Alcohol

1
Alcohol

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

2
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

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Albertus Magnus (1193-1280)
German saint, teacher of Thomas Aquinas
4
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

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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

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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

7
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.


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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.
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The gin epidemic in Britain
Significant Events By Year Gallons Sold
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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)

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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

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

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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

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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
  

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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

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Pharmacodynamics of alcohol

• Perhaps not unitary
• High doses may disrupt membrane functioning
  (fluidization)
  
• Low doses act on synapses, particularly
  glutamate.
  
• 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
  receptors
  
• Increased glutamate release during withdrawal is
  excitotoxic on up-regulated NMDA receptors brain
  damage
  

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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

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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

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Lipid solubility of alcohols