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Puritans used alcohol, but put progressive legal and social controls on abuse ... All women, alcoholic or not, have 60% less stomach alcohol dehydrogenase than men ... – PowerPoint PPT presentation

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Title: Alcohol

  • Ethyl alcohol or ethanol
  • Only caffeine is used more widely
  • Recreational, not therapeutic

Vocabulary of alcohol
  • A series of organic compounds w/ OH
  • Isopropyl alcohol, methanol, ethanol
  • Fermentation
  • Sugar water yeast --- ethanol CO2
  • Distillation Perhaps discovered in Arabia,
    first described in detail by the Dominican
    scholar Albertus Magnus

Albertus Magnus (1193-1280)
German saint, teacher of Thomas Aquinas
More vocabulary of alcohol
  • Fermented beverages Beer, wine, cider, and mead
  • Distilled beverages Brandy, rum,
    usquebaugh/whiskey/bourbon, schnapps Aqua vitae
  • Fortified beverages Sherry, port, madeira,
    muscatel, vermouth, Cisco
  • Mixed beverages Gin, vodka, liqueurs

Still more vocabulary
  • Measuring alcohol content
  • The moonshiners test
  • The proof system
  • Proof spirits
  • Overproof liquor
  • Proof numbers
  • The US system Percentage by volume
  • The British system Percentage by weight

History of alcohol
  • Multiple people groups, except native North
    Americans and Pacific Islanders
  • Ancient Egypt, Babylonia, and Israel
  • Classical Greece
  • Rome and the Christians
  • Britain

Gin Lane, a woodcut by English painter and engr
aver William Hogarth (1697-1764). Hogarth sati
rized contemporary English life. Note the dep
lorable Conditions, gender alienation, and the
implied connection to gin.

The picture is different on Beer Street, as Hoga
rth depicts a scene of prosperity for the masse
s, a flourishing of the arts and learning in the
public square, affection between the genders,
and ruination for the pawnbroker.
The gin epidemic in Britain
Significant Events By Year Gallons Sold
America and alcohol
  • British immigrants brought heavy drinking habits
    to the colonies
  • Spanish settlers in California brought
    grapevines Cortez, Jesuits, Franciscans
  • Puritans landed at Plymouth Rock perhaps
    because they ran out of beer Crews supply
  • Brewing began almost immediately in taverns
    commercially at New Amsterdam (1633) and
    (legally) at Charlestown, MA (1637)

More American history
  • Puritans used alcohol, but put progressive legal
    and social controls on abuse
  • Colonial Harvard had its own brewery
    Commencements became uproars.
  • American Revolution brought social changes and
    problem drinking
  • Business first
  • The Triangular Trade
  • Fur trading with Native Americans

  • The Whiskey Rebellion
  • Western Expansion
  • Industrial Revolution
  • The temperance movement and respectability
  • The Webb-Kenyon Law (1913)
  • The Eighteenth Amendment (1920) and the Volstead
    Act (1919) Effective?
  • The Twenty-First Amendment (1933)

Pharmacokinetics of alcohol
  • Administration and absorption
  • Oral
  • Both water and fat soluble
  • 80 absorption from upper intestine
  • Thus, rate limiting factor is stomach emptying
  • Total absorption is unaffected by food
  • 90 access to all body compartments

Pharmacokinetics of alcohol 2
  • Metabolism and excretion
  • 95 of alcohol is metabolized by alcohol
    dehydrogenase enzyme and CYP450 enzymes
  • 85 of that metabolism is in the liver
  • up to 15 is done in the stomach
  • All women, alcoholic or not, have 60 less
    stomach alcohol dehydrogenase than men
  • Women appear to be even more vulnerable than men
    to intoxication and chronic effects

Pharmacokinetics of alcohol 3
  • More on metabolism
  • Two-step metabolism
  • Alcohol is converted by alcohol dehydrogenase to
    acetaldehyde (co-factor NAD to NADH)
  • Acetaldehyde is converted by aldehyde
    dehydrogenase (ALDH)to acetic acid, then to CO2
    and water in the Krebs cycle (ATP to AMP)
  • Most Europeans and Africans are homozygous for
    the active form of ALDH 10 of Koreans,
    Japanese, and Chinese are homozygous for the
    inactive form, and another 40 are heterozygous.
  • Zero order metabolism
  • Disulfiram/Antabuse

Pharmacodynamics of alcohol
  • Perhaps not unitary
  • High doses may disrupt membrane functioning
  • Low doses act on synapses, particularly
  • Inhibits NMDA receptors for glutamate and
    decreases glutamate release
  • Intoxication produces memory loss glutamate
    transmission is reduced at BAC of 0.03
  • Abstinence syndrome hyperexcitability from
    up-regulation of NMDA receptors
  • Withdrawal seizures due to up-regulated NMDA
  • Increased glutamate release during withdrawal is
    excitotoxic on up-regulated NMDA receptors brain

GABA effects
  • GABAA-2L subunit EtOH is an agonist
  • protein kinase phosphorylation
  • intracellular mRNA changes
  • GABA antagonists picrotoxin (Cl- channel blocker)
    and bicuculline (GABA competitor) are partial
    antagonists for EtOH
  • GABA agonists increase ethanols effects
  • GABA-consequent effects on Ach, NMDA, and DA

Other neurotransmitter effects
  • Inhibits release of Ach Cognitive impairment
  • Agonizes DA from VTA to nucleus accumbens, the
    reward center.
  • Addiction is thus a combination of DA positive
    reinforcement and GABA negative reinforcement.
  • Opioid effects

Lipid solubility of alcohols