Lecture 5 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Includes epidemiology, pharmacokinetics, pharmacodynamics, and overdose.

1. 1.0 Alcohol
Brian J. Piper, Ph.D.

2. 1.2
Goals
• Chemistry
• Pharmacokinetics
• Pharmacodynamics
• Physiological effects
• Public health consequences
• Teratology
• Epidemiology

3. 1.2
Chemistry
• Ethanol: CH3CH2OH

4. 1.3 Getting in:
• 1. Mouth
• 2. Stomach
• 3. Small intestine
• 4. Heart
• 5. Brain
• 6. Liver

5. 3.7 Getting out
• Alcohol dehydrogenase (AlcDH):
• Aldehyde dehydrogenase (AldDH)
AlcDH 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
See also: http://endeavor.med.nyu.edu/~strone01/doctor.html

6. 2.7
Sex Differences
• Lower level of AlcDH in stomach of
females
• Fat content
• Sex hormones
• Tolerance

7. 1.8
Pharmacodynamics
• Primary
– decrease glutamate
– increase GABA
• Secondary
– increase Dopamine

8. 3.1
Doyon, W.M.,et al. (2005). J Neurochem, 93, 1469-1481.

9. Physiological Blood Alcohol
Concentration Symptom
5.1
Effects Low (O.01%*) relaxation
• Dose dependent: Decreased
alertness
– low dose-stimulant
Loss of coordination/
– high dose-depressant reaction time
Difficulty standing/
walking
Slurred speech
Unable to walk
Table From Inaba, D.S. (2007).
unaided
*Mass/Volume Difficulty rousing
mg/dL
Coma
High (0.50) Death

10. 2004 Fatalities in Motor Vehicle Traffic Crashes
by Driver BAC – Massachusetts
2.9
.01-.07
BAC .08-.09 BAC 11.0%
4.7%
.10-.14 BAC
26.4%
Zero BAC .08+ BAC
61.1% 34.5%
.15+ BAC
62.6%
The average BAC among drunk drivers
involved in fatal crashes was 0.17 (2004).
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).

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

12. Chronic EtOH & Neurophsyiology
3.3
Find X among other letters,
“Oddball” task
Chorlian, D.B. (1995). Alcohol Health & Research World 19(4):315–320.

13. Chronic EtOH & Neuroanatomy
2.6
Rosenbloom, M., et al. (2003). Alcohol Research & Health 27(2):146–152.

14. 1.5
Teratology: High dose
Warren, Kenneth (2011). Perspectives on Fetal Alcohol Syndrome and Fetal Alcohol Spectrum Disorders. Available at: http://videocast.nih.gov/launch.asp?16613

15. 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
http://www.nlm.nih.gov/medlineplus/ency/images/ency/fu
– 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.

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

17. 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/

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

20. Frequency of Alcohol Use
• Monitoring
the Future
• Nationally
representative
• 15,000+

21. Frequency of Alcohol Use
• Monitoring
the Future
• Nationally
representative
• 15,000+

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

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

25. Drug Abuse Warning Network
• Nationwide reports of ER/ED visits
• 242 hospitals nationwide
• Drug/alcohol is “implicated”
– Overdose
– Suicide
– Accident

26. Drug Abuse Warning Network

27. 3.5 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 ?

28. Public Health
Premature Safety in Brain Interpersonal Traffic cirrhosis Heart Cost
Deaths overdose Damage Violence Accidents Damage to society
(UK) (Billion
Per year
Pounds)
10,000 +/year
ethanol 22,000 1500
10 x Yes ++ ++ 18.5
Pleasure
dose
ecstasy 0.01
10 15 x ? 0 0 0 0
Nutt, D.J. (2006) J. Psychopharmacology, 20, 315-317.

29. 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