Test 2 PSYC 345A Flashcards
Notable Dates Amphetamines
Some Notable Dates in History
* Origin: chinese herb: Ma Huang
* 1887: active ingredient in herb isolated: ephedrine
* 1927: Alles: synthetic: amphetamine
* 1932: Benzedrine marketed (french, nasal inhalant, dl-amphetamine)
1885 - ephdrine purified from plant form
Benzedrin - Use of amphetamine
Ephedrine - similar to epinephrine , powerful SNS stimulant
- SUPER powerful stimulant,
Hitler used? still used in military - some though that amphetamine was used by military, abused … caused issues
- BUT used to treat athsma - better than epinephrine bc didnt need injection
- amphetamine could be made cheaper, good substitute for ephedrine
- 1970s, ephedrine used as weight loss aid, energy booster, dietary supplement
** ppls enjoyed how it enhanced concentration and cognitive performance, used by doctors and academics
Theraputic Uses of Amphetamines?
- Petit-mal epilepsy
- person loses consciousness for a small period of tiem
- narcolepsy
- sleeping condition
- ADHD
- worry that this is overprescribed to individuals …
** adderall is a prescription amphetamine - Weight problems
tolerance
Non-Therapeutic Uses of Amphetamines
- euphoriant
- Performance enhancer
- will not increase rxn time but can help with fatigue
- General stimulant
- study enhancement
meth: iniatially trade name Methedrine, treatment of narcolepsy, alchoholism, hay fever…
Methamphetamine - also called speed, ice, crank, glass
powdered meth - recrystalized to form chunks of concentrated d-methampheramine hydrochloried (HCl), for smoking. street name ice as this is for glass or crystal meth.
Cocaine - history
Cocaine
Some Notable Dates in History
* 13c: Used by the Incas
- increased endurance and strength … used daily? chewing leaves, made in a drink.
- 16c: Spanish bring coca leaves to Europe
- w colonization, spanish stole and exported
- 1850: Active ingredient in leaves chemically isolated
- 1859: German Chemist discovered anesthetic
properties - 1863: Corsican chemist creates “Vin Mariana”,
popular alcohol and coca combination - very popular beverage
- 1884: Freud samples cocaine, becomes advocate for its widespread use
- his weird psychosocial stuff was during coke use
- he got a friend hooked on it
- loved it, recommended it to all of his friends
- 1885: American pharmacist removes alcohol, adds soda water and syrup from African Kola Nut, and creates “Coca Cola”, touted as a “brain tonic”
- 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
- at this time became a scheduled drug
- with Harrison narcotic act ( also morphine and opium)
- 1920s to 1960s: use of cocaine gradually declined; decline associated with intro of amphetamines
1970s: resurgence of cocaine’s popularity/ use as
well as incidence rates of abuse
- Middle 1980s: Crack introduced
- v cheap addictive form of cocaine
- 1990s onward: high use/abuse of drug still a concern, but numbers using have declined from 70s and 80s; relaxed attitude re: use among users
khat and cathinones
khat plant contrains psychostimulant compounds - principal one called cathinone (structurally related to amphetamine)
synthetic cathinones are alternatives to meth and MDMA (bath salts)
Forms of Amphetamine:
- Two isomers: l and d amphetamine
- two isomers, different versions (mirror)
D amphetamine is more potent, this is the one being marketed.
d-Amphetamine is markedly more potent an inhibitor of catecholamine uptake by norepinephrine neurons in the brain than is l-amphetamine, whereas the two isomers are equally active in inhibiting catecholamine uptake by the dopamine neurons of the corpus striatum.
methampatamine is more potent
- Synthetic: Methedrine
- Structurally related compounds
–methyphenidate
– Phenmetrazine
– Methcathinone
KHAT - naturally derived substance - cathinone, from chewing leaves. - this synthetically is bath salts
methamphetamine has highest abuse potential of the amphetamine family
Forms of Cocaine
COCAINE
Forms
(1) Coca Paste
– Created by chemically treating and
mashing leaves of coca shrub leaves, liquid drained off
(leaves contain about .5-2% cocaine)
- coca paste is 60% pure cocaine
- not water soluble, cannot be injected or snorted.
(2) Cocaine Hydrochloride (Salt)
– Created by treating coca paste with
hydrochloric acid to produce a crystalline
powder
- some ammonia added to make milky substance then powder
- cannot be smoked - heating this will break down the cocaine
(3) Freebase or Crack
– Created by mixing cocaine HCL in an alkaline
solution (e.g., baking soda and water), then
boiling off water
- called freebase bc the base element of it is removed
- boiling off the water
- crack can be reheated without breaking down -
very pure, up to 90% cocaine
Amphetamine Administation and Absorption
(1) Orally
- psychoactive effets in 15-20 mins, peak at 3 hrs
(2) Intranasally
- snorting, CVand peak subjective effects @ 5-15 mins, beak blood @ 4hrs
3) Intravenous Injection
- with IV, d-amphetamine reaches peak blood levels in 20 mins. (or, 2- 10 mins?)
(4) Inhalation
- smoking meth, peak subjective effects in 5-15 mins
COCAINE
Administration & Absorption
(1) Orally
- chewing leaves, 25mins - 2hrs of chewing (this method is not usual)
(2) Intra-nasally
Problems with method:
Absorption limited due to vasoconstriction
Chronic users have stuffy or runny noses,
nasal lesions, frequent nose bleeds
- HCl, white powder.
- peak effets 10-15 mins
(3) Intravenously injected
- dissolved in water for this
2-5 mins
(4) Smoked
Crystalline “rocks” i.e., crack heated in pipes and vapours inhaled
- freebase, heated in pipes
- peak blood plasma levels 3-4 mins, 2-5 mins
AMPHETAMINE
Metabolization and Elimination
- Excretion affected by urine acidity
– Acidic: quicker
– Basic: slower
11-14 hrs for L amphetamine
9-11 hrs for D amphetamine (when taken as adderall)
9-13 hrs for methamphetamine (longer when snorted or smoked)
– Half-life ranges fom 7-14 hrs for L amphetamine vs. 16-34 hrs for D
- Excreted in urine, sweat, saliva - most thru urine ** a significant amount is eliminated unchanged - 30-40% is unchanges (30-50% unchanged for methamphetamine)
- for ppl using meth, more amphetamine metabolites
- Have behaviorally active metabolites:
detectable for 2-3 days
most are not psychoactive when excreted
highest concentration in kidneys and lungs, then the stomach, pancreas spleen and liver (lower in heart and brain)
after repeated dose or one large dose, meth is detectable in urine for up to 1 week, and amphetamine is detectable as a metabolite for even longer.
** meth metabolism is not altered by repeated drug use, suggests that escalations are result of pharmaco-dynamic (neuropharmacological) rather than pharmokinetic (enzymatic) alterations.
Cocaine
Metabolization and Elimination
average half life is 1 hr
30 mins - 5 hrs when snorted
when smoked, half life is similar to IV admin, 15 mins and longer
* Plasma half-life of 30 min, but more slowly
removed from brain
*** coke tends to concentrate in the brain more than other organs - peak brain concentrations @ 4-5 mins after use
- Urine can test positive for IV cocaine upto 12 hrs:
a metabolite can be detected in urine upto
48 hrs - a metabolite can be detected in urine up to 10 days with chronic IV use
*** the metabolites or cocaine can stay present for much longer than the cocaine itself in blood - Metabolically interacts with alcohol:
metabolite cocaethylene is pharmacologically
active - very little
cocaine has a shorter half life than amphetamine
cocaine is eliminated quicker, does not last as long
AMPHETAMINE & COCAINE
Mechanism of Action
- Block re-uptake of DA, NE, and 5-HT
- increased in synaptic spaces, increase activity in neural spaces
- Cocaine blocks Na+ ion channels
- this causes the numbing effect - slows down areas
- Amphetamine has 3 additional effects
– Increase amounts of NT released
– Cause spontaneous leakage of NT - without AP, there are still randomly released NT
– Induce release and block re-uptake of glutamate - Special target is the mesotelencephalic dopamine pathway projecting to limbic system and nucleus acumbens
** V powerful CNS stimulants
AMPHETAMINE & COCAINE
Physiological Effects
- Activate sympathetic nervous system
activates the fight or flight system - increased HR, BP, RR, body temp,
- pupils dialated, appetite supressed.
- decrease food consumption
this can make it lif threatening … cause heart attack or cardiac arrthynmia
-respiratory collapse
- cerebral strokes
- anoxia, brain not getting enough O2
- Physiological effects can be life threatening,
particularly with cocaine
at high doses, amphetamines can cuase abdominal cramps, nausea, vomiting, tremors, exasperate motor tics
could happen with one time use
subjective effects , make ppl feel good, improved mood.
feel decreased fatigue, a clear and organized mind
some ppl report anxiety
rushes of euphoria and pleasure
IV and smoking have the fastest feelngs / best rushes
IV cocaine has identical subjective effects to amphetamines
energy and clear throughts for 20-30 mins
cocaine induced rushes show rapid tolerance.
snorting coke gives freezing effect
amphetamines used in WW2 because they prevented need for sleep, increased endurance, prevent fatigue (maybe same as caffeine … BUT increased agression and fighting
AMPHETAMINE & COCAINE
Behavioral/Psychological Fx
- Euphoria - Intense with IV and Smoking
- Giddiness
- Enhanced Self-Esteem/Self-Confidence
- Feelings of Invincibility (pronounced with methamphetamine)
- Increased talkativeness
- Reduced sleep/Increased mental alertness -
subjective experience of “improved thinking”, “clarity of thought” - can cause insomnia
-can treat narcolepst - Greatly increased sexual response & desire
(pronounced with meth-amphetamine)
amphetamine caused increase rxn time and performance, induces tunnell vision
*** performance deficits:
- stimulants can impair performance on tasks requiring cognitive flexibility, new strategies
- higher doses, ppl become impatient, easily distracted and have impaired judgement
ephedrine is related to amphetamine and is often found in cold meds, decongestancts … athletes must be careful w these
AMPHETAMINE & COCAINE
Toxic Fx with Long-Term/High Dose Use
- Tremors
- Restlessness
- picking, pulling, shifting, rocking
- Agitation/Hypervigilance/Suspiciousness
- this has to do with sympathetic NS response stress
- Paranoid Persecutory Fears
- Stereotyped, compulsive repetitive behaviors
- Vivid Visual, auditory, and tactile hallucinations
- Rawson et al (2005) re: prevalence and length of psychotic state
some ppl, with extreme lack of sleep, there is psychosis due to this rather than the drug itself
- Marked, pervasive anxiety
- Depression - may not be with initial use of drug, but between drug uses (not able to get out of bed until they do some coke)
- Impaired Thinking/Reasoning
- Memory disturbances
- Motor problems (slowed mov’t)
- Brain Damage/Neurotoxicity
- excess glutamate activity has been associated with neuronal death
- significant reduction in gray matter for meth addicts _mris show
- loss of dopamine receptors and damage to serotonergic terminals (bounces back in 3-6 month)
- Death (psychosis-related or depression related
suicides, cocaine sudden death syndrome) - some depression is due to the change in brain chemistry (serotonergic…OR could also be due to mood issues prior to drug use) - killed in interactions w police
- Cocaine Sudden Death Syndrome/Caine Reaction
– Two phases - Excitement, severe headaches, nausea, vomiting, severe
convulsions - 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 to 1-2 grams per hour - Malnutrition, infections
- street nurses, living on street, skin infections …
- Tooth decay (with meth-amphetamine)
- Abdominal Pain, Ulcers
Story about Matt - Formication Hallucinations
Formication hallucinations - coke bugs, feeling that there are bugs/snakes in you or on you
picking, taking knives to themselves … ppl will harm themelves to get the bugs out
- feeling that little bugs are coming up thru the shower drain
- seeing these bugs burrow into skin… found he was a coke dealer (arrested)
Matt shows up at this guys house ones
- finds a man, Matt tries to offer him cocaine
- ppl using tweezers to peel skin away
matt has worries about skin bugs, or sti?
psychotic states can last up to 6 months
Memory Problems - cocaine or prescription stim
Memory Problems?
* Reske et al (2010)
– 154, 18 -25 years, cocaine or prescription stimulants
– Auditory memory tested with CVLT (california verbal learning test)
– Statistically greater # of intrusions (6 vs 3) fewer
words in learning trials (52 vs 57) and delayed recall
(11.45 vs 12.67)
* they would more likely remember a word that wasnt there, recall fewer words
– 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)
- Chang et al (2005)
– Methamphetamine users abstinent for 9 months
showed normal performance of tests of attention,
executive functioning, and memory functioning
Tolerance to AMPHETAMINE & COCAINE
after 12 hrs, no euphoria at all
* Acute tolerance develops to “the orgasmic 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”
body cannot replenish dopamine quickly enough
desensitization, downregulation, pharmacodynamic
** we do NOT see pharmakokenitic tolerance - we do not see a greater amount of enzymes **
- no tolerance to increased motor activity
- we see reversed tolerance occuring with steryotypical behaviours
- see repetitive, tweaky behaviour
- greater risk for potentially lethal convulsions
- Acute tolerance dissipates rapidly
- Later developing tolerance to heart rate, blood
pressure, and appetite suppressant effects - No tolerance to increased motor activity
- Reverse tolerance seen with cocaine re:
stereotypical, repetitive behavior and convulsant
effects
no tolerance to the sleep stuff
AMPHETAMINE & COCAINE
Dependence
- No life-threatening physical symptoms seen with termination
of even long-term use
Cessation of amphetamine or cocaine is not associated with severe or medically serious withdrawal symptoms
Come down effects are associated with depression (drop in dopamine)
Withdrawal occurs 30 mins after using cocaine, but several hours with the use of amphetamine
Sleeping during withdrawals are normally accompanied by night terrors and frequent awakenings as monoamines begin to equalize back to normal values
Increased appetite, disturbed sleep and depression can last for weeks to months after the initial withdrawal phase
- Termination of long-term or stopping a “binge” use can lead to:
– Significant increases in sleeping and eating - could sleep for days
– Rebound of REM sleep
nightmares
– Possible permanent depression
- Strong psychological dependence
- HUGE craving to use the drugs for its psychological effects
quote on 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”
case study of meth cook, in explosion and suffered significant burns … person used meth shortly after
movie tweak, beautiful boy
story of person who started w weed, moves to alcohol, starts stealng from parents and stealing stuff in general .
