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• 21st repealed 18th in 1933 – Happy Days are Here Again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 Budget90% 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 Acetaldehyde 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%)

Alcoholdehydrogenase

Aldehydedehydrogenase

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

EnkephalinInhibitoryNeuron

REWARD

Glutamate Excitatory InputEnkephalin or

DynorphinInhibitory Neuron

GABAInhibitory

Neuron

GABA Inhibitory Feedback

Dopamine Neuron GABANeuron

Ventral Tegmental Area(VTA)

Nucleus Accumbens(NAc)

Dopamine Receptors

GABA-A Receptors

PresynapticOpioid

Receptors(, ?)

OpioidReceptors

OpioidReceptors

Neuropharmacology: Summary

Experience Transmitter/Receptor

euphoria/pleasure Dopamine, Opioids

anxiolysis/ataxia GABA

sedation/amnesia GABA + NMDA

nausea 5HT3

neuroadaptation NMDA, 5HT

stress CRF

withdrawal 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