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Alcohol

Alcohol. Ethyl alcohol or ethanol Only caffeine is used more widely Recreational, not therapeutic. Vocabulary of alcohol. < Arabic al kuhl , powder of antimony A series of organic compounds w/ OH Isopropyl alcohol, methanol, ethanol Fermentation: Sugar + water + yeast ---> ethanol +CO 2

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Alcohol

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  1. Alcohol Ethyl alcohol or ethanol Only caffeine is used more widely Recreational, not therapeutic

  2. Vocabulary of alcohol • < Arabic al kuhl, powder of antimony • 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

  3. 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

  5. Still more vocabulary • Measuring alcohol content: • The moonshiner’s test • The proof system • Proof spirits • Overproof liquor • Proof numbers • The US system: Percentage by volume • The British system: Percentage by weight

  6. 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 engraver William Hogarth (1697-1764). Hogarth satirized contemporary English life. Note the deplorable Conditions, gender alienation, and the implied connection to gin.

  8. The picture is different on Beer Street, as Hogarth depicts a scene of prosperity for the masses, a flourishing of the arts and learning in the public square, affection between the genders, and ruination for the pawnbroker.

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

  10. 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: Crew’s supply • Brewing began almost immediately in taverns; commercially at New Amsterdam (1633) and (legally) at Charlestown, MA (1637)

  11. 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

  12. 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)

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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 ethanol’s effects • GABA-consequent effects on Ach, NMDA, and DA

  18. 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

  19. Lipid solubility of alcohols

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