After midterm #2 - Ch 10: cocaine and amphetamine

Question 1

amphetamines (made + 4 types)

Answer 1

synthetic
- Levoamphetimine (Benzedrine)
- Dextroamphetamine (Dexedrine), more potent isomer, treat ADHD and narcolepsy
- Di-amphetamine (Adderall). Treat ADHD
- methamphetamine (methedrine/desoxyn) treat ADHD and obesity

Question 2

amphetamine street aliases

Answer 2

uppers, pep pills, bennies, whites, deixes, hearts, speed, meth, crystal, crank, ice

Question 3

cocaine

Answer 3

white colourless crystalline powder derived from coca leaf paste; stabilized as said using HCl (ccaine hydrochloride)

Question 4

cocaine street aliases

Answer 4

coke, C, snow, blow, toot, leaf, flake, freeze, happy dust, Peruvian lady, white girl

Question 5

Pharmacokinetics - route of admin. amphetamines

Answer 5

weak bases (pKa 9-10)
more potent when administered by inaction or inhalation than p.o. (p.o. used or medicinal purposes (decrease in sleep or fatigue); easy to control blood levels

Question 6

cocaine methods of administration (7)

Answer 6

weak base (aka 8.6).
1) typically injected or inhaled
2) inhalation: tooting: place cocaine HCl on foil; head until it vaporizes, inhale vapour
3) oral: chewing/sucking coca leaves 92% cocaine by Andean Indians
4) snorting
5) intravenous
6) freebasing

Question 7

cocaine - snorting

Answer 7

sniff cocaïne HCl into nostrils; absorbed into blood through nasal mucosa. Into brain in 3-5 minutes; effects peak after 10-15 minutes; one line (10-40 minutes of stimulation/euphoria. Snorter may not experience a crash

Question 8

cocaine - intravenous

Answer 8

produces intense initial rush of pleasure within 2 minutes that lasts about 10 minutes followed by a crash

Question 9

freebasing - cocaine

Answer 9

convert cocaine HCl into smokable, pure form called “base” or “free base”
- separate cocain molecule form HCl; more potent due to increase in lipid solubility
- free base smoked in pipe or sprinkled on cigarette/joint; produces sudden, intense high in a few minutes

Question 10

Crack cocaine

Answer 10

Cocaine HCl mixed with baking soda solution evaporates water, crystalline heated in pipe: inhale vapours. Rocks crackle when burned. Smoked in pipe or mixed with marijuana; reaches brain in seconds. One of the Most addictive substances ever known (> heroin, barbiturates, alcohol). Few minutes after high, uses experience “Hangover”

Question 11

Absorption - AMPHETAMINES

Answer 11

P.o. effects in 30 minutes, peak blood levels in 30 minutes - 4 hours.

i.v. onset of effects in 5-10 minutes

Question 12

Absorption - cocaine

Answer 12

intranasal, onset within 2 minutes, peak blood levels 10-20 minutes. Freebasing and smoking crack - rapid absorption, effects in 7-10 seconds

Question 13

Distribution - both

Answer 13

readily cross BBB and placental barriers. Distributed rapidly throughout the tissues and organs of the body.

The highest [] of methamphetamine are in kidneys, lungs, then stomach, pancreas, spleen and liver. Lower in the heart and brain.

Cocaine - concentrates more in brain than other bodily organs. A greater total % of cocaine dose enters the brain compared to a dose of methamphetamine.

Question 14

Metabolism and excretion - amphetamine

Answer 14

metabolized in liver, 50% excreted unchanged

• excretion depends on urine pH (acidic –> excreted , base –> reabsorbed
• amphetamine t1/2 = 9-14 hours if urine acidic; 16-34 hours if urine is basic

Question 15

Metabolism and excretion - cocaine

Answer 15

metabolized by enzymes in the blood and liver; t1/2 - ~60 minutes. Excretion via urine- contains metabolites (benzoylecgogine) 48-72 hours after use; during testing

• drug or metabolites also deposited in hair; hair testing can determine if using cocaine and how long ago wishing the last 90 days

Question 16

Neurophysiology - cocaine

Answer 16

reuptake inhibitor, binds to transporter, prevents uptake (molecules of monoamine are forced to remain in the cleft longer and in higher []s where they can exert a greater effect on the postsynaptic neutron

Question 17

Amphetamines

Answer 17

substrate-type releaser: enter presynaptic neutron and get packaged in vesticles, alter vesticle pH, reverse VMAT (vesicular monoamine transporters), releases monoamines into cytoplasm, reverse MAT transporters in membrane to pump nommonoamines out in to the extracellular space

• MAO inhibitors: prevent MAO from breaking down monoamines in cytoplasm
• Block BMAT tp prevent vesicular storage and cause release of MA into cytoplasm

Question 18

Peripheral sympathetic nervous system (both)

Answer 18

release epinephrine from the PSNS, fight-or-flight response. This explains the strong cardiovascular effects.

Question 19

Peripheral sympathetic nervous system - cocaine - local anesthetic effects

Answer 19

Cocaine also blocks Na+ channels (prevents the conduction of action potentials along nerve axons. Explains local anesthetic effects. Used to be applied to gums to release teething pain. Today, it’s a local anaesthetic (procaine) for dentistry - without stimulant properties. Procaine still acts as a positive reinforcer in rats and monkeys.

Question 20

Effects on the body

Answer 20

• elevations in heart rate and blood pressure, increase body temperature and dilate pupils, basodilation, bronchodilator (dilation of air passages in lungs - historically used for asthma). High doses, amphetamines cause abdominal cramps, nausea, vomiting, tremors, exacerbate motor tics.

Question 21

Effects on appetite

Answer 21

Decrease food consumption. Mechanism responsible for this effect not well understood, may be achieved secondarily through drugs’ impact on other behaviours. Satiety response.

Question 22

Stereotyped behaviour

Answer 22

pending: the repetitive performance of some (usually purposeles) act for an extended period) - taking apart and putting together a watch, sorting and resorting, cleaning and re-cleaning. Often don’d eat or drink or pee, and are annoyed if the activity is interrupted. Seen in rats. Caused by stimulation of nigrostriatal DA system that has input into the extrapyramidal motor system

Question 23

Subjective effects (amphetamine)

Answer 23

make people feel good, improve mood, sense of sell being, bubbling inside, decrease in fatigue, increase in energy, clear, organized mind, desire to get to work. Confirmed. Rushes, intense euphoria in high doses (iv and smoking). Oral and intranasal don’e give rush (slower absorption rates and lower blood concentrations over a longer period of time.

Question 24

Subjective effects - cocaine

Answer 24

iv, same as iv amphetamine (shorter acting) - rush felt within seconds, lasts less than a minute. Described sexually/as orgasmic. Then a feeling of energy, clear thoughts, perceptions (20-30 minutes), then a mild depression (crash/comedown). With repeated administrations, cocaine-induced rushes show rapid tolerance.
- subjective reports of good are greater after smoking than injecting iv (time to reach peak subjective effects faster for smoked than iv cocaine)
- intranasally - numbing sensation felt within a couple minutes. Then 5 minutes started well-being and peak subjective effects reached in 15 minutes.

Question 25

Effects on sleep - amphetaminea

Answer 25

prevents fatigue and need for sleep. Increases alertness, energy, attention, concentration. Causes insomnia.Treats narcolepsy.

Question 26

sensory

Answer 26

increase in visual acuity slightly auditory

Question 27

effects on performance

Answer 27

improvements in endurance, less fatigue, reaction time, short-term memory, vigilance - deficits in divided attention tasks (tunnel vision) - overcome deterioration in performance caused by other factors such as reduced oxygen levels, and time.

Question 28

performance deficits

Answer 28

may impair performance on tasks that require the ability to adopt new strategies (tunnel vision)

Question 29

At high doses

Answer 29

most for the beneficial effects are lost, people become impatient, easily distracted, impaired judgement

Question 30

Athletic performance

Answer 30

1% improvement in swimmers, track and field (shot-put),

Question 31

Effects on driving

Answer 31

2.3 more likely to be killed in a car accident.18 times greater odds of crash (amphetamine) - not as much with cocaine

Question 32

Psychosis

Answer 32

high doses or used frequently for extended periods , both can elusive monoamine psychosis. Virtually indistinguishable symptoms from schizophrenia (positive symptoms, auditory, visual hallucinations; delusion of reference, persecution, grandeur, odd speech, anxiety/agitation, extreme paranoia that can evoke hostility and violence. - negative symptoms - flattened affect (severe reduction in emotional expression and depression) - feeling bugs crawling under skin (cocaine bugs or crank bugs) - Symptoms disappear within several hours to days of emergence without residual effects. However, in some, they persist indefinitely (28% more than 6 months). Triggered by small amounts of the drug, periods of methamphetamine abstinence by environmental stressors, heavy alcohol consumption.

Question 33

Acute tolerance

Answer 33

subjective effects of amphetamine/cocaine greater when blood levels of the drug are rising compared to when they are falling. Indicative of acute tolerance. - permitted to administer cocaine i.v. once every 10 minute for 1 hour - positive mood increased after the first infusion but not after even through the blood levels of cocaine rose steadily after each additional infusion - Acute tolerance - fast dissipation (24 hours). - affects subjective, not cardiovascular effects (danger of having heart attach or cerebral hemorrhage) - decrease in potency but not effectiveness as a discriminative stimulus

Question 34

Chronic tolerance

Answer 34

appetite-suppressing effect disappears within 2 weeks, and the effect heart and blood pressure diminish over time. - lethal effects show tolerance with repeated use - chronic amphetamine users increase their dose due to extremely high levels wihtough experiencing a fatal overdose - No tolerance: ability to prevent sleep

Question 35

Sensitization

Answer 35

reverse tolerance - stereotyped and psychotic behaviours appear more frequently after repressed doses and well beyond period of last use

Question 36

Withdrawl

Answer 36

- not associated with severe or medically serious syndrome - single dose 0 crash or comedown (depression and lthargy) that is immediacy relieved by another dose of drug - appear within 1/2 hour (cocaine, delayed for number of hours (amphetamine). - after chronic heavy use --- appearance within 24 hours of last dose. Severity of depression related to the dose and duration of intake period and may lead to suicidal thoughts or attempts - withdrawal symptom of depression can be treaded with antidepressants medications. - if perdiod of use long enough to interfere with sleep of eating, compensatory increase in these behaviours. - lead to poor sleep quality, insomnia, vivid dreams, frequent awakenings. Initial phase, up to a week. In creased appetite, sleep, depression -- continue for many weeks or months. - disrupt performance -- bad decision making skills. (decrease in dorsolateral prefrontal cortical activation)

Question 37

Harmful effects: cocaine

Answer 37

snorting causes damage to nasal septum; ulceration/inflammation of mucous membranes - intense compassion to use - leases to individuals to sell homes and cars to finance intake - disturbing physical/psychological symptoms (paranoid delusions, hallucinations, cravings, antisocial behaviour, concentration problems, weightless, blurred vision Fatal: induces seizures, cardiac arrhythmia, hypothermia (impairs sweating and cutaneous vasodilation, mortality form overdose increases in hot weather.

Question 38

Harmful effects: amphetamine

Answer 38

- psychological symptoms (restlessness; excessive talking; confusion, dizziness - cardiovascular abnormalities: irregular heartbeat - internal bleeding and strokes in the brain from increased blood pressure, irreversible brain damage due to rupturing of small blood vessels

Question 39

Overdose

Answer 39

Ld50 of cocaine depends on route of administration, snorting - low as 30 mg. 150 lb man = 500 mg. Two phases: excitement followed by severe headaches, nausea, vomiting, convulsions. Then loss f consciousness, respiratory depression, cardiac failure Treat: with diazepam (seizures), chlorpromazine

Question 40

Treatment

Answer 40

initial phase is detoxification and total abstinence (profound depression, headaches, irritability, and sleep disturbances. Inpatient treatment in hospital or outpatient program with regular visits to treatment facility

Question 41

Behavioural techniques for treatment

Answer 41

CBT: teach strategies to avoid maladaptive behaviour and prevent relapse Contingency management/community reinforcement: monetary reward for clean urine samples and enjoyable social activity combined with counseling

Question 42

Pharmacological therapies

Answer 42

Modaphinil - simulates DA, NE, glutamate transmisison - sued to treat narcolepsy and ADHD Bupropion - DA and NE reuptake inhibitor - Wellbutrin (antidepressant), Zyban (smoking cessation) - reduces cravings in light users of meth Methylphenidate - DA and NE reuptake inhibitor - used to treat ADHD - reduces cravings; increased retention in treatment Oral amphetamine - safest route of administrateion - treats ADHD - decreases meth use in users Naltrexone - decreases amphetamine use in addicted users - blocks subjective effects and cravings for amphetamine in addicts