Class#9-EtOH

Question 1

EtOH effects?

Answer 1

disinhibition/relaxation (stimulation at low level), sedation, hypnosis, general anaestesia, coma, death

Question 2

CNS depressants 5 majors concepts?

Answer 2

1. Additive effects: add to one another
2. Can’t reverse with stimulants
3. General depressants are not totally general
4. Chronic use ->rebound effect
5. Cross-tolerance: tolerance to one will be tolerant to another

Question 3

Higher [] =

Answer 3

more widespread effect

Question 4

Amnesia types?

Answer 4

1. Partial: Universal, dose related

2. Blackouts: NO memory, susceptibility varies

Question 5

Level of BAC driving impairment starts at?

Answer 5

0.03%

Question 6

Etoh effect on cortex, hippocampus/cerebellum

Answer 6

judgment, memory and coordination

Question 7

EtOH effets on receptors/dynamics (8)?

Answer 7

1. GABA a (major inhibitory): opens channel and maximize Cl- crossing. Affect subsynaptic and postsynaptic receptor + extra synaptic receptors for GABA inducing tonic inhibition = substained inhibition of a neuron. Can also increase release of presynaptic GABA.
2. Release glycine and enhance postsynaptic 1 response (inhibitory pathway). Mainly in spinal cord (coordination) and brainsteam (resp/cardiac functions),. Pathway coupled to ion channel through GPCR
3. Decrease excitatory. Block glutamate transmission by blocking NMDA receptors (impaired intellectual functions). Chronic use upregulate GluN1 and GluN2B. This contribute to EtOH tolerance.
4. Block release of Ach = amnesia/cognitive impairments
5. Decrease serotonin = impulsivness and aggression
6. Facilitate release of dopamine in reward pathway, lead to addiction
7. Facilitate release of endorphins - addiction
8. Blocks voltage-operated calcium channels (VOCC) = reduce neurotransmitter release

Question 8

Effect on kidneys.

Answer 8

decrease reabsorption = increase excretion

Question 9

Absorption?

Answer 9

1. Highly lipid soluble and readily absorbed. If drink rapidly rate of absorption increase and rate of metabolism decrease.
2. 20% in stomach, 80% in SI
3. If gastric emptying rate higher = higher absorption rate. Carbonation.
4. Emptying rate decreased by food, particularly lipid
5. Peak BAC level lower when stomach full then empty

Question 10

Metabolism?

Answer 10

1. 20% in stomach mucosa by ADH (lower in women)
2. Low dose first order kinetics (1/2 drink per hours), high dose zero order kinetics.
3. Alcohol Dehydrogenase (ADH) -> acetyldehyde, then Acetyldehyde Dehydrogenase (ALDH) -> Acetate

Question 11

Distribution

Answer 11

1. Goes everywhere. AVD = to total body water. More [] in women b/c less water%.
2. Easily BBB
3. Can stimulate directly vomiting center in medula and CTZ

Question 12

Elimination

Answer 12

10%: breath, urine, sweat
10%: MIcrosomal enz. P450
80%: ADH in cytosol

Question 13

ADH molecule?

Answer 13

Dimer with 6 potential subunits

Question 14

ALDH subtypes? most important?

Answer 14

9, ALDH2

Question 15

chronic etoh P450?

Answer 15

4. Chronic use: CYP2E1

Question 16

Etoh therapeutic index

Answer 16

4

Question 17

Liver diseases?

Answer 17

Hepatitis - reversible
Fatty liver -reversible
Fibrosis- irr.
Cirrhosis - irr.
#Also affect vasc. in SI = lower blood flow to liver
#Hepatic encephalopathy: liver cannot metabolize

Question 18

Tolerance

Answer 18

Acute:
Chronic: More NMDA, more metabolism, behavioral

Question 19

Disulfiram?

Answer 19

Block ALDH = flushing, headaches, nausea, vomiting, hypotension