-V criteria for Substance Use Disorder include the following symptoms, within 12 months:
Tolerance
Withdrawl *marker for physiological dependence*
Use of larger amounts than intended
Persistent desire, inability to control use
Excessive time spent obtaining, using and recovering
Normal activities given up or reduced
Use despite knowledge of problem drugs cause, unable to cut back
How many symptoms would indicate…
“Mild” substance use disorder? 2-3
“Moderate” substance use disorder? 4-5
“Severe” substance use disorder? 5+
When do WITHDRAWAL signs and symptoms emerge?
Can signs/sx be reversed? If so, how?
When do WITHDRAWAL signs and symptoms emerge?
When use of the drug is stopped
Can signs/sx be reversed?
Yes, reversed when drug is administered again
What are the two ways to define drug tolerance?
Drug tolerance:
Decreased effect with repeated use of the drug (effect vs duration of use graph)
Need to use more drug to have the same effect (RIGHT shift in dose-effect curve)
The _____________ system is the major target of addictive drugs,
it originates in ____ (location) and projects to nucleus _____, and _____, _____ (two other areas in the brain).
Which pathway is activated by all drugs of dependence?
Activation of this pathway results in the release of
____ [neurotransmitter]?
The MESOLIMBIC DOPAMINE SYSTEM is the major target of addictive drugs,
it originates in VENTRAL TEGMENTAL AREA (VTA) and projects to NUCLEUS ACCUMBENS and AMYGDALA and PREFRONTAL CORTEX
Which pathway is activated by all drugs of dependence?
VTA-NUCLEUS ACCUMBENS PATHWAY
Activation of this pathway results in the release of
DOPAMINE
What inhibitory interneurons act on dopaminergic neurons in the VTA?
GABA-ergic inhibitory interneurons
What are the two different ways in which an individual could experience withdrawal?
- due to natural decay of drug/agonist half-life (agonist is out of circulation and no longer stimulating its specific receptors)
- presence of an antagonist with a higher affinity for the same receptor as the drug
Cocaine is derived from _____ plant cultivated in South America
Historically, it has been used as a powerful CNS stimulant and appetite suppressant, and now used for what type of surgery?
Cocaine is derived from Erythxylon cocoa plant cultivated in South America
Historically, it has been used as a powerful CNS stimulant and appetite suppressant, and now used for what type of surgery? nasal and lacrimal duct surgery
Cocaine MOA:
Cocaine works by _____ [stimulating/inhibiting] the action of ________ transporters at the ___[pre/post] synaptic terminal, which leads to what type of neurotransmitter change within the synaptic cleft?
Cocaine works by INHIBITING the action of DOPAMINE TRANSPORTERS at the PRESYNAPTIC terminal –> INCREASE of DOPAMINE within the cleft (mostly @ nucleus accumbens)
Amphetamines are synthetic _________
MOA: AMPHETAMINES work by _____ [stimulating/inhibiting] the action of ________ transporters inside the ___[pre/post] synaptic terminal. This [increases/decreases] the free levels of _____ (neurotransmitter).
What subsequent change does this cause (think of other transporters..)
Amphetamines are SYNTHETIC PHENYLETHYLAMINE
MOA: AMPHETAMINES work by INHIBITING the action of VESICULAR MONOAMINE TRANSPORTER 2 (VMAT2) inside the PRE-SYNAPTIC TERMINAL. This INCREASES the free levels of cytoplasmic DOPAMINE by preventing filling of the synaptic vesicles –> reversal of DAT direction and INCREASE of DOPAMINE concentration within the synpaic cleft.
Cocaine and amphetamine mimicks what types of behavioral and physiological effects of our nervous system?
What are the acute effects of psychostimulants (11)?
Cocaine and amphetamine mimicks what types of behavioral and physiological effects of our nervous system?
sympathomimetic, mimicking the effects of the sympathetic nervous system
Acute effects of psychostimulants:
Rush (orgasmic)
Euphoria / arousal (feeling of well-being)
INC energy
Feelings of competency
DEC feelings of fatigue/boredom
DEC appetite
INC heart rate
INC blood pressure
INC temperature
INC bronchodilation
INC pupillary dilation
Pharmacokinetics of Cocaine:
What does onset, magnitude/potency and duration depend on?
If I was a coke addict and wanted to get my cocaine peak levels within 15 seconds, what should be my route of choice?
Half-life:
Acute effects last less than ____ minutes
How does do these parameters contribute to its use?
Pharmacokinetics of Cocaine:
RAPIDLY ABSORBED IN THE BRAIN & SHORT-ACTING
What does onset, magnitude/potency and duration depend on?
ROUTE OF ADMINISTRATION
If I was a coke addict and wanted to get my cocaine peak levels within 15 seconds, what should be my route of choice?
TAKEN IV OR SMOKED
Half-life: 40-80 minutes –> req. repeated administration
Acute effects last less than 30 minutes –> binge use!
Where and how is cocaine metabolized?
[name the enzyme/s and any metabolites, are they active?]
If someone wanted to monitor/check if I have consumed cocaine, how can it be monitored and what tests could be done? ..what is being measured?
What if I am trying to avoid someone finding out I’ve used cocaine- how long will it remain detectable?
Metabolism of cocaine: Cocaine is metabolized in the LIVER by cholinesterases into benzoylecgonin (inactive compound) and ecgonine methy ester
MONITORED:
biological fluids (saliva, blood, urine, milk) and hair.
MEASURED:
Urine test measures benzoylecgnonine, remains detectable 36 hours - 8 days.
cocaine metabolites could also be measured in saliva, hair and breast milk
I get real crazy after a long night studying psych, and go to the club. I snort some cocaine and have some drankks…
How does cocaine in the presence of ethanol change?
How does this change the effects of cocaine (3)?
How does cocaine in the presence of ethanol change?
Cocaine in the presence of ethanol is TRANSESTRIFIED -into cocaethylene
How does this change the effects of cocaine (3)?
INC euphoria and longer duration of action than cocaine alone
Cocaethylene is MORE CARDIOTOXIC than cocaine alone, could lead to cardiac arrest
Long term use of psychostimulants could result in (5):
Sensitization OR tolerance
Impairment of neurocognitive functions (visuomotor performance, attention, verbal memory)
Increased risk of developing rare autoimmune or connective tissue dieases such as lupus, Goodpasture’s syndrome, Stevens-Johnsons Syndrome
INC risk of infections (viral heptatitis, HIV)
controversial: physical dependence
What are signs and symptoms of psychostimulant overdose? (12)
Which one of the signs/sx is the culprit that can be fatal in case of overdose?
Hyperactivity
Sweating
Dilated pupils
Agitation/tremor
Tachycardia/chest pain
*CARDIAC ARRYTHMIAS*
Hypertension
Hyperpyrexia
Stereotypical behavior such as pacing, nail-biting
Seizures / coma
Paranoia / tactile hallucinations
Confusion
(other: chills, N/V, wt loss, muscle weakness)
Death can occur due to cardiac arrythmias! (Also, secondary to MI, cerebrovascular accident, seizures or respiratory depression)
When does withdrawal to psychostimulants occur?
What are sign/sx someone is experiencing psychostimulant withdrawl? (11)
Withdrawl peaks at 2-4 days
Anxiety
Agitaiton
Insomnia / hypersomnia
Nightmares
Fatigue
Depression
Headaches
Sweating (note- also a sx of overdose!)
Muscle cramps
Hunger / cravings
Erectile dysfunction
Detection of use (3 big categories)-
Signs/symtoms and urine tests are two ways to detect cocaine use, what are some (6) indirect indicators of cocaine use?
Detection of Use:
- Observe for signs and symptoms
- Urine tests (2-4 days..so annoyed)
* (recall: measures cocaine metabolite benzoylecgnonine)*
3. Indirect indicators - AIDS, hepatitits, track marks, abscesses, bacterial endocarditis, chronic respiratory symptoms
SHORT TERM treatment of Cocaine withdrawal:
What are 2 treatments that can be used for acute withdrawal?
- MOA*
- what would be the benefit of using one over the other*
Bromocriptine - dopamine agonist
ameliorates dopamine deficiency state of cocaine withdrawal
Benzodiazepines (lorazepam) - enhances effects of GABA
in patients with severe agitation and sleep disturbance
LONG TERM treatment of cocaine withdrawal:
Is there effective treatment for long-term addiction?
No FDA approved pharmacological therapies
Cognitive-behavior therapies could be tried…
two components:
- Functional analysis - identify patient’s thoughts, feelings and circumstances before and after the cocaine use to udnerstand reson for using cocaine
- Skills training - help cocaine users cope with intrapersonal and interpersonal problems
Opium is derived from extracts of juice of the opium poppy _____
Examples (2) of opiods derived directly from opium
Example of a (2) semi-synthetic opioid
Example of (1) synthetic opioid
Opium is derived from extracts of juice of the opium poppy PAPAVER SOMNIFERUM
Examples (2) of opiods derived directly from opium:
Morphine and codeine
Example of a (2) semi-synthetic opioid:
Heroin, hydromorphone
Example of (1) synthetic opioid:
Fentanyl
What receptors do opioids exert its pharmacodynamic effects (3)?
Which receptor do opioids exert its dependence producing properties?
What is the MOA of opioids in the CNS, specifically?
Opiods exert their pharmacodynamic effects through:
mu, delta and kappa receptors
the _dependence producing properties_ of opioids are mediated through the mu receptors
MOA: opioids cause disinhibition of mesolimbic dopaminergic sys -
By binding the mu R on GABA-interneuros in the VTA, opioids act as agonist and inhibit the inhibitory action of GABA neurons –> disinhibition of the dopaminergic system
What are the different patterns of opioid abuse? (5)
Oral (prescription drugs)
Intravenous
subcutaneous (“skin popping”)
smoking
snorting (become more prevalent because of fear of AIDS)
Opioid Patterns of Use:
Heroins’ effects last about _____ hours.
The average addict uses heroin _____ X per day.
Tolerance and physical dependce develop____ [slow/gradual/fast]. How does this affect the use of heroin, in terms of frequency and quantity?
Opioid Patterns of Use:
Heroins’ effects last about 3-5 hours.
The average addict uses heroin 2-4 X per day.
Tolerance and physical dependce develop gradually, leading to both frequency and quantity of drug consumed.
