Alcohol: The Biology, Chemistry, Alcohol: The Biology, Chemistry, & Pharmacology& Pharmacology

Rochelle D. Schwartz-Bloom, PhDRochelle D. Schwartz-Bloom, PhDJ. Suzanne Sikes, PhDJ. Suzanne Sikes, PhD

Myra J. Halpin, PhDMyra J. Halpin, PhD

Pharmacology principlesPharmacology principles

AbsorptionAbsorptionDistributionDistributionMetabolismMetabolismExcretionExcretion

PharmacokineticsPharmacokinetics

Pharmacology principlesPharmacology principles

How alcohol worksHow alcohol worksAdverse effectsAdverse effectsToxicityToxicityDrug interactionsDrug interactions

PharmacodynamicsPharmacodynamics

Pharmacology is biologyPharmacology is biology

• cell typescell types• cell membrane structurecell membrane structure• filtration, passive diffusion, active tr.filtration, passive diffusion, active tr.• R vs L circulatory system R vs L circulatory system • geneticsgenetics

Pharmacology is chemistryPharmacology is chemistry

• polaritypolarity• bond formation bond formation • concentration gradientconcentration gradient• chemical reactionschemical reactions• enzymes as catalystsenzymes as catalysts

Alcohol AbsorptionAlcohol Absorption

Absorption: Stomach vs IntestineAbsorption: Stomach vs Intestine

greater surface area

Alcohol moves into the blood passivelypassively

Water moves through poresWater moves through pores

Ethanol is small and polar

Ethanol has some non-polar characterEthanol has some non-polar character

Alcohol moves by filtration & passive diffusionAlcohol moves by filtration & passive diffusion

Alcohol moves into the blood passivelypassively

Water & small solutes move through Water & small solutes move through holes in capillariesholes in capillaries

Ethanol is distributed everywhereEthanol is distributed everywhere

Ethanol distributes into water spacesEthanol distributes into water spaces

Males: low fat:water Females: high fat:water

BAC: males < females

The blood-brain-barrier: Not for alcohol!The blood-brain-barrier: Not for alcohol!

The blood-brain-barrier: Not for alcohol!The blood-brain-barrier: Not for alcohol!

Passive diffusion is key

Symptoms of intoxicationSymptoms of intoxication

Symptoms of intoxication depend onSymptoms of intoxication depend on brain region affectedbrain region affected

judgmentriskimpulsivity

motor

memory

breathing,heart rate

balance

vomiting

pleasure

Neurons fire electrical impulsesNeurons fire electrical impulses

GABA receptorsGABA receptors

glutamate receptorsglutamate receptors

Alcohol depresses neuron firingAlcohol depresses neuron firing

How does alcohol work?How does alcohol work?

Glutamate increases firingGlutamate increases firing

Alcohol blocks glutamate receptorsAlcohol blocks glutamate receptors• affects judgmentaffects judgment• reduces memoryreduces memory

How does alcohol work?How does alcohol work?

GABA decreases firingGABA decreases firing

Alcohol opens GABA receptorsAlcohol opens GABA receptors• incoordinationincoordination• reduces memoryreduces memory• slurred speechslurred speech• disinhibits (obnoxious!)disinhibits (obnoxious!)

Alcohol increases ClAlcohol increases Cl-- entry into neurons entry into neuronsthrough GABA receptor channelsthrough GABA receptor channels

More negative charges inside the cell decreases firing

Blackouts: Disruption in the hippocampusBlackouts: Disruption in the hippocampus

Hippocampus = memory!

Alcohol can shrink the hippocampusAlcohol can shrink the hippocampus

Alcohol decreases neurogenesisAlcohol decreases neurogenesis

Alcohol causes cell suicide (apoptosis)Alcohol causes cell suicide (apoptosis)

…….5 minute break.5 minute break

Getting rid of alcoholGetting rid of alcohol

The “first pass” effect:The “first pass” effect:Metabolism in the stomachMetabolism in the stomach

guys yes, girls no

The “first pass” effect:The “first pass” effect:Metabolism in the liverMetabolism in the liver

guys +++, girls ++

Ethanol metabolism: oxidation x 2Ethanol metabolism: oxidation x 2

All about acetaldehydeAll about acetaldehyde

sweatingsweatingrapid heart raterapid heart ratenauseanauseadizzinessdizzinessheadacheheadache

hangover symptomshangover symptomscellular damagecellular damage

H3C C

O

H

ethanol ---> acetaldehyde

Ethanol OxidationEthanol Oxidation

Alcohol Dehydrogenase (ADH)Alcohol Dehydrogenase (ADH)

Acetaldehyde Dehydrogenase (ALDH)Acetaldehyde Dehydrogenase (ALDH)

acetaldehyde ---> acetic acid

Ethanol binds to an active siteEthanol binds to an active site

HH

O

London forces ON

H

Oxidation: ethanol loses 2 e- (a H atom)Oxidation: ethanol loses 2 e- (a H atom)

HH

O

London forces ON

H

Many types of ADH & ALDHMany types of ADH & ALDH

ADH: 7 proteins

ALDH: 2 major proteins

Genetic PolymorphismsGenetic Polymorphisms

ADH1 ADH2 ADH3 ADH4 ADH5 ADH6 ADH7

Polymorphic (in liver)

Monomorphic (in stomach)

*1*2

*3

Slow: increased risk of Alcoholism(Caucasians)

Fast: decreased risk of alcoholism(Asians)

ethanol ---> acetaldehyde

Exhaling alcohol and the BreathalyzerExhaling alcohol and the Breathalyzer

Alcohol vaporizes in the airsacsAlcohol vaporizes in the airsacs

Alcohol vaporizes easier than waterAlcohol vaporizes easier than water

Less H bonds to break

Why teach about alcohol?Why teach about alcohol?

Biology…..Biology…..

• cell typescell types• cell membrane structurecell membrane structure• filtration, passive diffusion, active tr.filtration, passive diffusion, active tr.• DNA structure, protein synthesis DNA structure, protein synthesis • R vs L circulatory system R vs L circulatory system • geneticsgenetics

& Chemistry& Chemistry

• polaritypolarity• bond formation bond formation • concentration gradientconcentration gradient• chemical reactionschemical reactions• enzymes as catalystsenzymes as catalysts