Transcript Cocaine

Stimulants:
Cocaine & Amphetamine
Chapter 6
Cocaine
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Coke, Dust, Snow,
Flake, Blow, Girl
History of Cocaine
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Dates back 5000
years in Peru &
Bolivia
Coca leaves (2%
cocaine) chewed by
Incas
Mid to late 1850s,
active ingredient of
coca plant extracted
by Alfred Nieman
History of Cocaine
Popularized in 1880s
 Sherlock Holmes (IV
cocaine user)
 Gave him energy &
increased powers of
deductive reasoning
 Sigmund Freud
 advocated cocaine for
depression,
indigestion, asthma,
various neuroses, drug
addiction & local
anesthetic
History of Cocaine
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Prescribed to morphine addicts & alcoholics
Available in patent medicines
Mariani's Coca Wine, mixture of red wine &
cocaine
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made by Angelo Mariani
received gold medal from Pope (cited as benefactor of
humanity)
In U.S. John Pemberton & French Wine Cola Ideal Nerve & Tonic
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mixture of coca leaf & kola nut (caffeine)
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Coca Cola
History of Cocaine
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In 1906, as many cocaine
users in US as in ’76 with
only half the population
1906 Food and Drug Act
 Eliminated cocaine
from patent medicines
& soft drinks
 1903 Coca Cola
decocainized Coke
Harrison Narcotic Act of
1914
 Further limited cocaine
use & drove up prices
History of Cocaine
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Use also declined in
popularity because of
public sentiment against
drug
By 1930s, cocaine pretty
much disappeared, but
was replaced by
amphetamine.
By the late 1970s, coke
began a comeback and
use levels exploded
around 1985….crack
Cocaine: Forms
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Coca leaf – < 2% cocaine
Cocaine HCL – Powder
Freebase – Paste
Crack – Rock cocaine
Amphetamine: A Brief History
•
1930s U.S. – benzedrine marketed for treatment of
asthma, narcolepsy, depression, appetite suppression
(bennies)
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Also used to keep soldiers alert during combat in WWII
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After war, prescribed for fatigue and appetite suppression
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Social problems began in 1940s -1950s
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Problems continued – particularly students, truck drivers,
athletes, businessmen – 75 cents for 1000 tablets in 60s
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1965 – FDA given authority to regulate manufacturing and
distribution
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But so easily made by amateur chemists, did not work
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1970s – still available, but from illegal manufacturers
•
1970s – $5-$10 for 100 tablets – widely used and readily
available
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Use declined in 1970s and 1980s but now back up – and
primarily methamphetamine that is smoked, snorted,
injected or taken orally – ice, crank, crystal, speed, meth,
chalk
Amphetamine: Forms
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Psychostimulant that produces
effects in CNS and PNS.
It is
more potent in CNS.
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d-amphetamine
l-amphetamine
methamphetamine
Methamphetamine is more
potent than d-amphetamine,
which is more potent than lamphetamine
d-amphetamine used as a
prescription medication for
ADHD, narcolepsy, and shortterm treatment of obesity
“Ice” or “Crank”
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Pure dmethylamphetamine HCL
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can be smoked because of
purity
Started in the West moved east
over time
Labs all over Duplin Co.
Very dangerous to synthesize
Routes of Administration
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Oral
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Intranasally - decent route for cocaine
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amphetamine good absorption
cocaine not well absorbed (In the Andes,
mixed with ashes)
However, causes blood vessels to constrict,
which limits absorption.
intranasal works for amphetamine, but painful
Intravenous - both very effective via this
route
Duration of Action
Duration of Action
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Cocaine - oral onset in 2-3 min with peak in 15-20
min
 duration less than 1 hr
 IV or smoked - onset in 10 sec & peak in 5-10
min
Amphetamine - oral effects after 30 min & peak in
2-3 hrs
 duration 10-12 hrs
 IV or smoked - onset 5 min & lasts up to 7 hrs
Actions of cocaine
Fowler et al. (2001)
Action of Meth
Smoked vs. Oral
Amphetamine
Hours
Cocaine and Neurotransmission
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Primary effect on DA
& NE with some 5HT
influence
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Block reuptake
Inhibit MAO
Amphetamine and
Neurotransmission
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Stimulates release
of DA and NE
Blocks reuptake of
DA and NE
Biotransformation & Excretion
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Drugs have different routes of
biotransformation
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cocaine broken down in bloodstream
amphetamine broken down in liver
Both are excreted by the kidneys
Physiological & Psychological
Effects
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Cocaine & amphetamine indistinguishable
to IV users
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Oral or nasal route - local anesthetic
properties would set them apart
Effects on Nervous System
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Actions - wide variety
of influences on PNS
& CNS
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Periphery sympathomimetics
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increase BP, HR, body
temp, metabolic rate
Increase physical
strength & endurance
Central Nervous System
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Low or acute doses
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increased arousal
level & alertness
improve performance
on simple tasks
produce mild euphoria
increase of sex drive
early on, but reverses
with prolong use
High Dose & CNS
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Higher doses - (i.e.,
smoking)
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intense feeling of euphoria
described as “whole body
orgasm”
hyperactivity
repetitive behaviors - hand
clasping, nose rubbing
manic condition can occur
drug wears off  severe
depression or crash
Side Effects and the Major
Stimulants
Common side effects
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Stimulant (e.g., cocaine) psychosis
Euphoria, turns to paranoid delusion
 With tactile & auditory hallucinations
 Disrupted associative thinking
 Commonly aggressiveness also found
Formication or parasitosis (bugs crawling
all over or under skin)
 occurs most commonly in repeat users
Toxicity & Tolerance of Major
Stimulants
Toxicity
 Related to peripheral actions on CV system
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Heart attack or cerebral hemorrhage (stroke)
Severe depression  lead to suicide??
May induce seizures with respiratory paralysis
Tolerance
 Decrease NT stores & receptor down regulation
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Induces depression found in chronic users
Appetite suppression develops rapid tolerance along
with CV actions
Amphetamine Neurotoxicity
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Amphetamine and
methamphetamine
are potentially
neurotoxic
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10 to 50 times normal
street dose (in rats;
primates may be more
sensitive)
Depletes DA and
degenerates DA terminals
Dependence & Major Stimulants
Dependence
 Moderate for occasional
use via oral or intranasal
route (e.g., Indians in
Andes develop no
dependence)
 IV or smoking, severe
dependence potential want to have more to
experience pleasure and
ward off depression
Other Stimulants
Khat
Cathinone
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active agent in Khat (shrub)
chewed
synthetic version (meth-cathinone)
O
C
CH
CH 3
Cathinone
NH 2
Betel Nut
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The fruit of the Areca
catechu tree
Contains Arecoline
Mild stimulant that is
a cholinergic agonist
Not a high abuse
potential
Ephedrine
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from Ma Huang (herbal tea)
isolated in 1920’s
bronchodilator for asthma
pseudoephedrine is an isomer of ephedrine
structure similar to epinephrine
OH
CH
CH
CH 3
Ephedrine
NH
CH 3