1. Alcohol: The Biology, Chemistry, & Pharmacology
Rochelle D. Schwartz-Bloom, PhD
J. Suzanne Sikes, PhD
Myra J. Halpin, PhD

2. Pharmacology principles
Pharmacokinetics
Absorption
Distribution
Metabolism
Excretion

3. Pharmacology principles
Pharmacodynamics
How alcohol works
Adverse effects
Toxicity
Drug interactions

4. Pharmacology is biology
cell types
cell membrane structure
filtration, passive diffusion, active tr.
R vs L circulatory system
genetics

5. Pharmacology is chemistry
polarity
bond formation
concentration gradient
chemical reactions
enzymes as catalysts

6. Alcohol Absorption

7. Absorption: Stomach vs Intestine
greater surface area

8. Alcohol moves into the blood passively

9. Water moves through pores

10. Ethanol is small and polar

11. Ethanol has some non-polar character

12. Alcohol moves by filtration & passive diffusion

13. Alcohol moves into the blood passively

14. Water & small solutes move through
holes in capillaries

16. Ethanol is distributed everywhere

17. Ethanol distributes into water spaces
Males: low fat:water
Females: high fat:water
BAC: males < females

18. The blood-brain-barrier: Not for alcohol!

19. The blood-brain-barrier: Not for alcohol!
Passive diffusion is key

21. Symptoms of intoxication

22. Symptoms of intoxication depend on
brain region affected
motor
memory
pleasure
judgment
risk
impulsivity
balance
vomiting
breathing,
heart rate

23. Neurons fire electrical impulses

25. glutamate receptors
GABA receptors

26. Alcohol depresses neuron firing

27. How does alcohol work? Glutamate increases firing
Alcohol blocks glutamate receptors
affects judgment
reduces memory

28. How does alcohol work? GABA decreases firing
Alcohol opens GABA receptors
incoordination
reduces memory
slurred speech
disinhibits (obnoxious!)

29. Alcohol increases Cl- entry into neurons
through GABA receptor channels
More negative charges inside
the cell decreases firing

30. Blackouts: Disruption in the hippocampus
Hippocampus = memory!

31. Alcohol can shrink the hippocampus

32. Alcohol decreases neurogenesis

33. Alcohol causes cell suicide (apoptosis)

34. ….5 minute break

35. Getting rid of alcohol

36. The “first pass” effect: Metabolism in the stomach
guys yes, girls no

37. The “first pass” effect: Metabolism in the liver
guys +++, girls ++

38. Ethanol metabolism: oxidation x 2

39. All about acetaldehyde
H3C C O H
sweating
rapid heart rate
nausea
dizziness
headache
hangover symptoms
cellular damage

40. ethanol ---> acetaldehyde acetaldehyde ---> acetic acid
Ethanol Oxidation
Alcohol Dehydrogenase (ADH)
ethanol ---> acetaldehyde
Acetaldehyde Dehydrogenase (ALDH)
acetaldehyde ---> acetic acid
coenzymes : small non-protein ligands that catalyze reactions… +/- electrons,  transfer a group,  form or break a covalent bond

41. Ethanol binds to an active site
London forces N
What does an ES Complex do?             - holds substrate out of aqueous solution             - holds substrate in specific orientation, close to transition state to allow reaction to occur             - reduces ability of free rotation & molecular collisions with non-reactive atoms             - allows amino acid side chains to alter local environment:                         changes ionic strength, pH, adds or removes H-bonds to substrate   

42. Oxidation: ethanol loses 2 e- (a H atom)
London forces N
What does an ES Complex do?             - holds substrate out of aqueous solution             - holds substrate in specific orientation, close to transition state to allow reaction to occur             - reduces ability of free rotation & molecular collisions with non-reactive atoms             - allows amino acid side chains to alter local environment:                         changes ionic strength, pH, adds or removes H-bonds to substrate   

43. Many types of ADH & ALDH
ADH: 7 proteins
ALDH: 2 major proteins

44. ethanol ---> acetaldehyde
Genetic Polymorphisms
ADH1
ADH2
ADH3
ADH4
ADH5
ADH6
ADH7
Polymorphic
(in liver)
Monomorphic
(in stomach) *1 *2 *3
ethanol ---> acetaldehyde
Slow: increased risk of
Alcoholism
(Caucasians)
Fast: decreased risk of
alcoholism
(Asians)

45. Exhaling alcohol and the Breathalyzer

46. Alcohol vaporizes in the airsacs

47. Alcohol vaporizes easier than water
Less H bonds to break

48. Why teach about alcohol?

49. Biology….. cell types cell membrane structure
filtration, passive diffusion, active tr.
DNA structure, protein synthesis
R vs L circulatory system
genetics

50. & Chemistry polarity bond formation concentration gradient
chemical reactions
enzymes as catalysts