neuropharmacology: alcohol

Alcohol

Brian J. Piper, Ph.D.

1.0

Goals

• Chemistry• Pharmacokinetics• Pharmacodynamics• Physiological effects• Public health consequences• Teratology• Epidemiology

1.2

Chemistry

• Ethanol: CH3CH2OH

1.2

Getting in:

• 1. Mouth• 2. Stomach• 3. Small intestine• 4. Heart• 5. Brain• 6. Liver

1.3

Getting out

• Alcohol dehydrogenase (AlcDH):

• Aldehyde dehydrogenase (AldDH)

• Ethanol --------> Acetaldehyde ------> Acetic Acid

CH3-CH2-OH CH3-CH=O CH3-C-OH

O

AlcDH: lower levels in stomach of women

AldDH: half of Asians have a dysfunctional version; this results in flushing and nausea, Antabuse inhibits

AlcDH AldDH

||

See also: http://endeavor.med.nyu.edu/~strone01/doctor.html

3.7

Sex Differences

• Lower level of AlcDH in stomach of females

• Fat content

• Sex hormones

• Tolerance

2.7

Pharmacodynamics

• Primary– decrease glutamate– increase GABA

• Secondary– increase Dopamine

1.8

Doyon, W.M.,et al. (2005). J Neurochem, 93, 1469-1481.

3.1

Physiological Effects

• Dose dependent: – low dose-stimulant– high dose-depressant

5.1

Blood Alcohol Concentration Symptom

Low (O.01%*) relaxationDecreased alertness

Loss of coordination/ reaction time

Difficulty standing/ walking

Slurred speech

Unable to walk unaided

Difficulty rousing

Coma

High (0.50) Death

Table From Inaba, D.S. (2007).

*Mass/Volumemg/dL

2004 Fatalities in Motor Vehicle Traffic Crashesby Driver BAC – Massachusetts

.15+ BAC 62.6%

.10-.14 BAC 26.4%

.08-.09 BAC 11.0%

.08+ BAC 34.5%

.01-.07BAC4.7%

Zero BAC 61.1%

Source: National Highway Traffic Safety Administration, U.S. Department of Transportation, 2005. Fatalities in motor vehicle traffic crashes by the highest driver BAC in the crash, 2004 Fatal Analysis Reporting System (FARS).

The average BAC among drunk drivers involved in fatal crashes was 0.17 (2004).

2.9

Preventabledeaths.

http://www-nrd.nhtsa.dot.gov/pdf/nrd-30/NCSA/TSF2005/810616.pdftp://.nhtsa.dot.gov/pdf/nrd-30/NCSA/TSF2005/810616.pdf

Alcohol related fatality = one member of accident (driver, nonoccupant) has detectable Alcohol (0.01 g/dl +) ,

There were 43,295 traffic fatalities (39% alcohol related).

Chronic EtOH & Neurophsyiology

Chorlian, D.B. (1995). Alcohol Health & Research World 19(4):315–320.

3.3

Find X among other letters,“Oddball” task

Chronic EtOH & Neuroanatomy

Rosenbloom, M., et al. (2003). Alcohol Research & Health 27(2):146–152.

2.6

Teratology: High dose1.5

Warren, Kenneth (2011). Perspectives on Fetal Alcohol Syndrome and Fetal Alcohol Spectrum Disorders. Available at: http://videocast.nih.gov/launch.asp?16613

Low-Dose?• Women in Capetown, South Africa were interviewed after giving birth and their

offspring were grouped as:

– Unexposed Control (N=29): no EtOH

– Fetal Alcohol Syndrome (N=12): 4.2 drinks/day

– Partial FAS (N=18): 2.8 drinks/day

– Heavy Exposed (N=34): 1.6 drinks/day

– Microencephalic (N=4): ?

• Children were tested at age 5

for classical conditioning:

Jacobson, S.W., et al. (2008). Alcohol: Clin Exp Res 37, 2, 365-372.

http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/17256.jpghttp://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/17256.jpg

Jacobson, S.W., et al. (2008). Alcohol: Clin Exp Res 37, 2, 365-372.

Monitoring the Future

• National survey, conducted annually by NIDA of secondary school (8th, 10th, or 12th), college students, and adults (<45 yrs)

• Missing data (drop-outs = 15%, not attending) = under-estimation

• Concern about labels (inadvertent marketing)• Self-report

– Knowledge (e.g. steroids, diet pills, club drugs)– Memory (e.g. How many drinks?)– Taboo

http://www.monitoringthefuture.org/

Demographics

• Compares use by:– Year (1975 – present)– Sex– Ethnicity– Parental education– Region– College plans

?

Frequency of Alcohol Use

• Monitoring the Future

• Nationally representative

• 15,000+

Frequency of Alcohol Use

• Monitoring the Future

• Nationally representative

• 15,000+

Epidemiology

MtF: http://www.monitoringthefuture.org/pubs/occpapers/occ63.pdf

http://www.monitoringthefuture.org/data/06data/fig06_14.pdf

Drug Abuse Warning Network

• Nationwide reports of ER/ED visits

• 242 hospitals nationwide

• Drug/alcohol is “implicated”– Overdose– Suicide– Accident

Drug Abuse Warning Network

Alcoholics Anonymous

• Founded by Bill Wilson & Bob Smith in 1935• Medical-Spiritual Approach based on:

– Alcoholism is a progressive disease.– Alcoholics must give themselves to a higher power.– Total abstinence

• Effectiveness ?

3.5

Public Health

Nutt, D.J. (2006) J. Psychopharmacology, 20, 315-317.

Premature Deaths (UK)

Safety in

overdose

Brain

Damage

Interpersonal

Violence

Traffic

Accidents

Per year

cirrhosis Heart Damage

Cost

to society (Billion Pounds)

ethanol 22,000 10 xPleasure

dose

Yes10,000 +/year 1500 ++ ++ 18.5

ecstasy 10 15 x ? 0 0 0 0 0.01

Summary

• Pharmacokinetics: enzymes

• Pharmacodynamics: neurotransmitters

• Teratology: consequences– Randall: http://videocast.nih.gov/launch.asp?10420

• Epidemiology: Who uses? What are risk factors?

Total Length = 57.4 minutes