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Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

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= ethanol + carbon dioxide • grapes: wine, grains: beer, ale • distillation: get higher and higher concentrations • historical documents indicate the Egyptians, Greeks and Romans all enjoyed drinking alcohol • interestingly, consumption of wine has been blamed for the fall of the Roman emperor ◦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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