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ETHYL ALCOHOL (ETOH) Alcohol An Arabic Word Meaning “Something Subtle” Alcohol • Made from the fermentation of carbohydrates • Fermented in every culture on earth at some point in time • Animals (monkeys and birds) consume fermented fruit Alcohol History • Probably the world’s oldest anodyne • Beers & wines since about 6400 BC – Berries, apples and honey • • • • Early use for spiritual ceremonies First brewery in Egypt 3700 BC Only natural fermentation until 800-900 BC Process of distillation in Arabia Alcohol History • 1500s - high alcohol consumption problems (reign of Henry VIII) • 1608 - first laws against drunkenness passed in England • Gin discovered in 1650 by Dutch physician – From corn mash poured over juniper berries • 1700s - gin epidemic - led to decline in British population – tried to regulate use - led to riots • Coffee & Tea & Methodist movement led to decline in alcohol use Alcohol History In the US • Was condoned to point of drunkenness • Used as anesthetic in Civil War • 18th Amendment (1920) – Illegal to produce alcoholic beverages – Increased number of drinking establishments – Increased strength of organized crime • 21st repealed 18th in 1933 – Happy Days are Here Again Alcohol: Forms • Naturally Fermented (max 14%) – Beer – Wine – Mead • Distilled (up to 95%) – Whiskey (40%) – Gin (40%) – Vodka (40%) – Tequila (40%) – Everclear (95%) • Proof – British Army used “proof” as a measure of concentration • Poor alcohol on gunpowder and tried to light it Alcohol Prevalence in US • 90% Ever drank • 65% Current drinkers (gender and age differences). 70% men and 60% women • >40% Temporary problems • 10-20% Abuse • 5-15% Dependence (Lifetime) • 5% point prevalence of dependence YEARLY COSTS IN US $300 Billion Overall $71 Billion Direct Costs 22,000 Deaths + 2,000,000 Injuries 4,600,000 Damaged Vehicles 15% - 25% Healthcare Budget 90% of Liver Disease 72% of Pancreatitis 41% of Seizure Disorders 13% of Breast Cancers Copyright Alcohol Medical Scholars Program 8 Closer to Home – Consequences in College Students • Death: 1,700 college students between the ages of 18 and 24 die each year from alcohol-related unintentional injuries, including motor vehicle crashes . • Injury: 599,000 students between the ages of 18 and 24 are unintentionally injured under the influence of alcohol. • Assault: More than 696,000 students between the ages of 18 and 24 are assaulted by another student who has been drinking. • Sexual Abuse: More than 97,000 students between the ages of 18 and 24 are victims of alcohol-related sexual assault or date rape. • Unsafe Sex: 400,000 students between the ages of 18 and 24 had unprotected sex and more than 100,000 students between the ages of 18 and 24 report having been too intoxicated to know if they consented to having sex. Closer to Home – Consequences in College Students • Academic Problems: About 25 percent of college students report academic consequences of their drinking including missing class, falling behind, doing poorly on exams or papers, and receiving lower grades overall. • Health Problems/Suicide Attempts: More than 150,000 students develop an alcohol-related health problem and between 1.2 and 1.5 percent of students indicate that they tried to commit suicide within the past year due to drinking or drug use. • Drunk Driving: 2.1 million students between the ages of 18 and 24 drove under the influence of alcohol last year. Vandalism: About 11 percent of college student drinkers report that they have damaged property while under the influence of alcohol . Route/Absorption • Oral is by far the route of choice • Rapidly absorbed, primarily from small intestine – 20% stomach, 80% small intestine • Peak blood alcohol concentration (BAC) depends on: – – – – – – Amount and alcohol concentration of beverage Rate of drinking Food consumption and composition Gastric emptying and gastric metabolism Hepatic (liver) first pass Gender Metabolism • Metabolism – 90-98% metabolized in liver Alcohol Alcohol dehydrogenase Acetaldehyde Aldehyde dehydrogenase Acetate • A constant 0.015% per hr metabolized • Accumulation of acetaldehyde associated with headache, gastritis, nausea, dizziness (hangover) • Those of certain Asian descent lack a gene that codes for ADH (50%) Pharmacokinetics: Gender Differences • Gender Differences – in absorption • Differences in gastric ADH activity – in volume of distribution • Differences in body composition and total body water (TBW) – in metabolism • Differences in liver volume, ADH activity? • Effect of menstrual cycle on alcohol pharmacokinetics • Effect of sex hormones (OC) on alcohol PK Pharmacodynamics: CNS Effects • Alcohol is a CNS depressant • Apparent stimulatory effects result from depression of inhibitory control mechanisms in the brain • Characteristic response: euphoria, impaired thought processes, decreased mechanical efficiency, sedation Concentration-Effect Relationship BAC [%] Effects 0.02-0.03 Mood elevation. Slight muscle relaxation. 0.05-0.06 Relaxation and warmth. Increased reaction time. Decreased fine muscle coordination. 0.08-0.09 Impaired balance, speech, vision, hearing, muscle coordination. Euphoria. 0.14-0.15 Gross impairment of physical and mental control. 0.20-0.30 Severely intoxicated. Very little control of mind or body. 0.40-0.50 Unconscious. Deep coma. Death from respiratory depression Alcohol as a Reinforcer • Reinforcer: a substance whose pharmacological effects drive the user to continue to use it • Positive reinforcing effects: – Gain pleasure – Altered consciousness – Conform to behavior of peers • Negative reinforcing effects: – Relief of stress and negative emotions – Relief of withdrawal symptoms Alcohol as a Reinforcer: Neural Systems Activation of mesocorticolimbic system Alcohol as a Reinforcer: Evidence • Animal models of alcohol preference – Selectively bred animal lines show innate differences in limbic structures and neurotransmitter function • Animal models of self-administration – Animals trained to chronically self-administer alcohol show differences in neurotransmitter levels in the mesolimbic system – Animals will bar-press repeatedly for intra-cranial injections of alcohol into the VTA (ventral tegmental area) Reinforcement: Neurochemical systems Enkephalin or Dynorphin Inhibitory Neuron Glutamate Excitatory Input k Opioid Receptors Enkephalin Inhibitory Neuron Dopamine Receptors Dopamine Neuron m Opioid Receptors REWARD GABA-A Receptors GABA Inhibitory Feedback GABA Inhibitory Neuron GABA Neuron Presynaptic Opioid Receptors (m, d?) Ventral Tegmental Area (VTA) Nucleus Accumbens (NAc) Neuropharmacology: Summary Experience euphoria/pleasure anxiolysis/ataxia sedation/amnesia nausea neuroadaptation stress withdrawal Transmitter/Receptor Dopamine, Opioids GABA GABA + NMDA 5HT3 NMDA, 5HT CRF GABA, NMDA ( Ca, Mg) Negative Health Effects • Exacerbates ulcers • Can cause cancer (head, neck, oral, GI) • Liver disease – Fatty Liver – Fibrosis – Cirrhosis • CVD • Accidents & Violence Health Benefits • Protective against CVD – Increases HDL • Stress inoculation???? • Bone mineral density • Men 3 or less/day • Women 2 or less/day • Never more than 5 Tolerance: Definitions • Acute Tolerance: during the time-course of a single exposure to drug • Chronic Tolerance: over repeated use of drug • Cross Tolerance: Tolerance to one drug leads to tolerance to other drugs in a class – – – – Benzos Barbs General Anesthesia GHB Tolerance: Significance • Why is tolerance to alcohol important? – One of the determinants of increased alcohol consumption • maintains or aggravates alcohol dependence • increases risk of organic complications of alcoholism – Cross-tolerance to other depressant drugs – Genetic determinants exist – Low response predicts alcoholism Withdrawal • Tremors, sweating, anxiety, perspiration, headache, nausea, vomiting • As withdrawal continues, one can have grand mal seizures • DTs – Severe agitation, hallucinations, high fever, delirium • The most likely of all drug withdrawals to be fatal Dependence • DSM-IV Disorder • It is the model for all other substance dependence • Public Health Model – Agent Factors – Host Factors – Environment Agent Factors • CNS Depressant • Potentiates GABA, Dopamine, Endorphins. Inhibits glutamate • Produces stimulation, sedation, motor incoordination • Withdrawal potential • Toxic to body/brain tissues • Direct Effects – GI/Liver – Heart – Brain Host Factors • • • • Genetic Susceptibility Males > Females Age – College years Personality/Psychopathology Environmental Factors • • • • • • Models Access Policy Peers Media Social Norms Ultimately • There is – – – – – Use – Most people who drink Misuse – College and/or drinking to cope Abuse – Continued misuse Dependence – Small percent - BIG TROUBLE Be Careful If • Family history • Depression Anxiety ADHD • If you can hold your liquor