Cocaine and amphetamine Flashcards by Spencer Farstad | Brainscape

Q

AMPHETAMINE dates

A

Some Notable Dates in History
* Origin: chinese herb: Ma Huang
* 1887: active ingredient in herb isolated: ephedrine
* 1927: Alles: synthetic: amphetamine
* 1932: smith cline and french marketed alles drug under: Benzedrine (nasal spray and inhalant to treat asthma)

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Q

AMPHETAMINES
Therapeutic Uses

A

Petit-mal epilepsy
-a person losses conciousness for a small period of time (staring blankly)
narcolepsy
triggered by stress to induce REM sleeping
ADHD
may be overprescribing it but effective for attention
Weight problems
suppresses apatite (but tolerance will occur) so not effective at treating this in the long term

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Q

AMPHETAMINES
Non-Therapeutic Uses

A

euphoriant (elevates mood)
Performance enhancer –> increase Resp/HR , not improve reaction time but if they are fatiguing it will (diinish fatgue)
General stimulant
help stay awake for a long period of time

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Q

Cocaine
Some Notable Dates in History

A

13c: Used by the Incas (to be stronger)
16c: Spanish bring coca leaves to Europe
was ignored
1850: Active ingredient in leaves chemically isolated
1859: German Chemist discovered anesthetic
properties –> numbing effect

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Q

Cocaine
Some Notable Dates in History

A

1863: Corsican chemist creates “Vin Mariana”,
popular alcohol and coca combination –> combo of coco leaves and alcohol (effect of alcohol was prolonged) –> increased alertness

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Q

Cocaine
Some Notable Dates in History

A

1863: Corsican chemist creates “Vin Mariana”,
popular alcohol and coca combination
1884: Freud samples cocaine, becomes advocate for its widespread use (launched a major period of cocaine use) –> said it can treat pain, alcohol addiction, can be a local anaesthetic (which is true)
–> found some wound benefit and some would not
–> he had a friend who was addicted –> he felt bad
–> psychosexual stages were from his coaine use
1885: American pharmacist removes alcohol, adds
soda water and syrup from African Kola Nut, and
creates “Coca Cola”, touted as a “brain tonic”
being sold in drug stores lol
it did contain cocaine

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Q

Cocaine
Some Notable Dates in History

A

1903: Responding to rising public concern re:
unregulated use of cocaine, Coca-Cola company
begins to use de-cocainized coca leaves
1906/1914: Cocaine banned in patent medications in Canada and US respectively
–> banned cocaine in patent medicines (became a Schedule 1 drug from then on)
1920s to 1960s: use of cocaine gradually declined;
decline associated with intro of amphetamines
–> cocaine was regulated when ampetamines wasn’t

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Q

Cocaine
Some Notable Dates in History

A

1970s: resurgence of cocaine’s popularity/ use as
well as incidence rates of abuse
Middle 1980s: Crack introduced –> saw huge resurgence after that
1990s onward: high use/abuse of drug still a concern, but numbers using have declined from 70s and 80s; relaxed attitude regarding use among users

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Q

AMPHETAMINE
Forms

A

Two isomers (same formula but different arrangement of the atoms): L and d amphetamine
L: form that was marketed as benzedrine
D: was more potent –> is the one bieng marketed today (dexadrine**)
Synthetic (modification of D isomer) –> adding of methanol molecule : Methedrine (methanphetamine) –> more potnet than D isomer*
Structurally related compounds
– methyphenidate (ritalin) drug for ADHD
– Phenmetrazine –> apetite suppresion drug
– Methcathinone –> combo of amphetamine and substance called khat

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Q

COCAINE
Forms
(1)

A

Coca Paste
– Created by chemically treating and mashing leaves of coca shrub leaves (leaves contain about .5-2% cocaine)
- leaves are dried (sun or heating light) –> mixed with water and sulfuric acid –> then mashed –> diesel fuel and bicarbonate added –> more mashing –> liquid is drained off –> paste (60% pure cocaine)

not water soluble (cant be injected or snorted)*****

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Q

COCAINE
Forms (2)

A

(2) Cocaine Hydrochloride (Salt) (what we think about with cocaine)*****

– Created by treating coca paste with
hydrochloric acid to produce a crystalline powder

more water, gasoline, acid, potassium, ammonia, –> creates reddish brown liquid –> drained–> dried –> in tank of HCl–> sediment at bottom is taken
is water soluble** injected and snorted
can’t be smoked (heating breaks it down)

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Q

(3) Freebase (base element of cocaine is removed) or Crack

A

Created by mixing cocaine HCl in an alkaline
solution (e.g., baking soda and water), then
boiling off water
- has a very low melting point (can be heated without cocoaine breaking down)
- very pure crack cocaine (99% cocaine)
- this is safe way to make crack

unsafe:
cocaine HCl with flammable substance –> can get things exploding

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Q

AMPHETAMINE
Administration & Absorption

A

(1) Orally –> tablet or capsule form swallowed
–> crush up a tablet in a paper and swallow it (parachuting)
–> onset of action is 10-30mins
–> lasts from 4-12 hours

(2) Intranasally –. snorted
–> OofA 10-15 mins
–> same duration of action as above

(3) Intravenous Injection (powder mixed with liquid)
–> 30s OofA
–> duration of action = same

(4) Inhalation –> typically meth (heat up on a spoon)
–> inhale the fumes
–> O of A less than 30s
–> D of A is same

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Q

COCAINE
Administration & Absorption

A

(1) Orally
(2) Intra-nasally –> dollar bill, nail
Problems with method:
-Absorption limited due to vasoconstriction (pores get smaller and interfere with absorption)
-Chronic users have stuffy or runny noses, nasal lesions, frequent nose bleeds

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Q

COCAINE
Administration & Absorption (3,4,5,6)

A

(3) Intravenously injected
- 16 mg
-peak effects in 3-4mins
-high lasts for about 20-30 mins

(4) Smoked
- Crystalline “rocks” i.e., crack heated in pipes and
vapours inhaled
- absorption through lungs and nasal cavity as well***
- affects in 1-2 mins
-high lasts for 5-10 mins

EXTRAS
(5) liquid cocaine into eyes –> eye drops
(6) liquid cocaine in GI tract –> died from carrying cocain across border

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Q

AMPHETAMINE
Metabolization and Elimination

A

Excretion affected by urine acidity
– Acidic: quicker
– Basic: slower
– Half-life ranges:
7-14 hrs (acidic urine) vs. 16-34 hrs. (basic urine)
- 11 -14 hours (l amphetamine)
- 9-11 hours (d-amphetamine –> more commonly used)
- 9-13 hours (methanphetamine)

Excreted in urine, sweat, saliva (majority of excretion in urine)
- significant amount eliminated in the urine unchanged ( not metabolized) 30-40% amph
30-50% methamphetamine (10% will be amphetamine)
- 7 metabolites in urine with meth –> but not psychoactive (affecting mental function at all)
- Have behaviourally active metabolites: detectable for 2-3 days

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Q

Cocaine
Metabolization and Elimination

plasma 1/2 life

A

Plasma half-life of 30 min, but more slowly
removed from brain

Urine can test positive for cocaine upto 12 hrs:
a metabolite can be dectected in urine upto
48 hrs

Urine can test positive for intravenous cocaine upto 12 hrs: a metabolite can be dectected in urine upto 10 days with chronic IV use

most of it biotransformed not staying the same as meth
shirter hlf life as welll –> gets eliminated quicker

1/2 life
oral: 1 hour
intranasal: 30-5 hours
15min-3.5 hours: intravenous
15 -3.5 hours: smoked

Metabolically interacts with alcohol:
metabolite cocaethylene is pharmacologically
active as cocaine is by itself in blocking dopamine reuptake
- euphoria can last longer with the combo

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Q

AMPHETAMINE & COCAINE
Mechanism of Action

A

Block re-uptake of DA, NE, and 5-HT (sero)
increased dop, NE, sero in synaptic spaces –> increased activity in neural circuits
dop = euphoria
NE= hightned endurance
sero= mood
Cocaine blocks Na+ ion channels
play role in nerve impulses
basis for analgesic effects for the drugs (numbing) slows down areas by blocking NA ion channels
Amphetamine has 3 additional effects (of above)
– Increase amounts of NT released –> higher levels of above than with cocaine

– Cause spontaneous leakage of NT –>

– Induce release and block re-uptake of glutamate –> major excitatory NT that plays a role in alertness and arousal in various areas in the brain

Special target is the mesotelencephalic dopamine pathway projecting to limbic system and nucleus acumbens (reinforcement, pleasure pathway)

Q

AMPHETAMINE & COCAINE
Physiological Effects

A

Activate sympathetic nervous system
CNS stimulants:
primary physiological function is to activate SNS*** fight or flight response
increased HR, BP, RR, Body temp, vasoconstriction, BF to large muscles, BF to the brain, pupil dilation, apatite is suppressed
Physiological effects can be life threatening, particularly with cocaine
increased HR and RR –> heart attack and cardiac arrhythmia, respiratory collapse,
w/ vasocon = strokes (cerebral stroke) –> bursting of BV in brain –> blood is toxic to neurons which kills neurons in brain
can have seizures as well
anoxia (brain not getting enough oxygen)

ALL these can occur with a single dose!!!!–> individual variability on how people handle drugs

Q

AMPHETAMINE & COCAINE
Behavioral/Psychological Fx

A

Euphoria - Intense with IV and Smoking
more intense with meth than cocaine
Giddiness
Enhanced Self-Esteem/Self-Confidence
Feelings of Invincibility (pronounced with methamphetamine)
–Bait Cars –> set up people to steal cars and get caught
Increased talkativeness –> quite tangential
difficult to follow train of thought

Q

AMPHETAMINE & COCAINE
Behavioral/Psychological Fx

A

Reduced sleep/Increased mental alertness -
subjective experience of “improved thinking”, “clarity of thought”
Greatly increased sexual response & desire
(pronounced with meth-amphetamine)

Q

AMPHETAMINE & COCAINE
Toxic Fx with Long-Term/High Dose Use

A

amphetamine and cocaine psychosis:

Tremors –> not seizures but lower

Restlessness –> rocking
Agitation/Hypervigilance/Suspiciousness
SNS agent –> activated makes you hypervigilance of surroundings (elevated fear response that you see)
Paranoid Persecutory Fears (comes with unnatural fear response) –> can be with one time use
Stereotyped, compulsive repetitive behaviours
Vivid Visual, auditory, and tactile hallucinations
Rawson et al (2005) re: prevalence and length of psychotic state –> can last for 6 months (thought disorders)

Q

AMPHETAMINE & COCAINE
Toxic Fx with Long-Term/High Dose
Use

A

Marked, pervasive anxiety
Depression
- above are shown in between the drug usage –> cant start the day until smoking or snorting

Impaired Thinking/Reasoning
Memory disturbances -

Q

Memory Problems?
* Reske et al (2010)

A

DOESN’T impair mems in short term or long term***

154, 18 -25 years, cocaine or prescription stimulants

– Auditory memory tested with California verbal learning test

– Statistically greater # of intrusions (remember a word that wasn’t there) (6 vs 3) fewer words in learning trials (52 vs 57) and delayed recall (11.45 vs 12.67)

– Differences not clinically meaningful and do not
reflect memory impairments/difficulties
* IR score of 52 = T score of 52 – average (58th %ile)
* IR score of 57 = T score of 56 – average (73rd %ile)
* DR score of 11 = z score of 0 – average (50th %ile)
* DR score of 13 = z score of .5 = average (69th %ile)

would not be IDed as impaired memory clinically* –> people with lifetime coke/meth use are not showing memory impairment*

Q

Memory Problems?
* Rapali et al (2005)

A

12 former amphetamine addicts
– Auditory memory tested with Digit Span, WMS-R, RAVLT
– No attention deficits, no immediate auditory
memory deficits
– Statistically significant differences in auditory
delayed recall: RAVLT 11. 9 vs 9.9 (given words and asked to recall later)

– Differences not clinically meaningful and do not
reflect memory impairments/difficulties
* Controls DR score of 11.9 = z of .32 = average (63%ile)
* Users DR score of 9.9 = z of -.39 = average (35% ile)

Q

Memory Problems?
* Chang et al (2005)

A

– Methamphetamine users abstinent for 9 months showed normal performance of tests of attention, executive functioning, and memory functioning

showing over time, there is not long term effects of memory functioning

Q

amphet have more

A

pharm actions than cocaine

Q

benzedrine: in prohibition

A

non prescription drug
- used recreationally
- soaked with amphetamine cotton
- drop in coffee or chew on it
- used by military by soldiers (still used) –> keep soldiers pepped up to reduce fatigue enhance endurance and elevate mood (part of their kit)
–> not in navy (purser would give them out) –> not on their person like the army
-

Q

2002 incident

A

air force pilots bombed a canadian military unit on a training mission
- defence attorney cited their use of amphetamine as impairing their judgment

Q

AMPHETAMINE & COCAINE
Behavioral/Psychological Fx

A

Reduced sleep/Increased mental alertness -
subjective experience of “improved thinking”, “clarity of thought”

Greatly increased sexual response & desire
(pronounced with methamphetamine)

Q

whispers book: by ronald seger albert:

A

formication hallucination: (coke bugs)
- delusion in which bugs are on or in you’
- try to get bugs out of them

something cam up through the shower drain and grabbed his leg
- sucking on his skin
- tiny welts to crawl inside
- chest, throat, in eyes
- up tot he brain
- they stopped
- sucking sound
- saw himself saggy
- arrested with a bunch of coke (he was a dealer)

Q

whispers book: by ronald seger matt:

A

looked like lumberjack
claimed to be a researcher
pulls out cocaine vials
probably a dealer
they are coke bugs not cocaine
purchased cocaine for holidays
close to 100% pure
makes crack out of it
gets fucked up
gets microscope
picking at his hands
snakes in his hands
peeling skin away from himself
snakes eating antibodies
took out chunks of his skin
H for hands
removed hair from hands
P for penis
ulcers on penis
spelled out DIE on his penis and though it was bugs that were doing it
cocaine bugs theory:
-bugs developed by CIA and DEA
-

Q

case study 18 year old

A

take meth
heard brother killed mom
ran away
got to hospital
flattened emotions (schizophrenia)
paranoid about hospital
over time symptoms diminished

Q

AMPHETAMINE & COCAINE
Toxic Fx with Long-Term/High Dose Use

A

Motor problems (slowed mov’t) –> may be due to physciological crash from body being on high for so long
Brain Damage/Neurotoxicity –> excess glutamate activity is associated with neuronal death ** (from constant firing of neuron)
significant reduction of gray matter (cell bodies) in meth addicts
loss of dopamine receptors
damage to serotonergic terminals
2 above can get resolved in 2-6 months (when not using)

Q

AMPHETAMINE & COCAINE
Toxic Fx with Long-Term/High Dose Use

A

Death (psychosis-related or depression related
suicides, cocaine sudden death syndrome)
depression from not using the drug –> can persist over time –> can lead to suicide
some depression may be related to loss of serotonin terminals and dopaminergic receptors (change in brain chem from mood) –> or can be mood issues that preceeded drug use

CSDS: powerful CNS actions causing arrhythia/stroke/anoxia/ respiratory collapse

Cocaine Sudden Death Syndrome/Caine Reaction

– Two phases
1. Excitement, severe headaches, nausea, vomiting, severe convulsions –> GET them to hospital here to save their lives

Loss of consciousness, respiratory depression, cardiac failure
- Time of death ranges from 2 to 30 minutes

Lethal doses of cocaine and amphetamine ranges from 30mg to 500 mg (coke) to 1-2 grams (amphetamine) per hour

Q

AMPHETAMINE & COCAINE
Toxic Fx with Long-Term/High Dose Use

A

Malnutrition,
not eating well
appetite suppression (get tolerance to this but still suppressed)
sweet food liking

infections
- skin lesions
- picking at skin
- can become infected
- can be bugs or just habitual
- primary street nurse treatment is infections from skin lesions

Tooth decay (with meth-amphetamine) OR meth mouth
crave sweet foods
lack of saliva
teeth grinding from excessive NE (high SNS)
vasoconstriction (loss of blood supply to mouth)
poor dental habits
Abdominal Pain, Ulcers
from parachuting method!!

Q

AMPHETAMINE & COCAINE
Tolerance

A

Acute tolerance develops to “the orgasmic rush”
—-> rapid tolerance to the orgasm rush
“… after that first hit, you spend the rest of the night trying for that same rush. You keep hoping the next hit will do it, and you add more to the pipe and breathe in deeper, but it’s never the same and I mean never the same. Nothing compares to that first hit”

Q

AMPHETAMINE & COCAINE
Tolerance

A

Acute tolerance dissipates rapidly –> can go back to get the same powerful effects
Later developing tolerance to heart rate, blood
pressure, and appetite suppressant effects
mechanism responsible for tolerance is depletion of NTs, loss of receptors, desensitization (pharmacodynamic toelrance**_

we dotn see pharmacokinetic tolerance –> no increase in # of enzymes to get the drug metaboized quikcer

Q

AMPHETAMINE & COCAINE
Tolerance

A

No tolerance to increased motor activity
no toelrance to the blocking of sleep either
Reverse tolerance seen with cocaine re:
stereotypical, repetitive behavior and convulsant
effects
see increase in side effects –> like above and become at a greater risk of a potential lethal effect of severe convulsions

–> the increase sensitivity across mesolimbic system (responsible for reverse toelrance)

Q

AMPHETAMINE & COCAINE
Dependence

A

No life-threatening physical symptoms seen with termination of even long-term use
Termination of long-term use can lead to:
– Significant increases in sleeping and eating
– Rebound of REM sleep –> from REM being suppressed for so long –> can lead to a lot of restless sleep (lead to taking a downer) = cycle of drug use (stimulants –> sedative hypnotic)
this rebound of REM can lead to nightmares as well
– Possible permanent depression (mixed research) –> damage to sero term and dop (gets resolved) so it is somethign else that causes this
Strong psychological dependence = primary psych dependence (for its + effects) (not physiological dependance –> look this up)

Q

Dependence
“I deliberately took a pair of shears
and pried loose a tooth that was
filled with gold , I then extracted the
tooth, smashed it up, and the gold
went to the nearest pawnshop (the
blood streaming down my face and
drenching my clothes) where I sold it
for 80 cents

A

shows how strong the dependance is

Q

CS on meth cook

A

explosion suffered burns (40% of body)
- 6 months in hospital

a month after release was aprehended for meth use

Q

example

A

DEA has a scale to rate how likely someone will become dependant on drug
- based on reuse likelihood how many out of 100 will return to use)
- THC = 21
heroine = 80

cocaine= 78

meth = 98

Q

beautiful boy and tweak book

A

drug use

tweak book:
- smoked pot every day
- heroine at college
- meth at college
- chasing first high
- dropped out of college
- steal money from family
- steals a guitar, sisters diary