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Ethanol The Physiology Behind the World’s Second Most Popular Drug Kevin T. Strang, PhD Department of Physiology
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Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Mar 30, 2018

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Page 1: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Ethanol

The Physiology Behind the World’s Second Most Popular Drug

Kevin T. Strang, PhDDepartment of Physiology

Page 2: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Alcohol Structure

CH

HH OH

CH

HH OH

CH

HH OH

CH

H

CH

HCH

H

Methanol

Ethanol

Propanol

Page 3: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Alcohol Structure

C

H

H

H OH

CH

HH OH

C

H

H

H OH

CH

H

C

H

H

C

H

H

Methanol

Ethanol

Propanol

THE alcohol

Ingestion blindess

Most “other” alcohols are highlytoxic to the body

Page 4: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

CH

HH OHC

H

H

Ethanol Structure

•Clear, colorless liquid, miscible with H20 and organics

This end interacts anddissolves in water(hydrophilic)

Carbon-Hydrogen chainsdissolve in lipids(hydrophobic)

Page 5: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Cell membranes are essentially oily bubbles formedfrom a bilayer of phospholipid molecules

Basic Structure of Body Cells

Page 6: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Proteins are the machinery that determine thefunction of different cell types; they’re foundfloating free and within membranes

Ion channels(Na+, K+, Ca+2)

Enzymes

Receptors

Signals

Basic Structure of Body Cells

Page 7: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Proteins are made of amino acid chains:

Different amino acids haveunique “R” groups:

• Some are hydrophilic• Some are hydrophobic

3

Basic Structure of Body Cells

Page 8: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Ethanol’s unique chemistry allows it to interact with protein machinery of cellsthroughout the body.

CH

HH OHC

H

H(hydrophilic)

(hydrophobic)

Ethanol Interacts with Cell Proteins

Page 9: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

e.g., Ethanol can alter gating properties of many different types of ion channels…

Page 10: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Why Does Whiskey “Burn”?

Page 11: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Why Does Whiskey “Burn”?

“Vanillin Receptor 1” (mouth, throat)

Page 12: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Why Does Whiskey “Burn”?

Heat, capsaicin….

Page 13: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Why Does Whiskey “Burn”?

Heat, capsaicin….and ethanol!

Nerve signalto brain

“HOT!!”

Page 14: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Ethanol Affects All Body Systems

CardiovascularGastrointestinal Urinary

Endocrine/Reproductive

Today’s Focus:Nervous System

Page 15: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Mood elevationMild euphoriaReduced social inhibitionsAnti-anxiety

Why Do People Drink ?

Page 16: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Mood elevationMild euphoriaReduced social inhibitionsAnti-anxiety

But the effects aren’t as predictable as other drugsand there are side effects……

Why Do People Drink ?

Page 17: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Ethanol affects synapses

Neuron signalsand networks

( x 100 billion!)

Synapses, Neurotransmittersand Receptors

Page 18: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut

Normal cognition depends on a balance of excitatoryand inhibitory synaptic activity:

50% of the brain’s synapses use Glutamate 40% use GABA (gamma-amino-butyric acid)

+ +

+

GABAGABA

_

_

Page 19: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut+ +

+

GABAGABA

_

_

Well-documented pharmacological effects of ethanolinclude stimulation of GABA signaling and inhibitionof glutamate signaling.

Dose-dependent decline in cognitive ability……

Page 20: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut+ +

+

GABAGABA

_

_

Global neural depression inhibits motor outputsand sensory inputs……

Page 21: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut

SIDE EFFECT: Depression of motor output and sensory input 1. Loss of coordination (see drunk driving stats)

+ +

+

GABAGABA

_

_

MotorOutput

SensoryInputs

Page 22: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut

SIDE EFFECT: Depression of motor output and sensory input 1. Loss of coordination (see drunk driving stats)2. 8th Cranial Nerve especially sensitive

(“Dude, turn it up!”) (Field sobriety test) (Bed spins)

+ +

+

GABAGABA

_

_

MotorOutput

SensoryInputs

Page 23: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

How Does Alcohol Affect Memory?

Page 24: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Long-term potentiationat glutamate synapsesis a cellular correlateof memory formation

How Does Alcohol Affect Memory?

Page 25: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Long-term potentiationat glutamate synapsesis a cellular correlateof memory formation

Even at moderate dosesalcohol begins to inhibit LTP….

How Does Alcohol Affect Memory?

Page 26: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Short-TermMemory(“Working

memory”)(RAM)

Long-TermMemory(“Learning”)(Hard-drive)

Assimilation

ALCOHOL AND LEARNING

Page 27: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Short-TermMemory

Long-TermMemory

NEW LEARNING RESEARCH

SLEEP

+

Page 28: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

WHAT IS LEARNING?

Short-TermMemory

Long-TermMemory

ETHANOL

Page 29: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

WHAT IS LEARNING?

Short-TermMemory

Long-TermMemory

THE GRAND DELUSION…

SLEEP

+

ETHANOL

Page 30: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut

Impaired long-term memory formation: After a single drink, LTP is reduced 30%

At BAC of 0.2%, LTP is reduced 80%Total amnesia/blackout can occur at higher levels

+ +

+

GABAGABA

_

_

Memory

Inhibition of memory formation

Page 31: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

What Makes a Mean Drunk Mean?(or happy or horny or depressed?)

Page 32: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut+ +

+

GABAGABA

_

_

Well-documented pharmacological effects of ethanolinclude stimulation of GABA signaling and inhibitionof glutamate signaling.

Overall MOOD effects are dose and situation dependent.

Page 33: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

“Alcohol Myopia” Can Explain Variable Neural Effects

The basic idea:

Ethanol globally suppresses cognition, reducingthe mental focus of an individual to immediateinternal thoughts or external stimuli.

Page 34: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

“Alcohol Myopia” Can Explain Variable Neural Effects

The basic idea:

Ethanol globally suppresses cognition, reducingthe mental focus of an individual to immediateinternal thoughts or external stimuli.

Example: Study demonstrating that ethanol isNOT a good anti-anxiety drug….

Page 35: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Alcohol, Anxiety, and Public Speaking

Volunteer subjectsinvited to a party

“In 15 minutes, you have to go on stage and give an impromptu speech:”What I dislike most about my body and physical appearance

Alcohol drinks Placebo drinks

Sit and think

Easy slidesorting task

Moderate difficulty slide sorting task

Complicated slidesorting task

ANXIETY ANXIETY

Page 36: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Alcohol, Anxiety, and Public Speaking

Page 37: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Myopia CAN boost self-esteem!

from:The Onion

Page 38: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Why is it So Hard to Have Just One?

Page 39: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut+ +

+

GABAGABA

_

_

Mood/Pleasure

SerotoninDopamine

Other Neurotransmitters: Ethanol stimulatesbrain “reward” centers.

Page 40: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Glut Glut

Glut

THIS EXPLAINS:Short-term: Drinking leads to more drinking Chronically: AddictionBoth related to “Rising Phase Effect”

+ +

+

GABAGABA

_

_

Mood/Pleasure

SerotoninDopamine

Page 41: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Rising Phase Effect

Time

Blo

od A

lcoh

ol C

onte

nt

Increasing Dose/Side Effects

Moderate Dose/Effects

Elevated Dopamine:Reward/Euphoria

Depressed Dopamine:Craving/Dependence

Moderate Dose and Rate

Page 42: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Rising Phase Effect

Time

Blo

od A

lcoh

ol C

onte

nt

Increasing Dose/Side Effects

Moderate Dose/Effects

Binge Drinking

Page 43: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Rising Phase Effect

Time

Blo

od A

lcoh

ol C

onte

nt

Increasing Dose/Side Effects

Moderate Dose/Effects

Binge DrinkingOptimized Drinking

Page 44: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

WHY DO BEER AND BRATS MAKE A GREAT TEAM?

Page 45: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

WHY DO BEER AND BRATS MAKE A GREAT TEAM?

Fatty foods are best at delaying the emptying of the stomach (enterogastric reflex)

Reduces the rate of rise of blood alcohol 3-fold!

Always eat before/during alcohol consumption!

Page 46: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

How Does the GI System Save Lives?

Page 47: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Normally:

stretch stomachbacteriotoxin wall brainstem vomitexcess acid receptors

How Does the GI System Save Lives?

Page 48: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

stretch stomachbacteriotoxin wall brainstemexcess acid receptors

High ethanol concentrations stimulate stomach wall receptors 2 ways:

direct

indirect

How Does the GI System Save Lives?

Page 49: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Prescription Illegal OTCOxycontin Cocaine TylenolProzac Ecstasy NyquilValium THC IpecacPenicillin Heroin Aspirin

What do all “drugs” (and ethanol) have in common?1. Sought-after effects2. Unintended side-effects3. The dose determines the effect/side-effect ratio

“Drug” isn’t a four-letter-word….

Page 50: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Think of alcohol as a “drug”

In moderate doses (<1-2 drinks/day),alcohol appears to cause no harm*,and much evidence suggests that itmay have positive effects.

*EXCEPT in those who are under 21, pregnant, or susceptibleto alcoholism.

Page 51: Ethanol - Wisconsin Initiative for Science LiteracyStrang-1-09].pdf · Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Endocrine/ Reproductive Today’s Focus:

Moderate doses seem to be good for you…..