14 - Ethanol

Question 1

What is the permeability of ethanol (EtOH)?

Answer 1

EtOH is water-soluble and crosses membranes

Question 2

How does stomach acid alter EtOH?

Answer 2

Has no affect

EtOH is not altered by low pH

Question 3

Drinking on a full stomach ______ absorption and _______ peak BAC

Answer 3

Drinking on a full stomach slows absorption and lowers peak BAC

Question 4

Where does most ethanol absorption occur?

Answer 4

Small intestine.

Starts in the stomach but most absorption occurs in the SI

Question 5

How is BAC measured?

Answer 5

BAC = mgEtOH/100mL of blood

Question 6

Ethanol is distributed throughout _______

Answer 6

Tissues

Question 7

Why do females tend to reach higher BAC?

Answer 7

They are smaller and less lean

Question 8

___ order kinetics describe metabolism of EtOH, what does this mean?

Answer 8

0 order kinetics describe metabolism of EtOH, what does this mean?

• Linear elimination curve
• Regardless of dose, there is a linear relation curve

Question 9

What are the two main enzymes for EtOH metabolism?

Answer 9

1. Alcohol dehydrogenase
2. Aldehyde dehydrogenase

Question 10

Because alcohol dehydrogenase and aldehyde dehydrogenase ______ quickly and require ____ to operate, the max rate of metabolism is:

Answer 10

Because alcohol dehydrogenase and aldehyde dehydrogenase saturate quickly and require NAD+ to operate, the max rate of metabolism is: 8g/hr

= 0.015 BAC elimination/hour

Question 11

Where is alcohol metabolized?

***** needs editing

Answer 11

Liver primarily

Oral mucosa (Breath AC)

Filtered in Kidney

Absorbed in GI tract

Question 12

EtOH modulates _____ and _______ receptor activity in the brain

• Tilts the balance of neuronal activation towards:

Answer 12

EtOH modulates Glutamate (Glu) and GABA (gamma-aminobutyric acid) receptor activity in the brain

• Tilts the balance of neuronal activation towards: hyperpolarization = inhibition

Question 13

Strong potentiation of _______ receptors at lower [EtOH]

Answer 13

Strong potentiation of GABAA receptors at lower [EtOH]

Question 14

Inhibition of ________ receptors and ________ channels at higher [EtOH]

Answer 14

Inhibition of Glu-NMDA receptors and voltage-gated Ca2+ channels at higher [EtOH]

Question 15

What is the overall effect of EtOH action on brain receptors?

Answer 15

neuronal inhibition, sedative-like effects

• Asphyxiation at lethal doses (0.4-0.5 BAC) via depressed activity in autonomic centres

Question 16

To which superfamily of channels do GABA_A receptors belong?

Answer 16

Cys-loop ligand-ligand channel superfamily

• heteropentameric receptors
  
  • 2 alpha subunits, 2 beta subunits and 1 other
  • Conduct negative chloride current INTO neurons

Question 17

GABA_A receptors conduct _______ into neurons

Answer 17

GABA_A receptors conduct Cl- into neurons

Question 18

To which receptor superfamily do NMDA receptors belong?

Answer 18

Ionotropic Glu receptor superfamily

• Heterotetrameric receptors
  
  • Contain 2NR1 subunits and either 2 NR2 or 2 NR3 subunits
• Conduct positive currents into neurons = depolarizing

Question 19

• NMDA receptors belong to the ________ receptor superfamily.
• They are Heterotetrameric and contain 2 _______ and either 2 _______or 2 _______
• They conduct ________ into neurons

Answer 19

• NMDA receptors belong to the Ionotropic Glu receptor superfamily.
• They are Heterotetrameric and contain 2 NR1 and either 2 NR3 or 2 NR3
• They conduct Positive currents (Ca2+ / Na+) into neurons = depolarizing

Question 20

Alcohol is addictive because it releases ____ in the brain

Answer 20

Alcohol is addictive because it releases dopamine in the brain

Question 21

________ gives the sensation of warm skin but the core temperature is _______

Answer 21

Vasodilation gives the sensation of warm skin but the core temperature is decreased = Autonomic Brainstem nuclei

Question 22

How can alcohol contribute to gastric ulcer formation?

Answer 22

Through the loss of mucosal lining

Question 23

Why does alcohol give the “spins” and at what BAC would you get this effect?

Answer 23

• BAC ~0.04
• EtOH permeates endolymph and cupula
• BAC starts to decline
• EtOH diffuses out of the cupula before the endolymph
  
  • Cupula is now denser than endolymph and does not stabilize when lying down
  • activates sensory fibres
  • Brain interprets this as motion

Question 24

How is metabolic tolerance achieved?

Answer 24

Up-regulation of enzymes in heavy drinkers

Question 25

What are some hangover symptoms? Physical and psychological? When do these symptoms PEAK?

Answer 25

* Physical: * headache * diarrhea * fatigue * restlessness * nausea * Psychological * haziness * slower cognition * impaired reaction times * poor reasoning * Symptoms peak as BAC reaches 0

Question 26

What is the possible immune component involved in causing hangover?

Answer 26

Increased cytokine production via thromboxane pathway

Question 27

What is a Congener?

Answer 27

Minor chemical constituent, especially one that gives a distinctive character to a wine or liquor or is responsible for some of its physiological effects * substances that flavour and colour drinks * More congeners = worse hangover

Question 28

Heavy drinking can cause the brain to metabolize ________ instead of \_\_\_\_\_\_

Answer 28

Heavy drinking can cause the brain to metabolize _acetate_ instead of _glucose_

Question 29

what stage of fetal development is most vulnerable to fetal alcohol spectrum disease? What does FASD affect?

Answer 29

Third trimester * synaptogenesis * Facial development

Question 30

How can EtOH change brain health?

Answer 30

* Metabolite of ethanol, **acetaldehyde**, is reactive * Modifies proteins = causes dysfunction * eg affects glucose metabolism, protein synthesis, myelin formation, all of which *damage neurons and cause cell death*

Question 31

What are four regions that are at an increased risk for cancer with EtOH use?

Answer 31

* Upper GI tract * Colorectal * Liver * Breast

Question 32

Why is the upper GI tract susceptible to cancer with high alcohol use?

Answer 32

Because microflora contribute to EtOH metabolism * Acetaldehyde can reach 10-100x higher concentrations than in the blood * Poor hygiene increases microbe count * Smoking increases acetaldehyde production

Question 33

How is acetaldehyde linked with cancer?

Answer 33

Acetaldehyde interferes with DNA synthesis and repair