Alcohol

Question 1

Where is alcohol dehydrogenase mainly found?

Answer 1

In the cytosol of cells in the liver and git

Question 2

Alcohol dehydrogenase function

Answer 2

Metabolizes low to moderate doses of ethanol (into acetaldehyde)

Question 3

Why does the alcohol dehydrogenase reaction exhibit 0 order kinetics

Answer 3

Because NAD+ is limiting

This means a constant amount of drug is eliminated per unit time

Question 4

ALD1B*2 genetic polymorphism

Answer 4

Mutation in Alcohol Dehydrogenase
40-fold higher Vmax than ALD1B
Reduced risk of heavy drinking
They metabolize it so quickly so they have less chance of feeling euphoric effects, but more chance of converting to acetaldehyde which can be averting

Question 5

How does acetaldehyde make you feel?

Answer 5

Nauseous, ill, sweating, trembling

Question 6

ALDH2*2 genetic polymorphism

Answer 6

Non-functional aldehyde dehydrogenase

Homozygotes have a severe reaction

Question 7

MEOS

Answer 7

Consists of cytochrome P450 2E1, 1A2 and 3A4
Uses NADPH as cofactor
Contributes to ethanol metabolism when ADH system is saturated
Chronic alcohol consumption induces MEOS

Question 8

Which membrane proteins does alcohol affect?

Answer 8

GABAa receptors
Inhibits the activity of glutamate at NDMA receptors
Effects ATPases and adenyl cyclases (cell signalling)
Ion channels (like K ones)

Question 9

3 steps in NMDAR activation

Answer 9

1. Activation of non-NDMA receptors leads to cell depolarization
2. Relieves NMDA receptors of Mg block
3. Channel opens allowing cation entry

Question 10

What causes blackouts?

Answer 10

Results from NMDA receptor blockade by ethanol

Not capable of forming new memories

Question 11

4 things that influence blood levels of alcohol

Answer 11

Body size and build (lean muscle = more water = decreased effects)
Gender (men have more lean muscle)
General health (liver function)
Food consumption (food slows absorption)

Question 12

Metabolic consequences of alcohol (6)

Answer 12

Oxidative stress
Depletion of antioxidants like glutathione
Dysregulation of fatty acid oxidation and synthesis
Damage to mitochondria
Inflammation
Cytokine damage

Question 13

2 serious effects of ethanol on the body

Answer 13

Myocardial contraction depressed
Vasodilation from depression of the vasomotor center in the CNS and direct actions on smooth muscle, which can lead to hypothermia

Question 14

Effects of chronic alcohol consumption (5)

Answer 14

Liver function decreased
Gluconeogensis reduced
Hypoglycemia
Fat accumulation in the liver (from depleted NAD+)
CIrrhosis

Question 15

Wernicke-Korsakoff syndrome is from…

Answer 15

Deficiencies in vitamin B1

Question 16

What are the delirium tremens

Answer 16

Tachycardia
Hypertension
Low-grade fever
Tremor
Diaphoresis
Delirum
Agitation

Question 17

What benzodiazepiene can you use to treat alcohol withdrawal?

Answer 17

Diazepam

Question 18

Why do you use a benzo to help with alcohol withdrawal?

Answer 18

To lower the withdrawal severity and keep it below the seizure threshold

Question 19

Disulfiram

Answer 19

Used to manage alcohol addiction
Can take it every day, no effects without alcohol
Causes extreme discomfort when alcohol is consumed
Flushing, headache, nausea, vomiting, sweating, hypotension and confusion
Binds to an inactivates aldehyde dehydrogenase

Question 20

Naltrexone

Answer 20

Will get abstinence in every 1 out of 10 people that you treat and significant reduction in everyone else
Functions as a competitive antagonist at opioid receptors and exhibits the highest affinity for the mu receptor isoform

Question 21

Ethanol and beta endorphins

Answer 21

Ethanol promotes beta endorphin release in regions of the brain involved in reward
Central effects are mediated through mu opioid receptors
Beta endorphins can directly stimulate dopamine release in the nucleus accumbens

Question 22

Acamprosate

Answer 22

Alters the activity of NMDA receptors
Highly dose dependent
Can lessen withdrawal and cravings

Question 23

Gabapentin and alcohol

Answer 23

Normalizes the stress-induced GABA activation in the amygdala that is associated with alcohol dependence

Question 24

Methanol poisoning

Answer 24

Can cause visual disturbances
Toxicity is related to build up of formaldehyde and formate (occurs slowly)
Can lead to bradycardia, coma, seizures, and cessation of respiration

Question 25

Ethylene Glycol poisoning

Answer 25

Antifreeze

Toxicity is related to build up of oxalate and other metabolites which can occur slowly

Question 26

2 inhibitors of ADH

Answer 26

Fomepizole
Ethanol
Can be used to treat ethylene glycol poisoning