Exam 2: Cocaine Flashcards
produce modest stimulatory effects in the CNS
nicotine, caffeine, not scheduled
low-efficacy stimulants
increase CNS activity by a significant amount
strong behavioral effects
addiction liability greater
abuse potential inc
high-efficacy stimulants
cocaine
psychoactive substance extracted from leaves of coca plant
- coca leaves have 0.6-1.8% cocaine
- coca paste extracted from soaked and mashed leaves has 60-80% cocaine
- discovered and processed in 1860s
cocaine created from coca paste
2nd most abused controlled substance
cocaine
what schedule drug is cocaine
schedule 2 drug
- high potential for abuse
- known established medical uses
- severe psychological or physical dependence liability
major current problem with cocaine
lack of purity!!
it is laced with ther substances only 50% is actually cocaine
- phentanol is a common laced substance - lethal = toxic
forms of cocaine
cocaine salt, cocaine HCl : mixture of coca paste with HCl, readily water soluble
basic cocaine:
- freebase: dissolve cocaine HCl and ammonia, extract cocaine and ether (organic solvent)
crack: dissolve cocaine HCl mix with baking soda, heat, dry
absorption of cocaine
route of administration:
- nasal (insufflation, snorting) - cocaine HCl
- IV injection, mainlined
- inhalation, smoking
- oral - rare since poor bioavailability
nasal absorption of cocaine HCl
- bioavailability, onset of action, peak levels in brain, duration of action
bioavailability: 70%
onset: 30s-5min - snorting cocaine constricts blood vessels, slowing the absorption
peak in brain: 10-20 min
duration of action: 60-90 min
injection absorption of cocaine HCl
bioavailability, onset of action, peak levels in brain, duration of action
bioavailability: 90%
onset: 10-60s
peak in brain: 3-5min
duration of action: 20-60 min
another absorption f cocaine HCl besides nasal and injection
topical
inhalation absorption - freebase/crack cocaine
bioavailability, onset of action, peak levels in brain, duration of action
bioavailability: 90%
onset: 1-2s
peak in brain: 10s-30min
duration of action: 5-15 min
distribution of cocaine
cocaine = lipophillic - easily penetrates BBB and placental barrier
brain concentrations FAR exceed blood plasma levels
- important for addiction - bc of the speed
metabolism of cocaine
rapidly broken down in about 2 hrs
by enzymes in BLOOD and liver into metabolites
cocaine metabolites
benzoylecognine - broken down in bloodstream, inactive metabolite
ecgnonine methyl ester - broken down in liver - inactive metabolite
norcocaine - active metabolite broken down in liver - cytochrome p450s
- acute intoxication
metabolism: alcohol and cocaine
alcohol slows cocaine metabolism
react together to form cocaethylene - greater effects than cocaine
cocaethylene
- only known example where body forms new psychoactive compound from 2 others
- longer half life, but lower LD50
- more euphoria, increased cardiac toxicity
- seizures, liver damage, compromised immune system
elimination of cocaine
-SLOWLY removed from brain but RAPIDLY removed from blood
1-5% excreted unchanged in urine
rapid fall of blood cocaine level: rush followed by a crash
half lifes cocaine
IV, nasal, benzoylecognine
IV half life: 30-90min
Nasal: 30min-4.5 hr
Benzoylecognine: 14.5-52 hrs - detected in urine 2-3 days later if nasal, if chronic IV can detect for up to 10 days
speed runs
to get the rush and avoid withdrawal
- short half life - snort every 40 min or inject every hr
=blood levels accummulate to toxic levels
- run continues until out of drug or something bad happens - seizure, overdose, heart stops
eyes of a cocaine user
dilated!!!
sympathetic response
stimulants are sympathomimetic - what does this mean?
they produce symptoms of sympathetic nervous system activation: dilated pupils, inc HR, vasoconstriction, hypertension, hyperthermia
low doses not harmful, high doses toxic or fatal
what are some acute behavioral effects
feelings of exhilaration or euphoria sense of wellbeing inc alertness and energy great self-confidence inc aggression - not good impulse control
immediately after smoking or IV: intense rush that is pleasurable
after oral or intranasal: euphoria without the rush - not as exhilarating
behavioral effects of chronic cocaine use
panic attacks - sympathetic activation
temporary paranoid psychosis:
- hallucinations of touch, sight, taste, smell
- confusion, anxiety
- formication syndrome: people think bugs crawling all over their skin - may take chunks out of their skin
physiological effects of chronic cocaine use
malnutrition and weight loss due to appetite suppression in sympathetic activation
snorting: cocaine HCl
- septal necrosis (tissue in nose dies off) or perforated septum (hole on inside of nose)
vasoconstriction brain interrupts… which can lead to ….
blood flow to brain
stroke
cocaine blocks what reuptake transporters
DA, NE, 5-HT
cocaine has highest binding affinity for
5-HT
but DA is most important for reinforcing and addictive properties
cocaine increases…
DA in the nucleus accumbens indirectly through PFC
glutamate neurons in the PFC ecite
DA neurons in the VTA
more NE leads to
inc glutamate and inc activation of VTW dopamine neurons
what is PET imaging used for
estimates DAT occupancy by cocaine
once a certainminimum level is reached the subject may feel a high
intensity of the high depends on
amount of DAT occupancy
- rate at which DAT occupancy occurs - distribution speed
- baseline level of DA activity in mesolimbic pathway
increased NE levels activates
arousl centers and sympathetic nervous system - dilates pupils
increased DA lvels associated with
euphoria, inc energym psychosis, sense of confidence
at high concentrations, cocaine inhibits…
voltage gated NA channels in axons, blocking nerve conduction
when cocaine is applied locally what does it act a
anesthetic
prevents transmission of signals along sensory nerves
what two numbing agents were developed from cocaine
procaine (novacaine) and lidocaine (xylocaine)
when using occaine most start by what route of administration
smoking
abstinence syndroe and cocaine (3steps)
crash: user feels exhausted and depressed mood
withdrawal: anhedonia, anergia, anxiety, crave cocaine
extinction: symptoms subside
intermittent access to self administered cocaine causes
behavioral sensitiztion instead of tolerance
sensitization is more likely following _______ in brain as opposed to high, constant concentrations
repeated spikes
disulfiram
used to treat alcoholism showing promise in clinicl trials since people frequently use cocaine and alcohol together
it prevents conversion of DA to NE
inc DA prevents cocaine cravings by blocking withdrawal effects
cocaine vaccine
cocaine is attached to a toxin
immune system produces antibodies aainst toxin and cocaine
prevents cocaine from reaching brain
no high - lose interest
cognitive behavioral therapyy (CBT)
restrcting thught processes and training perso to avoid their triggers
structural abnormalities in chronic cocaine users
PFC ACC insula dorsal striatum amygdala thalamus
functional changes in chronic cocaine users
impulse control and working memory - PFC
verbal learning an memory - temporal lobe
performance on psychomotor tasks - dorsal striatum
decision making - PFC
