Stimulants Flashcards
How do stimulants work?
Increase existing levels of neurotransmitters in the CNS
By what mechanisms can stimulants increase existing levels of neurotransmitters?
Blocking reuptake
Stimulating release
Preventing breakdown
What are effects of stimulants?
Increase alertness, decrease fatigue, improve mood and increase self-confidence
What can low doses of CNS stimulants often lead to?
Euphoria, exaggerated reflexes, compensation for some fatigue
What can high doses of CNS stimulants cause?
Dizziness, loss of coordination, hallucinations, paranoia, anxiety
What is cocaine harvested from?
Coca plant
Where is cocaine predominantly found and why?
South America
Elevation creates better yield
What were some recommendations for cocaine use by Sigmond Freud in Uber Coca?
Mental stimulant
Possible treatment for digestive disorders
Appetite stimulant
Treatment for morphine and alcohol addiction
Local anesthetic
Describe the effects of cocaine when taken orally.
Highly susceptible to first-pass metabolism
Much slower peak
Less intense high
Describe the basic pharmacology of cocaine
Cocaine alkaloid extracted from coca leaves and then converted to hydrochloride salt and crystallized
Considering that cocaine HCl is water-soluble, what are possible administration routes for cocaine?
Orally
Insufflation/snorting
IV injection
Is cocaine heat stable? What is the significance of this?
No.
Cannot be smoked
What is freebasing?
Smoking cocaine obtained by dissolving in water, adding alkaline solution (e.g., ammonia), extracting cocaine base with organic solvent, typically ether.
In addition to freebasing, what is another way for cocaine to be smoked?
Mix dissolved cocaine HCl with baking soda, heat the mixture, then dry it
Crack
Describe the important factors in the strong addictive properties of cocaine
Cocaine is lipophilic and readily passes through blood-brain barrier.
Smoking results in large surge of cocaine in the brain that is not reflected in peripheral blood concentrations
Describe the mechanisms of cocaine action
Blocks reuptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT)
DA, NE and 5-HT are cleared from synaptic cleft by membrane transporters
Cocaine binds to transporters, inhibiting function
Increased transmission
Rank the transporter affinities of cocaine
5-HT
DA
NE
What is considered the most important factor for cocaine’s stimulating, reinforcing and addictive properties?
Blocking DA reuptake
What is a cocaine binge?
When cocaine is taken in multiple hits over several hours or days.
What causes cocaine to lose effectiveness in a binge?
saturation of reuptake transmitters
What happens during the accumulation of dopamine in the synaptic cleft?
Downregulation of dopamine receptors
What causes the crash/craving phase of cocaine?
Without cocaine, reduced DA receptor numbers are insufficient for normal activation
What are the common routes of administration for cocaine?
Insufflation, IV, smoking
What is the most common administration route for cocaine in North America?
Smoking and snorting
What are other possible routes of administration? Why are they less common?
Chewing of coca leaves or coca paste
Primarily of regional and cultural use
Oral administration gives less intense high
What are the effects of cocaine dependent on
Mode of administration and dose
How does the speed of the onset of cocaine effects affect the high and duration?
Faster onset = stronger high = shorter duration
What is the half-life of cocaine?
Average 1 hour
range 30-90 mins
What does cocaine metabolize into?
Benzolecgonine
What is the half-life of benzoylecgonine?
5-7 hours
In which situations does cocaine break down into benzoylecgonine?
In vivo and in vitro
What affects the interpretation of cocaine blood concentrations?
Instability of cocaine makes interpretation difficult
What does a high blood concentration of cocaine and low blood concentration of bze indicate?
Recent use
What does a low blood concentration of cocaine and high bze concentration indicate?
Recent use OR prior use
What does low cocaine blood concentration and low bze concentration indicate?
Recent use of small amount?
What are typical aspects of the cocaine high?
Feelings of exhilaration and euphoria
A sense of wellbeing
Enhanced alertness
Heightened energy
Great self-confidence
What may contribute to the street violence associated with cocaine use?
Increased aggressive behaviour
What generally produces mild to moderate effects of cocaine?
Single, low to moderate doses in naive subjects or in users who have not yet progressed to heavy, chronic use
When are severe effects of cocaine most likely?
With high dosages, particularly in chronic users
What state of mind can cocaine induce?
Temporary paranoid psychosis with delusions and hallucinations
What are the risk factors for cocaine psychosis?
Male
Increased dose and/or increased duration of use
IV route
What are cocaine bugs?
Sensation that hundreds of bugs are crawling over or under the user’s skin
What is the hallucination of cocaine bugs called?
Delusional parasitosis
Describe the structure of amphetamine
The parent compound of a family of synthetic psychostimulants that are structurally related to DA.
What is the mechanisms of amphetamine and methamphetamine action?
Both are indirect agonists of the catecholaminergic systems
What are the two actions of amphetamines and methamphetamine?
Molecules enter DA nerve terminals via uptake by DAT and cause vesicles to release DA.
DA is then transported out of the cell by a reversale of the DAT.
Result is very high DA in the synaptic cleft.
When and where did methamphetamine hydrochloride in a crystalline form suitable for smoking begin showing up?
1980s
Hawaii
What are methamphetamine HCl crystals called?
Ice or crystal
Why is meth “ice” used?
Inexpensive to make and highly addictive
What is methamphetamine usually synthesized from?
Peseudoephedrine
Describe an amphetamine “run”
Some users (“speed freaks”) go on binges (“runs”) of repeated IV injections to experience recurrent highs.
What happens during an amphetamine run?
Drug is typically injected about every 2 hours for as long as 3 to 6 days, with little sleep or eating
What is speedball?
IV amphetamine or methamphetamine combined with heroin
Describe the rate of metabolism for amphetamine and methamphetamine
Slow
Why do users of amphetamines obtain a longer-lasting high than do users of cocaine?
Amphetamines have long half-lives
Why do amphetamines have potent sympathomimetic actions?
NE-releasing effects occur in the brain and sympathetic nervous system
Describe the behavioural and neuronal effects of amphetamine
Heightened alertness
Increased confidence
Feelings of exhilaration
Reduced fatigue
Generalized sense of well-being
Delay in sleep onset
Sustained physical effort without rest
Highly reinforcing
Why are amphetamines banned in athletic competitions?
Can enhance athletic performance
When and where was crystallized meth first discovered?
Japan 1919
What were the original effects of meth determined to be?
Alleviate fatigue
Induce alertness
Well-being
Why was meth popular in WWII?
Used by pilots to sustain them on long missions
What effects does methamphetamine have in addition to its effects on DA?
Influences serotonin and norepinephrine levels
What can long-term effects on serotonin levels by meth lead to?
Changes in behaviour and increased aggression
Name the stereoisomers of meth
I- and d-
What is the use of I-Meth (levomethamphetamine)?
Used clinically, e.g., Vicks inhaler
What is the use of D-Meth (dextromethamphetamine)?
Available via prescription
What isomer is generally used in abused meth?
mixture of d-Meth, which is much more active centrally, and I-Meth
What is Desoxyn?
Meth still prescribes in US
What is Desoxyn prescribed for?
Weight loss
Narcolepsy
ADHD
What are the possible routes of administration for meth?
Smoking
Inhalation
Injection
Oral
What are the short-term effects of meth?
Euphoria
Increased energy levels
Restlessness and irritability
Increased heart rate/blood pressure
Hyperthermia
Describe the methamphetamine rush
Smoking, inhalation and injection produce rapid effects and the initial rush can last up to 5 mins
Describe the meth high
Duration of a longer lasting drug-induced high can last over 12 hours
What are the long-term effects of meth?
Psychosis - paranoid delusions, hallucinations
Aggressive behaviour
Changes in brain functions
Severe tooth decay (“meth mouth”)
What is the half-life of meth?
12 hours
Compare meth and cocaine
Meth has a slower metabolism
Smoking meth can induce a high lasting well over 8 hours, cocaine high usually lasts up to one hour
This can lead to prolonged effects and may be associated with an increased risk of psychosis
What is MDMA (3,4-methylenedioxy-methamphetamine)?
A synthetic drug that alters mood and perception
Describe the chemical structure of MDMA.
Chemically similar to both stimulants and hallucinogens
What are the general effects of MDMA?
Produces feelings of increased energy, pleasure, emotional warmth
Distorted sensory and time perception
Where was MDMA initially popular?
Nightclub scene and raves
Since MDMA has properties that fit into stimulant and hallucinogen categories of drugs, what is it often categorized as?
An entactogen
Describe the 5-HT mechanisms of MDMA.
Enhances 5-HT neurotransmission, which is important for characteristic effects of MDMA
Increased social interaction, friendliness, empathy
What are the effects of the DA mechanisms of action of MDMA?
Produces increased energy/activity and acts in the reward system to reinforce behaviours
What are the effects of the NE mechanism of action of MDMA?
Increases heart rate and blood pressure
Through which route of injection is MDMA rapidly absorbed?
Oral
What is the half-life of MDMA?
6-8
How long do the psychoactive effects of MDMA last?
2-4 hours
Which lasts longer in MDMA - objective impairment of mental function or subjective effects?
Objective
Describe the long term toxicity of MDMA.
Increase in 5-HT in the synapse leads to improved mood and sensory alterations
At high doses the extensive release of 5-HT may produce acute psychotic symptoms AND chemical damage to cells.
What are the long-term psychiatric problems of MDMA?
Greater impulsivity and lack of self-control
Panic attacks
Paranoia
Hallucinations
Severe depression
What is molly? Ecstasy?
Molly - powdered MDMA
Ecstasy - pill form of MDMA
Why is it unlikely someone will use MDMA for the intent of SA?
Can make you more reactive
No memory loss
Not sedating
How could MDMA be used for SA?
Those on it may be more sexually aroused, feel loved, and thus ‘consent’ to sex
What is the traditional definition of drug-facilitated SA?
Offenses in which victims are subjected to nonconsensual sexual acts while they are incapacitated or unconscious due to the effects alcohol and/or drugs, and are therefore unable to consent
Why is a complainants state of incapacitation an important consideration in cases of SA?
It has implications for the issue of being able to provide consent
What is methylphenidate (ritalin)
CNS stimulant
What is methylphenidate’s mechanism of action?
To release and increase dopamine
Describe the mechanism of action of methylphenidate in the brain.
Binds to DAT and NET, blocking reuptake of DA and NE, elevating extracellular levels of both transmitters and stimulating overall catecholaminergic neurotransmission
What is the abuse potential of methylphenidate?
High
When are the effects of ritalin similar to those of cocaine? Why?
When used intranasally
Leads to a rapid release of synaptic dopamine producing a significant high
What are the psychiatric symptoms of methylphenidate acute toxicity?
Euphoria
Delirium
Confusion
Toxic psychosis
Hallucinations
Extreme anger with threats have also been reported
What are the guidelines for abuse prevention of Ritalin?
Shared responsibility between physician, parents and patient (usually a child)
Education about abuse potential
Strict use by patient only
Extreme consequences of abuse should be addressed
