Neuropharmacology: Alcohol
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Alcohol
Brian J. Piper, Ph.D.
1.0
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Goals
• Chemistry• Pharmacokinetics• Pharmacodynamics• Physiological effects• Public health consequences• Teratology• Epidemiology
1.2
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Chemistry
• Ethanol: CH3CH2OH
1.2
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Getting in:
• 1. Mouth• 2. Stomach• 3. Small intestine• 4. Heart• 5. Brain• 6. Liver
1.3
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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
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Sex Differences
• Lower level of AlcDH in stomach of females
• Fat content
• Sex hormones
• Tolerance
2.7
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Pharmacodynamics
• Primary– decrease glutamate– increase GABA
• Secondary– increase Dopamine
1.8
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Doyon, W.M.,et al. (2005). J Neurochem, 93, 1469-1481.
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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
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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
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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).
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Chronic EtOH & Neurophsyiology
Chorlian, D.B. (1995). Alcohol Health & Research World 19(4):315–320.
3.3
Find X among other letters,“Oddball” task
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Chronic EtOH & Neuroanatomy
Rosenbloom, M., et al. (2003). Alcohol Research & Health 27(2):146–152.
2.6
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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
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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
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Jacobson, S.W., et al. (2008). Alcohol: Clin Exp Res 37, 2, 365-372.
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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/
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Demographics
• Compares use by:– Year (1975 – present)– Sex– Ethnicity– Parental education– Region– College plans
?
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Frequency of Alcohol Use
• Monitoring the Future
• Nationally representative
• 15,000+
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Frequency of Alcohol Use
• Monitoring the Future
• Nationally representative
• 15,000+
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Epidemiology
MtF: http://www.monitoringthefuture.org/pubs/occpapers/occ63.pdf
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http://www.monitoringthefuture.org/data/06data/fig06_14.pdf
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Drug Abuse Warning Network
• Nationwide reports of ER/ED visits
• 242 hospitals nationwide
• Drug/alcohol is “implicated”– Overdose– Suicide– Accident
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Drug Abuse Warning Network
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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 ?
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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
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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