Alcohol

Question 1

What 3 things influence the rate of alcohol absorption?

Answer 1

1. Ethanol concentration.
2. Rate of consumption.
3. Gastric contents.

Question 2

What is the first major metabolite of alcohol?

Answer 2

Acetaldehyde

Question 3

Alcohol MOA:

Answer 3

Activates GABA receptor ligand-gated Cl- channels (suppress neuronal transmission, help maintain resting membrane potential in some neurons), and inhibits NMDA receptor ligand-gated cation channel (affects cognitive function, learning, memory).

Question 4

Effects of chronic alcoholism:

Answer 4

1. Liver disease (due to fatty liver, Hep C, cirrhosis (due to necrosis and chronic inflammation)).
2. GI pathologies (chronic gastritis, malabsorption of vitamins).
3. Neurotoxicity due to thiamine deficiency. Cerebellar atrophy.

Question 5

Consequences of alcohol tolerance:

Answer 5

Chronic ethanol leads to CNS depression leads to up-regulation of excitatory neurons.

Question 6

Alcohol metabolic tolerance MOA:

Answer 6

Upregulation of CYP2E1.

Question 7

Effects of alcohol on acetaminophen metabolism:

Answer 7

More likely to cause liver toxicity due to to either upregulation of CYP2E1 in alcoholics or inhibition of CYP2E1 along with decreased glutathione in acute toxicity.

Question 8

Major concern for alcohol withdrawal:

Answer 8

Seizures

Question 9

Fetal alcohol syndrome:

Answer 9

Failure to thrive, microcephaly, facial abnormalities. Is a direct result of ethanol or acetaldehyde on embryonic cellular proliferation.

Question 10

Signs of alcohol withdrawal syndrome & goal of treatment:

Answer 10

• Craving, agitation, anxiety, insomnia, seizures, mood swings, sweating, tachycardia.
• Goal is to prevent seizures, delirium, arrhythmias.

Question 11

2 specifics on alcohol dehydrogenase pathway:

Answer 11

1. Is RLS in alcohol metabolism.

2. Requires NAD+, zero-order kinetics.

Question 12

2 major consequences of ethanol metabolism:

Answer 12

1. Increased NADH results in inhibition of TCA cycle and decreased oxidation of fats (basis behind fatty liver).
2. Increased acetaldehyde leads to a generation of protein adducts, decreased glutathione, inhibition of microtubules.

Question 13

Microsomal ethanol oxidizing system:

Answer 13

Induced in alcoholics - requires high concentrations of alcohol to kick in. Influences metabolism of other drugs because of increased levels of CYP2E1. Uses NADPH as a co-factor.

Question 14

Aldehyde dehydrogenase:

Answer 14

• Mitochondrial enzyme; oxidizes acetaldehyde to acetate.
• NAD+ co-factor.
• Genetic polymorphisms (in a lot of Asian populations) contribute to accumulation of acetaldehyde.

Question 15

Disulfiram MOA:

Answer 15

Inhibitor of aldehyde dehydrogenase. Aversion therapy.

Question 16

Can be used as “substitutes” of alcohol for therapy:

Answer 16

Benzodiazepines, Diazepam, Chlordiazepoxide.

Question 17

Naltrexone MOA and use:

Answer 17

Opioid receptor antagonist. Reduces the urge to drink. Best with psychosocial therapy.

Question 18

Acamprosate MOA and use:

Answer 18

GABA mimetic. Decreases drinking frequency and reduces relapse.