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III' Cocaine

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unlike man-made amphetamine, cocaine comes from the coca plant (native to Peru, ... use for strength and stamina dates back 5000 yrs; cultivated since A.D. 1000 ... – PowerPoint PPT presentation

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Title: III' Cocaine


1
  • III. Cocaine
  • stimulant with somewhat similar acute action as
    methamphetamine
  • unlike man-made amphetamine, cocaine comes from
    the coca plant (native to Peru, Bolivia, and
    Columbia)
  • use for strength and stamina dates back 5000
    yrs cultivated since A.D. 1000
  • medical uses today short-acting local
    anesthetic (related to longer acting Novacaine
    and Lidocaine) cocaine used to deaden nose,
    mouth, or throat during quick procedures (putting
    tube in)

2
  • III. Cocaine
  • effects are similar to that of methamphetamine
    with 2 exceptions
  • Effects last only 20-30 minutes (half-life of 1
    hour)
  • Less neurotoxic following chronic use does not
    destroy DA and SE neurons full recovery is
    possible following high levels of abuse (idea is
    that the shorter duration of action is less
    damaging)

3
  • III. Cocaine
  • History
  • Spanish Conquistadors (16th century) arrived in
    South America and recruited Incas for labor via
    coca leaf payments
  • Took coca leaves back to Europe, but lost potency
    along the way and had no effect. Europeans
    accused Incans of imagining the effects.
  • Mid 1800s active alkaloids were identified by
    scientist, Albert Niemann named it cocaine

4
  • III. Cocaine
  • History
  • Soon after a French chemist, Mariani, put it in
    teas, lozenges, then wine sold in Europe
  • Vin Mariani wine with cocaine very popular
    president McKinley, Thomas Edison, Pope Leo XIII
  • The Pope gave Mariani a gold medal as a
    benefactor of humanity

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8
  • III. Cocaine
  • History
  • In 1884, Freud wrote Song of Praise singing
    praises of cocaine as lifter of spirits
    treatment for depression inducing exhiliration
    and lasting euphoria which in no way differs from
    the normal euphoria of the healthy person
  • 1885 advertised by Parke-Davis as a wonder drug
  • Marketed in medicine, soda, and wine prescribed
    for opium, morphine, and alcohol addiction
  • 1885-1905 Great Cocaine Explosion

9
  • III. Cocaine
  • History
  • 1885-1905 Great Cocaine Explosion
  • 1885 Pemberton introduced French Wine Cola in
    Georgia became CocaCola the intellectual
    beverage and temperance drink
  • This carbonated beverage is one reason why soda
    fountains became associated with drug stores
  • Then addictive potential became clear
  • Freud and others retracted original statements
  • 1906 Pure Food and Drug Law forced to remove
    cocaine from the coca leaves used in CocaCola

10
  • III. Cocaine
  • History
  • Then addictive potential became clear
  • Freud and others retracted original statements
  • 1906 Pure Food and Drug Law forced to remove
    cocaine from the coca leaves used in CocaCola
  • In 1906 there were as many cocaine users as in
    1976, with only half the population Palfai and
    Jankowicz 1991 (Cocaine was 10 cents a gram)
  • 1914 Harrison Act regulated sales
  • 1920s 30/ounce
  • By 1930s, replaced by cheaper amphetamines

11
  • III. Cocaine
  • By 1930s, replaced by cheaper amphetamines
  • Then in late 60s and 70s, law enforcement and
    education reduced amphetamine use and increased
    its costs cocaine rose again
  • 1970s cocaine viewed as an expensive and
    glamorous upscale treat
  • Demand reduced prices and increased purity in
    1980s much increased use
  • In 80s, yuppies were the main users
  • 1985 average user was a 30 year old white male
    earning 25000 (salary 45,000 73,000 for
    2005)

12
  • II. Cocaine
  • 1986 big change introduction of crack
  • Crack smokable cocaine
  • small white chunks of cocaine that have been
    freed from the base (cocaine hydrochloride) and
    crack when smoked
  • Sold in 1-2 rock quantities for 10-20 (compared
    to 100 minimums for cocaine by the gram)
  • 5-10x more powerful effect when smoked than when
    cocaine is snorted
  • Those who would snort but not inject, now would
    smoke
  • Those who could not afford cocaine before, now
    could

13
  • B. Cocaine Pharmacokinetics
  • Routes
  • Chewing coca leaves absorbed through mouth. In
    past, ashes (contain lime) added to leaves to
    improve absorption.
  • Now South American people still add lime.
  • Cocaine poorly absorbed by oral route to gut.
    Mostly snorted, smoked, or injected IV.
  • Snorting 25-100 mg dose effects in 3-4
    minutes, peak in 15 min, last maybe an hour. Not
    an intense rush no clear crash, but anxiety,
    fatigue, depression
  • IV use 10-25 mg dose onset in less than 2
    minutes peaks in 5-10 min. Euphoric rush, then
    intense crash fatigue, depression, craving.
  • Crack or freebase inhalation intense rush in 10
    sec sharp letdown in a few minutes

14
  • B. Cocaine Pharmacokinetics
  • Routes
  • abusers normally escalate from snorting to
    smoking to injecting
  • 2. Metabolism
  • Rapidly metabolized by enzymes in blood and liver
    so rapid delivery to brain important
  • Moderate dose only active for 15 minutes before
    breakdown
  • Half-life is 1 hour
  • Excreted in urine and metabolites found for 24-36
    hours

15
  • B. Cocaine Pharmacokinetics
  • Routes
  • 2. Metabolism
  • 3. Mechanisms of action
  • Potentiates release of NE, DA, SE
  • Blocks DA reuptake appears responsible for rush
    and reinforcement
  • In PNS, actions on norepinephrine receptors
    similar to amphetamines
  • As a local anesthetic, it blocks action
    potentials in neurons by interference with
    incoming Na

16
4. Acute effects similar to methamphetamine
(coke bugs a cocaine psychosis stroke) 5.
Chronic effects Tolerance and addiction On
withdrawal, fatigue, depression, craving
oversleeping overeating. After 2 weeks, feel
great about being clean, then anhedonia
(inability to feel pleasure or reward) sets
in. Snorting constricts blood vessels in nose,
then a rebound stuffiness. Constriction reduces
oxygen delivery and damages tissues, ultimately
causes tender, bleeding membranes. Lung damage
from smoking. All routes challenge cardiovascular
system - can damage the heart.
17
  • 4. Acute effects similar to methamphetamine
    (coke bugs a cocaine psychosis stroke)
  • 5. Chronic effects
  • Effects on the fetus initially quite overblown
    and more showing alcohol than cocaine effects
    over long term cocaine withdrawal effects in
    neonatal period
  • Increased miscarriage rate
  • Increased prematurity
  • Increased birth complications
  • Withdrawal symptoms in infants irritability
    poor suck sleep disturbances
  • Long term behavioral effects seen in animals
    still unclear in humans, but growing concern.

18
7. Drug combinations 60-90 of cocaine abusers
are also alcohol abusers Co-use prolongs euphoria
and shortens dysphoria on withdrawal. Combo
causes an active metabolite to be formed
cocaethylene. Cocaethylene is active blocks
dopamine reuptake transporter. Has 3-5x longer
half-life than cocaine. Cocaine and alcohol combo
increases cardiac effects and associated risk for
death. Death rate is 18x higher from combo than
for cocaine alone.
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