high efficacy stimulants - cocaine Flashcards
what is a stimulant?
a drug that increases central nervous system activity and sympathetic nervous system activity (aka known as uppers)
what are low efficacy stimulants? give an example. what would the dose response curve look like?
produces a WEAK response
ex. nicotine and caffeine
dose response: would have a high y axis
what are high efficacy stimulants? give an example. what would the dose response curve look like?
produces a STRONG response
ex. amphetamine and cocaine
dose response: would have a low y axis
what occurs when stimulants activate the sympathetic nervous system?
it activates your flight or fight
examples:
- dilates pupils
- inhibits salivation
- increases heartbeat
- relaxes airways
-stimulates sweat glands
- relaxes bladder
where does cocaine come from?
it is extracted from the leaves of the coca plant
what are the street names for cocaine?
- crack
- rock
- blow
what schedule drug is cocaine? explain what that schedule indicates.
schedule II - high abuse likelihood but there is accepted medical use
what is the major problem associated with cocaine?
lack of purity
a lot of coke is now contaminated with fentanyl and there is more likelihood to die from it compared to the 80s
what are INSTRUMENTAL uses of cocaine?
topically
when is cocaine used topically?
ENTs use cocaine as a topical anesthetic during eye surgery to numb as well as preventing bleeding.
It can be topically places in nasal passage to treat certain bleeding disorders.
what are other forms of cocaine that is used as a topical anesthetic rather than cocaine itself?
novocain and lidocaine
what is the mechanism of action of cocaine in the body?
cocaine inhibits voltage-gated Na+ channels in axons, blocking nerve conduction soo… when applied locally - transmission of signals along sensory nerves does not occur hence the numbness
what are the forms of cocaine?
- cocaine hydrochloride
- base cocaine (no hydrochloride)
what are characteristics of cocaine hydrochloride?
- white powder
- water soluble
- cocaine alkaloid is extracted from coca leaves & converted into a hydrochloride salt (HCl) & crystalized
what are the 2 types of base cocaine and what are their characteristics?
- freebase
a. dissolve cocaine HCL in water +
ammonia, extract cocaine + organic
solvent (ether) - crack
a. dissolve cocaine HCl in water, mix with
baking soda, heat, dry
know the pharmacokinetic differences between forms of cocaine table on slide 11 - picture is camera roll
what are routes of administration for cocaine?
- nasal (snort)
- IV (mainline)
- inhaled (typically freebased or crack)
- oral
how does route of administration of cocaine affect its bioavailability?
- snorting (intranasal)
absorption: slowly because blood vessels
are constricted
bioavailability: 70% - iv injection
absorption: rapid because it bypasses all
barriers to absorption
bioavailability: 100% - oral
absorption: real slow
NOT COMMON - freebase/crack inhalation
bioavailability: 90%
can cocaine be smoked?
no, it decomposed before it volatizes when heated
what term describes cocaine distribution?
lipophilic – it easily penetrates the BBB and placental barriers
cocaine is a teratogen
what is true regarding cocaine’s movement in blood?
it moves about of blood very rapidly and into brain much quicker due to the fat in the brain. therefore, your concentration in the brain is much higher than the blood. this is why addiction exists because the biological action reaches the brain very quick
is cocaine metabolized only in liver?
no, it is broken down in all different parts of the body
what enzymes break down cocaine in the blood plasma, tissues, and live?
blood plasma: butrylcholinesterase (BChE)
tissue: esterases
liver: CYP3A4 enzyme
when CYP3A4 enzyme in the liver breaks down cocaine, what metabolites are formed?
inactive:
- benzoylecgonine
- ecgonine methyl ester
active:
- norcocaine (acute intoxication)
what occurs when alcohol and cocaine are taken together?
alcohol slows cocaine metabolism (antagonistic and synergistic drug interactions occur)
what occurs when alcohol and cocaine are reacting in the liver?
the liver forms a new psychoactive drug called cocaethylene
what are the characteristics of cocaethylene?
- produces synergistic drug effects
- increases overdose risk due to longer half life but lower LD50 (less can kill you)
- similar effects to cocaine but more euphoria and increased cardiac toxicity
- can cause seizures, liver damage, and a compromised immune system
what is the most common route of elimination of cocaine?
urine
what is the half life of cocaine and benzoylecgonine?
cocaine: 30 minutes
benzoylecgonine: 12 h4w but can be detected in urine 2-3 days if taken nasally or upto 10 days by IC
what occurs when blood cocaine levels fall suddenly?
our body has a rush followed by a crash
what do most cocaine drug tests look for?
benzoylecgonine OR ecgonine methyl ester because of their longer half lifes
what is the issue with the rapid rise and rapid falls of cocaine?
what do we see in the eyes of an individual who is using cocaine?
dilated pupils
what physiological effects do we see with an individual who takes cocaine?
- increased bpm
- high bp
- dry mouth
- no hunger (mild anorexia)
- increased body temp
- tooth decay
- pupil dilation
why do people take cocaine?
- feelings of exhilaration & euphoria
- sense of wellbeing
- enhanced alertness
- heightened energy
- great self-confidence
- increased aggression
VERY ACUTE BEHAVIORAL EFFECTS
what is true about taking low doses of cocaine?
it increases purposeful behavior
know synapse chart on slide 26
what does acute cocaine intake do at the synapse?
cocaine blocks reuptake transporters DAT (dopamine system) and NET (norepinephrine)
what does cocaethylene do at the synapse?
it blocks DAT, NET, SERT (serotonin)
what is the cause of cocaine’s stimulating, reinforcing, and addictive properties?
the blocking of the dopamine reuptake channel
what occurs when there is a cocaine surge in norepinephrine?
- increase activation of a-adergenic receptors
- OBJECTIVE cns effects- wakefullness, decreased appetite, increased resp
what occurs when there is a build up of dopamine in the synapse?
- increase activation of postsynaptic DA receptors
- SUBJECTIVE cns effects - Well-being, euphoria, increased sense of energy/ confidence, psychosis
what are the dopamine contributions in cocaine use?
Mesolimbic DA: motivation/ pleasure effects
Nigrostriatal DA: motor-stimulating effects
what are the norepinephrine contributions in cocaine use?
Inhibits NE uptake in PFC (attention)
Arousal/ wakefulness, hunger suppression
why do people become addicted to cocaine?
they use a lot at once (binge) and is followed by bad withdrawal (abstinence syndrome)
what are the components of the abstinence syndrome?
Crash, withdrawal, extinction
Crash: user feels exhausted & depressed mood (in the 1st week)
Withdrawal: anhedonia, anergia, anxiety, craving for cocaine (1-4 weeks after)
Extinction: symptoms subside (after week 5)
what is the reasons for cocaine relapse?
environmental cues and cocaine priming
what is chronic cocaine use comorbid with?
other psychiatric disorder, stress, financial issues, job stress
what is true about cocaine withdrawal symptoms?
Withdrawal symptoms are OPPOSITE of what is seen while on cocaine
- dysphoria
- depression
- lethargy
- increased appetite
- drug craving, mental depression, & suicidality
what occurs when there is chronic cocaine use?
people develop pharmacodynamic tolerance, specifically seen for euphoric effects
what is seen in the nucleus accumbens during chronic cocaine use that explains tolerance?
Reduced presynaptic DA levels and reduced release
Reduced rate of DA uptake, even when cocaine is not present
Reduced ability of cocaine to block DAT
Reduced sensitivity or downregulation of DA receptors
what type of tolerance is observed between different stimulants and cocaine?
cross tolerance , when u take chronic cocaine, taking another stimulant will not work as well
what happens to the dose response curve when a user takes the same dose chronically?
the curve will be lower because it does not have the same efficacy.
in response, the user will take more and then the curve will shift to the right
how does cocaine cause taxyphylaxis (acute tolerance)?
Users taking cocaine again and againe within a single drug session will experience diminished responses after the initial dose! the inital dose will be the strongest
what is seen in users with interittent cocaine use?
they have sensitization - so less drugs will produce the same response or the same drug will develop a high response
what are the structural differences in the brain between users and non users?
long term cocaine users have…
- reduction in gray matter (less neurons)
- reduction in prefrontal cortex (exec decision)
- reduction in ACC ( conflict detector)
- reduction in insula (are the butterflied in my stomach cuz im nervous, i ate something weird)
- reduction in dorsal striatum
- reduction in amygdala (reduction in fear )
- reduction in thalamus
what are the functional differences in the brain between users and non users?
deficits in…
- Impulse control
- Working memory
- Verbal learning and memory
- Performance on psychomotor tasks
- Decision making
MORE COMPULSIVE BEHAVIOR
what behavioral changes does cocaine bring?
- Panic attacks
- Temporary paranoid psychosis
a. Hallucinations of touch, sight, taste, smell
b. Confusion/ anxiety
c. Formication syndrome - u feel like you have bugs crawling all over your skin
what physiological changes does cocaine bring?
- Malnutrition & weight loss
- Snorting:
a. physicial damage to inside of nose - Septal
necrosis or perforated septum
Example: comedian Arty Lange
what are more adverse effects of cocaine?
- Cocaine can kill in minutes!
- Vasoconstriction in blood vessels interrupts blood flow to the brain and can lead to stroke
