What is the active ingredient? Ethanol- Body wants to get rid of this. Does so by turning into: Metabolic products 1) Acetaldehyde – causes oxidative damage, flushing 2) Acetate – is converted to fat and stored- why alcohol has so many calories. Congeners (other substances in the beverage) Beer – hops, malt, asbestos, yeast, cobalt Wine – resveratrol (antioxidant) Hard liquor – contaminants, asbestosAbsorption Highly efficient In stomach and small intestine: Males metabolize ~25% of drink in digestive tract, so it never reaches the bloodstream! Female metabolizes ~5% of drink in digestive tract Women make lower levels of this enzyme Per drink, females absorb 20% more than do men! Food slows alcohol absorption-Food with mass to slow absorption and lower blood alc level. “Oil shots” & other gimmicks won’tGenes Affect Ethanol Disposal Rate ADH: turns Ethanol into Acetaldehyde Fast version more common in African Americans See a lower risk for fetal alcohol syndrome Slow version more common in Native Americans Prolongs ethanol action, increased addiction risk ALDH: turns Acetaldehyde into Acetate Slow version more common in Asians Acetaldehyde lingers, is unpleasant, lower alcoholism ratesGender Differences Women are more sensitive to alcohol because: Absorb more per drink, 5% (vs 20%) of alcohol is metabolized by digestive tract Weigh less, so it takes less alcohol to achieve the same BAC Alcohol stays in water & away from fat, women have higher fat %, thusalcohol is more concentrated. Thus women have a higher risk for cirrhosis & breast cancer. Also - fetal alcohol syndromeDefinition of 1 drink 15 g of EtOH 12 oz of beer 5 oz of wine 1 oz of hard liquor Legal limit for intoxication 0.08% 0.08% = 80 mg ethanol/100 ml blood Men: ~4 drinks in 1 hr Women: ~3 drinks in 1 hrLiver’s job is to remove alcohol In repeat drinkers, alcohol induces Cyp2E1, an enzyme that removes alcohol faster. Cyp2E1 is sloppy, makes lots of free-radicals These free radicals can damage liver Cyp2E1 metabolizes many other drugs Makes drug metabolism unpredictable Cyp2E1 turns procarcinogens into carcinogens Cancer risk increases at all alcohol intakes Per drink, woman’s liver sees more Alc than man’s Women are more likely to get liver cirrhosisMetabolic Consequences - 1Alcohol is Liquid Fat Ethanol has 7 kcal/g Ethanol calories are stored as fat, not carbo “Joe Six-Pack” and his “love handles” Ethanol inhibits muscle burning of fat Some acetate is turned into ketones This is what the “breathalyzer” detectsEthanol Metabolism is Costly “Screws up” cellular redox levels 1 drink = 0.33 moles etoh = 0.66 moles NADH get rid of NADH by making Lactate Lactate lowers blood pH This is major hangover symptom (no cure but time!)Cardiovascular Disease Risk 3-9 drinks/wk – lowers CVD risk by HDL more than this stops this benefit ³ 2-5 drink/wk – blood pressure 5-10 points heart rate and stroke risk 4-6 drinks per sitting ¯ fat burning by 33% “Holiday heart” – angina from energy-starved heart Polyphenols in grape juice & red wine (dark beer) ¯ blood clotting, so ¯ heart attack & stroke riskCancer & Cell Damage Ethanol is mutagenic Acetaldehyde & free radicals damage the DNA cancer risk at all intakes stomach, pancreas, liver, colorectal, breast, prostate Alcohol calories displace protective nutrients Especially antioxidants, increased free radical levels Beverage content is unregulated Nitrosamines, asbestos, dioxins, hydrocarbonsFAS BrainFetal Alcohol Syndrome Largest known cause of mental retardation US: 1/100 live births are affected by alcohol South Africa: 4.5/100 births are FAS No safe time in pregnancy or nursing 1 drink per day causes serious mental losses Fetus can’t metabolize etoh, so it lasts longer Targets “executive function” more than IQ Attention deficit, impulsive, can’t tell cause-and-effect, hard to refocus on tasks Kills neurons, blocks synapse formationWhat is Alcoholism? Alcohol is a “dirty” drug – no alcohol “receptor” it binds & activates brain receptors that control pleasure, anxiety, rewards targets opioid, cannabinoid, GABA, dopamine It rewires the brain to enforce reward, pleasure Craving is stronger than heroin, cocaine, nicotine 50:50 Genes : Environment Genetic variance in receptors makes alcohol’s effects last longer & harder → addiction Environmental cues stimulate the brain to anticipate its alcohol reward = cravingNew Drugs to Treat Alcoholism! Disulfuram – blocks etoh metabolism Naltrexone (oral) – reduces craving monthly injection also available Acamprosate – reduces craving Treatment varies with the individualAlcoholism – Definition (DSM-IV) Tolerance = need more to get same effect Withdrawal symptoms Unsuccessful attempt to cut down use Lots of time spent drinking/recovering Giving up important events to drink Drink more and longer than intended Continue use despite seeing the negative
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