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PHAR 100 (175)
Lecture

9Alcohol.pdf

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Department
Pharmacology and Toxicology
Course
PHAR 100
Professor
Hisham Elbatarny
Semester
Fall

Description
Alcohol Outline Introduction History Pharmacokinetics Mechanism ofAction Pharmacological and Psychological effects Tolerance and dependence Teratogenic effects (FASD) Reference: Chapter 13 Introduction • chemical term that covers a class of substances • only few are ever consumed • isopropyl alcohol (rubbing alcohol) • methyl alcohol (methanol or wood alcohol) • ethanol (alcohol) ◦ consumable History • when water sanitation techniques weren't that good: watered down alcohol • fulfill liquid requirement in diet • fermentation: sugar + water + yeast = ethanol + carbon dioxide • grapes: wine, grains: beer, ale • distillation: get higher and higher concentrations • historical documents indicate the Egyptians, Greeks and Romans all enjoyed drinking alcohol • interestingly, consumption of wine has been blamed for the fall of the Roman emperor ◦ when making alcohol added lead: thought to enhance colour and taste History • 1742: consumption reached 19 million gallons • Parliament banned distillation and regulated manufacturing • 1782: consumption dropped to 4 million gallons • 1830-1860: some decline due to the temperance movement • 1917: prohibition • 1933: end of prohibition Pharmacokinetics • oral administration • rapid absorption by passive diffusion: alcohol is a very small molecule • alcohol distributes evenly throughout body and readily distributes across the blood-brain barrier ◦ soluble in both water and fat • in pregnant women ethanol is readily transferred across the placenta and distributes throughout the body of the fetus ◦ don't have same ability to metabolize alcohol Alcohol Metabolism Zero order rxn • alcohol dehydrogenase is rate-limiting • acetaldehyde accumulation → headache, gastritis, nausea, dizziness (hangover) • acetate is broken down into carbon dioxide and water • aldehyde dehydrogenase inhibition (*disulfiram = antabuse) ◦ inhibits aldehyde dehydrogenase ◦ higher accumulation of acetaldehyde → hangover ◦ negative reinforcement • average adult metabolizes 10-14 mL of 100% alcohol/hour, independent of blood alcohol level Pharmacokinetics • 95% of ethanol in the body is eliminated by biotransformation (metabolism) • primarily in the liver (15% gastric) • 5% is excreted unchanged in breath, urine and sweat • women have 50% less gastric metabolism due lower levels of gastric alcohol dehydrogenase • men have a greater muscle-to-fat ratio therefore alcohol concentration is more diluted b/c larger vascular compartment • women concentrate alcohol in plasma more than men (due to higher fat content) • various other factors influence metabolism: ◦ alcohol flush (ALDH2 deficiency) What effects are associated with alcohol consumption? • perhaps you even know someone who has had too much to drink…… • what happened? • pharmacological Effects →Disinhibition →Sedation →Hypnosis →GeneralAnesthesia →Coma →graded, dose-dependent progression Pharmacological Effects Low dose: (1-2 drinks) High dose: (> 3 drinks) Disinhibition Sedation Relaxed Hypnosis Talkative General anesthesia Gregarious Coma Self-confident Death (respiratory depression) Self-pitying ↓Memory/cognition ↓ability to concentrate Risk-taking Blood Ethanol Concentration Vs Pharmacological Effect [EtOH] mg/100 mL Effect 50 (2 drinks) Euphoria & minor motor problems 60 Nystagmus, more errors on math tests, increased motor incoordination 80 Impaired driving ability, EEG changes 100 - 150 Gross motor incoordination 200 - 300 Amnesia wrt drinking experience 300 - 350 Coma 355 - 600 May cause or contribute to death Mechanism of Action • CNS depressant ◦ no EtOH receptor • disrupts glutaminergic neurotransmission (major excitatory neurotransmitter) ◦ decreases NMDA-R responsiveness to glutamate ◦ upregulation of NMDA-R in alcoholics • activates GABA-mediated neuronal transmission leading to inhibition (major inhib) ◦ GABAinhibition can produce an indirect increase in dopaminergic activity ◦ positive reinforcing effects Long-Term Pharmacological Effects • neurological & mental disorders associated with ethanol ◦ cerebral atrophy: parts of brain dying ◦ memory loss ◦ alcoholic psychosis • neuropsychiatric syndromes
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