Ethanol

Question 1

1. Is alcohol potent?
2. What is a “single dose”?
   What is the liquid beverage equivalent?

Answer 1

1. No it is not potent
2. “Single dose” is 14 grams.
   12 ounces of beer, 5 ounces of wine, 1.5 oz of 80 proof

Question 2

What is the blood alcohol effect of 14g ETOH on 70kg person?

Answer 2

0.03 % w/v = 30mg/dL

Question 3

1. What determines distribution of ETOH?
2. Why does a breathalizer work?
3. What determines indivual organ distribution of ETOH?

Answer 3

1. Total body water
2. ETOH crosses membranes freely, including alveoli.
3. Dependent on amount of blood flow

Question 4

1. What is ETOH primarily metabolized into?
2. What role do gastric and liver alcohol dehydrogenases have?

Answer 4

1. Acetaldehyde
2. They create a first pass effect

Question 5

1. What are the two major enzymes that metabolize ETOH into acetaldehyde?
2. What type of kinetics are involved with ETOH? Why?
3. How is Acetaldehyde metabolized for elimination?

Answer 5

1. Alcohol dehydrogenase and CYP2E1
2. Zero order kinetics. ADH is rapidly saturated.
3. Aldehyde dehydrogenase

Question 6

1. How much alcohol is required to saturate ADH and begin accumulating alcohol?
2. How long does one 14g drink take to be metabolized?

Answer 6

1. 10g/hr in 70kg person
2. 1.5 hours

Question 7

1. How does Disulfiram (Antabuse) work?
2. Why do those of Asian decent have impaired ETOH metabolism?

Answer 7

1. It inhibits Aldehyde dehydrogenase and causes an increase acetaldehyde and nausea/vomiting symptoms.
2. Genetic polymorphism that impairs activity of aldehyde dehydrogenase

Question 8

Why do alcoholics become hypoglycemic?

Answer 8

1. Increased NADH impairs TCA cycle and reduces gluconeogenesis.
2. There is also reduced fatty acid oxidation.
3. Ethanol promotes insulin secretion

Question 9

What does the metabolite of ETOH, acetaldehyde, cause?

Answer 9

1. Protein adduct formation which results in inflammation.
2. Inhibition of microtubules
3. Depletion of glutathione.

Question 10

1. What is the most important receptor for ETOH?
2. Why does ETOH promote inhibition?

Answer 10

1. GABA_A receptor-ligand gated Cl^-
2. It disturbs the balance between excitatory and inhibitory neurotransmission

Question 11

Why is ETOH withdrawal dangerous?

Answer 11

Removal of chronic CNS depression can result in over-excitation/seizures. These are significantly worse in the presence of metabolic derangement.

Question 12

Chronic alcohol use can result in Thiamine deficiency. What three significant clinical effects result from this?

Answer 12

1. Cerebral/cerebellar atrophy
2. Wernicke’s encephalopathy
3. Korsakoff’s psychosis

Question 13

What amount of alcohol generally causes “acute intoxication”?

Answer 13

400mg/dl = 12 drinks

Question 14

1. What is a Mu Opiate Receptor antagonist that is used to treat alcoholism?
2. What is Acamprosate?

Answer 14

1. Naltrexone
2. GABA_A agonist that can decrease drinking frequency and relapse. It is thought to normalize dysregulated neurotransmission.