A Small Dose of Alcohol – 04/03/10

An Introduction To The Health Effects of Alcohol

A Small Dose of Alcohol

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

What Is This?

CH

H

H

OHC

H

H

(CH3-CH2-OH)

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Ethanol

CH

H

H

OH

Ethyl Alcohol

C

H

H

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Methanol

CH

H

H

OH

Methyl Alcohol

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

"You will conceive and bear a son…now then be careful to take no wine or strong drink and to eat nothing unclean".

Bible - Judges 13:3-4

Ancient Awareness

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

’T is not the drinking that is to be blamed, but the excess.

John Selden (1584–1654)

In “Table Talk” 1689

Historical Perspective

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

“Alcohol is the number one drug of choice among our Nation’s youth. Yet the seriousness of this issue does not register with the general public or policymakers.”

Enoch Gordis, M.D. Director, National Institute on Alcohol Abuse and Alcoholism.

Current Views

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

7.4% of adult population in U.S. alcoholic $185 Billion – cost of alcohol abuse in U.S. 100,000 deaths annual in U.S. related to $1.2 Billion spent on wine, beer and liquor

advertisements in U.S.

Some Current Facts

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Production of Alcohol

Fermentation – Sugar to Alcohol and Carbon dioxide

C6H12O6→ 2(CH3-CH2-OH) + 2CO2

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Health Effects

What are the pleasant effects of alcohol?

The adverse effects (toxicity)?

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

• CNS Depressant• Depression of inhibitory control• Vasodilation, warm, flushed, reddish skin• Emotional outbursts• Decreased memory & concentration• Poor judgment• Decreased reflexes

Acute Effects

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Obvious• Alcoholism, death, cancer (oral cavity,

esophagus, liver), fetal effects (FAS)

Alcoholism• Cirrhosis of liver, appetite loss, poor

judgment Subtle

• Lost productivity, impaired performance, motor impairment, cost to society

Long Term Adverse Effects

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Alcohol & Cancer

Ethanol consumption increases risk of cancer

Oral CavityPharynx and Larynx

EsophagusLiver

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Fetal Alcohol Syndrome (FAS)

Most common preventable cause of adverse CNS development

4,000-12,000 infants per year in US

CharacteristicsGrowth retardation

Facial malformationsSmall head

Greatly reduce intelligence

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Fetal Alcohol Syndrome (FAS)

1 to 3 births per 1,000 world wide??

1968 first association by French researchers at the University of Nantes

Early 1970’s FAS as condition – University of Washington, Seattle WA, USA

4,000-12,000 infants per year in US

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Fetal Alcohol Effect (FAE)

Milder form of FAS

7,000-36,000 infants per year in US

CharacteristicsGrowth deficiency

Learning dysfunctionNervous systems disabilities

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Effects of Prenatal Alcohol

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Effects of Prenatal Alcohol

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10FAS Child (National Geographic, George Steinmetz, Feb 1992)

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Mouse – Scanning EM

(National Geographic, George Steinmetz, Feb 1992)

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Rapidly absorbed from stomach, small intestine, and colon

Maximal blood concentration within 30 to 90 minutes

Can be absorbed through the lungs

Absorption

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Uniformly distributed throughout tissues and body fluids

Readily crosses placenta, to exposure fetus

Distribution

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Urinary ExcretionExhalationMetabolism

Elimination

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Metabolism I

CH OH

Ethanol

H

H

C

H

H

CH

H

H

C O

H

=

Acetaldehyde

(ADH – Alcohol Dehydrogenase)

ADH

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Metabolism II

CH

H

H

C O

H

=

Acetaldehyde(ALDH – Acetaldehyde Dehydrogenase)

ALDH

Acetate

CH

H

H

C O

OH

=

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Metabolism III

80-90% Metabolized Rate is constant (not increased

by concentrations in the blood) About 30 ml (1 oz) in 3 hours

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Gender Differences

Females higher blood alcohol levels than males

Males have higher stomach metabolism of alcohol than females

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Genetic Variation in ALDH

Acetaldehyde Dehydrogenase (ALDH) varies in Caucasians, Blacks and Asians.

50% of Asians have inactive ALDH

Elevated acetaldehyde cause increased flushing, tachycardia (elevated heart rate), nausea, vomiting & hyperventilation.

Disulfiram – inhibits ALDH

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Alcoholism - Disulfiram

Alcoholism Treatment with Disulfiram

Inhibits acetaldehyde dehydrogenase (ALDH)

Elevated acetaldehyde cause increased flushing, tachycardia (elevated heart rate),

nausea, vomiting & hyperventilation.

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Alcoholism – Alcohol Dependence

Characterized by the following:

• Craving: A strong need, or compulsion, to drink. • Loss of control: The inability to limit one’s drinking

on any given occasion. • Physical dependence: Withdrawal symptoms, such

as nausea, sweating, shakiness, and anxiety, occur when alcohol use is stopped after a period of heavy drinking.

• Tolerance: The need to drink greater amounts of alcohol in order to “get high.”

(from: U.S. Alcohol & Drug Information - http://ncadi.samhsa.gov/)

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Alcoholism – Alcohol Dependence

Approximately 14 million Americans—7.4 percent of the population —meet the diagnostic criteria for alcohol

abuse or alcoholism

(from: U.S. Alcohol & Drug Information - http://ncadi.samhsa.gov/)

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

• Tremor• Nausea• Irritability• Agitation• Tachycardia• Hypertension• Seizers• Hallucinations

Alcohol Withdrawal Effects

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Ethanol as Antidote

Antidote for Poisoning by:

Methanol

Ethylene glycol

Diethylene glycol

Inhibits metabolic activation by alcohol dehydrogenase (ADH)

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

U.S. Government Warning

The Alcoholic Beverage Labeling Act of 1988 requires that the following health warning statement appear on the labels of all containers of alcohol beverages offered for sale or distribution in the United States:

U.S. GOVERNMENT WARNING: (1) According to the Surgeon General, women should not drink alcoholic beverages during pregnancy because of the risk of birth defects. (2) Consumption of alcoholic beverages impairs your ability to drive a car or operate machinery, and may cause health problems.

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

• 1981 - U.S. Surgeon General first advised that women should not drink alcoholic beverages during pregnancy.

• 1988 - U.S. requires warning labels on all alcoholic beverages sold in the United States.

• 1990 - U.S. Dietary Guidelines state that women who are pregnant or planning to become pregnant should not drink alcohol.

• 1998 - 19 states require the posting of alcohol health warning signs where alcoholic beverages are sold

Regulatory Status

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

A Small Dose of ™ Alcohol

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Additional Information

Web Sites• England – Department of Health (DOH) Alcohol

Misuse Information. Online: <http://www.dh.gov.uk/en/publichealth/healthimprovement/alcoholmisuse/index.htm> (accessed: 3 April 2010).

• Health Canada – Fetal Alcohol Spectrum Disorder. Online: <http://www.phac-aspc.gc.ca/fasd-etcaf/index-eng.php> (accessed: 3 April 2010).

A Small Dose of Toxicology A Small Dose of Alcohol – 04/03/10

Authorship Information

For Additional Information ContactSteven G. Gilbert, PhD, DABT

E-mail: sgilbert@innd.orgWeb: www.asmalldoseof.org

This presentation is supplement to “A Small Dose of Toxicology”