Neuropharmacology of Alcohol

Question 1

How many grams of alcohol are in a “unit”?

Answer 1

14g

Question 2

By how much does one unit of alcohol raise BAC, on average?

Answer 2

0.03 percentage points (but this varies so much as to be almost useless)

Question 3

Why is alcohol able to partially eliminated by exhalation?

Answer 3

It’s soluble in water, but has a high diffusion coefficient, so it crosses the alveolar membrane easily. (and it’s volatile)

Question 4

Why can alcohol get pretty much everywhere in the body?

Answer 4

It’s both hydrophilic and lipophilic, giving it a high volume of distribution and access to all compartments of the body.

Question 5

Where is alcohol best absorbed? Is it active or passive transport?

Answer 5

In the small intestine.

Passive diffusion.

Question 6

What 4 variables affect the rate of absorption of alcohol?

Answer 6

Concentration: shot faster than beer
Food in stomach
Type of food (fatty food delays absorption more).
How frequently the individual drinks. (habitual drinkers absorb EtOH more quickly)

Question 7

Into what tissue does EtOH enter most slowly?

Answer 7

Fat

Question 8

2 distribution-related reasons for why women get a higher BAL for a given dose of EtOH?

Answer 8

Women have higher fat content and lower body water content.

Question 9

What percentage of EtOH is metabolized?

Answer 9

90%

Question 10

What are 2 ways in which EtOH is converted to acetaldehyde?

Answer 10

Microsomal ethanol oxidizing system (MEOS), using especially CYP 2E1. 
Alcohol dehydrogenase (ADH).

Question 11

What’s a metabolic reason for why men get a lower BAL than women from the same dose of EtOH?

Answer 11

Men have more ADH in their stomach cells.

Question 12

Where is ADH?

Answer 12

Mainly liver. Also in brain and stomach.

Question 13

When is MEOS used?

Answer 13

When ADH is saturated (and NAD is depleted)

Question 14

What enzyme converts acetaldehyde to acetate? What happens if yours doesn’t work very well?

Answer 14

Acetaldehyde dehydrogenase.

If it doesn’t work, acetaldehyde build up causes flushing, vomiting, dizziness.

Question 15

Which enzyme does disulfiram target?

Answer 15

Acetaldehyde dehydrogenase.

Question 16

By what kinetics is alcohol metabolized?

Answer 16

At low levels, up to 100mg/dL, first order.

At higher levels, ADH is saturated, and EtOH is eliminated at a constant rate of about 8g /hr.

Question 17

Is CYP 2E1 the only thing that gets induced by regular EtOH consumption?

Answer 17

No, other P450 molecules are upregulated, such as 3A4, often resulting in faster metabolism of drugs, reducing their effectiveness / increasing production of toxic metabolites of acetominophen.

Question 18

Why is a BAL of 100 - 199mg / 100ml the danger zone?

Answer 18

Because people fall asleep and you can’t see worsening symptoms easily.

Question 19

4 effects of chronic alcohol abuse on the CNS?

Answer 19

Loss of white and grey matter (esp. frontal lobe).
Reduced brain metabolism.
Wernicke’s / Korsakoff syndrome.
Neuropathy

Question 20

3 acute cardiovascular effects of EtOH?

Answer 20

Vasodilatation
Reduced myocardial contractility
Atrial and ventricular arrhythmias (via higher catecholamine levels)

Question 21

3 chronic cardiovascular negative effects of EtOH?

Answer 21

Increased BP.
Dilated cardiomyopathy
Increased triglyceride levels.

Question 22

3 cardioprotective effects of moderate EtOH?

Answer 22

Raised HDL??
Antioxidant content??
Increases tPA

Question 23

3 effects of EtOH on the kidney?

Answer 23

Decreased ADH (anti-diuretic hormone) -> diuresis and K+ loss
Vasodilation -> diuresis
Decreased uric acid excretion -> gout

Question 24

5 effects of EtOH on the GI tract?

Answer 24

Stimulates gastrin, pepsin, histamine, and gastricacid.
Peptic ulcers.
Emesis.
Pancreatitis.
Gastric and esophageal cancers (maybe via acetaldehyde)

Question 25

Is EtOH consumption a risk factor for lots of different cacners?

Answer 25

Yep. GI tract stuff, liver, breast.

Question 26

4 effects of chronic EtOH on hematopoeisis and immune function?

Answer 26

Reduced platelets
Reduced folate stores / absorption -> macrocytosis
Reduced PMN function
Reduced T-cell function

Question 27

Effect of EtOH on sleep?

Answer 27

Reduces sleep latency and time to REM, but reduces sleep quality overall.
Increases number of apneic episodes.

Question 28

Chronic effects of EtOH on endocrine function (esp in men)?

Answer 28

Testicular atrophy

Gynecomastia

Question 29

Acute effects of EtOH on endocrine function?

Answer 29

Hypoglycema (why late-night burritos are delicious)

Hypokalemia -> vomiting, diarrhea

Question 30

Effects of EtOH on sexual performance?

Answer 30

“…provokes desire, takes away performance…” is probably enough. (but this happens for both sexes.

Question 31

Why can’t fetuses handle EtOH?

Answer 31

It crosses the placenta easily, and they don’t have metabolic machinery (no ADH) to break it down.
Fetal alcohol syndrome is no good.