Alcohol: The Biology, Chemistry,
& Pharmacology
Rochelle D. Schwartz-Bloom, PhD
J. Suzanne Sikes, PhD
Myra J. Halpin, PhD
Pharmacology principles
Pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
Pharmacology principles
Pharmacodynamics
How alcohol works
Adverse effects
Toxicity
Drug interactions
Pharmacology is biology
• cell types
• cell membrane structure
• filtration, passive diffusion, active tr.
• R vs L circulatory system
• genetics
Pharmacology is chemistry
• polarity
• bond formation
• concentration gradient
• chemical reactions
• enzymes as catalysts
Alcohol Absorption
Absorption: Stomach vs Intestine
greater surface area
Alcohol moves into the blood passively
Water moves through pores
Ethanol is small and polar
Ethanol has some non-polar character
Alcohol moves by filtration & passive diffusion
Alcohol moves into the blood passively
Water & small solutes move through
holes in capillaries
Ethanol is distributed everywhere
Ethanol distributes into water spaces
Males: low fat:water
Females: high fat:water
BAC: males < females
The blood-brain-barrier: Not for alcohol!
The blood-brain-barrier: Not for alcohol!
Passive diffusion is key
Symptoms of intoxication
Symptoms of intoxication depend on
brain region affected
motor
memory
pleasure
judgment
risk
impulsivity
balance
breathing,
heart rate
vomiting
Neurons fire electrical impulses
glutamate receptors
GABA receptors
Alcohol depresses neuron firing
How does alcohol work?
Glutamate increases firing
Alcohol blocks glutamate receptors
• affects judgment
• reduces memory
How does alcohol work?
GABA decreases firing
Alcohol opens GABA receptors
• incoordination
• reduces memory
• slurred speech
• disinhibits (obnoxious!)
Alcohol increases Cl- entry into neurons
through GABA receptor channels
More negative charges inside
the cell decreases firing
Blackouts: Disruption in the hippocampus
Hippocampus = memory!
Alcohol can shrink the hippocampus
Alcohol decreases neurogenesis
Alcohol causes cell suicide (apoptosis)
….5 minute break
Getting rid of alcohol
The “first pass” effect:
Metabolism in the stomach
guys yes, girls no
The “first pass” effect:
Metabolism in the liver
guys +++, girls ++
Ethanol metabolism: oxidation x 2
All about acetaldehyde
H
sweating
rapid heart rate
nausea
dizziness
headache
H3C
hangover symptoms
cellular damage
C
O
Ethanol Oxidation
Alcohol Dehydrogenase (ADH)
ethanol ---> acetaldehyde
Acetaldehyde Dehydrogenase (ALDH)
acetaldehyde ---> acetic acid
Ethanol binds to an active site
H
O
London forces
H
O
H
N
Oxidation: ethanol loses 2 e- (a H atom)
H
O
London forces
H
O
H
N
Many types of ADH & ALDH
ADH: 7 proteins
ALDH: 2 major proteins
Genetic Polymorphisms
ADH1
ADH2
ADH3
ADH4
ADH5
ADH6
ADH7
ethanol ---> acetaldehyde
*1
*2
*3
Polymorphic
(in liver)
Slow: increased risk of
Alcoholism
(Caucasians)
Monomorphic
(in stomach)
Fast: decreased risk of
alcoholism
(Asians)
Exhaling alcohol and the Breathalyzer
Alcohol vaporizes in the airsacs
Alcohol vaporizes easier than water
Less H bonds to break
Why teach about alcohol?
Biology…..
• cell types
• cell membrane structure
• filtration, passive diffusion, active tr.
• DNA structure, protein synthesis
• R vs L circulatory system
• genetics
& Chemistry
• polarity
• bond formation
• concentration gradient
• chemical reactions
• enzymes as catalysts