Cocaine and Amphetamine

Question 1

Cocaine Formulation- Powder

Answer 1

Cocaine hydrochloric salt
White flakes, or powdery form
Relatively stable, transports well
Dissolves easily in water
Intranasal and intravenous routes
Most common form
Often "cut" with many chemicals until final product is 12% cocaine

Question 2

Alduterants to Cocaine

Answer 2

Mannitol- Mild baby laxative, low toxicity
Inositol- B vitamin, harmless but irritates nasal passages
Lidocaine- “active” adulterant is also a local anesthetic so difficult to detect; no euphoria but is self administered
PPA- phenylpropanolamine, an OTC nasal decongestant, high toxicity at high doses
Lactose- harmless, cheap and easy to get

Question 3

Cocaine Formulation- other

Answer 3

Freebase
Pure alkaloid waxy paste becomes oil
Not very stable, breaks down easily
Dissolves in lipid or fat
Must be smoked
Special small pipes are used

Question 4

Crack Formulation

Answer 4

Freebase, less dangerous to make
Smoked in special crack pipes
Marketed in single doses
Epidemic in 1980

Question 5

Cocaine Mechanism of Action

Answer 5

Dopamine is released –> Cocaine blocks reuptake inhibitors –> Increased dopamine levels in the synapse - Positive reinforcement Blocks sodium ion channels in the cell

Question 6

Medical Uses- Cocaine

Answer 6

Schedule II
Local anesthetic for ophthalmic surgery and testing due to direct blockade on nerve impulses
Very effective in nasal, laryngeal and esophagus mucus membranes
Causes vasoconstriction, reduces bleeding
Can cause positive urine screening 2 days later
CNS energizing use ended due to short duration of action, rapid tolerance, dependence and side effects

Question 7

Cocaine Absorption

Answer 7

Rapidly absorbed through IV, smoking, intranasal, oral

Short plasma life of 40-60 minutes

Question 8

Cocaine Metabolism

Answer 8

Plasma and liver esterases metabolizes cocaine
50% metabolized within an hour
Rapid rise and fall of cocaine plasma levels causes a crash, leaves user wanting more

Question 9

Cocaine Effects on CNS

Answer 9

Euphoria- sense of well being, greater self-esteem, alertness, energy

Question 10

Cocaine Physiological Effects

Answer 10

Increased heart rate and increased blood pressure

Question 11

Cocaine Patterns of Use

Answer 11

Chippers- Occasional use
“Binge”- finish all cocaine available
Other behaviors reduce- sleep, eating, sexual
If supply is limited than human and animals use until death
Crash at the end of use

Question 12

Speedball

Answer 12

Cocaine + heroine
Heroine takes the edge of cocaine high
Can result in death if dose is too high

Question 13

Cocaethylene

Answer 13

Cocaine + Ethyl Alcohol
Major metabolite benzoylecgonine is transesterified by ethanol to produce this
More toxic than cocaine and may contribute to overdoses when cocaine is used with alcohol

Question 14

Tolerance- Cocaine

Answer 14

Unclear whether there is tolerance or sensitization
Sensitization to locomotor, stereotypic behaviors and convulsions
Tolerance to constant use
Sensitization- interval in between uses
No tolerance to blood pressure effects

Question 15

Withdrawal- Cocaine

Answer 15

Thought that dependence did not occur
Abstinence causes crash, intense craving to cocaine
Individual will sleep and eat, but depressed, thoughts consumed by cocaine
More rapid of a crash= more frequent use

Question 16

Treatment Cocaine

Answer 16

No approved medications, trials still being conducted
New knowledge of how the brain is changed by cocaine provides newer targets, ex- disturbes GABA glutamate balance
D3 receptors constitute novel molecular target of high interest
vigabatrin- anti- epileptic
modafinil- anti-nacrolepsy
tiagabine- anti-epileptic
disulfiram- ALDH inhibitor

Question 17

Programs cocaine

Answer 17

Contingency Management and/or Motivational Incentive Program
Voucher or based prize system that rewards people from abstaining for cocaine
Drug free urine tests –> points or chips that can be exchanged for healthy lifestyle prizes

Question 18

Phases of Cocaine Withdrawal

Answer 18

Crash (24-48 hr)- agitated, depressed, suicidal, fatigue/exhaustion, no cravings
Withdrawal (1-10 weeks) mood swings, sleep returns, anhedonia, drug seeking anxiety
Extinction (indefinite)- mood swing, cue induced cravings

Question 19

Stimulant- Cocaine

Answer 19

Slow release form of cocaine should reduce cocaine use
Transdermal path or transbccal
Open trial of oral cocaine tea was found effective in Peru
Not likely to be accepted

Question 20

Disulfiram

Answer 20

Inhibits dopamine-beta-hydroxylase
Patients with normal DBH dropped from a 84 to a 56, while patients with a low DBH genotype had no disulfiram effect
DBH genotype of a patient could be used to identify whether nor not treatment may be effective

Question 21

Current Cocaine Treatment Strategiees

Answer 21

Long term dopamine agonists
GABAb agonist
cocaine vaccine
Bind to DA transporter

Question 22

Cocaine Vaccine

Answer 22

Antibodies made to cocaine
Likely an adjunct treatment
Need 47% of the DA transporter to be occupied for cocaine to feel effects
Vaccine reduces this to 20%
Cocaine antibodies persist for one year
Cocaine use was lower after subjects had received higher dose vaccine- needs further testing

Question 23

Profile of Use Amphetamine

Answer 23

Primarily diverted legal tablets that were meant for prescription use
Similar effects as cocaine, longer duration of action because metabolized slowly
Different mechanism of action
Injected as speed and d-methamphetamine

Question 24

Medical Use Amphetamine

Answer 24

Narcolepsy
ADHD
Weight reduction- limited use for this

Question 25

Designer Amphetamine

Answer 25

Chemically similar to amphetamine Underground chemist alter structure to have psychoactive effects Very common in 1970s and 1980s Because they were not amphetamine, they were not illegal, made illegal in 1986

Question 26

Amphetamine Mechanism of Action

Answer 26

Amphetamine enters terminal, causes dopamine to be released from terminal Dopamine concentrations in synapse increases and continue to bind to receptor

Question 27

Methylphenidate

Answer 27

Non-Amphetamine behavioral stimulant Used primarily to treat ADHD Blocks reuptake of dopamine- similar to cocaine Promotes dopamine release- like amphetamine Sluggish effect, takes 60% to block 50% of the transporter, accounts for lower abuse liability

Question 28

Ritalin Abuse

Answer 28

Growing trend for non-medical use for individuals without a prescription Derived from belief that it is a cognitive enhancer- increases learning and memory

Question 29

Trends of Ritalin Abuse

Answer 29

White male college students In frats and sororities NE United States, more competitive admission rates More likely to also report abuse of alcohol, drugs, and ecstasy Studies also show that it does not increase learning capacity or memory Only promotes wakefulness, alertness, reduces sleep

Question 30

Methylphenidate(Concerta)

Answer 30

Recently developed but has taken over 40% of the ADHD market Once a day treatment MPH coating, rigid membrane covering high concentration MPH with a hole drilled through

Question 31

Methylphenidate and SUD

Answer 31

Through that those with ADHD given drugs would have a higher rate of substance abuse Study found that two fold lowered risk in having substance use disorder when receiving medication during childhood, as well as a similar decrease in risk in alcohol and other drug abuse disorders Greater risk of SUD if medications not administered before puberty

Question 32

Health Consequences of Cocaine

Answer 32

High abuse liability Problems at school, work, job Increased blood pressure can increase strokes Arrhthmias due to direct effects of the heart Convulsions typically only occur after high doses CRACk smoking may damage lung tissue Cocaine use during pregnancy can harm fetus

Question 33

Crack Baby Syndrome

Answer 33

Small heads, agitated, prone to agitation, lack of social skills Through studies, found confounding issues of alcohol and tobacco, poverty Cocaine still isn't good for babies, but it is not inevitable that they grow into addicts and criminals

Question 34

Toxic Psychosis

Answer 34

Dose related progression from nervousness, aggression, irritability, tremors Acute psychotic reaction that resembles schizophrenic psychosis Typically occurs in chronic users Urine screen for differential diagnosis Supportive treatment