Lecture 40: Pharmacology of Alcohol

Question 1

What is the standard 1 unit serving of alcohol?

Answer 1

14 grams of alcohol

12 oz can of beer = 5 oz wine = 1.5 oz shot of liquor = 14 grams of alcohol

Question 2

What is BAL? What is BAC?

Answer 2

Blood alcohol level
and
blood alcohol content
BAL = BAC

Question 3

What is the legal limit of alcohol?

Answer 3

.08% or 80-100 mg/dL for 21+
One drink = .03%
<10mg/dL for people under 21

Question 4

How is BAL measured?

Answer 4

Through expire air because alcohol has a high diffusion coefficient

Question 5

What is the significance of hydrophilicicity?

Answer 5

It has a high volume of distribution

But ethanol is also lipid soluble

Question 6

Where is alcohol absorbed?

Answer 6

Small intestine
Accelerated by CO2
Example: Champagne

Question 7

What influences rate of absorption of alcohol? Significance?

Answer 7

Concentration (shot vs. wine vs. beer)
Food in stomach
Fat > glucose > protein for rate
Rate of absorption predicts BAL

Question 8

What do women achieve a higher BAL for a given dose than men?

Answer 8

Women have higher body fat content (which absorbs alcohol faster)
Lower body water content

Question 9

What does maximum BAL depend on?

Answer 9

1. volume of distribution
2. rate of absorption
3. rate of metabolism

Question 10

What is the oxidative pathways in the liver for alcohol?

Answer 10

Microsomal ethanol oxidizing system (MEOS)
-the more you drink the more effective the MEOS system
Same shit as cytochrome P450 2E1

Question 11

What causes the hangover?

Answer 11

Acetaldehyde

Question 12

What is the significance of acetaldehyde?

Answer 12

The protein that causes hangover

Question 13

What enzyme is used to metabolize alcohol?

Answer 13

Alcohol Dehydrogenase

-ADH is higher in men

Question 14

How much of alcohol is metabolized in body?

Answer 14

90% but variable depending on genetics and gender

Question 15

What are the three key enzymes in alcohol metabolism?

Answer 15

1. Alcohol dehydrogenase
2. Acetaldehyde Dehydrogenase (ALDH)
3. MEOS (CYP 2E1, 3A4)
   - converts ethanol to acetaldehyde
   - kicks in when ADH is saturated
   - upregulated in habitual drinkers

Question 16

What is the significance of alcohol dehydrogenase?

Answer 16

Converts Ethanol to ACETALDEHYDE

-present mainly in liver

Question 17

How much alcohol is metabolized?

Answer 17

90%

Question 18

What is the significance of acetaldehyde dehydrogenase (ALDh)?

Answer 18

Enzyme that converts Acetaladehyde to acetate

Asians lack this enzyme which leads to greater feeling of hangover

Question 19

What is the significance of CYP 2E1 (MEOS)?

Answer 19

Converts ethanol to acetaldehyde
Kicks in after ADH
The more you drink the more effective MEOS is
Byproducts = H2O2 = toxins

Question 20

What do Asian people lack in alcohol metabolism?

Answer 20

Acetaldehyde dehydrogenase deficiency (Asians feel worse when drinking alcohol)
Because acetaldehyde is NOT broken down and have higher symptoms of hangover

Question 21

What is disulfuram?

Answer 21

A competitive antagonist of acetaldehyde dehydrogenase

It is an anti-alcohol drug because you feel shitty after you drink

Question 22

What is the kinetics of alcohol metabolism?

Answer 22

1. First order kinetics up to 100 mg/dl
2. zero order kinetics then apply (which means that elimination rate is a steady 8g/hour)
   Therefore, as BAL increases, the t1/2 increases

Question 23

: If you have someone with 250 mg/dl BAL in body, 140 grams, what is BAL after 3 hours if t1/2 is 1 hours?

Answer 23

If first order kinetics were applied then
250
125
62.5
31.25 mg/dl after 3 hours
But what happens in reality?
Zero order kinetics only applies once ADH is saturated
So alcohol is actually metabolized at rate of 8 grams/hour
So after 3 hours, 24 grams metabolized and 116 grams left in body
So that’s why police are stationed early in the morning…to catch drunk drivers who just woke up from a night of intoxication

Question 24

What is the rate of alcohol metabolism once ADH is saturated?

Answer 24

8 grams per hour in NON habitual drinkers

Question 25

Do habitual drinkers have higher or lower BAL after same number of drinks?

Answer 25

Lower BAL because able to metabolise it faster

Question 26

What are drug interactions of alcohol?

Answer 26

1. Acetaminophen toxicity - alcohol increases P450 conversion of acetaminophen to hepatotoxic metabolites 2. Competitive inhibition of warfarin 3. increased metabolism of oral contraceptives - so avoid drinking when on the pill

Question 27

What are the CNS diseases alcohol is an etiology for?

Answer 27

1. Loss of white and grey matter (frontal lobe) 2. Wernickes syndrome 3. Korsakoff (amnestic) syndrome 4. Neuropathy, central vs. peripheral Saturday night palsy 5. Reduced brain metabolism

Question 28

How does alcohol affect your sleep?

Answer 28

Reduces initial sleep latency Reduces latency to REM sleep Increases wake time Increases number of apneic episodes

Question 29

Why don’t you want pregnant women to drink?

Answer 29

Alcohol diffuses readily through placenta/into breast milk Fetal alcohol syndrome Microcephaly

Question 30

What is the effect of ETOH?

Answer 30

ETOH affects EVERY organ in the body and impact is dose dependent