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Stimulants: Cocaine & Amphetamine. Chapter 6. Cocaine. Coke, Dust, Snow, Flake, Blow, Girl. History of Cocaine . 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.

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cocaine
Cocaine
  • Coke, Dust, Snow, Flake, Blow, Girl
history of cocaine
History of Cocaine
  • 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 cocaine4
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 cocaine5
History of Cocaine
  • Prescribed to morphine addicts & alcoholics
  • Available in patent medicines
  • Mariani's Coca Wine, mixture of red wine & cocaine
    • 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
    • mixture of coca leaf & kola nut (caffeine)
      • Coca Cola
history of cocaine6
History of Cocaine
  • 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 cocaine7
History of Cocaine
  • 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
Cocaine: Forms
  • Coca leaf – < 2% cocaine
  • Cocaine HCL – Powder
  • Freebase – Paste
  • Crack – Rock cocaine
slide9

Amphetamine: A Brief History

  • 1930s U.S. – benzedrine marketed for treatment of asthma, narcolepsy, depression, appetite suppression (bennies)
  • Also used to keep soldiers alert during combat in WWII
  • After war, prescribed for fatigue and appetite suppression
  • Social problems began in 1940s -1950s
  • Problems continued – particularly students, truck drivers, athletes, businessmen – 75 cents for 1000 tablets in 60s
slide10

1965 – FDA given authority to regulate manufacturing and distribution

  • But so easily made by amateur chemists, did not work
  • 1970s – still available, but from illegal manufacturers
  • 1970s – $5-$10 for 100 tablets – widely used and readily available
  • 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
Amphetamine: Forms
  • Psychostimulant that produces effects in CNS and PNS. It is more potent in CNS.
    • d-amphetamine
    • l-amphetamine
    • methamphetamine
  • Methamphetamine is more potent than d-amphetamine, which is more potent than l-amphetamine
  • d-amphetamine used as a prescription medication for ADHD, narcolepsy, and short-term treatment of obesity
ice or crank
“Ice” or “Crank”
  • Pure d-methylamphetamine HCL
    • 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
Routes of Administration
  • Oral
    • amphetamine good absorption
    • cocaine not well absorbed (In the Andes, mixed with ashes)
  • Intranasally - decent route for cocaine
    • 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

Duration of Action

  • 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
Actions of cocaine

Fowler et al. (2001)

action of meth
Action of Meth

Smoked vs. OralAmphetamine

Hours

cocaine and neurotransmission
Cocaine and Neurotransmission
  • Primary effect on DA & NE with some 5HT influence
    • Block reuptake
    • Inhibit MAO
amphetamine and neurotransmission
Amphetamine and Neurotransmission
  • Stimulates release of DA and NE
  • Blocks reuptake of DA and NE
biotransformation excretion
Biotransformation & Excretion
  • Drugs have different routes of biotransformation
    • cocaine broken down in bloodstream
    • amphetamine broken down in liver
  • Both are excreted by the kidneys
physiological psychological effects
Physiological & Psychological Effects
  • Cocaine & amphetamine indistinguishable to IV users
  • Oral or nasal route - local anesthetic properties would set them apart
effects on nervous system
Effects on Nervous System
  • Actions - wide variety of influences on PNS & CNS
    • Periphery - sympathomimetics
      • increase BP, HR, body temp, metabolic rate
    • Increase physical strength & endurance
central nervous system
Central Nervous System
  • Low or acute doses
    • 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
High Dose & CNS
  • Higher doses - (i.e., smoking)
    • 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
Side Effects and the Major Stimulants

Common side effects

  • 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 & Tolerance of Major Stimulants

Toxicity

  • Related to peripheral actions on CV system
    • Heart attack or cerebral hemorrhage (stroke)
    • Severe depression  lead to suicide??
    • May induce seizures with respiratory paralysis

Tolerance

  • Decrease NT stores & receptor down regulation
    • Induces depression found in chronic users
    • Appetite suppression develops rapid tolerance along with CV actions
amphetamine neurotoxicity
Amphetamine Neurotoxicity
  • Amphetamine and methamphetamineare potentially neurotoxic
    • 10 to 50 times normal street dose (in rats; primates may be more sensitive)
    • Depletes DA and degenerates DA terminals
dependence major stimulants
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
slide32
Khat

Cathinone

  • active agent in Khat (shrub)
  • chewed
  • synthetic version (meth-cathinone)
betel nut
Betel Nut
  • The fruit of the Areca catechu tree
  • Contains Arecoline
  • Mild stimulant that is a cholinergic agonist
  • Not a high abuse potential
ephedrine
Ephedrine
  • from Ma Huang (herbal tea)
  • isolated in 1920’s
  • bronchodilator for asthma
  • pseudoephedrine is an isomer of ephedrine
  • structure similar to epinephrine